Indoor residual spraying (IRS) using neonicotinoid-based insecticides (clothianidin and combined clothianidin with deltamethrin) was deployed in two previously unsprayed districts of Côte d’Ivoire in 2020 and 2021 to complement standard pyrethroid insecticide-treated nets. This retrospective observational study uses health facility register data to assess the impact of IRS on clinically reported malaria case incidence.
Health facility data were abstracted from consultation registers for the period September 2018 to April 2022 in two IRS districts and two control districts that did not receive IRS. Malaria cases reported by community health workers (CHWs) were obtained from district reports and District Health Information Systems 2. Facilities missing complete data were excluded. Controlled interrupted time series models were used to estimate the effect of IRS on monthly all-ages population-adjusted confirmed malaria cases and cases averted by IRS. Models controlled for transmission season, precipitation, vegetation, temperature, proportion of cases reported by CHWs, proportion of tested out of suspected cases and non-malaria outpatient visits.
An estimated 10 988 (95% CI 5694 to 18 188) malaria cases were averted in IRS districts the year following the 2020 IRS campaign, representing a 15.9% reduction compared with if IRS had not been deployed. Case incidence in IRS districts dropped by 27.7% (incidence rate ratio (IRR) 0.723, 95% CI 0.592 to 0.885) the month after the campaign. In the 8 months after the 2021 campaign, 14 170 (95% CI 13 133 to 15 025) estimated cases were averted, a 24.7% reduction, and incidence in IRS districts dropped by 37.9% (IRR 0.621, 95% CI 0.462 to 0.835) immediately after IRS. Case incidence in control districts did not change following IRS either year (p>0.05) and the difference in incidence level change between IRS and control districts was significant both years (p<0.05).
Deployment of clothianidin-based IRS was associated with a reduction in malaria case rates in two districts of Côte d’Ivoire following IRS deployment in 2020 and 2021.
Lack of transparent communication between patients and physicians regarding the use of herbal medicine (HM) presents a major public health challenge, as inappropriate HM use poses health risks. Considering the widespread use of HM and the risk of adverse events, it is crucial for pregnant women to openly discuss their HM use with healthcare providers. Therefore, this systematic review and meta-analysis aims to estimate the pooled prevalence of pregnant women’s HM use and disclosure to healthcare providers and to examine the relationship between HM disclosure and various maternal and child health (MCH) measures.
A systematic search of five databases was conducted for cross-sectional studies on HM use during pregnancy published from 2000 to 2023. Data extraction followed a standardised approach, and Stata V.16.0 was used for data analysis. Also, Spearman’s correlation coefficient was calculated to examine the association between use and disclosure of HM and various MCH indicators.
This review included 111 studies across 51 countries on the use of HM among pregnant women. Our findings showed that 34.4% of women used HM during pregnancy, driven by the perception that HM is presumably safer and more natural than conventional medical therapies. However, only 27.9% of the HM users disclosed their use to healthcare providers because they considered HM as harmless and were not prompted by the healthcare providers to discuss their self-care practices. Furthermore, a significant correlation was observed between HM disclosure and improved MCH outcomes.
Inadequate communication between pregnant women and physicians on HM use highlights a deficiency in the quality of care that may be associated with unfavourable maternal outcomes. Thus, physician engagement in effective and unbiased communication about HM during antenatal care, along with evidence-based guidance on HM use, can help mitigate the potential risks associated with inappropriate HM use.
Neglected tropical diseases (NTDs) are a diverse group of debilitating diseases and conditions afflicting more than one billion people in impoverished communities. Control of these diseases is crucial to achieve Sustainable Development Goal 3 and the pledge to ‘leave no one behind’. Relying on large-scale delivery of wide-spectrum drugs to individuals in at-risk communities irrespective of their health status, mass drug administration is a core strategy for tackling half of the NTDs targeted by the latest WHO roadmap (2021–2030). However, ethical challenges surround its implementation and long-term impact. This systematic review aims to give a comprehensive picture of the variety of ethical reasons for and against mass drug administration for NTD control and elimination, facilitating further debate in ethics and policy.
PubMed and Web of Science Core Collection were searched for all relevant publications. Of the 486 retrieved records, 60 met the inclusion criteria for qualitative analysis. Ethical reasons discussing the topic at hand were extracted from full texts and synthesised through the Kuckartz method of qualitative content analysis.
Data extraction revealed 61 ethical reasons, of which 20 (32.7%) had positive, 13 (21.3%) had ambivalent and 28 (45.9%) had negative implications regarding mass drug administration for NTDs. The health benefits and cost-effectiveness of the measure were extensively highlighted. However, equity, autonomy and sustainability emerged as the domains with the most pressing ethical concerns. Many issues related to implementation are yet to be adequately addressed in policy documents.
This is the first systematic review of ethical reasons pertaining to mass drug administration for NTD control and elimination. Due to the diversity of included studies, no general recommendations can be made. Instead, context-specific strategies seem necessary. Alternative approaches tackling socioecological determinants of ill health are needed for long-term sustainability. Future research could benefit from contributions of non-Western philosophies and perspectives by local researchers.
Global tuberculosis (TB) drug resistance (DR) surveillance focuses on rifampicin. We examined the potential of public and surveillance Mycobacterium tuberculosis (Mtb) whole-genome sequencing (WGS) data, to generate expanded country-level resistance prevalence estimates (antibiograms) using in silico resistance prediction.
We curated and quality-controlled Mtb WGS data. We used a validated random forest model to predict phenotypic resistance to 12 drugs and bias-corrected for model performance, outbreak sampling and rifampicin resistance oversampling. Validation leveraged a national DR survey conducted in South Africa.
Mtb isolates from 29 countries (n=19 149) met sequence quality criteria. Global marginal genotypic resistance among mono-resistant TB estimates overlapped with the South African DR survey, except for isoniazid, ethionamide and second-line injectables, which were underestimated (n=3134). Among multidrug resistant (MDR) TB (n=268), estimates overlapped for the fluoroquinolones but overestimated other drugs. Globally pooled mono-resistance to isoniazid was 10.9% (95% CI: 10.2-11.7%, n=14 012). Mono-levofloxacin resistance rates were highest in South Asia (Pakistan 3.4% (0.1–11%), n=111 and India 2.8% (0.08–9.4%), n=114). Given the recent interest in drugs enhancing ethionamide activity and their expected activity against isolates with resistance discordance between isoniazid and ethionamide, we measured this rate and found it to be high at 74.4% (IQR: 64.5–79.7%) of isoniazid-resistant isolates predicted to be ethionamide susceptible. The global susceptibility rate to pyrazinamide and levofloxacin among MDR was 15.1% (95% CI: 10.2-19.9%, n=3964).
This is the first attempt at global Mtb antibiogram estimation. DR prevalence in Mtb can be reliably estimated using public WGS and phenotypic resistance prediction for key antibiotics, but public WGS data demonstrates oversampling of isolates with higher resistance levels than MDR. Nevertheless, our results raise concerns about the empiric use of short-course fluoroquinolone regimens for drug-susceptible TB in South Asia and indicate underutilisation of ethionamide in MDR treatment.
Achieving the Sustainable Development Goals to reduce maternal and neonatal mortality rates will require the expansion and strengthening of quality maternal health services. Midwife-led birth centres (MLBCs) are an alternative to hospital-based care for low-risk pregnancies where the lead professional at the time of birth is a trained midwife. These have been used in many countries to improve birth outcomes.
The cost analysis used primary data collection from four MLBCs in Bangladesh, Pakistan and Uganda (n=12 MLBC sites). Modelled cost-effectiveness analysis was conducted to compare the incremental cost-effectiveness ratio (ICER), measured as incremental cost per disability-adjusted life-year (DALY) averted, of MLBCs to standard care in each country. Results were presented in 2022 US dollars.
Cost per birth in MLBCs varied greatly within and between countries, from US$21 per birth at site 3, Bangladesh to US$2374 at site 2, Uganda. Midwife salary and facility operation costs were the primary drivers of costs in most MLBCs. Six of the 12 MLBCs produced better health outcomes at a lower cost (dominated) compared with standard care; and three produced better health outcomes at a higher cost compared with standard care, with ICERs ranging from US$571/DALY averted to US$55 942/DALY averted.
MLBCs appear to be able to produce better health outcomes at lower cost or be highly cost-effective compared with standard care. Costs do vary across sites and settings, and so further exploration of costs and cost-effectiveness as a part of implementation and establishment activities should be a priority.
Infectious disease outbreaks have historically led to widespread disruptions in routine essential health services. Disruptions due to COVID-19 responses led to excess deaths, including among women and children. This review builds on earlier reviews of essential health services in national COVID-19 response and preparedness plans, focusing specifically on maternal, newborn, child, adolescent and ageing health (MNCAAH) in the context of renewed global emphasis on monitoring, recovering and strengthening these services.
Using Google searches, we identified publicly available COVID-19 response and preparedness plans authored by a national government body or Public Health Institute from any country, territory and/or area, published between January 2020 and December 2022. We assessed whether each plan considered maintenance of MNCAAH services with related activities, costing or monitoring plans, and whether these considerations were integrated into the national incident management system for COVID-19.
We identified plans from 110 countries, representing 56% of our sample, in 10 languages. Most plans came from low-income and middle-income countries. Three quarters of dated documents were published between February and April 2020. 22% of plans referenced the impact of COVID-19 on MNCAAH, but only 13% included a planned activity for monitoring or mitigating this impact and less than 5% included relevant indicators, costing or integration of services in the incident management system.
We propose that unless content specifically related to the services and needs of these populations is integrated, these services will suffer in a future disruptive event. The COVID-19 response demonstrated the need for an interdisciplinary response to address the unforeseen impacts that arose, yet plans continue to have a narrow focus and a generic approach which may be limiting.
In the past decade, global health research has seen a growing emphasis on research integrity and fairness. The concept of research integrity emerged in response to the reproducibility crisis in science during the late 2000s. Research fairness initiatives aim to enhance ownership and inclusivity in research involving partners with varying powers, decision-making roles and resource capacities, ultimately prioritising local health research needs. Despite extensive academic discussions, empirical data on these aspects, especially in the context of global health, remain limited.
To address this gap, we conducted a mixed-methods study focusing on research integrity and fairness. The study included an online frequency survey and in-depth key informant interviews with researchers from international research networks. The dual objectives were to quantify the frequency of practices related to research integrity and fairness and explore the determinants influencing these practices in global health.
Out of 145 participants in the quantitative survey (8.4% response rate), findings indicate that global health researchers generally adhere to principles of research integrity and fairness, with variations in reported behaviours. The study identified structural, institutional and individual factors influencing these patterns, including donor landscape rigidity, institutional investments in relationship building, guidelines, mentoring and power differentials among researchers.
This research highlights that, despite some variations, there is a substantial alignment between research integrity and fairness, with both sharing similar determinants and the overarching goal of enhancing research quality and societal benefits. The study emphasises the potential to explicitly recognise and leverage these synergies, aligning both agendas to further advance global health research.
A designathon is a three-stage participatory activity informed by design thinking. There is a growing literature on designathons in health. This study synthesised designathons’ effectiveness and implementation-related factors to address health challenges.
We searched Cochrane Library, Embase, PubMed, Scopus and the ClinicalTrials.gov registry for articles containing primary data on designathons for health from their dates of inception to 29 November 2022. We retrieved additional studies from citation searching and a complementary open call. We synthesised data on designathons’ effectiveness (ie, engagement, outputs and implementation), required resources and implementation-related factors (ie, resources, facilitators, barriers, strengths and limitations). We assessed the risk of bias using a checklist adapted from Joanna Briggs Institute Critical Appraisal tools.
In total, 4973 citations were identified, and 42 studies were included. In total, 26 studies (62%) were from high-income countries. The median number of total participants was 49, divided into a median of 8 teams. The duration of the intensive collaboration phase ranged from 3 hours to 7 days. Common evaluation criteria were feasibility, innovation and impact. Idea and prototype outputs included mobile phone applications, educational programmes and medical devices. Interventions developed from a designathon was estimated to be highly cost-effective. The most common facilitators were interdisciplinary participants and high-quality mentorship. The most common barriers were suboptimal execution of the events, difficulties in balancing interdisciplinary participants across teams and limited support for participants along the process. There were limited data on required resources and further implementation of solutions after designathons.
Given designathons’ adaptability in terms of budget, mode of delivery, type of output and involvement of diverse participants, including end users, designathons can be implemented in a wide range of contexts to address various health issues.
CRD42023389685.
Food reformulation is promoted as a tool to improve the nutritional quality of population diets. However, the potential impact of industry-wide reformulation on dietary intake has been investigated minimally.
The aim was to estimate the impact on the French population nutrient intakes of industry-wide reformulation towards healthier products using the updated nutrient profiling system underpinning the front-of-pack nutrition label Nutri-Score (uNS-NPS).
Dietary data were retrieved from the Nutrinet-Santé cohort at baseline (N=100 418), providing detailed information regarding participants’ food choices (N>3000 generic food items). Each individual food from 24 hours dietary record was matched with French food market data from OpenFoodFacts database (N=119 073 products). Three scenarios were constructed using nutrient content of currently existing food products: (1) all products available (baseline situation); (2) only existing products of better nutritional quality were available as potential substitutes and (3) only existing products of poorer quality were available. The assessment of the nutritional quality was based on the uNS-NPS score. Finally, dietary intakes were calculated for each scenario after random attribution of healthier/less healthy products as dietary choices. Monte-Carlo iterations (n=300) were conducted to generate uncertainty intervals.
After simulation of reformulation using scenario 2, reduction in daily intake in comparison with the baseline situation was observed for energy (–55 kcal/day, –2.9%), saturated fat (–2.4g/day, –7.6%), sugar (–4.8g/day, –5.3%) and salt (–0.54g/day, –8.3%) and increase was observed for fibre (+1.0g/day, +4.9%). Improvements in diet quality were observed regardless of the overall quality of diet. The most important contributors to diet improvement were the followings: (1) sugars: sugary products, sweet bakery products and dairy products; (2) saturated fat: sweet bakery products, dairy products and prepared dishes and (3) salt: bread, prepared dishes, vegetable preparations and soups.
Widespread reformulation of food offer appeared to be an opportunity for improving nutritional status at population level in France.
Pregnant women and their offspring are often at increased direct and indirect risks of adverse outcomes during epidemics and pandemics. A coordinated research response is paramount to ensure that this group is offered at least the same level of disease prevention, diagnosis, and care as the general population. We conducted a landscape analysis and held expert consultations to identify research efforts relevant to pregnant women affected by disease outbreaks, highlight gaps and challenges, and propose solutions to addressing them in a coordinated manner.
Literature searches were conducted from 1 January 2015 to 22 March 2022 using Web of Science, Google Scholar and PubMed augmented by key informant interviews. Findings were reviewed and Quid analysis was performed to identify clusters and connectors across research networks followed by two expert consultations. These formed the basis for the development of an operational framework for maternal and perinatal research during epidemics.
Ninety-four relevant research efforts were identified. Although well suited to generating epidemiological data, the entire infrastructure to support a robust research response remains insufficient, particularly for use of medical products in pregnancy. Limitations in global governance, coordination, funding and data-gathering systems have slowed down research responses.
Leveraging current research efforts while engaging multinational and regional networks may be the most effective way to scale up maternal and perinatal research preparedness and response. The findings of this landscape analysis and proposed operational framework will pave the way for developing a roadmap to guide coordination efforts, facilitate collaboration and ultimately promote rapid access to countermeasures and clinical care for pregnant women and their offspring in future epidemics.
Global health collaborations between individuals from high-resource and low-resource settings are complex and often built on hierarchical structures and power differentials that are difficult to change. There have been many calls and frameworks developed to facilitate more equity within these collaborations, yet little is known about the lived experiences of global health donors and recipients working within such collaborations and how those experiences can facilitate more equitable collaboration. Liberia, a postconflict, post-Ebola country, provides an ideal setting to study lived experiences of global health collaborations.
Methods
Our qualitative analysis used key informant interviews representing the perspectives of those working on behalf of the Liberian government, Liberian academics, foreign donors and non-governmental organisations and implementing partners. Thematic analysis guided this analysis to explore topics such as financial control, accountability and decision making.
Results
The first phase of the analysis mapped the existing patterns of priority setting. Priority-setting power was most strongly held by those with financial control (donors), and implementation plans tended to be built on metrics that aim to meet donor expectations. The second phase of the analysis explored the interplay between underlying factors that we identified in our data associated with driving collaborative inequity: history of prior of engagement, level of transparency and patterns of accountability.
Conclusions
Our findings highlight that global health collaborations in Liberia are structured to hinder equitable partnerships. The power structure tied to financial ownership offers little space for recipients to have an equitable role in collaborations, which maintains dependence on external aid and ensures that weak systems remain weak. While our study is limited to Liberia, we anticipate that these dynamics are common elsewhere and reinforce the importance of intentional efforts to ensure equitable decision making and power structures in similar settings worldwide.
]]>Equitable access to vaccines for migrants and refugees is necessary to ensure their right to health and to achieve public health goals of reducing vaccine-preventable illness. Public health policies require regulatory frameworks and communication to effect uptake of effective vaccines among the target population. In Colombia, the National COVID-19 Vaccination Plan implicitly included Venezuelan refugees and migrants; however, initial communication of the policy indicated that vaccine availability was restricted to people with regular migration status. We estimated the impact of a public announcement, which clarified access for refugees and migrants, on vaccination coverage among Venezuelans living in Colombia.
Between 30 July 2021 and 5 February 2022, 6221 adult Venezuelans participated in a cross-sectional, population-based health survey. We used a comparative cross-sectional time-series analysis to estimate the effect of the October 2021 announcement on the average biweekly change in COVID-19 vaccine coverage of Venezuelans with regular and irregular migration status.
71% of Venezuelans had an irregular status. The baseline (preannouncement) vaccine coverage was lower among people with an irregular status but increased at similar rates as those with a regular status. After the announcement, there was a level change of 14.49% (95% CI: 1.57 to 27.42, p=0.03) in vaccination rates among individuals with irregular migration status with a 4.61% increase in vaccination rate per biweekly period (95% CI: 1.71 to 7.51, p=0.004). By February 2022, there was a 26.2% relative increase in vaccinations among individuals with irregular migration status compared with what was expected without the announcement.
While there was no policy change, communication clarifying the policy drastically reduced vaccination inequalities across migration status. Lessons can be translated from the COVID-19 pandemic into more effective global, regional and local public health emergency preparedness and response to displacement.
Citizen science (CS) is an emerging approach in public health to harness the collective intelligence of individuals to augment traditional scientific efforts. However, citizens’ viewpoint, especially the hard-to-reach population, is lacking in current outbreak-related literature. We aim to understand the awareness, readiness and feasibility of outbreak-related CS, including digitally enabled CS, in low-income and middle-income countries.
This mixed-method study was conducted in nine countries between October 2022 and June 2023. Recruitment through civil society targeted the general population, marginalised/indigenous groups, youth and community health workers. Participants (aged ≥18 years) completed a quantitative survey, and a subset participated in focus group discussions (FGDs).
2912 participants completed the survey and 4 FGDs were conducted in each country. Incorporating participants’ perspectives, CS is defined as the practice of active public participation, collaboration and communication in all aspects of scientific research to increase public knowledge, create awareness, build trust and facilitate information flow between citizens, governments and scientists. In Bangladesh, Indonesia, the Philippines, Cameroon and Kenya, majority were unaware of outbreak-related CS. In India and Uganda, majority were aware but unengaged, while in Nepal and Zimbabwe, majority participated in CS before. Engagement approaches should consider different social and cultural contexts, while addressing incentivisation, attitudes and practicality factors. Overall, 76.0% expressed interest in digital CS but needed training to build skills and confidence. Digital CS was perceived as convenient, safer for outbreak-related activities and producing better quality and quantity of data. However, there were concerns over non-inclusion of certain groups, data security and unclear communication.
CS interventions need to be relatable and address context-specific factors influencing CS participation. Digital CS has the potential to facilitate collaboration, but capacity and access issues must be considered to ensure inclusive and sustainable engagement.
One of the ultimate goals of strengthening the health system is to achieve health equity. Vietnam is considered one of the ‘fast-track countries’ to achieve the health-related Millennium Development Goals, but research on its equity strategies remains inadequate.
Using Vietnamese official health statistics, we investigated inequity in four dimensions including health resources, service delivery, service utilisation and residents’ health status from the perspectives of income levels, poverty rates and subnational regions. The Slope Index of Inequality, concentration curve/Concentration Index, absolute difference and Theil Index were used.
Four indicators showed ‘pro-poor’ inequality in health resources, including the per capita health budget, per capita health personnel, per capita health personnel at the community level and per capita hospital beds at the community level, while provincial hospital beds showed ‘pro-rich’ inequality. Two health service delivery indicators (delivery of antenatal care ≥3 times and proportion of community health service centres with medical doctors) show ‘pro-rich’ inequality, although two health status indicators, mortality and malnutrition rates for children under five, showed ‘pro-poor’ inequality. The Northern Midlands and Mountain Areas, and the Central Highlands were disadvantaged regarding service delivery and health status. Intraregional differences were the main factors contributing to the inequalities in delivery of antenatal care ≥3 times, provincial hospital beds and percentage of community health centres with medical doctors, with the Red River Delta and the South East region experiencing the greatest inequalities.
The overall level of health equity in Vietnam has increased over the past decade, although inequality in health service delivery has hindered progress towards health equity based on income, poverty and subnational regions. Targeted policies need to be introduced to reduce inequities relating to the health workforce and service delivery capacity.
Antivenom is a lifesaving medicine for treating snakebite envenoming, yet there has been a crisis in antivenom supply for many decades. Despite this, substantial quantities of antivenom stocks expire before use. This study has investigated whether expired antivenoms retain preclinical quality and efficacy, with the rationale that they could be used in emergency situations when in-date antivenom is unavailable.
Using WHO guidelines and industry test requirements, we examined the in vitro stability and murine in vivo efficacy of eight batches of the sub-Saharan African antivenom, South African Institute for Medical Research polyvalent, that had expired at various times over a period of 30 years.
We demonstrate modest declines in immunochemical stability, with antivenoms older than 25 years having high levels of turbidity. In vitro preclinical analysis demonstrated all expired antivenoms retained immunological recognition of venom antigens and the ability to inhibit key toxin families. All expired antivenoms retained comparable in vivo preclinical efficacy in preventing the lethal effects of envenoming in mice versus three regionally and medically important venoms.
This study provides strong rationale for stakeholders, including manufacturers, regulators and health authorities, to explore the use of expired antivenom more broadly, to aid in alleviating critical shortages in antivenom supply in the short term and the extension of antivenom shelf life in the longer term.
Limited information on costs and the cost-effectiveness of hospital interventions to reduce antibiotic resistance (ABR) hinder efficient resource allocation.
We conducted a systematic literature review for studies evaluating the costs and cost-effectiveness of pharmaceutical and non-pharmaceutical interventions aimed at reducing, monitoring and controlling ABR in patients. Articles published until 12 December 2023 were explored using EconLit, EMBASE and PubMed. We focused on critical or high-priority bacteria, as defined by the WHO, and intervention costs and incremental cost-effectiveness ratio (ICER). Following Preferred Reporting Items for Systematic review and Meta-Analysis guidelines, we extracted unit costs, ICERs and essential study information including country, intervention, bacteria-drug combination, discount rates, type of model and outcomes. Costs were reported in 2022 US dollars ($), adopting the healthcare system perspective. Country willingness-to-pay (WTP) thresholds from Woods et al 2016 guided cost-effectiveness assessments. We assessed the studies reporting checklist using Drummond’s method.
Among 20 958 articles, 59 (32 pharmaceutical and 27 non-pharmaceutical interventions) met the inclusion criteria. Non-pharmaceutical interventions, such as hygiene measures, had unit costs as low as $1 per patient, contrasting with generally higher pharmaceutical intervention costs. Several studies found that linezolid-based treatments for methicillin-resistant Staphylococcus aureus were cost-effective compared with vancomycin (ICER up to $21 488 per treatment success, all 16 studies’ ICERs<WTP). Infection control measures such as hand hygiene and gown usage (ICER=$1160/QALY or $4949 per ABR case averted, all ICERs<WTP) and PCR or chromogenic agar screening for ABR detection were highly cost-effective (eg, ICER=$1206 and $1115 per life-year saved in Europe and the USA). Comparisons were hindered by within-study differences.
Robust information on ABR interventions is critical for efficient resource allocation. We highlight cost-effective strategies for mitigating ABR in hospitals, emphasising substantial knowledge gaps, especially in low-income and middle-income countries. Our study serves as a resource for guiding future cost-effectiveness study design and analyses.
PROSPERO registration number CRD42020341827 and CRD42022340064
Attempts to understand biosocial phenomena using scientific methods are often presented as value-neutral and objective; however, when used to reduce the complexity of open systems such as epidemics, these forms of inquiry necessarily entail normative considerations and are therefore fashioned by political worldviews (ideologies). From the standpoint of poststructural theory, the character of these representations is at most limited and partial. In addition, these modes of representation (as stories) do work (as technologies) in the service of, or in resistance to, power.
We focus on a single Ebola case cluster from the 2013–2016 outbreak in West Africa and examine how different disciplinary forms of knowledge production (including outbreak forecasting, active epidemiological surveillance, post-outbreak serosurveys, political economic analyses, and ethnography) function as Story Technologies. We then explore how these technologies are used to curate ‘data,’ analysing the erasures, values, and imperatives evoked by each.
We call attention to the instrumental—in addition to the descriptive—role Story Technologies play in ordering contingencies and establishing relationships in the wake of health crises.
By connecting each type of knowledge production with the systems of power it reinforces or disrupts, we illustrate how Story Technologies do ideological work. These findings encourage research from pluriversal perspectives and advocacy for measures that promote more inclusive modes of knowledge production.
Local coalitions can advance public health initiatives such as smoke-free air but have not been widely used or well-studied in low-income and middle-income countries.
We conducted a matched-pairs community-randomised controlled trial in 28 communities in Armenia and Georgia (N=14/country) in which we helped establish local coalitions in 2019 and provided training and technical assistance for coalition activity promoting smoke-free policy development and enforcement (2019–2021). Surveys of ~1450 households (Fall 2018, May–June 2022) were conducted to evaluate coalition impact on smoke-free policy support, smoke-free home adoption, secondhand smoke exposure (SHSe), and coalition awareness and activity exposure, using multivariable mixed modelling.
Bivariate analyses indicated that, at follow-up versus baseline, both conditions reported greater smoke-free home rates (53.6% vs 38.5%) and fewer days of SHSe on average (~11 vs ~12 days), and that intervention versus control condition communities reported greater coalition awareness (24.3% vs 12.2%) and activity exposure (71.2% vs 64.5%). Multivariable modelling indicated that intervention (vs control) communities reported greater rates of complete smoke-free homes (adjusted Odds Ratio [aOR] 1.55, 95% confiedence interval [CI] 1.11 to 2.18, p=0.011) and coalition awareness (aOR 2.89, 95% CI 1.44 to 8.05, p=0.043) at follow-up. However, there were no intervention effects on policy support, SHSe or community-based activity exposure.
Findings must be considered alongside several sociopolitical factors during the study, including national smoke-free policies implementation (Georgia, 2018; Armenia, 2022), these countries’ participation in an international tobacco legislation initiative, the COVID-19 pandemic and regional/local war). The intervention effect on smoke-free homes is critical, as smoke-free policy implementation provides opportunities to accelerate smoke-free home adoption via local coalitions.
The development of strategies to better detect and manage patients with multiple long-term conditions requires estimates of the most prevalent condition combinations. However, standard meta-analysis tools are not well suited to synthesising heterogeneous multimorbidity data.
We developed a statistical model to synthesise data on associations between diseases and nationally representative prevalence estimates and applied the model to South Africa. Published and unpublished data were reviewed, and meta-regression analysis was conducted to assess pairwise associations between 10 conditions: arthritis, asthma, chronic obstructive pulmonary disease (COPD), depression, diabetes, HIV, hypertension, ischaemic heart disease (IHD), stroke and tuberculosis. The national prevalence of each condition in individuals aged 15 and older was then independently estimated, and these estimates were integrated with the ORs from the meta-regressions in a statistical model, to estimate the national prevalence of each condition combination.
The strongest disease associations in South Africa are between COPD and asthma (OR 14.6, 95% CI 10.3 to 19.9), COPD and IHD (OR 9.2, 95% CI 8.3 to 10.2) and IHD and stroke (OR 7.2, 95% CI 5.9 to 8.4). The most prevalent condition combinations in individuals aged 15+ are hypertension and arthritis (7.6%, 95% CI 5.8% to 9.5%), hypertension and diabetes (7.5%, 95% CI 6.4% to 8.6%) and hypertension and HIV (4.8%, 95% CI 3.3% to 6.6%). The average numbers of comorbidities are greatest in the case of COPD (2.3, 95% CI 2.1 to 2.6), stroke (2.1, 95% CI 1.8 to 2.4) and IHD (1.9, 95% CI 1.6 to 2.2).
South Africa has high levels of HIV, hypertension, diabetes and arthritis, by international standards, and these are reflected in the most prevalent condition combinations. However, less prevalent conditions such as COPD, stroke and IHD contribute disproportionately to the multimorbidity burden, with high rates of comorbidity. This modelling approach can be used in other settings to characterise the most important disease combinations and levels of comorbidity.
China initialised the expanded hepatitis A vaccination programme (EHAP) in 2008. However, the effectiveness of the programme remains unclear. We aimed to comprehensively evaluate the effectiveness of EHAP in the country.
Based on the provincial data on the incidence of hepatitis A (HepA), the population and meteorological variables in China, we developed interrupted time series (ITS) models to estimate the effectiveness of EHAP with the autocorrelation, seasonality and the meteorological confounders being controlled. Results were also stratified by economic zones, age groups and provinces.
We found a 0.9% reduction (RR=0.991, 95% CI: 0.990 to 0.991) in monthly HepA incidence after EHAP, which was 0.3% greater than the reduction rate before EHAP in China. Across the three economic regions, we found a 1.1% reduction in HepA incidence in both central and western regions after EHAP, which were 0.3% and 1.2% greater than the reduction rates before EHAP, respectively. We found a decreased reduction rate for the eastern region. In addition, we found generally increased reduction rate after EHAP for age groups of 0–4, 5–14 and 15–24 years. However, we found decreased reduction rate among the 25–64 and ≥65 years groups. We found a slight increased rate after EHAP in Shanxi Province but not elsewhere.
Our finding provides comprehensive evidence on the effectiveness of EHAP in China, particularly in the central and western regions, and among the population aged 0–24 years old. This study has important implications for the adjustment of vaccination strategies for other regions and populations.
The exploitation of migrant workers ranks high on global political agendas including the Sustainable Development Goals. Research on exploited workers, using assessment tools where exploitation is defined by professional experts, indicates serious health concerns and needs. Yet, migrant workers are rarely asked about their understanding of a phenomenon they may experience. Our study aimed to conceptualise ‘labour exploitation’ from the perspective of migrant workers employed in manual low-skilled jobs.
Twenty-seven Latin Americans working in London (UK) participated in Group Concept Mapping; a participatory mixed-method where qualitative data are collected to define a concept’s content and then analysed using quantitative methods to generate a structured conceptual framework. Participants generated statements describing the concept content during brainstorming sessions, and structured them during sorting-rating exercises. Multi-Dimensional Scaling and Cluster Analysis were performed, generating a conceptual framework that clarified the dimensions, subdimensions and constituent statements of the concept of labour exploitation from migrant workers’ perspectives.
Three key dimensions were identified: ‘poor employment conditions and lack of protection’, covering contractual arrangements and employment relations; ‘disposability and abuse of power’ (or ‘dehumanisation’) covering mechanisms or means which make migrant workers feel disposable and abused; and ‘health and safety and psychosocial hazards’ encompassing issues from physical and psychosocial hazards to a lack of health and social protection. ‘Dehumanisation’ has not been included in mainstream tools assessing exploitation, despite its importance for study participants who also described harsh situations at work including sexual, physical and verbal abuse.
Our study provides a conceptual framework of labour exploitation that gives voice to migrant workers and can be operationalised into a measure of migrant labour exploitation. It also calls for the dimension ‘dehumanisation’ and structural forms of coercion to be integrated into mainstream conceptualisations, and their workplace hazards to be urgently addressed.
Hospital-based studies have demonstrated topical applications of sunflower seed oil (SSO) to skin of preterm infants can reduce nosocomial infections and improve survival. In South Asia, replacing traditional mustard with SSO might have similar benefits.
340 communities in Sarlahi, Nepal were randomised to use mustard oil (MO) or SSO for community practice of daily newborn massage. Women were provided oil in late pregnancy and the first month post partum, and visited daily through the first week of life to encourage massage practice. A separate data collection team visited on days 1, 3, 7, 10, 14, 21 and 28 to record vital status and assess serious bacterial infection.
Between November 2010 and January 2017, we enrolled 39 479 pregnancies. 32 114 live births were analysed. Neonatal mortality rates (NMRs) were 31.8/1000 (520 deaths, 16 327 births) and 30.5/1000 (478 deaths, 15 676 births) in control and intervention, respectively (relative risk (RR)=0.95, 95% CI: 0.84, 1.08). Among preterm births, NMR was 90.4/1000 (229 deaths, 2533 births) and 79.2/1000 (188 deaths, 2373 births) in control and intervention, respectively (RR=0.88; 95% CI: 0.74, 1.05). Among preterm births <34 weeks, the RR was 0.83 (95% CI: 0.67, 1.02). No statistically significant differences were observed in incidence of serious bacterial infection.
We did not find any neonatal mortality or morbidity benefit of using SSO instead of MO as emollient therapy in the early neonatal period. Further studies examining whether very preterm babies may benefit are warranted.
ClinicalTrials.gov Registry (NCT01177111).
Community engagement and participatory research are widely used and considered important for ethical health research and interventions. Based on calls to unpack their complexity and observed biases in their favour, we conducted a realist review with a focus on non-communicable disease prevention. The aim was to generate an understanding of how and why engagement or participatory practices enhance or hinder the benefits of non-communicable disease research and interventions in low- and middle-income countries.
We retroductively formulated theories based on existing literature and realist interviews. After initial searches, preliminary theories and a search strategy were developed. We searched three databases and screened records with a focus on theoretical and empirical relevance. Insights about contexts, strategies, mechanisms and outcomes were extracted and synthesised into six theories. Five realist interviews were conducted to complement literature-based theorising. The final synthesis included 17 quality-appraised articles describing 15 studies.
We developed six theories explaining how community engagement or participatory research practices either enhance or hinder the benefits of non-communicable disease research or interventions. Benefit-enhancing mechanisms include community members’ agency being realised, a shared understanding of the benefits of health promotion, communities feeling empowered, and community members feeling solidarity and unity. Benefit-hindering mechanisms include community members’ agency remaining unrealised and participation being driven by financial motives or reputational expectations.
Our review challenges assumptions about community engagement and participatory research being solely beneficial in the context of non-communicable disease prevention in low- and middle-income countries. We present both helpful and harmful pathways through which health and research outcomes are affected. Our practical recommendations relate to maximising benefits and minimising harm by addressing institutional inflexibility and researcher capabilities, managing expectations on research, promoting solidarity in solving public health challenges and sharing decision-making power.
Existing health system challenges in Afghanistan were amplified by the Taliban’s August 2021 government takeover during which the country faced an evolving security situation, border closures, banking interruptions, donor funding disruptions and international staff evacuations. We investigated factors that influenced health sector and health service delivery following the takeover.
We purposively sampled individuals knowledgeable about Afghanistan’s health sector and health professionals working in underserved areas of the country. We identified codes and themes of the data using framework analysis.
Factors identified as supporting continued health service delivery following August 2021 include external funding and operational flexibilities, ongoing care provision by local implementers and providers, health worker motivation, flexible contracting out arrangements and improved security. Factors identified as contributing to disruptions include damaged infrastructure, limited supplies, ineffective government implementation efforts and changes in government leadership and policies resulting in new coordination and capacity challenges. There were mixed views on the role pay-for-performance schemes played. Participants also shared concerns about the new working environment. These included loss of qualified health professionals and the associated impact on quality of care, continued dependency on external funding, women’s inability to finish their studies or take on any leadership positions, various impacts of the Mahram policy, mental stress, the future of care provision for female patients and widespread economic hardship which impacts nearly every aspect of Afghan life.
Afghanistan’s health sector presents a compelling case of adaptability in the face of crisis. Despite the anticipated and reported total collapse due to the country’s power shift, various factors enabled health services to continue in some settings while others acted as barriers. The potential role of these factors should be considered in the context of future service delivery in Afghanistan and other settings at risk of political and societal disruption.
The scale-up of parenting programmes to support early childhood development (ECD) is poorly understood. Little is known about how and when early interventions are most effective. Sustainability of ECD programming requires a better understanding of the mechanisms of real-world interventions. We examined the effects on caregiving practices of Primeira Infância Melhor (PIM), a state-wide home-visiting programme in Brazil.
This propensity score matched, longitudinal, quasiexperimental study uses data from the 2015 Pelotas Birth Cohort. We matched children who received PIM at any age with other cohort children on 25 key covariates. Sensitivity, guidance and responsiveness were assessed using video-recorded play tasks. Coerciveness and the parent–child relationship were assessed using the Parenting and Family Adjustment Scales. All parenting outcomes were examined at age 4 years. Separate moderation analyses were conducted for each effect modifier: family income, child age and duration of participation.
Out of 4275 children in the cohort, 797 were enrolled in PIM up to age 4 years. 3018 children (70.6%) were included in the analytic sample, of whom 587 received PIM and 2431 were potential controls. We found a positive effect of PIM on responsiveness (β=0.08, 95% CIs 0.002 to 0.16) and sensitivity (β=0.10, 95% CIs 0.02 to 0.19). No effect was found for any secondary outcomes. Moderation analyses revealed a stronger positive effect on sensitivity for low-income parents (β=0.18, 95% CIs 0.03 to 0.34).
A state-wide, home-visiting programme in Brazil improved aspects of responsive caregiving. Effects were more pronounced for low-income families, suggesting benefits of purposeful targeting.
Unsafe water, sanitation and hygiene (WASH) contributes to a high burden of disease and exacerbates factors that promote the development of antimicrobial resistance (AMR). Enforceable policies are foundational to curbing inappropriate use of antimicrobials and providing safe WASH. While many countries have established National Action Plans for AMR that include provisions for WASH, few have codified these plans into legally enforceable policy. Here, we provide a comprehensive map and describe the current regulatory environment for WASH.
We conducted a comprehensive analysis of the WASH-related policies in 193 countries. Policies were identified, collated, and categorised into a publicly available repository.
A total of 672 policies met the criteria for inclusion in the dataset. No category of WASH-related policies had been adopted by all countries included in the study. Policy categories that were potentially more difficult to enforce in light of economic and governance limitations tended to be more prevalent and diverse, whereas policies in categories that were highly resource intensive and specific were less universal. Countries with gaps in policy categories also tended to be regionally clustered. While countries in the South Asian and European WHO regions had nearly universal policy coverage across all countries, the presence of policies was inconsistent across countries in the African and Eastern Mediterranean regions.
While decision-makers should rely on knowing which policies work best to mitigate the burden of WASH-related disease and AMR development, they must first have a comprehensive understanding of the current regulatory environment. Researchers and decision-makers need to know which policies work best and under what circumstances. The global mapping of WASH policies, which may have implications for AMR development, serves as a foundation for future policy analysis for AMR.
Declining smoking prevalence and denormalisation of tobacco in developed countries reduced transnational tobacco company (TTC) profit during 1990s and 2000s. As these companies faced increasingly restrictive policies and lawsuits, they planned to shift their business to socially acceptable reduced-harm products. We describe the internal motivations and strategies to achieve this goal.
We analysed previously secret tobacco industry documents available through the Truth Tobacco Documents Library. These documents were triangulated with TTCs’ investor and other professional reports, websites and public statements.
Mimicking pharmaceutical business models, tobacco companies sought to refurbish their image and ensure long-term profitability by creating and selling pharmaceutical-like products as smoking declined. These products included snus, heated tobacco products, e-cigarettes, nicotine gums and inhalers. Tobacco companies created separate divisions to develop and roll out these products, and the majority developed medical research programmes to steer these products through regulatory agencies, seeking certification as reduced-harm or pharmaceutical products. These products were regarded as key to the survival of the tobacco industry in an unfriendly political and social climate.
Pharmaceuticalisation was pursued to perpetuate the profitability of tobacco and nicotine for tobacco companies, not as a sincere search to mitigate the harms of smoking in society. Promotion of new pharmaceuticalised products has split the tobacco control community, with some public health professionals and institutions advocating for the use of ‘clean’ reduced-harm nicotine and tobacco products, essentially carrying out tobacco industry objectives.
Seasonal malaria chemoprevention (SMC) is a main intervention to prevent and reduce childhood malaria. Since 2015, Guinea has implemented SMC targeting children aged 3–59 months (CU5) in districts with high and seasonal malaria transmission.
We assessed the programmatic impact of SMC in Guinea’s context of scaled up malaria intervention programming by comparing malaria-related outcomes in 14 districts that had or had not been targeted for SMC.
Using routine health management information system data, we compared the district-level monthly test positivity rate (TPR) and monthly uncomplicated and severe malaria incidence for the whole population and disaggregated age groups (<5 years and ≥5 years of age). Changes in malaria indicators through time were analysed by calculating the district-level compound annual growth rate (CAGR) from 2014 to 2021; we used statistical analyses to describe trends in tested clinical cases, TPR, uncomplicated malaria incidence and severe malaria incidence.
The CAGR of TPR of all age groups was statistically lower in SMC (median=–7.8%) compared with non-SMC (median=–3.0%) districts. Similarly, the CAGR in uncomplicated malaria incidence was significantly lower in SMC (median=1.8%) compared with non-SMC (median=11.5%) districts. For both TPR and uncomplicated malaria incidence, the observed difference was also significant when age disaggregated. The CAGR of severe malaria incidence showed that all age groups experienced a decline in severe malaria in both SMC and non-SMC districts. However, this decline was significantly higher in SMC (median=–22.3%) than in non-SMC (median=–5.1%) districts for the entire population, as well as both CU5 and people over 5 years of age.
Even in an operational programming context, adding SMC to the malaria intervention package yields a positive epidemiological impact and results in a greater reduction in TPR, as well as the incidence of uncomplicated and severe malaria in CU5.
Assessment of the use of travel measures during COVID-19 has focused on their effectiveness in achieving public health objectives. However, the prolonged use of highly varied and frequently changing measures by governments, and their unintended consequences caused, has been controversial. This has led to a call for coordinated decision-making focused on risk-based approaches, which requires better understanding of the broader impacts of international travel measures (ITMs) on individuals and societies.
Our scoping review investigates the literature on the economic impact of COVID-19 ITMs. We searched health, social science and COVID-19-specific databases for empirical studies preprinted or published between 1 January 2020 and 31 October 2023. Evidence was charted using a narrative approach and included jurisdiction of study, ITMs studied, study design, outcome categories, and main findings.
Twenty-six studies met the inclusion criteria and were included for data extraction. Twelve of them focused on the international travel restrictions implemented in early 2020. Limited attention was given to measures such as entry/exit screening and vaccination requirements. Eight studies focused on high-income countries, 6 on low-income and middle-income countries and 10 studies were comparative although did not select countries by income. Economic outcomes assessed included financial markets (n=13), economic growth (n=4), economic activities (n=1), performance of industries central to international travel (n=9), household-level economic status (n=3) and consumer behaviour (n=1). Empirical methods employed included linear regression (n=17), mathematical modelling (n=3) and mixed strategies (n=6).
Existing studies have begun to provide evidence of the wide-ranging economic impacts resulting from ITMs. However, the small body of research combined with difficulties in isolating the effects of such measures and limitations in available data mean that it is challenging to draw general and robust conclusions. Future research using rigorous empirical methods and high-quality data is needed on this topic.
To assess the effect of providing BCG and oral polio vaccine (OPV) at an early home visit after delivery.
Cluster-randomised trial, randomising 92 geographically defined clusters 1:1 to intervention/control arms.
Bandim Health Project Health and Demographic Surveillance System, Guinea-Bissau.
2226 newborns enrolled between July 2016 and August 2019.
In both arms, newborns received a home visit within 72 hours after birth. In intervention clusters (n=46), BCG and OPV were provided at the home visit.
Rates of non-accidental mortality were compared in Cox proportional hazards models from (last of) day 1 or enrolment, until (first of) day 60 or registration of non-trial vaccines.
A total of 35 deaths (intervention: 7, control: 28) were registered during the trial. Providing BCG and OPV reduced non-accidental early infant mortality by 59% (8–82%). The intervention also reduced non-accidental hospital admissions. The intervention had little impact on growth and BCG scarring and tended to increase the risk of consultations.
The trial was stopped early due to lower-than-expected enrolment and event rates when 33% of the planned number of newborns had been enrolled. Despite the small size of the trial, the results support that early BCG and OPV vaccinations are beneficial and reduce early child mortality and morbidity.
ClinicalTrials.gov Registry (NCT02504203).
High-income countries increasingly look to the international recruitment of health workers to address domestic shortages, especially from low-income and middle-income countries. We adapt conceptual frameworks from migration studies to examine the networked and commercialised nature of the Indian market for nurse migration to the UK.
We draw on data from 27 expert interviews conducted with migration intermediaries, healthcare providers and policymakers in India and the UK.
India–UK nurse migration occurs within a complex and evolving market encompassing ways to educate, train and recruit nursing candidates. For-profit actors shape the international orientation of nursing curricula, broker on-the-job training and offer language, exam and specialised clinical training. Rather than merely facilitate travel, these brokers produce both generic, emigratory nurses as well as more customised nurses ready to meet specific shortages in the UK.
The dialectic of producing emigratory and customised nurses is similar to that seen in the Post-Fordist manufacturing model characterised by flexible specialisation and a networked structure. As the commodity in this case are people attempting to improve their position in life, these markets require attention from health policy makers. Nurse production regimes based on international market opportunities are liable to change, subjecting nurses to the risk of having trained for a market that can no longer accommodate them. The commercial nature of activities further entrenches existing socioeconomic inequalities in the Indian nurse force. Negative repercussions for the source healthcare system can be anticipated as highly qualified, specialised nurses leave to work in healthcare systems abroad.
The interaction between restrictions and contradictions within the law disproportionately impacts some populations’ health access and outcomes. Restrictions based on third-party authorisations and age are the most common restriction types, disproportionately impacting young women. Contraception, emergency contraception and abortion face the greatest number of restrictions, indicating a significant layering of barriers to family planning services. Further, plural legal systems commonly contradict guarantees of contraceptive services and emergency contraception. Our analyses suggest that one of the populations most affected by restrictions to SRH services as they appear in legal and regulatory frameworks is adolescent girls and young women in sub-Saharan Africa seeking abortion or contraceptive services.
Study findings provide a critical starting point for advocacy to address legal barriers to SRH services and evidence for future policy and programming. For individual countries, this study can serve as a model for analysis of their own legal and regulatory frameworks to identify priority areas for reform efforts.
]]>Use of local data for health system planning and decision-making in maternal, newborn and child health services is limited in low-income and middle-income countries, despite decentralisation and advances in data gathering. An improved culture of data-sharing and collaborative planning is needed. The Data-Informed Platform for Health is a system-strengthening strategy which promotes structured decision-making by district health officials using local data. Here, we describe implementation including process evaluation at district level in Ethiopia, and evaluation through a cluster-randomised trial.
We supported district health teams in 4-month cycles of data-driven decision-making by: (a) defining problems using a health system framework; (b) reviewing data; (c) considering possible solutions; (d) value-based prioritising; and (e) a consultative process to develop, commit to and follow up on action plans. 12 districts were randomly selected from 24 in the North Shewa zone of Ethiopia between October 2020 and June 2022. The remaining districts formed the trial’s comparison arm. Outcomes included health information system performance and governance of data-driven decision-making. Analysis was conducted using difference-in-differences.
58 4-month cycles were implemented, four or five in each district. Each focused on a health service delivery challenge at district level. Administrators’ practice of, and competence in, data-driven decision-making showed a net increase of 77% (95% CI: 40%, 114%) in the regularity of monthly reviews of service performance, and 48% (95% CI: 9%, 87%) in data-based feedback to health facilities. Statistically significant improvement was also found in administrators’ use of information to appraise services. Qualitative findings also suggested that district health staff reported enhanced data use and collaborative decision-making.
This study generated robust evidence that 20 months’ implementation of the Data-Informed Platform for Health strengthened health management through better data use and appraisal practices, systemised problem analysis to follow up on action points and improved stakeholder engagement.
To find what proportion of a broad set of health journals have published on climate change and health, how many articles they have published, and when they first published on the subject.
Bibliometric study.
We conducted electronic searches in Ovid MEDLINE ALL for articles about climate change and human health published from 1860 to 31 December 2022 in 330 health journals. There were no limits by language or publication type. Results were independently screened by two raters for article eligibility.
After screening there were 2932 eligible articles published across 253 of the 330 journals between 1947 and 2022; most (2795/2932; 95%) were published in English. A few journals published articles in the early 90s, but there has been a rapid increase since about 2006. We were unable to categorise the types of publication but estimate that fewer than half are research papers. While articles were published in journals in 39 countries, two-thirds (1929/2932; 66%) were published in a journal published in the UK or the USA. Almost a quarter (77/330; 23%) of the journals published no eligible articles, and almost three-quarters (241/330; 73%) published five articles or fewer. The publication of joint editorials in over 200 journals in 2021 and 2022 boosted the number of journals publishing something on climate change and health. A third of the (112/330; 34%) journals in our sample published at least one of the joint editorials, and almost a third of those (32/112; 29%) were publishing on climate change and health for the first time.
Health journals are rapidly increasing the amount they publish on climate change and health, but despite climate change being the major threat to global health many journals had until recently published little or nothing. A joint editorial published in multiple journals increased coverage, and for many journals it was the first thing they published on climate change and health.
Research mentorship is critical for advancing science, but there are few practical strategies for cultivating mentorship in health research resource-limited settings. WHO/TDR Global commissioned a group to develop a practical guide on research mentorship. This global qualitative evidence synthesis included data from a crowdsourcing open call and scoping review to identify and propose strategies to enhance research mentorship in low/middle-income country (LMIC) institutions.
The crowdsourcing open call used methods recommended by WHO/TDR and solicited descriptions of strategies to enhance research mentorship in LMICs. The scoping review used the Cochrane Handbook and predefined the approach in a protocol. We extracted studies focused on enhancing health research mentorship in LMICs. Textual data describing research mentorship strategies from the open call and studies from the scoping review were coded into themes. The quality of evidence supporting themes was assessed using the Confidence in the Evidence from Reviews of Qualitative research approach.
The open call solicited 46 practical strategies and the scoping review identified 77 studies. We identified the following strategies to enhance research mentorship: recognising mentorship as an institutional responsibility that should be provided and expected from all team members (8 strategies, 15 studies; moderate confidence); leveraging existing research and training resources to enhance research mentorship (15 strategies, 49 studies; moderate confidence); digital tools to match mentors and mentees and sustain mentorship relations over time (14 strategies, 11 studies; low confidence); nurturing a culture of generosity so that people who receive mentorship then become mentors to others (7 strategies, 7 studies; low confidence); peer mentorship defined as informal and formal support from one researcher to another who is at a similar career stage (16 strategies, 12 studies; low confidence).
Research mentorship is a collective institutional responsibility, and it can be strengthened in resource-limited institutions by leveraging already existing resources. The evidence from the crowdsourcing open call and scoping review informed a WHO/TDR practical guide. There is a need for more formal research mentorship programmes in LMIC institutions.
Globally, resources for health spending, including HIV and tuberculosis (TB), are constrained, and a substantial gap exists between spending and estimated needs. Optima is an allocative efficiency modelling tool that has been used since 2010 in over 50 settings to generate evidence for country-level HIV and TB resource allocation decisions. This evaluation assessed the utilisation of modelling to inform financing priorities from the perspective of country stakeholders and their international partners.
In October to December 2021, the World Bank and Burnet Institute led 16 semi-structured small-group virtual interviews with 54 representatives from national governments and international health and funding organisations. Interviews probed participants’ roles and satisfaction with Optima analyses and how model findings have had been used and impacted resource allocation. Interviewed stakeholders represented nine countries and 11 different disease programme-country contexts with prior Optima modelling analyses. Interview notes were thematically analysed to assess factors influencing the utilisation of modelling evidence in health policy and outcomes.
Common influences on utilisation of Optima findings encompassed the perceived validity of findings, health system financing mechanisms, the extent of stakeholder participation in the modelling process–including engagement of funding organisations, sociopolitical context and timeliness of the analysis. Using workshops can facilitate effective stakeholder engagement and collaboration. Model findings were often used conceptually to localise global evidence and facilitate discussion. Secondary outputs included informing strategic and financial planning, funding advocacy, grant proposals and influencing investment shifts.
Allocative efficiency modelling has supported evidence-informed decision-making in numerous contexts and enhanced the conceptual and practical understanding of allocative efficiency. Most immediately, greater involvement of country stakeholders in modelling studies and timing studies to key strategic and financial planning decisions may increase the impact on decision-making. Better consideration for integrated disease modelling, equity goals and financing constraints may improve relevance and utilisation of modelling findings.
The WHO neglected tropical disease (NTD) roadmap stresses the importance of integrating NTDs requiring case management (CM) within the health system. The NTDs programme of Liberia is among the first to implement an integrated approach and evaluate its impact.
A retrospective study of three of five CM-NTD-endemic counties that implemented the integrated approach was compared with cluster-matched counties with non-integrated CM-NTD. We compared trends in CM-NTD integrated versus non-integrated county clusters. We conducted a pre-post comparison of WHO high-level outcomes using data collected during intervention years compared with baseline in control counties. Changes in health outcomes, effect sizes for different diseases and rate ratios with statistically significant differences were determined. Complementary qualitative research explored CM-NTD stakeholders’ perceptions, analysed through the framework approach, which is a transparent, multistage approach for qualitative thematic interdisciplinary data analysis.
The detection rates for all diseases combined improved significantly in the intervention compared with the control clusters. Besides leprosy, detection rates improved with large effects, over fourfold increase with statistically significant effects for individual diseases (p<0.000; 95% CI 3.5 to 5.4). Access to CM-NTD services increased in integrated counties by 71 facilities, compared with three facilities in non-integrated counties. Qualitative findings highlight training and supervision as inputs underpinning increases in case detection, but challenges with refresher training, medicine supply and incentives negatively impact quality, equity and access.
Integrating CM-NTDs improves case detection, accessibility and availability of CM-NTD services, promoting universal health coverage. Early case detection and the quality of care need further strengthening.
As people living with HIV (PLHIV) are experiencing longer survival, the co-occurrence of HIV and non-communicable diseases has become a public health priority. In response to this emerging challenge, we aimed to characterise the spatial structure of convergence of chronic health conditions in an HIV hyperendemic community in KwaZulu-Natal, South Africa.
In this cross-sectional study, we used data from a comprehensive population-based disease survey conducted in KwaZulu-Natal, South Africa, which collected data on HIV, diabetes and hypertension. We implemented a novel health needs scale to categorise participants as: diagnosed and well-controlled (Needs Score 1), diagnosed and suboptimally controlled (Score 2), diagnosed but not engaged in care (Score 3) or undiagnosed and uncontrolled (Score 4). Scores 2–4 were indicative of unmet health needs. We explored the geospatial structure of unmet health needs using different spatial clustering methods.
The analytical sample comprised 18 041 individuals. We observed a similar spatial structure for HIV among those with combined needs Score 2–3 (diagnosed but uncontrolled) and Score 4 (undiagnosed and uncontrolled), with most PLHIV with unmet needs clustered in the southern urban and peri-urban areas. Conversely, a high prevalence of need Scores 2 and 3 for diabetes and hypertension was mostly distributed in the more rural central and northern part of the surveillance area. A high prevalence of need Score 4 for diabetes and hypertension was mostly distributed in the rural southern part of the surveillance area. Multivariate clustering analysis revealed a significant overlap of all three diseases in individuals with undiagnosed and uncontrolled diseases (unmet needs Score 4) in the southern part of the catchment area.
In an HIV hyperendemic community in South Africa, areas with the highest needs for PLHIV with undiagnosed and uncontrolled disease are also areas with the highest burden of unmet needs for other chronic health conditions, such as diabetes and hypertension. Our study has revealed remarkable differences in the distribution of health needs across the rural to urban continuum even within this relatively small study site. The identification and prioritisation of geographically clustered vulnerable communities with unmet health needs for both HIV and non-communicable diseases provide a basis for policy and implementation strategies to target communities with the highest health needs.
Neonatal mortality remains significant in low-income and middle-income countries (LMICs) with in-hospital mortality rates similar to those following discharge from healthcare facilities. Care continuity interventions have been suggested as a way of reducing postdischarge mortality by better linking care between facilities and communities. This scoping review aims to map and describe interventions used in LMICs to improve care continuity for newborns after discharge and examine assumptions underpinning the design and delivery of continuity.
We searched seven databases (MEDLINE, CINAHL, Scopus, Web of Science, EMBASE, Cochrane library and (Ovid) Global health). Publications with primary data on interventions focused on continuity of care for newborns in LMICs were included. Extracted data included year of publication, study location, study design and type of intervention. Drawing on relevant theoretical frameworks and classifications, we assessed the extent to which interventions adopted participatory methods and how they attempted to establish continuity.
A total of 65 papers were included in this review; 28 core articles with rich descriptions were prioritised for more in-depth analysis. Most articles adopted quantitative designs. Interventions focused on improving continuity and flow of information via education sessions led by community health workers during home visits. Extending previous frameworks, our findings highlight the importance of interpersonal continuity in LMICs where communication and relationships between family members, healthcare workers and members of the wider community play a vital role in creating support systems for postdischarge care. Only a small proportion of studies focused on high-risk babies. Some studies used participatory methods, although often without meaningful engagement in problem definition and intervention implementation.
Efforts to reduce neonatal mortality and morbidity should draw across multiple continuity logics (informational, relational, interpersonal and managerial) to strengthen care after hospital discharge in LMIC settings and further focus on high-risk neonates, as they often have the worst outcomes.
Rising facility births in sub-Saharan Africa (SSA) mask inequalities in higher-level emergency care—typically in hospitals. Limited research has addressed hospital use in women at risk of or with complications, such as high parity, linked to poverty and rurality, for whom hospital care is essential. We aimed to address this gap, by comparatively assessing hospital use in rural SSA by wealth and parity.
Countries in SSA with a Demographic and Health Survey since 2015 were included. We assessed rural hospital childbirth stratifying by wealth (wealthier/poorer) and parity (nulliparity/high parity≥5), and their combination. We computed percentages, 95% CIs and percentage-point differences, by stratifier level. To compare hospital use across countries, we produced a composite index, including six utilisation and equality indicators.
This cross-sectional study included 18 countries. In all, a minority of rural women used hospitals for childbirth (2%–29%). There were disparities by wealth and parity, and poorer, high-parity women used hospitals least. The poorer/wealthier difference in utilisation among high-parity women ranged between 1.3% (Mali) and 13.2% (Rwanda). We found use and equality of hospitals in rural settings were greater in Malawi and Liberia, followed by Zimbabwe, the Gambia and Rwanda.
Inequalities identified across 18 countries in rural SSA indicate poor, higher-risk women of high parity had lower use of hospitals for childbirth. Specific policy attention is urgently needed for this group where disadvantage accumulates.
The willingness to pay per quality-adjusted life year gained (WTP/Q) is commonly used to determine whether an intervention is cost-effective in health technology assessment. This study aimed to evaluate the WTP/Q for different disease scenarios in a Chinese population.
The study employed a quadruple-bounded dichotomous choice contingent valuation method to estimate the WTP/Q in the general public. The estimation was conducted across chronic, terminal and rare disease scenarios. Face-to-face interviews were conducted in a Chinese general population recruited from Jiangsu province using a convenience sampling method. Interval regression analysis was performed to determine the relationship between respondents’ demographic and socioeconomic conditions and WTP/Q. Sensitivity analyses of removing protest responses and open question analyses were conducted.
A total of 896 individuals participated in the study. The WTP/Q thresholds were 128 000 Chinese renminbi (RMB) ($36 364) for chronic diseases, 149 500 RMB ($42 472) for rare diseases and 140 800 RMB ($40 000) for terminal diseases, equivalent to 1.76, 2.06 and 1.94 times the gross domestic product per capita in China, respectively. The starting bid value had a positive influence on participants’ WTP/Q. Additionally, residing in an urban area (p<0.01), and higher household expenditure (p<0.01), educational attainment (p<0.02) and quality of life (p<0.02) were significantly associated with higher WTP/Q. Sensitivity analyses demonstrated the robustness of the results.
This study implies that tailored or varied rather than a single cost-effectiveness threshold could better reflect community preferences for the value of a healthy year. Our estimates hold significance in informing reimbursement decision-making in health technology assessment in China.
Pre-COVID-19, individuals with tuberculosis (TB) in Nigeria were often underdiagnosed and untreated. TB services were mostly in the public sector with only 15% of new cases in 2019 reported from the private sector. Reports highlighted challenges in accessing care in the private sector, which accounted for 67% of all initial care-seeking. Our study examined patients’ health seeking pathways for TB in Nigeria’s private sector and explored any changes to care pathways during COVID-19.
We conducted 180 cross-sectional surveys and 20 in-depth interviews with individuals having chest symptoms attending 18 high-volume private clinics and hospitals in Kano and Lagos States. Questions focused on sociodemographic characteristics, health-seeking behaviour, and pathways to care during the COVID-19 pandemic. All surveys and interviews were conducted in May 2021.
Most participants were male (111/180), with an average age of 37. Half (96/180) sought healthcare within a week of symptoms, while few (20/180) waited over 2 months. Individuals testing positive for TB had more health-seeking delays, and those testing negative for TB had more provider delays. On average, participants visited two providers in Kano and 1.69 in Lagos, with 61 of 180 in Kano and 48 of 180 in Lagos visiting other providers before the recruitment facility. Private providers were the initial encounters for most participants (60/180 in Kano, 83/180 in Lagos). Most respondents (164/180) experienced short-lived pandemic-related restrictions, affecting access to transportation, and closed facilities.
This study showed a few challenges in accessing TB care, necessitating continued investment in healthcare infrastructure and resources, particularly in the private sector. Understanding the different care pathways and delays in care provides opportunities for targeted interventions to improve deployment of services closer to where patients first seek care.
Musculoskeletal disorders, experienced as joint pain, are a significant global health problem, but little is known about how joint pain is categorised and understood in Tanzania. Understanding existing conceptualisations of and responses to joint pain is important to ensure both research and interventions are equitable and avoid biomedical imposition.
Rapid ethnographic appraisal was conducted in a periurban and rural community in Kilimanjaro, documenting language used to describe joint pain, ideas about causes, understandings of who experiences such pain, the impacts pain has and how people respond to it. We conducted 66 interviews with community leaders, traditional healers, community members and pharmacists.
Photographs were taken and included in fieldnotes to supplement the interview data and develop thick descriptions. Data were analysed by constant comparison using QDA Miner software.
Across the sample, dominant concepts of joint pain were named ugonjwa wa baridi, cold disease; ugonjwa wa uzee, old age disease; rimatizim, disease of the joints; and gauti, gout. Causes mentioned included exposure to the cold, old age, alcohol and red meat consumption, witchcraft, demons and injuries/falls. Age, gender and occupation were seen as important factors for developing joint pain. Perceived impacts of joint pain included loss of mobility, economic and family problems, developing new health conditions, death, reduction in sexual functioning and negative self-perceptions. Responses to joint pain blended biomedical treatments, herbal remedies, consultations with traditional healers and religious rituals.
Conceptualisations of and responses to joint pain in the two communities were syncretic, mixing folk and biomedical practices. Narratives about who is affected by joint pain mirror emerging epidemiological findings, suggesting a strong ‘lay epidemiology’ in these communities. Anthropological methods can support the decolonisation of global health by decentring the imposition of English language biomedicine and pursuing synthetic, dignified languages of care.
The COVID-19 pandemic had large impacts on mental health; however, most existing evidence is focused on the initial lockdown period and high-income contexts. By assessing trajectories of mental health symptoms in India over 2 years, we aim to understand the effect of later time periods and pandemic characteristics on mental health in a lower-middle income context.
We used data from the Real-Time Insights of COVID-19 in India cohort study (N=3709). We used covariate-adjusted linear regression models with generalised estimating equations to assess associations between mental health (Patient Health Questionnaire (PHQ-4) score; range 0–12) and pandemic periods as well as pandemic characteristics (COVID-19 cases and deaths, government stringency, self-reported financial impact, COVID-19 infection in the household) and explored effect modification by age, gender and rural/urban residence.
Mental health symptoms dropped immediately following the lockdown period but rose again during the delta and omicron waves. Associations between mental health and later pandemic stages were stronger for adults 45 years of age and older (p<0.001). PHQ-4 scores were significantly associated with all pandemic characteristics considered, including estimated COVID-19 deaths (PHQ-4 difference of 0.10 units; 95% CI 0.06 to 0.13), government stringency index (0.14 units; 95% CI 0.11 to 0.18), self-reported major financial impacts (1.20 units; 95% CI 1.09 to 1.32) and COVID-19 infection in the household (0.36 units; 95% CI 0.23 to 0.50).
While the lockdown period and associated financial stress had the largest mental health impacts on Indian adults, the effects of the pandemic on mental health persisted over time, especially among middle-aged and older adults. Results highlight the importance of investments in mental health supports and services to address the consequences of cyclical waves of infections and disease burden due to COVID-19 or other emerging pandemics.
Perinatal anxiety (PNA) is a major public health concern.
A hybrid effectiveness-implementation trial was conducted in two antenatal clinics in Hefei, China, to assess the effectiveness and cost-effectiveness of application-based tiered care (Mom’s Good Mood, MGM) in treating PNA and to understand how well it fits into routine practices. Pregnant women who scored at least 5 points on the 7-Item Generalised Anxiety Disorder Scale (GAD-7) scale were successively assigned to the control group or the intervention group, which were given the usual care and MGM on usual care, respectively. At 6 months post partum, anxiety, depression and life satisfaction were assessed. Intention-to-treat analysis and the Reach, Effectiveness, Adoption, Implementation and Maintenance framework were adopted.
A total of 214 women were assigned to the control group and 341 to the intervention group. The mean changes in GAD-7 scores (Least-squares means, LSM, –1.42, 95% CI –2.18 to –0.66) and the risk of anxiety (adjusted odds ratio, aOR 0.30, 95% CI 0.18 to 0.51) were decreased, and the anxiety remission rate (aOR 2.72, 95% CI 1.69 to 4.40) were improved in the intervention group. Similar findings were observed regarding the change in Edinburgh Postnatal Depression Scale scores (LS –1.92, 95% CI –2.85 to –0.99), depression remission rate (aOR 2.24, 95% CI 1.39 to 3.63) and the risk of depression (aOR 0.57, 95% CI 0.33 to 0.98). MGM only costs ¥1.88 (US$0.27) per pregnant woman to boost the postpartum anxiety remission rate by 1% and was revealed to have a high reach rate of 78.3%, an adoption rate of 51.3%–80.8%.
MGM is a cost-effective and accessible tool in coping with PNA.
ChiCTR2100053419.
We analysed 50 semi-structured interview responses from 10 LMICs across three regions—South Asia, Latin America, and Western Africa—using an interpretative phenomenological analysis approach.
The bodily, social, and system experiences of illness by respondents were multidirectional and interactive, and largely captured the complexity of living with multimorbidity. Despite expensive treatments, many experienced little improvements in their conditions and felt that healthcare was not tailored to their needs. Disease management involved multiple and fragmented healthcare providers with lack of guidance, resulting in repetitive procedures, loss of time, confusion, and frustration. Financial burden was exacerbated by lost productivity and extreme finance coping strategies, creating a vicious cycle. Against the backdrop of uncertainty and disruption due to illness, many demonstrated an ability to cope with their conditions and navigate the healthcare system. Respondents’ priorities were reflective of their desire to return to a pre-illness way of life—resuming work, caring for family, and maintaining a sense of independence and normalcy despite illness. Respondents had a wide range of needs that required financial, health education, integrated care, and mental health support.
In discussion with respondents on outcomes, it appeared that many have complementary views about what is important and relevant, which may differ from the outcomes established by clinicians and researchers. This knowledge needs to complement and be incorporated into existing research and treatment models to ensure healthcare remains focused on the human and our evolving needs.
]]>Medical schools, as significant and influential organisations within their communities, have the potential and the capacity to impact abortion policy. Organisations often engage in advocacy by issuing public statements that clarify their stance on specific policies. This study analyses the quantity and quality of publicly discoverable statements that US medical schools issued regarding Dobbs v Jackson Women’s Health Organization.
We conducted a mixed methods study using an explanatory sequential design. Using qualitative analysis, an inductive thematic approach was used to identify themes from public statements made within 6 months of 2 May 2022, Dobbs leak. Descriptive statistics and logistic regression analysis were used to assess the association between themes and institutional characteristics.
Most institutions (n=124/188, 65.96%) did not issue public statements regarding Dobbs. Among all 188 US medical schools, allopathic institutions (OR=12.19, 95% CI (2.83 to 52.57), p=0.001), schools in protective states (OR=3.35, 95% CI (1.78 to 6.29), p<0.0001) and those with family planning divisions (OR=4.60, 95% CI (2.33 to 9.08), p<0.0001) were at increased odds of issuing statements. Of the 64 medical schools with statements, 64.06% (n=41/64) espoused pro-choice views, 34.37% (n=22) were neutral/non-committal and 1.56% (n=1) expressed antiabortion views. Those in protective states were at 3.35 times increased odds of issuing pro-choice statements (95% CI (1.16 to 9.72), p=0.03) compared with restrictive counterparts.
Medical schools largely did not take a public stance on Dobbs. By refraining from actively engaging in this critical discourse, medical schools are foregoing a leadership opportunity to affect meaningful sociopolitical change, particularly in states with restrictive abortion laws.
Neglected diseases are a significant global health challenge. Encouraging the development of therapeutics and vaccines for these diseases would address an important unmet medical need. We propose a priority review voucher programme for the European Union (EU). The developer of a drug or vaccine for a neglected disease would receive a voucher for accelerated assessment of a different product at the European Medicines Agency (EMA).
This study uses retrospective observational data to estimate the potential commercial value of the proposed voucher programme using a five-step approach: (1) estimating the time saved in the EMA accelerated regulatory review; (2) gauging time reductions in accelerated pricing and reimbursement decisions by EU member states; (3) selecting 10 high-revenue products launched between 2015 and 2020 representing typical voucher users; (4) analysing IQVIA MIDAS sales data for the selected products and (5) calculating the net present value (NPV) of the voucher based on the 10 products.
The accelerated EMA review would reduce regulatory time by an average of 182 days. Additionally, products could save more than a year in many member states through an expedited 120-day pricing and reimbursement review. The estimated NPV of regulatory acceleration by two quarters would be 100 million. In addition, if France, Italy and Spain reviewed pricing and reimbursement in only 120 days, then the value would double.
An EU voucher estimated at more than 100 million, coupled with a US$100 million counterpart, offers a meaningful incentive for novel product development. However, the voucher programme should be part of a comprehensive strategy for tackling neglected diseases, rather than a standalone solution.
Sexually transmitted infections (STIs) are a significant public health challenge, but there is a perceived lack of political priority in addressing STIs as a global health issue. Our study aimed to understand the determinants of global political priority for STIs since the 1980s and to discern implications for future prioritisation.
Through semistructured interviews from July 2021 to February 2022, we engaged 20 key stakeholders (8 women, 12 men) from academia, United Nations agencies, international non-governmental organisations, philanthropic organisations and national public health agencies. A published policy framework was employed for thematic analysis, and findings triangulated with relevant literature and policy documents. We examined issue characteristics, prevailing ideas, actor power dynamics and political contexts.
A contrast in perspectives before and after the year 2000 emerged. STI control was high on the global health agenda during the late 1980s and 1990s, as a means to control HIV. A strong policy community agreed on evidence about the high burden of STIs and that STI management could reduce the incidence of HIV. The level of importance decreased when further research evidence did not find an impact of STI control interventions on HIV incidence. Since 2000, cohesion in the STI community has decreased. New framing for broad STI control has not emerged. Interventions that have been funded, such as human papillomavirus vaccination and congenital syphilis elimination have been framed as cancer control or improving newborn survival, rather than as STI control.
Globally, the perceived decline in STI control priority might stem from discrepancies between investment choices and experts’ views on STI priorities. Addressing STIs requires understanding the intertwined nature of politics and empirical evidence in resource allocation. The ascent of universal health coverage presents an opportunity for integrated STI strategies but high-quality care, sustainable funding and strategic coordination are essential.
The use of technology to enhance medicine regulation in Africa, particularly through the establishment of the African Medicines Agency (AMA), will help drive efficiencies within national regulatory agencies. By adopting electronic tools and platforms, national regulatory agencies can streamline their regulatory processes, reducing the time and cost of regulatory review, and enabling faster access to safe and effective medicines.
Electronic submission systems, for example, can reduce the need for paper-based submissions, simplifying the review process and minimizing errors. Electronic data capture systems can improve the quality of data collected in clinical trials, reducing the need for manual data entry and enhancing data security. This can enable regulatory agencies to more efficiently and effectively review applications and monitor clinical trials, ensuring the safety and efficacy of new medicines.
Moreover, the harmonization of regulatory requirements across Africa, facilitated by AMA’s collaboration with other regulatory bodies, can help reduce the regulatory burden on national agencies. By adopting common regulatory standards and guidelines, national agencies can better align their processes with those of their counterparts in other African countries, reducing duplication and improving efficiency.
Overall, the use of technology and the establishment of a continental regulatory body such as AMA can help national regulatory agencies in Africa improve their regulatory processes, enhance transparency and accountability, and ensure faster access to safe and effective medicines for their populations.
]]>Although infants are thought to be protected against malaria during the first months of life mainly due to maternal antibodies, malaria in early childhood is not uncommon in high-transmission settings and susceptibility to Plasmodium falciparum infections varies between infants. This study aimed to investigate how different categories of prenatal malaria exposure (PME) influence levels of maternal antibodies in cord blood samples and examined the effect of maternal antibody concentrations at birth on subsequent risk of malaria in early childhood.
A birth cohort study (N=661) was nested within the COSMIC clinical trial (NCT01941264) in Burkina Faso. P. falciparum infections during pregnancy and infants’ clinical malaria episodes detected during the first year of life were recorded. The levels of maternal IgG and IgG1-4 to 15 P. falciparum antigens were measured in cord blood by quantitative suspension array technology.
Results showed a significant variation in the magnitude of maternal antibody levels in cord blood, depending on the PME category, with past placental malaria (PM) more frequently associated with significant increases of IgG and/or subclass levels across three groups of antigens defined as pre-erythrocytic, erythrocytic and markers of PM, as compared to those from the cord of non-exposed control mothers. High levels of antibodies to certain erythrocytic antigens (EBA140, EBA175, MSP142, and MSP5) were independent predictors of protection from clinical malaria while antibodies to VAR2CSA-DBL1-2 and DBL3-4 were significantly associated with an increased malaria risk during the first year of life. Remarkably, ratios of protective-to-risk antibodies above 1 at individual level were associated with protection from clinical malaria during the first year of life.
These findings indicate that PME categories have different effects on the levels of maternal-derived antibodies to malaria antigens in children at birth and that, this might drive heterogeneity to clinical malaria susceptibility in early childhood.
Calls to decolonise global health have highlighted the continued existence of colonial structures in research into diseases of public health importance, particularly in low- and middle-income countries (LMICs). A key step towards restructuring the system is equitable leadership in global health partnerships whereby researchers in LMICs are given the opportunity to successfully secure grant funding to lead and drive their own research based on locally defined priorities.
In February 2022, the Tuberculosis (TB) Centre of the London School of Hygiene and Tropical Medicine (LSHTM) hosted a virtual multi-stakeholder workshop aimed at bringing together funders and early- and mid-career researchers (EMCRs) to identify funder initiatives that have worked to improve equitable leadership, to better understand barriers faced by EMCRs, and collectively brainstorm approaches to overcome these barriers. The workshop transcript was analysed using a deductive thematic approach to identify key emerging themes.
The workshop was attended by 140 diverse participants representing funders, research institutions, and researchers from Africa, Europe, Asia, and South America. 83 participants self-identified as early- or mid-career researcher, and 19 as senior scientists, with varied areas of interest including communicable and non-communicable diseases and neglected tropical diseases. Major barriers identified were lack of individual and institutional level support, and flawed funding structures for EMCRs in LMIC settings. Strategies on how equitable leadership can be further facilitated included institutional reforms for funders to facilitate equity, diversity, and inclusion in their partners through consultative engagement, and reshaping how research priorities are defined. Other strategies identified included diversified funding streams for research institutions, promoting south-south partnerships, and dedicated funding for capacity building of EMCRs.
Advances to overcome funding barriers in global health speak directly to its decolonisation. Complex changes in practice, which are intentional and require uncomfortable shifts, are urgently required.
Funding: Wellcome Trust Institutional Strategic Support Fund.
Current diagnostic methods for VL include parasitology and serology (with rK39 dipstick test and direct agglutination test). These methods have limitations (patient safety or diagnostic accuracy), and molecular testing is proposed to improve diagnosis. Current molecular tools have high accuracy for detecting VL, however their complexity and high costs make their use unsuitable for endemic areas with limited resources. Consequently, there is a need for a simple molecular diagnostic test that can be implemented in resource limited setting.
We have developed a miniaturized direct-on-blood PCR nucleic acid lateral flow immunoassay (mini-dbPCR-NALFIA) as an innovative, easy-to-use molecular assay for the diagnosis of VL in these particular settings. Unlike other simplified molecular methods, such as LAMP, the mini-dbPCR-NALFIA does not require DNA extraction and utilizes a handheld, portable thermal cycler powered by a solar-charged power pack enabling to perform the test without any laboratory infrastructure. Reading of results is done using a rapid lateral flow strip. In the present study we have conducted a laboratory evaluation on the mini db-PCR-NALFIA to determine its diagnostic accuracy. Patient samples (N=146) with suspected VL were tested using the mini db-PCR-NALFIA and compared to conventional PCR (reference test). Sensitivity and specificity represented the accuracy. Cohen’s k determined the degree or agreeableness between the mini db-PCR-NALFIA and other diagnostic tests (PCR and rk39 rapid test).
Compared to qPCR, the mini db-PCR-NALFIA for VL had a sensitivity of 95.83% (95% CI, 88.30%-99.13%) and a specificity of 97.22% (95% CI, 90.32% - 99.66%). The agreement between both tests was excellent (k-value: 0.93). The Limit of Detection of the platform is around 10 parasites per microliter of blood (spiked with promastigotes).
The VL-mini-db-PCR-NALFIA has a very good diagnostic performance and is now ready for large field evaluations in disease endemic countries.
Tuberculosis (TB)-affected communities are often highly vulnerable, with social, economic, and biological factors increasing risk of TB and other chronic conditions, whilst impeding healthcare access. Traditional approaches to TB contact tracing do not address non-TB related health needs.
Nested in an EDCTP-funded TB household contact (HHC) cohort (ERASE-TB), we invited HHC (aged ≥10 years) and people with TB (aged ≥18 years, at treatment completion) to participate in a health-check. The health-check was collaboratively developed and, in addition to TB, included conditions which have high local prevalence (e.g. HIV, hypertension), are associated with TB (e.g. undernutrition, diabetes, mental health, alcohol and smoking), or were of importance to the community (e.g. vision). Testing was performed using point-of-care tools. Participants with a positive result were referred; linkage to care was assessed. The health-check component was funded by Wellcome Trust.
From 197 households, 482 HHC and 60 people with TB participated in the health-check. Reasons for non-attendance among people with TB included having moved away, death and not having time. 62% HHC and 32% people with TB were women. 2.4% people reported currently/recently taking TB preventative therapy. Overall, 15% HHC and 31% people with TB were living with HIV, of whom 9% were diagnosed through screening. Six percent of HHC and 27% people with TB were underweight; 22% HHC and 12% people with TB had hypertension; 3% HHC and 13% people with TB had diabetes; 31% HHC and 41% people with TB had mental health symptoms; 15% HHC and 19% people with TB had visual impairment. Most chronic conditions were previously undiagnosed. Successful linkage to care varied by condition.
Members of TB-affected households experience a high burden of chronic conditions. Inclusion of strategies to identify and address these factors within TB screening may reduce TB incidence and improve health.
Repurposing established antibiotics for TB has been successful, notably for fluoroquinolones, linezolid, and clofazimine. Meropenem co-administered with amoxicillin/clavulanate (A/Clav) demonstrated early bactericidal activity (EBA) in clinical trials (Diacon 2016; de Jager 2020; de Jager 2022). This study evaluated different regimens of carbapenems, A/Clav, and rifampicin, alone or in combinations.
This phase 2a, open-label, randomized trial recruited 132 HIV-negative adults with newly diagnosed, smear-positive, rifampicin-susceptible pulmonary TB. Participants received 14 days of treatment in one of 8 experimental arms, or standard-of-care (HRZE). EBA was determined with mixed effects modelling and reported as change in time (hours) to sputum culture positivity (TTP0-14) of samples collected overnight with 95% confidence intervals. Adverse events (AE) were assessed daily.
A/Clav 2x1000/62.5mg orally twice daily showed no activity. TTP0-14 of other drugs in combination with A/Clav was, for meropenem 6g over 6 hours(6Mero6): 58.02 hours (18.72–192.92), meropenem 6g over 1 hour(6Mero1): 58.13 hours (27.26–121.83), meropenem 3g over 1 hour twice daily(3x2Mero): 60.07 hours (19.89–884.71), and meropenem 4g over 1 hour(4Mero1): 35.28 hours (25.31–84.74). Ertapenem 1g daily intravenously (ErtaIV) or intramuscularly (ErtaIM) was not active. The activity of rifampicin 35mg/kg daily plus A/Clav was 136.92 hours (103.21–400.64) and HRZE 134.30 hours (106.28–160.23). In 58 participants, 111 adverse events were reported. Most commonly diarrhoea (15 participants: four ErtaIM, three ErtaIV, four 6Mero6, two rifampicin, one each A/Clav and HRZE), injection site reactions (six participants: four ErtaIM, one each 6Mero6 and 3x2Mero), and raised transaminases (four participants: A/Clav, ErtaIM, Erta IV, rifampicin). Three SAEs occurred (pneumonia in ErtaIV, haemoptysis in rifampicin and 6Mero1) unrelated to treatment.
Rifampicin-based treatments showed the highest EBA. A/Clav and meropenem given at 6g per day, in single or divided doses, had higher EBA than lower doses, and shorter infusions were better tolerated. Ertapenem-based treatments and A/Clav alone showed no anti-TB activity.
Funding: EDCTP 733079-H2020-SC1-2016-RTD
In the past decades, Africa witnessed increased biomedical research and transnational collaborations making the continent vulnerable to exploitation. Research ethics committees (REC) are the cornerstone; however, many lack an accreditation system. A self-assessment tool can be feasible for reviewing processes and policies against recognized standards. This study aimed to describe Mozambique’s RECs network and its operational and functional characteristics.
A descriptive cross-sectional study was conducted. In 2019, Mozambique had seven RECs; the study population was the president of each existing REC. A self-assessment tool developed by researchers from Africa was used. Participants were recruited by telephone, and after informed consent, the questionnaire was emailed to each participant and returned to the investigators. A descriptive statistical analysis was done to describe the frequency of the events.
The existing seven RECs in 2019 accepted to participate in the study. A total of six RECs has a policy for appointing the president. The most common criteria for the president’s selection were prior training in ethics (six), followed by prior research experience (five). Regarding resources, only one of the seven RECs reported having a yearly budget, and only one has a full-time administrative staff. The reported number of RECs that meet as a full committee to review research studies once a month was four, and two referred meeting once a week. All the RECs stated they have policies for protocol reviewing. Out of seven, six RECs have a policy on expedited review, on how decisions are made and communicated to investigators.
This study is the first attempt to document Mozambique’s RECs network. The process of self-assessment raises knowledge regarding strengths and challenges. Results can serve as a quality improvement mechanism detecting specific areas needing upgrading and as a reference on how they are operating compared to others.
HIV and schistosomiasis are the most widespread infections worldwide. The two diseases share the same epidemiological space, especially in poor regions where endemicity is high. Co-infections are therefore common. We conducted a clinical study to determine the effect of efavirenz and ritonavir on the pharmacokinetics of R- and S-praziquantel (PZQ) in healthy male participants. The aim was to increase knowledge towards the safe and efficacious use of PZQ especially in cases of coinfection and mass drug treatment programs where HIV status and concomitant drug intake is not considered prior to administration.
We conducted a non-randomized, open-label, single-dose, one sequence crossover study with 2 arms. A single oral dose of 40 mg/kg PZQ followed by a daily oral dose of either 400 mg efavirenz or 100 mg ritonavir was given to participants for 14 consecutive days. On day 14, they ingested a single 40 mg/kg dose of PZQ. We measured plasma levels up to 12 h on day 1 and day 14. Samples were analyzed by LC-MS. Pharmacokinetic analysis was conducted in WinNonlin to determine the primary endpoints (plasma T1/2, Cmin, and AUC).
Efavirenz had a significant effect on the pharmacokinetics of PZQ (p < .05), reducing the AUC by 4-fold (1213.15 vs. 281.35 h·ng/ml for R-PZQ and 5669 vs. 871.84 h·ng/ml for S-PZQ). Ritonavir had no significant effect on R-PZQ but increased the AUC 2-fold for S-PZQ (p < .05) (4154.79 vs. 7291.05 h·ng/ml).
Our study showed clinically significant drug-drug interactions involving PZQ and efavirenz that should be considered in the treatment of schistosomiasis in regions where efavirenz-based ART is common. Using PZQ in HIV patients needs investigation, as there is a risk of both treatment failure and adverse effects because of induction and inhibition. Strategies to avoid these detrimental DDI should therefore be explored.
MRC The Gambia and MRC Uganda joined London School of Hygiene and Tropical Medicine (LSHTM) in 2018 to form a family of institutions committed to high quality research. Each institution supports Clinical Trials through a formally-constituted Clinical Trials Unit (CTU) or equivalent resources, where the function is to provide end-to-end support for high quality clinical trials (CTs). Until recently, the three CTUs worked as islets, supporting only trials involving their respective institutions as sponsor or partner. In late 2022, the CTUs started a dialogue with the aim of creating regionally-based yet internationally-networked hubs. Our ambition is to leverage the strengths of each CTU and enhance support for high quality CTs through collaborative working and coordinated sharing of resources, expertise and training.
We applied an informal SWOT (Strengths, Weaknesses, Opportunities, Threats) analysis. This identified Strengths where one CTU might take the lead, Weaknesses where a CTU needed support from the others, and where there were Opportunities to be gained from collaboration. We also discussed limitations that might pose Threats to achieving our aims. We adopted principles of equitable partnership. Early conversations took place remotely, followed by in-person meetings which helped to build relationships, deepen contextual understanding and identify specific areas for collaboration.
Preliminary collaborative activities underway to foster interdependence between our CTUs include: i) running joint seminar series, ii) co-developing an electronic trial Masterfile (eTMF) system compliant with international standards, iii) developing a searchable database of all trials at LSHTM, iv) working towards shared digital infrastructure for the design, implementation, management and analysis of trials and shared human resources.
Collaboration is key for successful clinical trials. Through leveraging unique strengths and counteracting individual weaknesses of three geographically dispersed CTUs, we will create a strong networked trials capacity that is more than the sum of its parts.
Malaria during pregnancy is an important driver of maternal and neonatal health especially among HIV-infected women. In Africa, at least one million pregnant women are annually co-infected with Plasmodium and HIV. The interaction between the two infections is particularly deleterious during pregnancy, leading to an increased risk of malaria and HIV viral load. Intermittent preventive treatment in pregnancy (IPTp) with sulphadoxine-pyrimethamine is recommended for malaria prevention in HIV-uninfected women but it is contraindicated in those HIV-infected women on cotrimoxazole prophylaxis (CTXp).
A randomized, double-blind, two-arm, placebo-controlled trial to evaluate the safety and efficacy of dihydroartemisinin-piperaquine (DHA-PPQ) for IPTp was conducted in HIV-infected pregnant women receiving CTXp, antiretroviral drugs and long lasting insecticide treated nets in five sites from Gabon and Mozambique. Women attending the first antenatal care clinic visit, resident in the study area and with a gestational age ≤28 weeks were randomized to receive either monthly IPTp with DHA-PPQ or placebo. The three day IPTp administration was always done under direct observation. Women were followed up until one month after the end of pregnancy.
A total of 666 HIV-infected pregnant women were enrolled in the trial between September 2019 and November 2021. The prevalence of maternal peripheral parasitemia at delivery (primary study endpoint) was unexpectedly low during the study period and no significant differences were found between groups. However, the composite of Plasmodium infection (detected by any diagnostic test during pregnancy or delivery) was significantly decreased in the DHA-PPQ group (RR=0.48, 95CI 0.27–0.84; p=0.010). There were no differences in the prevalence of adverse pregnancy outcomes and serious adverse events across groups.
In a context of low malaria transmission, adding monthly IPTp- DHA-PPQ to CTXp in HIV-pregnant women is safe and it is associated with a decreased risk of clinical malaria and overall Plasmodium infection in pregnancy.
The gamma-herpesviruses Kaposi’s sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV) both have oncogenic potential, particularly in immunosuppressed patients such as in Human Immunodeficiency Virus (HIV)-infected individuals. Both oncogenic viruses display latent and lytic lifecycles with differing outcomes for associated pathologies. Co-infection with SARS-CoV-2, the causative agent for Covid-19, poses additional unknown risks of cancer development, affecting already vulnerable populations. Indeed, in South Africa, the Covid-19 pandemic occurs against the backdrop of high HIV, tuberculosis and non-communicable disease burdens as well as highly prevalent herpesviruses infections, such as EBV and KSHV. Mounting evidence points to potential interplay between several co-infections and reactivation of opportunistic herpesvirus infections.
This study therefore assessed the risk of KSHV and EBV lytic reactivation in the context of SARS-CoV-2 and HIV infection in a patient cohort (n=400) enrolled at the Gugulethu ART clinic in Cape Town, South Africa, between September 2020 and April 2023.
While almost all patients displayed positive EBV serology, 40% were seropositive for KSHV. About 70% of the cohort was SARS-CoV-2 seropositive already before national Covid-19 vaccination roll-out, demonstrating high prevalence of SARS-CoV-2 in this population. KSHV seropositive patients (with or without positive SARS-CoV-2 serology) were followed up every 6 months to measure reactivation of KSHV and EBV in the peripheral blood. We found that oncogenic herpesvirus reactivation primarily occurred in patients with underlying uncontrolled inflammatory conditions, potentially caused by SARS-CoV-2 infection, which exacerbated clinical outcome.
While the design of this study cannot distinguish if disease synergy exists between KSHV and/or EBV and Covid-19 nor if either viral infection is indeed fuelling the other, these data point to potential contributions of oncogenic herpesvirus infection to clinical outcome, particularly in the South African context of high disease burden which warrants further investigation.
This study was funded by the EDCTP (Training and Mobility Action TMA2018SF-2446-KSHV/HIV morbidity).
Recently, the World Health Organization (WHO) has recommended to extend the seasonal malaria chemoprevention (SMC) with Sulfadoxine-pyrimethamine plus amodiaquine (SP-AQ) strategy to school aged children and to use alternative artemisinin-based combination therapies (ACTs). There is less data on the efficacy of ACTs in SMC and their impact on the selection of drugs resistant parasites. The aim of this trial was to assess the efficacy of Dihydroartemisinin-Piperaquine (DHA-PPQ) in school aged children during and after SMCs and to assess the prevalence of resistance markers to ACT, amodiaquine and piperaquine.
We conducted a randomized trial from September to December 2020 including 345 children of 6–15 years old. Study participants were randomized in 1:1:1 ratio to receive monthly 3 consecutives doses of DHA-PQ, SP-AQ or control drug (Albendazole). Study drugs were administrated for 3 consecutive days at each SMC round. All drugs were administrated under direct supervision of a study pharmacist. Dried blood specimens (DBS) were collected at the start of each SMC round and 7 days after the first dose of SMC. Dynamic of malaria parasites prevalence and the resistance markers to drugs were assessed by molecular assays in DHA-PQ, SP-AQ and control arms over 4 months of SMC and 8 months following SMC using q-PCR assay.
Preliminary data from 100 participants showed a significant decrease in the prevalence of Plasmodium falciparum parasites carriage from 67% to 10% at days 1 and 31 after the first SMC round. The prevalence remained low during SMC follow-up period. Molecular assays of resistance markers are ongoing. Full results will be presented at the meeting.
DHA-PPQ is suitable for SMC, assessment of parasites prevalence and resistance markers selection is ongoing.
Cure research is the new frontier in the fight against HIV as prioritized by organizations like the International AIDS Society, the EDCTP and the National Institutes of Health. However, though 70% of people living with HIV are in Africa, the literature shows that very little of the current cure research efforts involve African scientists or patients. Important questions such as how co-infections like malaria, helminths, tuberculosis, and different HIV clades affect the viral reservoir can only be answered in Africa, to ensure that an eventual cure is effective and appropriate for African patients.
With support from the EDCTP through a senior fellowship grant in 2019, we set up the HIV Cure Research Infrastructure Study (H-CRIS) at the University of Ghana with partnership from Washington University in St Louis and Amsterdam University Medical Centre. Our approach was to leverage the initial EDCTP grant, to obtain more grants to sustain the cure research training.
Through H-CRIS, we have set up a cohort of 390 patients with HIV that we monitor on a regular basis for viral load, CD4 counts, co-morbidities and other parameters. We have trained 3 postdoctoral scientists, 2 PhD students, 3 MPhil students and 10 research assistants in HIV cure research methods. We have collected data on patient perspectives on cure research, performed laboratory screening of compounds towards cure, and obtained additional funding to perform cutting edge studies on how co-infections such as tuberculosis and hepatitis impact the HIV reservoir. Through mentorship and guidance of trainees, we have quadrupled the initial EDCTP grant by obtaining additional funding of over 2 million dollars from various sources to sustain the cure research.
We will share our model of starting and sustaining a basic and translational HIV cure research programme which is feasible and replicable in other Africa settings.
Uganda is an ecological hot-spot with infectious disease transmission belts which exacerbates its vulnerability to epidemics. Its proximity to the Congo Basin, influx of refugees and the intrusion of humans into ecological areas formerly occupied by animals and other pathogen carriers, has resulted in an increased risk of Ebola virus disease (EVD) over the last two decades. This study aimed to determine the spatial clustering, hot spot analysis and temporal distribution of the recent EVD outbreak in Uganda.
The study used an ecological design based on the 2184 subcounties in Uganda as the spatial units. Initial exploratory analysis used measures of spatial autocorrelation in the R statistical package. Using the Anselin’s Local Moran test cluster detection method, spatial autocorrelation was applied to determine the presence of statistically significant clusters and hotspots.
Overall, 142 confirmed cases of Sudan virus disease (SVD) were reported, of which 55 died (CFR: 39%), and 87 recovered. In addition, 22 deaths among probable cases were reported in individuals who died before samples could be taken (overall CFR: 47%). Overall, nine Ugandan districts were affected by this outbreak: Bunyangabu, Jinja, Kagadi, Kampala, Kassanda, Kyegegwa, Masaka, Mubende, and Wakiso. When the number of permutation test was set to 9999, Moran’s I = 0.37261, P = 0.0085, and was significant at significance level of 0.01. Spatial cluster analysis identified two most likely cluster; one large multi-centered cluster in districts of Mubende and Kassanda with 13 locations and one cluster in Rubaga division in Kampala district.
Substantial spatial clustering of EVD was detected at sub-county level in the recent outbreak at two districts of Mubende and Kassanda in the central region of Uganda. This study identifies hotspot areas for efficient implementation of early-targeted interventions for the prevention and control of the outbreak.
Schistosomiasis is caused by infection with parasitic worms, schistosomes, and affects hundreds of millions people worldwide. The detection of schistosome circulating cathodic and anodic antigens (CCA and CAA) has proven to be highly valuable in diagnosing intestinal and urinary schistosomiasis. Within the freeBILy project, a CCA/CAA duplex test was developed which detects both antigens simultaneously to improve the diagnostic accuracy and potentially identify Schistosoma spp based on CAA/CCA ratios.
CAA and CCA were incorporated into the current laboratory-based UCP-LF test platform utilizing a duplex test-format; i.e. a single prototype device with two parallel lateral flow (LF) strips. Test performance was evaluated using banked sample sets (serum and urine) from two different Schistosoma endemic areas using standardized protocols. Samples were available from both cross-sectional as well as school-age children based population studies. In a subset, CCA/CAA ratios were determined.
CAA-levels in urine were lower compared to CAA-levels in serum, both for S. mansoni (Sm) and S. haematobium (Sh). Significantly more CCA was observed in Sm urines compared to Sh urines. In urine the CCA/CAA ratio for Sm was significantly higher compared to the CAA/CCA ratio for Sh, while no differences were observed in serum. Species could not be identified unequivocally based on the CCA/CAA ratio.
Combined detection of CAA and CCA improved diagnostic accuracy and showed added value compared to detection either antigen separately, particularly in Sh settings where the POC-CCA performance is limited. Identification of Schistosoma species based on the CCA/CAA ratio seems challenging due to multiple factors. Generally, CAA and CCA levels in serum and urine show marked differences which would benefit from further focused in-depth studies.
Almost 40% of persons newly diagnosed with TB are unreported. Detecting cases in TB/HIV endemic communities have been restricted by a lack of sensitive and user-friendly point-of-care (POC) diagnostic tools. Computer-aided detection (CAD) has been recommended by the WHO for screening for TB, however, implementation of CAD in community-based active case finding (ACF) is unclear. We aimed determine the adjunctive role of CAD in Xpert-orientated community-based ACF for TB.
In this ongoing, EDCTP-funded (RIA2020S-3295), open-labelled randomised controlled trial (RCT), high-risk persons (symptomatic and/or HIV-infected) with presumed TB were recruited from TB/HIV endemic communities in South Africa and Zambia (Zimbabwe is an additional site). Using a low-cost mobile van staffed by three healthcare workers and equipped with an ultra-portable x-ray and GeneXpert® system, participants were randomized into either ‘CAD + POC Xpert’ (Arm 1: CAD followed by Xpert MTB/RIF Ultra in CAD-positive participants using a CAD4TB v7 threshold of 10 [South Africa] and 50 [Zambia] based on prior population-specific calibration), or ‘POC Xpert alone’ (Arm 2: POC Xpert MTB/RIF Ultra only). The primary outcome was time to detection of microbiologically proven TB (Xpert and/or culture positivity). Here we present an interim trial progress report.
From Feb 2022, a total of 505 participants have been enrolled (256 [50.7%] from South Africa and 249 [49.3%] from Zambia). 26.9% (136/505) of participants were HIV-infected (median CD4 of 609). 33/505 (6.5%) tested positive for TB (25/256 [9.8%] in South Africa and 8/249 [3.2%] in Zambia). 15 participants underwent screening to detect 1 case of TB. Of TB-positive participants, 7/33 (21.2%) were smear positive.
Community-based ACF detected a high burden of TB, of which a significant minority (~20%) was probably infectious. These data have implications for ACF strategies in high burden settings.
HIV in adolescents with perinatal HIV (PHIV) is associated with an increased risk of cardiac disease, which is not well characterised. We characterised myocardial structure and function in adolescents with PHIV and established on antiretroviral therapy (ART) using advanced imaging with cardiac magnetic resonance (CMR).
We conducted a cross-sectional study in PHIV aged 10–19 years taking antiretroviral therapy and an HIV-negative comparison group in Harare, Zimbabwe. Participants underwent a 3-Tesla CMR examination including assessment of myocardial structure and function (cine) and myocardial fibrosis (late gadolinium enhancement, LGE). Groups were compared using unpaired t-test, and potential predictors were assessed with multiple linear regression.
Forty-four participants were included in the analysis (n= 23 with HIV; 52% female and 21 uninfected controls; 48% female]). Participants with PHIV were older [median (IQR) 18 (16–19) vs 15 (13–17) years; p=0.002] compared to uninfected controls. They also had lower height-for-age and weight-for-age z-scores [Mean (SD), -1.84 (1.0) vs 1.17 (1.0); p=0.044] and [-1.35 (1.4) vs -0.21 (1.4); p=0.011] respectively. In the PHIV group, median age at HIV diagnosis was 5.5 (IQR, 4–8) years and 18 (82%) were virally suppressed (<19 copies/ml). The PHIV group had a larger indexed left ventricular (LV) mass [Mean (SD), 39.2 (5.4) vs 35.3 (6.4) g/m2; p=0.047] and LV end-diastolic volume [75.0 (8.2) vs 67.5 (12.5) mL/m2; p=0.026] compared to controls. LV and right ventricular systolic function measured by either ejection fraction or strain was normal in both groups, and no LGE was observed. No association of LV systolic function was observed with age, sex, and HIV viral load.
In this interim analysis, an increased indexed LV mass and end-diastolic LV volume in the PHIV group relative to those HIV-negative may suggest LV structural changes. Recruitment is ongoing and comprehensive regression modelling shall be performed.
Funding: EDCTP TMA2019CDF-2776
Paediatric second line antiretroviral therapy (ART) formulations are limited. CHAPAS-4 (ISRCTN22964075), a 2X4 factorial randomised trial investigated efficacy and safety of 4 anchor drugs.
Children from Uganda, Zambia and Zimbabwe on non-nucleoside reverse transcriptase inhibitor-based regimens, requiring second line ART, were randomised to dolutegravir (DTG) or ritonavir-boosted darunavir(DRV/r), atazanavir(ATV/r) or lopinavir(LPV/r) dosed according to WHO weight-bands. Primary endpoint was week-96 viral load(VL)<400copies/mL. We hypothesised ATV/r would be non-inferior to LPV/r(12% margin); both DRV/r and DTG superior to LPV/r and ATV/r arms combined (superiority threshold p≤0.03; multiple comparisons). Analysis was intention-to-treat, based on logistic regression. Results of second randomisation (tenofovir alafenamide(TAF)-based vs. SOC backbone) will be reported separately.
919 children aged 3–15years (54%male, median[IQR] viral load 17,573copies/mL[5549, 55,700]; CD4 count 669[413, 971]) were randomised and spent 98% of time on allocated regimen. At week-96 208/226(92.0%) on DTG, 203/230(88.3%) on DRV/r, 193/229(84.3%) on ATV/r, 180/223(80.7%) on LPV/r had VL<400c/ml. DTG was superior to LPV/r and ATV/r (adjusted difference 9.7%[4.8, 14.5],p<0.0001); DRV/r showed a trend to superiority to LPV/r and ATV/r (5.6%[0.3, 11.0],p=0.04); ATV/r was non-inferior to LPV/r (3.4%[-3.4, 10.2],p=0.33). Results were similar for VL<60copies/mL and <1000copies/mL and at weeks 48 and 144. CD4 count improved in all arms. More grade 3/4 adverse events(AE), predominantly hyperbilirubinemia, occurred for ATV/r vs LPV/r(p<0.0001); DTG had fewer AE vs. LPV/r(p=0.02). There was no evidence of excess weight-gain. Improvement in growth parameters were lowest with LPV/r. Renal and bone health was similar between arms. One child died (treatment-unrelated); 3% had serious adverse events.
These results supports current WHO guidelines for preferred and alternative second line ART. In the future children will require second line ART after first line DTG. Ongoing development of child-friendly boosted DRV and ATV will be key to ensure robust treatment options are available for children in Africa.
Understanding pre-existing, cross-reactive immunity to SARS-CoV-2 is important for pan-coronavirus vaccine design. Since pre-existing T cell immunity has been associated with prior infection by circulating, endemic human coronaviruses (hCoVs), there has been recent interest in mapping hCoV exposure and immunity. However, few of these studies have been performed in Africa, where hCoV exposure may differ. We measured antibodies to endemic hCoVs in South African adults and adolescents, to gain insights into baseline exposure across different age groups.
Using an established ELISA, we measured IgG specific for HKU1, 229E, OC43 and NL63 in pre-pandemic plasma from adolescents (n=14, ages 15–19) and adults (n=13, ages 20–50). A technical repeat was included for each sample, and samples were randomised within each assay plate. Data were analysed using non-parametric statistical tests.
In preliminary findings, antibodies specific for NL63, an alphacoronavirus, were detected in all adults and most adolescents (93%). Interestingly, fewer participants had antibodies to the other human alphacoronavirus, 229E, with IgG detected in 54% of adults and 50% of adolescents. Antibodies to the betacoronavirus, HKU-1, were present in all participants. We found no differences in the magnitude of responses between adults and adolescents for NL63, 229E and HKU-1, although a weak association with age was observed for NL63 (p=0.04, r=0.39) and HKU-1 (p=0.04, r=0.4). Finally, antibodies against OC43, another betacoronavirus, were measured in a subset (n=9) of adult participants, with responses detected in all.
Our data suggest childhood exposure to endemic coronaviruses, such that adolescents already have detectable antibodies. Importantly, hCoV 229E may not circulate as frequently in South Africa compared to the global north, where reports confirm durable and detectable 229E antibody responses in adults. These geographical differences in exposure have important implications when considering the SARS-CoV-2 shift to endemicity, and the design of pan-coronavirus vaccines.
In settings with low routine coverage of pneumococcal conjugate vaccines (PCVs), mass campaigns targeting multi-age cohorts (MAC) might accelerate herd protection but would be costly. Mass campaigns using fractional dose PCV would decrease cost and increase access, but their effect on pneumococcal carriage is unknown.
We conducted a cluster-randomized trial in Niger to evaluate the effect of mass campaigns on pneumococcal carriage. 63 villages were randomized in a 3:3:1 ratio to receive mass campaigns targeting children aged 1–9 years with a single full dose of Pneumosil, a single 1/5 fractional dose, or no campaign. We conducted surveys among 2268 households before and 6 months after vaccination. Data were collected about household composition and sociodemographics; a nasopharyngeal swab (NPS) was collected from a child aged 1–9 years. NPS were collected in STGG media and stored at -80°C within 8 hours of collection. Culture and Quellung reactions were performed in Kilifi, Kenya, in accordance with WHO-recommended procedures.
Pre-vaccination results are currently available; post-vaccination results will be available in September 2023. In the baseline survey, 2223 children were included, with median age of 4 years (IQR 2–6). Median household size was 7 (IQR 5–10), and a median of 4 people (IQR 2–5) slept in the same room as the child. 41% of children received 3 recorded doses of PCV in EPI, which increased to 80% when considering self-report. Baseline pneumococcal carriage prevalence was 87%, and the prevalence of vaccine-type (VT) carriage was 17%. Serotypes 19A, 19F, 23F, and 6A accounted for 74% of VT carriage. The most common non-VT serotypes isolated were 34, 11A, 23B and 16F.
Eight years after PCV13 introduction, residual VT carriage was 17%, which is lower than expected. The effect of MAC mass campaigns on VT carriage will be known in September 2023.
Funding: EDCTP
East and Southern African countries are susceptible to disease outbreaks, and vulnerable to public health emergencies due to constrained health systems. We aim to promote the development of a critical mass of epidemiologists to work with National Public Health Institutes and Ministries of Health to strengthen response capacity.
The East and Southern Africa Consortium for Outbreak Epidemiology Training (ENTRANT) programme was established with funding from EDCTP and Africa CDC, to provide epidemiological training and mentorship to early- to mid-career public health professionals working in the region. ENTRANT is coordinated by a consortium of institutional partners relevant to outbreak response in the region, and supported by an independent Advisory Committee comprising experts in capacity strengthening in sub-Saharan Africa. A competitive application process was implemented to identify high-calibre public health professionals for entry into the programme. Fellows undertake MSc Epidemiology at London School of Hygiene and Tropical Medicine (LSHTM) followed by further focussed short course multidisciplinary training on the emergence, spread and response to pandemics. Fellows receive mentorship from experienced epidemiologists in their home country, and take part in regular transferable skills training and networking activities.
From a total of 324 applications, 15 public health professionals (eight female, seven male) from Botswana, Ethiopia, Kenya, Tanzania, Uganda and Zambia have been awarded Fellowships. To date, six have completed their MSc Epidemiology training, with the remaining Fellows due to complete in October 2023. Fellows who have completed formal training have gone on to work for Ministries of Health and public health research institutions. Fellows at all stages of the programme have formed a strong network through regular meetings and networking events.
The ENTRANT programme has been successfully established. Further funding will be sought to further expand the programme and promote a long-term mutually-supporting network of outbreak and pandemic control practitioners.
Skin diseases are common human illnesses globally. Improved diagnostic skills of health staff working in underserved communities may uncover a wide range of diseases, including skin Neglected Tropical Diseases (NTDs). Integrated skin screening is an approach used in PEP4LEP, a research project in Ethiopia, Mozambique, and Tanzania that is aimed at identifying the most effective and feasible method for screening people at risk of developing leprosy and administering chemoprophylaxis. We present preliminary results on the skin diseases and their frequency patterns as found during integrated skin screening in communities in three Tanzanian districts.
Data on the skin diseases identified and the frequency of diagnosis were collected in the skin camps that took place in Morogoro, Mvomero, and Lindi districts in Tanzania as part of the PEP4LEP study
A total of 7,721 participants were screened from July 2020 to January 2023 in 74 skin camps, 4,871 (63.1%) had skin conditions. A total of 77 (1.0%) contacts were newly diagnosed with leprosy. Frequently detected skin diseases were: tinea capitis (2,230 cases, 29.0%), pityriasis versicolor (1,173, 15.2%), and atopic dermatitis (610, 7.9%). Apart from leprosy, other diagnosed skin NTDs included: scabies (695, 9.0%), and onchocerciasis (54, 0.7%). These findings are preliminary as recruitment is still ongoing, an in-depth analysis is expected towards the end of the project.
Integrated skin screening in community skin health interventions contributes to reducing the barriers to the identification and management of skin conditions, including skin NTDs like leprosy.
This project was supported by the EDCTP2 program under Horizon 2020 (grant number RIA2017NIM-1839-441 PEP4LEP). The project also received funding from the Leprosy Research Initiative (LRI; www.leprosyresearch.org, grant number 707.19.58). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the abstract.
Loss to follow-up of presumptive TB patients is a major challenge towards the realization of the End-TB strategy. SMS reminders and mobile money (MM) incentives have shown promise by improving health outcomes. However, there is limited knowledge on whether these interventions can increase linkage to care/treatment for presumptive TB patients in Uganda. We explored views about using SMS reminders and MM incentives in improving linkage to care of presumptive TB patients.
A qualitative study was conducted, involving; 20 key informants with health workers (HCW), 25 in-depths interviews with presumptive TB patients and 8 focus group discussions with TB patients. Interviews were audio recorded and transcribed verbatim. Data was analyzed using Atlas.ti V12.0.
Almost all respondents viewed SMS as not a good communication channel to remind presumptive TB patients to complete diagnosis. They expressed concerns that the SMS reminders could lead to unintended disclosure of one’s TB status if they were accessed by another person. Also mentioned the existing fatigue with SMS from telecom companies hence most likely to ignore/delete any messages coming in without reading, lack of real-time interactive communication and not useful for patients who can’t read. Phone calls were preferred to SMS because they are private, foster a two-way communication in real-time and felt that a phone call is personal and makes them feel that the HCW cares about them. There were divergent views on MM incentives, majority disagreed to MM sent before the patient comes to the health facility as it may tempt the patient to divert it rather than the intended use.
The findings from this study showed limited preference of the SMS reminders. As we embrace mHealth, the human interaction between patient and HCW needs to be maintained. MM sent to the patient prior to the clinic visit, might be diverted.
Diagnostic testing for TB needs to optimize access, turnaround time and thus time to treatment initiation and cost. Point of care (POC) testing optimizes the former, but additional costs beyond the test cost alone might be drivers of overall cost in a POC testing strategy, especially in low-and-middle-income settings.
We estimated the health system cost per participant tested for TB on-site via the novel Molbio Truenat MTB/RIF platform (Molbio Diagnostics, Verna, Goa, India) versus the hub-and-spoke standard of care, predominantly off-site testing with Xpert MTB/RIF (Cepheid, Inc., Sunnyvale, CA, USA). We used a health systems perspective, nested in a pragmatic, cluster-randomized trial across 29 clinics (15 intervention, 14 standard of care) among four sites in Mozambique (Sites A and B) and Tanzania (Sites C and D). We estimated ranges for health service delivery costs using trial expense reports, facility assessments, and project staff interviews.
The estimated cost per participant tested using on-site Molbio Truenat was $53 (95% credible interval: $45-$63) in Mozambique [$55 ($47-$64) for Site A and $57 ($50-$64) for Site B], and $42 ($35-$50) in Tanzania [$41 ($36-$47) for Site C and $48 ($39-$57) for Site D]. For the standard-of-care (hub-and-spoke) arm, the cost per participant tested was $40 ($35-$45) in Mozambique [$35 ($33–39) for Site A and $48 ($45-$52) for site B], and $21 ($19-$24) in Tanzania [$23 ($21-$24) for Site C and $20 ($18-$22) for Site D]. Equipment and staffing costs for testing were higher in the decentralized arm, as many of these costs were shared between clinics in the standard-of-care arm. Costs for consumables, training, and communication were comparable across arms.
From a health system perspective, decentralized molecular testing for tuberculosis is more expensive than using a hub-and-spoke approach.
Infants living with HIV are at high risk of tuberculosis and death. Optimal antituberculosis therapy is essential for favourable clinical outcomes particularly in severely ill children. Using WHO-recommended weight-band dosing, younger children weighing <8kg are at risk of suboptimal exposures. We aimed to evaluate plasma concentration of first line antituberculosis drugs in infants with HIV.
EMPIRICAL trial (#NCT03915366; EDCTP2-funded (RIA2017MC-2013)) is a randomized controlled trial evaluating empirical antituberculosis and cytomegalovirus treatment in infants with HIV hospitalized for severe pneumonia in 5 African countries. Eligible infants aged <1 year, weighing ≥3kg, on antituberculosis treatment had a blood sample taken 2-hours post-dose at days 30, 90 and 180 in a pharmacokinetic sub-study. Antituberculosis drugs were dosed according to WHO weight-bands using fixed-dose-combination dispersible tablets of rifampicin(15mg/kg)/isoniazid(10mg/kg)/pyrazinamide(35mg/kg) 75/50/150mg with ethambutol(20mg/kg) 100mg. Antiretroviral-naïve infants initiated treatment in accordance with national guidelines. We compared C2hr plasma concentrations for rifampicin, isoniazid, pyrazinamide, and ethambutol with published Cmax references.
Forty-nine infants of whom 21 were female, median (range) age 6.1(2.5–13.5) months and weighing 5.3(3.4–8.7) kg were included in the analysis of study day 30. The geometric mean (CV%) C2hr for rifampicin, isoniazid, pyrazinamide and ethambutol were 3.66(161) mg/L, 2.80(102) mg/L, 22.27(97) mg/L, and 0.56(101) mg/L, respectively. The C2hr values were substantially below adult reference Cmax for rifampicin [ref in adults (10 mg/kg dose): 8–24 mg/L] and ethambutol [ref: 2–6 mg/L], slightly lower for isoniazid [ref: 3–6 mg/L], and within range for pyrazinamide [ref: 20–60 mg/L].
Plasma levels of first-line TB drugs in infants with HIV and severe pneumonia were low compared to adults. This is consistent with other studies showing that infants and younger children do not achieve adult references for first-line TB drugs at current recommended doses. Our data support considerations for optimising dosing of first-line TB drugs for infants.
The prevalence of hypertension (HTN) is increasing among people with HIV (PHIV) across sub-Saharan Africa. However, little data exist on the effectiveness of integrated HIV and HTN care delivery systems on blood pressure [BP] screening and control.
We conducted a cluster-randomized trial among PHIV (≥18 years) to evaluate a multicomponent integrated HIV/HTN care model (intervention) versus standard-of-care (control) in 52 health centres (HCs, 2/district and 26/arm) in rural Southwestern Uganda (NCT04624061), with districts as unit of randomization. The intervention included: 1) health worker training on integrating HTN care, 2) promoting HTN screening and care; 3) introduction/improvement of NCD registers, patient care cards, and HTN data capture in electronic medical records; 4) WhatsApp messages for coordination among providers and district health teams. Both arms received BP machines, NCD registers, patient cards, and buffer HTN medicines. Evaluation included: cross-sectional surveys administered annually to a random sample of patients in each HC. Primary endpoints were recent HTN screening and HTN control (<= 140/90 mm Hg) at 24-months. We examined differences in screening (intervention vs. control) within subgroups and change in HTN control (BP<140/90mmHg) from 12-to-24-months within intervention clinic participants with HIV and HTN. Analyses were adjusted for clustering.
Among 3,603 PHIV (2,114 intervention; 1,489 control; 53% women; 47% aged ≤40years) surveyed at 24-months, HTN screening was 76% in intervention vs. 22% in control clinics; risk ratio (RR)=3.44 (95%CI:2.50–4.72; p<0001). Effects were seen for women (RR=3.16), men (RR=3.84), adults aged 18–40years (RR=4.29), and adults aged 41+years (RR=2.96). In the intervention arm, HTN control improved from 33% at 12-months to 57% at 24-months for a risk difference=24% (95%CI:17–30%; p<0.001).
The integrated HIV/HTN care model dramatically improved overall HTN screening and BP control among PHIV and HTN. This presents opportunities to reduce NCD related morbidity and mortality and improve HIV/HTN care.
Disease outbreaks and management are a huge challenge for public health systems worldwide. With globalization, spread of pathogens through trade and travel increases the demand for suitable medicines. At the same time, the excessive use of drugs in veterinary and human medicine leads to a reduction in effectiveness and even to the development of resistances. Antimicrobial resistance (AMR) has become a major problem worldwide. While most high-income countries have already developed a strong surveillance system for AMR, low- and middle-income countries have an urgent need for monitoring AMR. This, as well as the coinfection with neglected tropical diseases (NTDs), remains a significant challenge, especially across sub-Saharan Africa.
The aim of this project is to strengthen the capacity across 7 Sub-Saharan African countries for improved management of AMR and NTDs. The focus here lies on identifying the linkages and transmission of AMR between humans, animals and the environment in a One Health context. In order to better control AMR, academic and research institutions from the eight participating countries have developed 6 work packages (WPs) to build the local capacity to identify the main transmission routes.
The WPs include screening for AMR in humans, environment and livestock, employing surveillance and genetic mapping of circulating AMR strains; investigating relationships between helminthic infections and drug resistant bacteria; developing capacities for point of need diagnostics of AMR and NTDs using mobile labs for field application; identifying any changes in antimicrobial use and AMR incidence during the COVID-19 pandemic in Sub-Saharan African contexts; controlling communicable disease transmission, by identifying and improving existing hygienic practices at the human-animal-environment interface; and building capacity for sustainable leadership in antimicrobial stewardship (AMS).
With the established consortium, this project proposes unique solutions for AMR/AMS through the development of both knowledge and technological infrastructure from a large, diverse, multidisciplinary team.
]]>Malaria transmission blocking vaccines (TBV) hold the potential to block malaria transmission in the population thereby contributing to malaria elimination by producing specific antibodies against functionally important proteins expressed during parasite development in the mosquito. The Plasmodium falciparum Pfs230 and Pfs48/45 proteins are leading candidates for a malaria TBV, while the Circumsporozoite Protein (CSP) remains the leading candidate for an anti-infection Vaccine.
A scalable and reproducible product process in Lactococcus lactis was developed for two candidates: R0.6C (a first-generation TBV) and ProC6C (a novel fusion protein, developed as a multi-stage malaria vaccine). Preclinical development led to a dual-adjuvant design for clinical evaluation, where the antigen is absorbed to Alhydrogel® and either administered directly or mixed at the bedside with the Matrix-M™ Adjuvant. A first-in-human Phase 1 study, conducted in Burkina Faso adults, evaluated R0.6C and ProC6C (at two dose levels, 30/100 µg) formulated on Alhydrogel® alone or in combination with Matrix-M (15/50 µg).
This clinical study demonstrated that both antigens, regardless of dosage, on either formulation were safe and well tolerated. Serology conducted against the immunogen, demonstrated that the addition of Matrix-M enhanced the immune response in adult Burkinabes, compared to Alhydrogel® alone. The functional antibody response, evaluated by an independent laboratory, demonstrated that R0.6C induces sporadic transmission reducing antibodies (TRA). In comparison, ProC6C induced significant transmission reducing antibodies (>75% TRA in > 75% of the cohort).
These results demonstrate that malaria proteins, produced L. lactis and when formulated on Alhydrogel® alone or in combination with Matrix-M are safe, well tolerated and immunogenic. The immunogenicity of ProC6C and its functional antibody response, lays the foundation for further clinical development of this novel chimeric antigen. This project is part of the EDCTP2 Programme supported by the European Union and Developing Countries Clinical Trials Partnership (Grant number RIA2018SV-2311).
Low- and middle-income countries (LMICs) across Africa face significant health challenges and yet there is vast disparity in where research happens across the globe. Nurses, midwives, and community health workers are the predominant healthcare provider in most care settings and so should be supported, trained and enabled to undertake research that can deliver evidence to improve health outcomes in their communities.
Global Research Nurses, part of The Global Health Network, is teaming up with the Nursing Now Challenge and other partners worldwide to utilize research as a leadership opportunity for nurses, midwives, and community health workers in LMICs. The goal of this collaboration is to register 1,000 research studies led by these healthcare professionals and provide them with the necessary skills and opportunities to generate new evidence that can improve health outcomes in low resource settings, supporting Health for All. Each study will deliver new skills and opportunities within the workplace, whilst generating missing data, supporting Health for All. The Global Health Network, a WHO collaborating centre and vast community of practice will provide the scaled support and mechanisms for the studies to be designed, operated, and reported. The Nursing Now Challenge campaign aims to improve health globally by creating leadership development opportunities for nurses and midwives.
The initiative will empower nurses and midwives to lead and innovate in healthcare and enhancing their professional development by delivering research leadership skills in the workplace. The program will provide lasting research capacity, achievable leadership and career development opportunities, and a comprehensive plan to ensure that it can work and leave strong, lasting impact.
By increasing the capacity for nursing, midwifery and community health workers’ research, this challenge will help to elevate these professions and demonstrate their crucial role in addressing African and global health challenges.
Based on the 2021–2030 WHO Neglected Tropical Diseases (NTDs) Roadmap, schistosomiasis elimination as public health challenge will require treatment of all populations at risk, as well as development of innovative products such as a pediatric medication to target specifically preschool-aged children. Access to treatments for NTDs is currently based primarily on philanthropic donations from pharmaceutical companies which have significantly contributed to decrease endemicity while ensuring access to targeted populations. However, new access models to provide innovations are a prerequisite to ensure long-term sustainable and equitable access to all at country level, strengthening country ownership and empowerment in the fight against NTDs.
Together with international stakeholders, the Pediatric Praziquantel Consortium is elaborating the various elements of an innovative procurement-based mechanism addressing the "4 As" of an access framework based on Availability, Affordability, Accessibility and Acceptability of the potential new pediatric treatment option, once it will be registered.
This is a new access path in the NTD community with many gaps to fill. Some elements have been already defined such as the establishment of a high-quality local manufacturing ensuring adequate production, a tailored regulatory approach allowing introduction of the product in countries, and a pricing structure leading to affordability. However other elements such as the demand path, the procurement mechanism and its funding remain critical gaps to be addressed with the support of the countries and international stakeholders.
Innovations needed to address the WHO 2030 Elimination agenda will also require an innovation in their accessibility as today this aspect of the value chain is the new valley of death hampering the translation of NTD R&D into impact.
People with Diabetes Mellitus (DM) are at increased risk for TB and those who have latent TB infection (LTBI) might be indicated for TB preventive therapy. We examined the prevalence and determinants of LTBI among people with DM as part of the PROTID project in Uganda and Tanzania.
A total of 2005 participants with DM were screened for LTBI at four sites in Uganda and Tanzania. LTBI was diagnosed using the tuberculin skin test (TST) with a cutoff of 10mm and or a positive QuantiFERON-TB plus (QFT-plus) after excluding ATB.
The overall prevalence of LTBI was high at 56.3% (lowest at 35.1% in Moshi, Tanzania, and highest at 77% in Kampala, Uganda). 780/2005 (38.9%) had a positive TST, 862 (43.0%) had a positive QFT-plus, and 515 (25.7%) had both a positive TST and QFT-plus. There was a good agreement of 72% (k=0.42; 95% CI: 0.38–0.46) between the two tests. On multivariable analysis, those aged between 36–45 [AOR=2.38 (CI: 1.44–3.92)]; 46–55 [AOR=1.98 (CI: 1.26–3.13)]; and 55 years and above [AOR=1.48 (CI: 0.95–2.29)]; previous TB [AOR=1.85(CI:1.15–2.99, p=0.01)], contacts with TB disease [AOR=1.51(CI:1.16–1.96)] were associated with increased odds of LTBI positivity while Female gender [AOR=0.59(CI: 0.48–0.73), p<0.001] and HIV positivity [AOR=0.66(CI:0.47–0.93), p=0.02] were statistically not associated with LTBI positivity. Overweight and obese DM patients had increased odds of LTBI [AOR=1.85 (1.02–3.35) p=0.04 and AOR=2.18 (1.19–3.97) p=0.01] respectively. Known factors such as current BCG scar, smoking, or alcohol use were not associated with LTBI in this population.
People with DM in East Africa are at a high risk of LTBI. Early detection and treatment of LTBI in this population could help prevent the progression to active TB and reduce morbidity and mortality associated with TB in people with DM.
Funding: EDCTP
The West African Network for Clinical Trials of Antimalarial drugs second edition (WANECAM2) is an Africa-Europe consortium funded by EDCTP2. In collaboration with Novartis and Medicines for Malaria Venture WANECAM2 is contributing to the development of KAF156-LUM SDF and improving clinical studies capacity in the sub-Region. A novel team was identified in Niger, where clinical trial capacity is lagging and was targeted for focused capacity building.
A series of trainings in clinical trial procedures, GCP and GLP were provided by the MRTC-team in July 2019 in Bamako, Mali. A second GCP training was done on site in Niamey, Niger by the MRTC in November 2019 where the entire Niger team participated. Two Niger Biologists visited the MRTC for training and certification in August 2022 while one physician received advanced training in clinical trial procedures, embedded in one of the Mali trial sites. Three nurses were trained on the REDcap platform on medication data entry. One PhD student and one MSc student were registered at USTTB, Mali. Site visits of WANECAM2 teams in Burkina-Faso were organized for the Niger leadership.
From November 2019 to December 2020, with on-site assistance from two experienced physicians and one laboratory certified technician from Mali, the Niger team conducted a Phase IV in vivo study on the efficacy of Artesunate-Pyronaridine versus Artemether-Lumefantrine and enrolled 240 participants. A second study on biological parameters completed in May 2022 with a total of 1052 participants enrolled. Quality control and data analysis are underway. A new building was refurbished and fully equipped.
A new study team and infrastructure was built from scratch in Niger through South-South collaboration and is ready to contribute to an upcoming Phase III trial.
Funding: WANECAM2 which is part of the EDCTP2 (RIA2017T-2018 WANECAM2).
The Biomedical Ethics and Regulatory Capacity Building for Portuguese Speaking African Countries Project (BERC-Luso) was a four-year initiative that aimed to enhance biomedical ethics and regulatory capacities in Angola, Cape-Verde, Guinea Bissau, Mozambique, São Tomé and Príncipe, and Portugal. The project established a network of National Ethics Committees (NCEs), National Regulatory Authorities (NRAs), and experts in biomedical research, developed a comparative legislative study, and created educational programs to promote capacity building. The digital repository in Portuguese language served as an example for similar projects and supported complementary actions beyond the project’s term.
A set of indicators was developed to measure the project’s impact, and the evaluation was carried out through public and grey literature and event reporting. The indicators were linked to concrete actions that leveraged institutional, legislative, and capacity-building development. Score points were attributed to each indicator, with calculation of score mean values.
In all partner countries, a high level of success (78.59%) was achieved by meeting the goals set at the beginning of the project via the roadmap. A total of 311 activities were developed, impacting at least 3,848 professionals from different backgrounds. Over 172 hours of training were delivered, and the project registered mass dissemination through television broadcast, radio, and media in at least six countries.
Overall, the BERC-Luso Project had a significant impact on every participating country, visible through the long-lasting effects of the successful implementation of the bottom-up and top-down approaches. The project trailblazed capacity building in ethical and regulatory revision in the partner countries, but there is still a need for further investment in legislative, institutional, and training levels to reinforce the implementation of best practices.
Children with advanced HIV disease (AHD) are at an increased risk of morbidity and mortality. We describe mortality rates among infants with AHD hospitalized with severe pneumonia.
EMPIRICAL is an ongoing Phase II-III, open-label randomized factorial (2x2) trial supported by EDCTP (GA RIA2017MC_2013/#NCT03915366) to assess the impact of empirical treatment against cytomegalovirus and tuberculosis in infants living with HIV hospitalized with severe pneumonia. The primary endpoint is all-cause mortality at 15-days and 12-months post enrolment. Recruitment is on-going and includes 22 hospitals from 6 African countries (Côte d’Ivoire, Malawi, Mozambique, Uganda, Zambia, Zimbabwe).
In March 2023, 431 infants had been recruited and 429 were included in analysis. Their median age was 4.36 months (IQR, 3.18–7.08) and 49% were female; 164 (38%) had a history of maternal and/or infant prophylaxis for prevention-mother-to-child-transmission (PMTCT); 306 (71%) were newly diagnosed of HIV during hospitalization; Median HIV viral load and CD4% were 6.3 logs copies/mL (IQR, 5.8–7.0) and 14.4% (IQR, 9.9–21.6) respectively. 196 (46%) of the infants died within a 6 months follow up period (2.16 months (IQR, 0.26–6.16), 110 (56%) in the first admission and 86 (44%) after it. The main register causes of death are pneumonia 91 (46%), sepsis 32 (16%) and gastroenteritis 10 (5%). An in-depth analysis of deaths is ongoing, including minimally invasive tissue sampling, microbiological and histopathological evaluation.
Children living with HIV and severe pneumonia have a very high mortality, both during the initial hospitalization and after hospital discharge. Measures focused on earlier identification and treatment as well as focused on decreasing post-discharge mortality are urgently needed. EMPIRICAL will report on the survival benefit of cytomegalovirus and tuberculosis treatment at trial conclusion. Emphasis should be put into reducing missed opportunities for PMTCT; strengthening early infant diagnosis and antiretrovirals initiation for those who fail PMTCT.
Morbidity and mortality rates after successful completion of a six-month course of tuberculosis (TB) treatment remain elevated. Persistent lung inflammation (PLI) on 18F-FDG-PET/CT has been associated with TB relapse and may also lead to post-TB lung disease (PTLD).
The ongoing EDCTP-funded StatinTB trial (RIA2017T-2004; NCT04147286) evaluates safety/efficacy of 40 mg atorvastatin to reduce PLI after TB treatment in HIV-/HIV+ adults measured by 18F-FDG-PET/CT with extended total follow-up of 96 weeks (ExtendTB, NIH-funded). We report findings at time of enrolment into StatinTB/ExtendTB of the first 106 participants. Participants with clinical response to TB treatment and a negative sputum culture for TB at 16 weeks were screened after completing 24 weeks of treatment for drug-sensitive TB. Complete pulmonary function and PLI were measured using EasyOne Pro®Lab and PET/CT. PLI was defined as total lung glycolysis (TLG)≥50 SUVbw*mL. StatinTB/ExtendTB are conducted according to ICH-GCP.
Of the 106 participants (32% women) aged 32.5±7.0 years who underwent PET/CT, 20.8% were HIV+, 57.5% smokers, 28.3% had previous TB; 13.2% reported ongoing cough, 3.8% chest pain and 8.5% shortness of breath. PLI was present in 49.1% of participants (mean TLG of 209±161 SUVbw*mL). Diffusing capacity of the lung for carbon monoxide (DLCO) was consistently reduced in participants with PLI (DLCO%Pred 73.4% vs. 93.7%; p=0.0002) as was FVC%Pred (82.1% vs. 94.9%; p=0.0004); FEV1%Pred was 82.1% vs 94.9%, p=0.0004. After accounting for other variables including HIV and smoking, every one percent increase in DLCO%Pred remained independently associated with a decrease of 4.7 SUVbw*mL of TLG (p=0.017).
PTLD is present in half of participants. Impaired DLCO is associated with PLI in adults after completing a 24-week treatment regimen for drug-sensitive TB. This highlights the need for treatment optimisation during and after TB treatment to reduce PTLD with persistent lung inflammation.
Rapid detection of resistance to key drugs such as fluoroquinolones (FQ) and bedaquiline (BDQ) is essential for appropriate management of multi-drug resistant tuberculosis (MDR-TB). . Molecular tests available require either infrastructures not available in peripheral laboratories in low resource countries, or do not detect resistance to BDQ. Recently, two tests have been developed: GeneXpert MTB/XDR (Cepheid, USA) detecting resistance to isoniazid (INH), FQ and ethionamide (ETH), and TrueNat XDR (Molbio Diagnostics, India) for detection of resistance to INH, FQ and BDQ.
In the EDCTP-funded project (DIAMA) aimed at developing culture free approaches for diagnosis and management of MDR-TB patients, we assessed the performances of these tests in field conditions compared to phenotypic drug-susceptibility testing (pDST) and whole genome sequencing (WGS) using 1711 unique samples consecutively collected in the Sub-Saharan African region (Benin, Cameroon, DRC, Ethiopia, Guinea, Mali, Nigeria, Rwanda and Senegal).
Using a composite reference standard comprising pDST and WGS, Xpert-XDR showed a sensitivity of 87.3% for INH, 37.8% for ETH and 66.7% for FQ, with a respective specificity of 96.5%, 98.3% and 99.7%. For TrueNat, the sensitivity was 88.1% for INH and 47.4% for FQ, with a specificity of 85.7% for INH, 97.7% for FQ and 98.5% for BDQ.
These tests showed promising results, particularly as screening test for detection of resistance to FQ and BDQ.
New safe and effective TB vaccine strategies to replace infant BCG vaccination are needed urgently. We evaluated the safety, reactogenicity and immunogenicity of three doses of the live-attenuated Mycobacterium tuberculosis (Mtb) vaccine candidate, MTBVAC, in comparison to BCG in South African newborns.
Healthy infants, HIV-unexposed, BCG-naïve newborns without history of close TB contact were randomly allocated into three sequential cohorts to receive a single intradermal dose of BCG (SSI, 2.5x105 CFU) or MTBVAC (2.5x104; 2.5x105 CFU; or 2.5x106 CFU).
228 pregnant women consented, and 99 newborns were enrolled. Seventy-eight infants across all 3 cohorts had local reactions, all rated mild, except one grade 2 erythema. Induration, swelling, and erythema was more common with increased MTBVAC dosage. Induration and swelling were more common in MTBVAC 2.5x106 than in BCG and reactogenicity in MTBVAC 2.5x105 was same as BCG. Twelve infants experienced 14 vaccine-unrelated SAEs including one death due to bronchopneumonia. Eight infants commenced TB treatment for unconfirmed pulmonary TB (BCG n=4 and MTBVAC 2.5x104 CFU n=4) and one for unconfirmed TB meningitis (BCG). MTBVAC was highly immunogenic at all 3 doses, inducing predominantly Th1-cytokine-expressing CD4 T-cells, which peaked at day 56 and waned thereafter. The 2.5x105 and 2.5x106 CFU MTBVAC doses were more immunogenic than BCG, inducing very similar response magnitudes and phenotypes. Vaccination with any MTBVAC dose resulted in QFT conversion in most infants at Day 56, but these responses waned and reverted to QFT-negative in more than half by the end of the 1-year follow-up period.
MTBVAC appeared safe and well tolerated and immunogenic at doses between 2.5x104 CFU and 2.5x106 CFU in South Africans newborns. The 2.5x105 CFU MTBVAC dose was selected for the ongoing phase 3 trial in a high TB prevalence setting.
Breastmilk optimizes child survival in low-middle income high HIV prevalence settings. However, breastmilk transmission of HIV-1 continues to contribute to residual vertical HIV transmission. The Phase 1 PedMAb clinical trial aims to define the optimal doses, ideal combination and timing of subcutaneous (SC) administration of two HIV-1 broadly neutralizing antibodies (bNAbs), VRC07-523LS and CAP256V2LS, separately or in combination, to prevent breastmilk transmission of HIV-1 in high incidence regions such as South Africa. The trial is being conducted at the South African Medical Research Council Chatsworth Clinical Research site and the RK Khan hospital. Here we first report the reactogenicity and safety events of CAP256V2LS for the first time in infants.
Between 1st September and end of October 2022, 8 eligible HIV exposed uninfected infants received 5mg/kg CAP256V2LS SC, within 72 hours of birth. All infants were observed for 4 hours post-dose, and followed up face-to-face at days 3, 14 and 28 post-dose for primary objective safety assessments, and until 6 months for secondary objective. A pictorial study diary handed to mothers and collected at day 14 post-dose helped mothers document reactogenicity and early adverse events (AEs). An internal study safety committee reviewed all safety data every two weeks. The Division of AIDS Table, version 2.1. July 2017, was used to grade AEs.
No reactogenicity events were observed at 4 hours or over the first 3 days post-dose. Thirteen AEs were documented during the 28-days post-bNAb administration, mostly common illnesses (except for low absolute neutrophils, a palatal cyst and an uncomplicated umbilical hernia); other 20 AEs were recorded during the following 5 months. AEs were deemed unrelated to study product.
CAP256V2LS administered SC at 5mg/kg to infants within 72 hours of birth is safe. The trial is proceeding to test bNAb’s safety at a higher dose (10mg/kg).
T.b. rhodesiense human African trypanosomiasis (r-HAT), the zoonotic, acute form of sleeping sickness in Eastern Africa, is lethal if untreated. Today only one arsenic-based, neurotoxic drug, melarsoprol, is available for intravenous treatment of advanced meningo-encephalitic disease, the most frequent presentation seen by health services. A new oral treatment would simplify HAT elimination as proposed by WHO. Fexinidazole was approved in 2018 as the first oral drug to treat T.b. gambiense HAT but was not yet evaluated for r-HAT.
A single-arm clinical trial beginning October 2019 in the two main known foci in Malawi and Uganda tested fexinidazole for r-HAT as an alternative to existing treatment. Complementary actions included training of prescribers and laboratory technicians of peripheral health facilities to improve diagnostic capacity, and ethnographic research to understand health-seeking behaviours of populations at risk. These studies supported the creation of community awareness materials and activities.
The primary efficacy result of the clinical trial was achieved with no related deaths during hospitalisation: 0 (C.I.=0.0–8.43%), against a benchmark of 8.5% lethality attributable to melarsoprol. Training covered health staff from twelve provinces in Uganda and three in Malawi, beyond initial plans. Two ethnographic studies provided updated information about perceptions of communities at risk regarding r-HAT, leading to four articles. Posters and leaflets were developed and disseminated in health facilities and community gatherings.
Fexinidazole has shown to be a good alternative to existing treatments for oral treatment of both stages of r-HAT. It will be submitted for EMA regulatory review in preparation for use in endemic countries. Disease awareness has increased among health staff and populations living in endemic areas of Uganda and Malawi. We expect fexinidazole to be deployed in 2024 as a new r-HAT therapeutic.
This project was funded by EDCTP and Fundacão para a Ciência e a Tecnologia
There are well-recognised ethical guidelines for biomedical research, though a lack of specific guidance for studies targeting healthy volunteers. Noting this, the Ethics Committee of the French National Institute for Health and Medical Research (Inserm) convened an initiative to propose elaboration of good practices to protect health volunteers in research, VolREthics. Online discussions and workshops were held at international and regional levels since February 2022 to debate experiences and best practices. This abstract presents the summary of findings from the African regional perspective.
An online Sub-Saharan Africa workshop was convened in May 2022. A pre-workshop questionnaire to capture the regional context better was distributed, and notes during the event taken. Feedback from all regional meetings and plans for developing international guidance were discussed at a workshop in Brussels, April 2023, with representatives from regulatory agencies, manufacturers, research institutions and funders, ethicists and healthy volunteers.
78 people from 21 (14 African) countries and 3 healthy volunteers attended the African workshop, 39 completing questionnaires. Concerns raised included inadequate community engagement, informed consent, feedback of results and guidance on/compensation for secondary use of data, plus economic and/or educational vulnerability of participants. The risk of exploitation or harm, and potential for compromised scientific validity of studies was also mentioned. Proposed solutions were better oversight through legislation and competent ethics committees, national guidelines for compensation, appropriate conditions for confinement, improved dialogue between stakeholders, and innovative learning and engagement to build trust in collaboration with relevant partners such as The Global Health Network’s African communities of practices.
This important initiative has established momentum for closing gaps in how studies enrolling healthy volunteers are conducted ethically and equitably. Further discussions with colleagues from other regions involved in VolREthics should enrich the approach toward sound good practices.
Sponsorship: European Commission, EDCTP, Inserm, Anrs-Inserm, EEIdF
In Cameroon, ethics review has made remarkable progress since 2009 thanks to a stronger political will and support from national and international partners. This progress however remains limited because existing regulations are not fully elaborate on ethical/administrative evaluation of clinical research and the protection of participants. The coverage and decentralization of the national ethics review system is still limited to ensure the evaluation and monitoring of protocols according to recommended standards while respecting socio-cultural particularities of communities.
The first phase of the BREEDSAFCA (Building Capacity for Research Ethics Evaluation and Drugs Safety Monitoring) project was implemented in Cameroon from 2018 to 2022 with funding from EDCTP to contribute to; among others aims to strengthen the regulatory framework of Cameroon’s ethical and administrative evaluation of clinical research, and to improve the national coverage with Research Ethics Committees (RECs). An assessment of the needs in terms of coverage and functioning of ethics committees as well as the reinforcement of regulatory aspects was conducted and the results presented to the competent actors.
The progress attributable to the BREEDSAFCA project included; the increase of regions covered by an ethics committee from 2 to 6 out of the 10 Cameroon regions; contributing to the development of the law on the protection of health research participants; the development of master SOPs for the establishment and functioning of RECs and for ethical and administrative review of research protocols; the training of existing RECs members in Cameroon in the evaluation of research protocols, the setting up of independent RECs financing system; and the providing of office space for all officially existing RECs.
The BREEDSAFCA project contributed to improving the regulatory framework of the ethics review system in Cameroon, the national coverage of regions by ethics committees and strengthening the capacity and skills of ethics committees to evaluate protocols.
UKCDR, the UK Collaborative on Development Research, amplifies the value and impact of research for global development by promoting coherence, collaboration, and joint action among UK research funders. For over a decade, UKCDR has been providing UK research funders with tools, analysis, and good practice to support their evidence-informed decision-making processes to address global challenges.
An underlying principle for effective collaboration and cooperation is the notion of equity. In partnership with ESSENCE on health, we have developed a good practice document supporting funders, institutions, and academics with recommendations on how to embed equity in research partnerships. Following this and of relevance to the work of EDCTP, we are analysing the types of partnerships funders of research for development are developing, the extent to which equity has been defined and/or put into practice, and lessons learned on how to support equitable relationships between research funders to guide future partnership development processes.
Among other strengths of UKCDR is our mapping and analysis work which has provided funders with crucial information on the research landscape on a variety of topics to help shape funding responses. This is exemplified by our COVID CIRCLE initiative (delivered in collaboration with GloPID-R) which features an online tool containing details of more than 20,000 projects awarded by more than 300 funders globally in relation to COVID-19 – which proved to be a valuable tool in helping funders, policymakers, and researchers understand research gaps and potential areas for collaboration to deliver a more effective and coherent global research response to the pandemic. Following its success, we are expanding this work (titled Pandemic PACT) to cover a wider range of epidemic prone diseases and broader epidemic and pandemic research preparedness activities – thereby enhancing collaboration and coherence at a larger scale.
Funding source: various funders (incl UK research funders, government)
]]>Children under five years are at high risk for malaria illness and death. In 2022 WHO updated and expanded its recommendation for Perennial Chemoprevention of Malaria (PMC), i.e. the delivery of regular doses of sulphadoxine-pyrimethamine (SP), integrated within existing Expanded Immunization Programmes (EPI), to prevent malaria in children under 2 years of age living in moderate-to-high transmission settings. We assessed the anticipated community acceptability of a pilot PMC intervention implemented in Massinga District (Mozambique).
We conducted a mixed methods study between June and July 2022. We collected 56 KAP questionnaires with healthcare workers (HCWs) of the 15 participating facilities and 32 recorded semi-structured interviews with HCWs, caregivers, and community healthcare workers (CHWs). For quantitative data, we performed descriptive statistics. Qualitative data were transcribed, analyzed, and synthesized through rapid qualitative analysis.
All respondents agreed on the heavy burden of malaria in children. Most HCWs (51.8%) HCWs were aware that malaria in children could be prevented through tablets (experience from SP in pregnant women). Administering PMC during a vaccination session was perceived as easy and feasible by 92.9% of HCWs. HCW agreed there is high (89.3%) care-seeking behavior in case of fever. However, 60.7% agreed that distance and lack of transport are barriers to accessing health facilities. Overall, the integration of PMC in routine EPI services was perceived as relevant. Community members reported trusting healthcare interventions and HCWs. Caregivers expressed their willingness to participate in active peer mobilization while community members emphasized the need for continuous community engagement to enhance acceptability and influence initially reluctant caregivers.
PMC in children was perceived as acceptable by HCWs and different community actors, as a strategy to prevent malaria and avoidable care seeking. Structural and logistical barriers were anticipated. Involving key community members in active mobilization was perceived as paramount.
Lassa fever (LF) is a severe re-emerging infectious disease caused by the Lassa virus (LV). LF is a priority disease on the World Health Organization’s R&D blueprint and affects a large number of countries in West Africa, with Nigeria carrying the highest case burden in the world. Current treatment options are limited to supportive care and the antiviral drug ribavirin. However, evidence for the efficacy of ribavirin in LF is poor. A recent study showed that in vivo plasma concentrations do not suffice to exert a relevant antiviral effect. New drugs for LF treatment are therefore urgently needed but no therapeutic trials have been conducted for this indication in the past decades. Favipiravir is a broad-spectrum antiviral registered for pandemic influenza that has also been clinically evaluated for other viral infections. It shows potent activity against LV in pre-clinical studies. To evaluate the safety and tolerability of favipiravir as repurposed drug in the treatment of LF, a phase II clinical trial was conducted.
LF patients were recruited at the Irrua Specialist Teaching Hospital and the Federal Medical Centre of Owo in Nigeria, which are the worldwide largest LF treatment centres. Blood sampling for virological, serological and immunological analyses, hematology and biochemistry as well as clinical assessments were done on days 1, 2, and then every other day until the end of the study.
In total, 40 LF patients were included in the trial between 2021 and 2022. Results on cure rates, safety and tolerability of this first GCP compliant phase II clinical trial will be presented to provide first insights into this new treatment option for LF.
HIV self-testing (HIVST) can improve HIV testing rates among highly mobile populations including the male-fisherfolk, but this is not well documented. We assessed HIVST uptake and linkage to HIV care among male fisherfolk in rural Uganda.
The peer-led HIVST intervention for men (PEST4MEN) was conducted among male fisherfolk in two fishing communities in Kalangala and Buvuma island districts in central Uganda, between July and September 2022. Before intervention implementation, 22 men were selected from existing social network groups and trained to serve as male HIV self-test kits distributors or "peer-leaders". Each peer-leader was then requested to nominate up to 20 men from their social networks, who were screened for eligibility and administered a baseline interview if they were eligible. Eligible men had to be 15+ years, self-report a HIV-negative or unknown HIV status and not tested for HIV at least three months prior to enrolment. After the baseline visit, men obtained free oral HIV self-test kits from their peer-leaders and used them to self-test for HIV. We assessed uptake of HIVST and linkage to HIV care among first-time HIV-positive testers using STATA (version 16.0).
Of 475 men screened for study eligibility, 400 (84%) were eligible and administered a baseline interview. Ninety percent (361) completed a follow-up interview. Of these, 98.3% (355) obtained at least one kit from their peer-leaders; 99.1% (352) used them to self-test for HIV. Of the 352 self-testers, 9.4% (33) tested HIV-positive; 81.8% (27) were first-time HIV-positive testers. Of the 27 first-time HIV-positive testers; 40.7% (11) went for confirmatory HIV testing, 10 were confirmed as HIV-positive and 9 were linked to HIV care.
Our peer-led HIVST intervention achieved high rates of HIV testing uptake and identified a high proportion of previously undiagnosed HIV-positive male fisherfolk but linkage to confirmatory HIV testing was sub-optimal.
Well before the COVID-19 pandemic, health experts from around the world identified major gaps in global preparedness for infectious diseases. In the EU, among others, investment was made in life sciences research infrastructures and infectious disease networks that federate facilities offering scientists access to cutting-edge research services, and that could be mobilized in times of crisis.
As one of the first actions of the European Health Emergency preparedness and Response Authority (HERA), the ISIDORe programme, "Integrated Services for Infectious Disease Outbreak Research", was launched in 2022.
ISIDORe is a new approach to epidemic preparedness and response research in Europe. It assembles and provides free access to an unprecedented One Health-driven integrated portfolio of cutting-edge research resources, dedicated to the study of any epidemic-prone disease.
Coordinated by ERINHA ("European Research Infrastructure on Highly Pathogenic Agents"), ISIDORe involves all the major European Research Infrastructures and networks in the field of biomedical research, from the most fundamental (e.g. structural biology) to the most applied (e.g. vaccine development and clinical trials), including social sciences. The ISIDORe programme has two overarching goals: i) to support rapid research responses to outbreaks and epidemics and ii) to contribute to the preparedness to any epidemic-prone pathogen threat. In line with its goals, during its first year ISIDORe contributed to fighting the rise of the SARS-CoV-2 variants through its dedicated call for proposals, and advance Mpox research.
The preparedness programme supports research on the pathogens with epidemic potential from RG 4 pathogens (such as Marburg virus, Nipah virus, Hendra virus, Lassa virus, CCHF virus) to pathogen X, including respiratory pathogens and vector-borne pathogens. This mechanism enabled transdisciplinary projects to be conducted, to improve preparedness, and accelerate research and innovation during times of emergencies.
We aim at showcasing the results of ISIDORe-supported research projects and ongoing opportunities for free access.
]]>Quality management is crucial for ensuring research ethics practices’ integrity and efficiency. The National Research Ethics Committee (CNERS) of Senegal has made strides by becoming the first African National Research Ethics Committee (NREC) to achieve ISO9001 certification. This globally recognized certification validates compliance with quality standards for managing systems and organizations. It also signifies the organization’s commitment to continuous improvement, monitoring, and evaluation of policies and practices, particularly amidst the recent COVID-19 pandemic.
This initiative is part of the EDCTP-funded BCA-WA-ETHICS-II project, aimed at strengthening research ethics capacities in West Africa. The CNERS’ ISO9001-2015 certification process included the development of a quality management system from early 2022, including a thorough assessment of the CNERS’s quality management system, which included a series of internal and external audits conducted by Bureau Veritas. Significant capacity building was undertaken, during which 15 CNERS members were trained in ISO9001-2015 quality management standards and received ISO9001 Internal Auditor certification.
The CNERS successfully completed the first stage of the audit in October 2022. Subsequently, with a quality management expert, they developed several quality management documents, including quality policy guidelines, process cartographies, work plans, and customer satisfaction evaluation tools. The final (certification) audit took place in March 2023, involving a comprehensive review of the CNERS’s quality management documents and interviews with administration and committee members. The CNERS achieved the ISO9001-2015 certification in March 2023, becoming the first African NREC to do so.
The CNERS’ ISO9001-2015 certification sets a valuable precedent for other African NRECs. The system offers multiple benefits, including enhanced customer satisfaction, service delivery, organizational credibility, internal quality management structure, communication, and responsiveness to unforeseen circumstances. It is relevant in the governance and management of NRECs, particularly post-COVID-19, where scientific research requires rigor and compliance with the principles of medical, public health, artificial intelligence, and research ethics.
In 2020, updated South African guidance on management of children with community-acquired pneumonia were published by the South African Thoracic Society. These guidelines recommend intravenous co-amoxiclav as first-line therapy for children hospitalised with World Health Organisation (WHO) defined severe pneumonia. We evaluated how this guideline change impacted on participant enrollment into the PediCAP Trial (https://projectpedicap.org/) at the Trial site in Johannesburg, as receipt of intravenous co-amoxiclav is an exclusion criterion for PediCAP enrollment.
A line list of all paediatric admissions to the Johannesburg PediCAP site is maintained, to facilitate screening for age-eligible paediatric patients with respiratory illness on weekdays. The total number of children hospitalised at the site, the total number of respiratory admissions, and the characteristics of children screened for PediCAP were assessed descriptively.
From 15 July 2021 to 15 May 2023, 11,998 children were hospitalised at the study site. On PediCAP screening days, 4,829 age-eligible children were hospitalised, 2,377 (49.2%) of whom had respiratory admission diagnoses. Five-hundred, twenty-seven children underwent point-of-care C-reactive protein (CRP) testing for eligibility screening into PediCAP and 239 (45.4%) were enrolled. A clinician decision to initiate intravenous co-amoxiclav was a common reason for non-eligibility (in 316 [13.1%] of 2,417 children). Formal CRP levels were significantly higher in children enrolled into PediCAP compared to those treated with intravenous co-amoxiclav (median 51.0 mg/L [Interquartile range (IQR), 29.0–111.0] vs. 18.0 mg/L [IQR, 5.0–57.5]; corrected P-value<0.001).
National guideline recommendations to use intravenous co-amoxiclav as first-line therapy for children hospitalised with severe pneumonia have impacted participant recruitment into PediCAP at the Trial site in Johannesburg. Significantly lower CRP levels in children treated empirically with intravenous co-amoxiclav indicates a disparity between clinician prescribing and the likely aetiology of disease in children hospitalised with severe pneumonia at the study site, warranting optimisation of antimicrobial stewardship practice.
In Uganda, complex clinical research projects that require regulatory oversight are a growing phenomenon. Although there are functional national regulatory agencies (NRAs) to provide oversight, various constraints, including the lack of a robust digital platform to facilitate their work make them inefficient. This scenario has necessitated the establishment of a sustainable digital system to support the work of the NRAs and research ethics committees (RECs). Against this background, the EDTCP-II grants supported a project on Scaling up the Capacity of RECs in Uganda (SCRECU), 2019–2022, and facilitated further development of a National Research Information Management System (NRIMS) which had been developed with support from an earlier EDCTP grant. The overarching objective of SCRECU was to build sustainable capacity for the NRIMS with capabilities of facilitating multi-REC ethical reviews, national registration of research protocols, and their subsequent monitoring by NRAs and RECs.
We trained RECs personnel on the use of NRIMS for online protocol submissions and management; post-approval processes and enrolment of RECs. We provided the RECs with ICT equipment and followed them up to ensure utilization. We tested the effectiveness of the NRIMS, evaluated its adoption, and developed guidelines for its operationalization.
We trained the chairperson, an administrator, and an IT officer from each of the 26 RECs in Uganda on the use of NRIMS and equipped them with Internet services and other relevant tools. Our study demonstrated the affordability of NRIMS and how digital tools can be leveraged to strengthen ethics and regulatory capacity in resource-constrained settings. The study also generated an inventory of equipment required for the operationalization of an NRIMS. The NRIMS has registered over 13,000 users, received over 6,000 applications, and granted 2,500 approvals online. The NRIMS has enhanced institutional workflows, reduced paperwork by over 95%, and turnaround time for protocol approvals by 50%. It has enhanced research ethics regulatory capacity in Uganda.
The NRIMs has revolutionized and strengthened research ethics and regulation in Uganda. It provides a secure, web-based solution for efficient submission, review, approval, and monitoring of research projects. Its success in Uganda provides a paradigm shift for other NRAs in sub-Saharan Africa.
A successful malaria vaccine should, depending on the targeted stage of the malaria life cycle, induce both humoral and cellular immune responses. Naturally acquired immunity (NAI) against malaria is thought to target mostly the blood stage and protects individuals against symptomatic and severe disease, but often fails to protect against infection per sé. A better understanding of the mechanisms of NAI and its role in all stages of the life cycle might lead to improved vaccine design of the next-generation malaria vaccine.
In Lambaréné, Gabon, a study was conducted in which semi-immune individuals underwent repeated controlled human malaria infections (CHMI) using direct venous inoculation of fully viable cryopreserved Plasmodium falciparum (Pf) sporozoites (PfSPZ, strains NF54 and 7G8). Participants were randomized into two arms allocated 1:1. In arm A, participants were infected using Pf strain 7G8 followed by five infections with Pf strain NF54. In arm B, participants were infected four times with Pf strain NF54 followed by one infection with Pf strain 7G8 and finally one infection with NF54. Here, we investigate the immune response against Pf antigens potentially relevant for the protective immune response against malaria. Selected antigens were expressed using mammalian or bacterial expression systems and subsequently purified. Humoral immune response was assessed by indirect ELISA.
In total 56 participants were enrolled. Their average age was 28 +/- 6 years. Most participants were male (82%). At baseline, Pf-specific antibodies ranged from 5 to 100 µg/ml in plasma, with a predominance of antibodies against blood stage antigens, such as AMA1 and merozoite surface proteins. The antibody responses against these antigens showed minor fluctuations during follow-up.
The investigation is ongoing, and further antigens will be investigated. Specifically, the dynamics of antibody responses throughout the study period, also regarding antibody isotype and function, will be presented.
HIV drug resistance (HIVDR) remains a major threat to achieving sustainable viral suppression on antiretroviral therapy (ART). In South Africa, dolutegravir (DTG) is the preferred first-line ART backbone since its rollout in December 2019.
We curated HIVDR genotypic data obtained from the National Health Laboratory Service (NHLS) for ART-experienced patients with virological failure (i.e., consecutive viral loads ≥1,000 copies/mL) receiving HIV-care at public-sector health facilities in KwaZulu-Natal (KZN) province, South Africa. We estimated levels of HIVDR from genotypes processed between January 2018 and June 2022, and assessed temporal trends of HIVDR across 11 districts of KZN, prior to- and following DTG-rollout in South Africa.
Of 4,069 genotypes curated, 3,511 (86.3% CI 85.2–87.3) had HIVDR mutations, with most resistance mutations occurring among adult females aged >15 years, p=0.01. Despite an annual decrease in protease inhibitor (PI)-specific mutations (p=0.0001), about one-third of genotypes had ≥3 drug-class resistance mutations, mainly nucleoside, and non-nucleoside reverse transcriptase inhibitor (NNRTI) mutations. Only 50 genotypes had integrase resistance data, from which 9 (18.0%) had intermediate to high-levels of resistance to DTG. Overall, rural districts had fewer HIVDR genotypes (598/4069, 15%) but with higher HIVDR prevalence (88.1% CI 85.3–90.6) compared to densely populated peri-urban and urban districts.
Six in every seven genotypes from patients with virologic failure had HIVDR mutations despite DTG-rollout, with persistent NNRTI resistance. Thus, whilst introduction of DTG is expected to alleviate HIVDR burden, a sub-population of people may not fully benefit from DTG-use due to multi-drug resistance, at which point PI-based ART is warranted. Higher proportions of HIVDR in rural districts and among adult women, highlight regions and individuals needing priority HIV care. Overall, these findings urge strengthening of HIV services in public healthcare systems to ensure sustainable DTG-use in first-line and subsequent ART regimens.
Elimination of gambiense Human African Trypanosomiasis (gHAT) as public health problem has been achieved in countries like Côte d’Ivoire and Burkina Faso. The World Health Organization (WHO) has set targets for interruption of transmission of gHAT by 2030. In this context, the performance of diagnostic algorithms for early detection of HAT re-emergence remains to be assessed.
Our study represents a further step in the analysis on 8,648 dried blood spots collected during HAT rapid diagnostic tests (RDT) screening in gHAT historical foci in South West Burkina Faso and Centre West Côte d’Ivoire. We assessed the specificity of three molecular tests on 1,000 randomly selected samples from each country. We performed the Trypanozoon subgenus-specific m18S qPCR and RIME LAMP and the Trypanosoma brucei gambiense-specific TgsGP qPCR.
No parasites were detected using parasitological investigations. The overall seroprevalence based on positivity to at least one RDT was 1.19% (103/8648, (0.83–1.55%). The specificities of m18S qPCR and TgsGP qPCR were 99% (990/1,000, 98.9–99.8%) and 99.8% (998/1,000, 95.5–100%) respectively. The RIME LAMP test was negative for all 1,000 specimens (specificity 100%).
All molecular tests qPCR m18S, qPCR TgsGP and RIME LAMP showed high diagnostic specificity. A previous study demonstrated low analytical sensitivities for qPCR m18S and qPCR TgsGP (respectively 1,000 and 10,000 trypanosomes/mL) while that of the RIME LAMP (100 trypanosomes/mL) was in the range of parasitaemias commonly observed in HAT patients. However, none of the three tests was entirely suitable for high-throughput use. To decide what is the best algorithm for HAT post-elimination monitoring, data on costs for all possible algorithms including serological and parasitological diagnostics need to be considered, according to the epidemiological context.
Funding from the EDCTP2 Programme supported by the European Union (Project DRIA-2014-306-DiTECT-HAT).
We evaluated the treatment outcomes of individuals experiencing low-level viremia (LLV) on dolutegravir (DTG) based first-line antiretroviral therapy (ART) in Botswana by determining the trends of LLV over a period of 6 years.
We used a large national observational cohort of individuals (aged≥18yrs) who initiated on DTG-based first-line ART for at least 3 months from June 2016 to December 2022. The prevalence of viral suppression (VL ≤50copies/mL), low-level viremia (VL:51-999copies/mL) and virologic failure (VF) (any VL>1000copies/mL) were estimated among PLWH. The prevalence of LLV was further classified into LLV ranges (low-LLV:VL:51-200copies/mL, medium-LLV:201-400copies/mL and high-LLV:VL:401-999copies/mL). Univariate and multivariable Cox proportional hazards regression determined whether LLV (exposure) is associated with VF (outcome).
Among 50,742 PLWH who have at least one VL measurement during the follow-up, the overall prevalence of LLV by duration strata was 2.2%, 1.8%, 1.7%, 2.3%, 3.1%, 3.7% and 3.9% at 0.25-<0.5, 0.5-≤1, 2, 3, 4, 5, 6+ years respectively. By LLV ranges, ≥90% had low-LLV in each duration strata. A total of 539 had reported LLV at year 0.25-<0.5 whereby 529(98.1%) had single instance of LLV, 9(1.7%) with 2-consecutive-LLV (confirmed) and 1 (0.2%) had at-least-3-LLV(persistent) measurements. The prevalence of PLWH with confirmed-LLV was 9.1%, 9.0%, 7.3%, 6.4%, 9.1% and 8.4% at 0.5-≤1, 2, 3, 4, 5, 6+ years of the follow-up period, respectively. The prevalence of persistent-LLV increased from 0.2% to 7.0% from year 0.25-<0.5 to 6+. PLWH with LLV had an increased risk of VF (adjusted-Hazards-Ratio [aHR] 2.65; 95%CI 2.16–3.26) at a later visit compared to suppressed VL group. High-LLV and persistent-LLV were the main LLV factors associated with VF.
The prevalence of LLV ranging from 1.7–3.9% was found in this cohort. Having a high or persistent-LLV is associated with a high risk of subsequent VF. Intensified clinical monitoring strategies are warranted for individuals with LLV.
In the last three decades, more than 2,500 national vaccination Campaigns with Oral Polio Vaccine (C-OPV) have distributed more than ten billion doses of OPV to children in the effort to eliminate wild poliovirus. C-OPVs have been demonstrated in several studies to reduce all-cause under-3-year mortality by ~25–35%, suggesting that C-OPV has beneficial non-specific effects (NSEs). We triangulated the evidence with different data sources and analytic approaches.
We used Health and Demographic Surveillance System data from several countries to compare all-cause and cause-specific under-3-year mortality after and before C-OPVs in Cox proportional hazards model adjusted for other campaign interventions and calendar year. We modelled the counterfactual number of deaths averted by C-OPVs. We distinguished between C-OPV administered alone and other campaign interventions.
In urban Bissau, Guinea-Bissau, between 2002–2014 C-OPVs reduced all-cause mortality by 25% (95% CI: 15–33%). In Chakaria, Bangladesh, between 2004–2019, the estimate was 31% (10–48%). In rural Burkina Faso between 2012–2016, C-OPV reduced mortality and hospitalisations (composite outcome) by 36% (6–56%). Limited effect was observed on all-cause mortality (5% (95% CI: -4–13%) reduction) in Navrongo, rural Ghana, between 1996–2015. However, C-OPVs were more frequent than in previous analyses and effects differed by routine vaccinations and age groups. In all studies, apart from Bangladesh, the effect of C-OPV was more beneficial in males than females. Based on the Guinea-Bissau results, OPV averted 10% (5–15%) of all childhood deaths during the analysis period. No similar effects were found for other campaign interventions.
There is now compelling evidence that C-OPVs have beneficial NSEs. OPV is planned to be stopped in 2026. Based on the existing evidence, this may paradoxically increase child mortality. It is urgent that we find ways to mitigate the potential negative impact. One drop may have saved more lives than anyone could have imagined.
Acute respiratory infections are a major global burden, with pneumonia being the leading cause of death. However, very little information has been available on their causative agents in Africa. In Gabon, Central Africa, although COVID-19 has been extensively studied since the pandemic emerged, the other respiratory viral diseases have been paid less attention compared to COVID-19 and no surveillance study has been conducted in the country. Therefore, this study aimed to reveal the situation of respiratory viral diseases in Gabon during the COVID-19 pandemic.
A total of 582 nasopharyngeal swab specimens were collected from SARS-CoV-2 negative patients with respiratory illness in several provinces of Gabon during the period from March to December, 2020. Viral RNA was extracted and screened by RT-qPCR for major 17 respiratory viruses. Epidemiological analysis was performed using patient demographic information and the detected viruses were analyzed genetically.
Of 582 samples, 156 were positive (26%) for eight viruses: enterovirus (EV), human rhinovirus (HRV), human coronavirus OC43, human parainfluenza virus 3 and 4a, adenovirus, influenza A virus (IAV) and human metapneumovirus. Genotyping of HRV based on 5’UTR and VP4/VP2 sequences identified all genotypes (A, B, and C). Gabonese hMPV and IAV strains were classified as group A and H3N2 respectively. Moreover, hMPV was detected for the first time in Gabon in this study.
This study revealed the circulation and distribution of respiratory viruses during the COVID-19 pandemic in Gabon. In particular, detection rate of EV in this study was higher than that reported in 2014 in Gabon. This study reports for the first time in Gabon the molecular characterization of HRV, hMPV and whole genome of IAV strains. Further investigation would be required to validate the effect of the COVID-19 pandemic on the incidence of other respiratory viral diseases.
Funding source: JSPS
The Covid pandemic has illustrated a substantial need for good Randomized Controlled Trials (RCTs) to better understand the benefits and hazards of medical interventions. The Good Clinical Trials Collaborative (GCTC) has created new guidance to promote and enable high-quality, ethical RCTs.
In 2020, the Collaborative convened two workshops with a diverse, global, multi-disciplinary, multi-stakeholder group of 84 members to design the guidance. Draft content was reviewed at workshops, exploring scientific and ethical considerations, clinical contexts and quality management. After public consultation, the Guidance was finalized and published on www.goodtrials.org in 2022.
The agreed Five Principles of Good RCTs are that they are designed to produce scientifically sound answers to relevant questions, respect the rights and well-being of participants, are collaborative and transparent, are appropriate for their context, manage quality effectively and efficiently. The Guidance is underpinned by considerations that help a trial to fulfil its ethical responsibilities regarding participants, future and current patients. It is designed to support all RCTs in all settings to be relevant, informative, and provide sound answers to clear questions, thereby driving the development of better interventions and the delivery of future care. For professionals, the Guidance can be a tool to prompt and justify tailored applications of the principles in a particular setting. However, the Guidance can also aid community engagement by improving understanding of what a good RCT looks like – and why – for non-professional audiences.
We hope that this Guidance can be a foundation of common understanding that good healthcare is informed by good evidence from good trials – and that it can help improve the standards of clinical trials and the way we collectively learn from and utilize their results.
The EDCTP Regional Networks of Excellence (NoE) have been increasing capacity for knowledge and training in data management and sharing as part of EDCTP2. The aim of this new work was to enhance and leverage the EDCTP Knowledge Hub to support secondary data analysis that could be utilised across all four NoEs. The hub would provide overarching content, as well as deeper-dive training materials allowing networks to develop tailored in-person sessions addressing local use cases.
This training initiative is a joint project of the EDCTP NoEs, The Global Health Network and the Infectious Diseases Data Observatory (IDDO) and has several components: enhanced online modules in English and French covering an essential curriculum in data management and sharing; dissemination through a Data Management and Sharing Technical Working Group consisting of NoE members to ensure that content meets their training needs; additional resources for local face-to-face training developed from the online training course, with tools and case studies made available alongside the online training package for download and use.
The content and delivery of this training have been tailored specifically for the needs of the EDCTP NoEs, enhancing knowledge on data management and sharing to support secondary analysis that responds directly to the clinical research context of sub-Saharan Africa. Leveraging the powerful web-based training platform, this initiative draws on experience from across EDCTP NoEs and partners to deliver a comprehensive curriculum in both English and French.
As the EDCTP NoEs continue to strengthen their capacity and look towards more advanced data management and sharing solutions that fit their context, this training platform will provide sustainable knowledge and training foundations for supporting this growth in expertise, aligned with the EDCTP NoE aims of research collaboration to further raise the quality of clinical research and practice across sub-Saharan Africa.
]]>The scale-up of antiretroviral therapy (ART) has resulted in large numbers of children with perinatally-acquired HIV who would have died in early childhood with untreated HIV, reaching adolescence and adulthood. However, it is becoming known that children growing up with HIV are at risk of multisystem co-morbidities, despite ART. In Africa (where 90% of the world’s children with HIV live), the majority of the current cohort of older children and adolescents with HIV did not start ART in infancy, and HIV viral suppression rates are lower than those observed in adults. These factors increase the risk of co-morbidities. Children with HIV experience a range of comorbidities including cardio-respiratory, musculoskeletal and neurocognitive disease.
While there is awareness of the burden of chronic comorbidities in adults who are ageing with HIV, there is much less awareness of the burden of comorbidities in children growing up with HIV. Thus, HIV management guidelines and programmes have hitherto focused almost exclusively on achieving viral suppression. These comorbidities result in considerable disability and have wide-ranging effects such as poorer adherence, lower educational attainment and premature mortality. Addressing these comorbidities is critical for the well-being of children as they enter adulthood. The talk will summarise the existing evidence on the range and spectrum of co-morbidities, underlying drivers and draw out the outstanding research agenda.
]]>To maximize the impact of the findings of clinical research, long-term plans for equitable access to new, innovative health products should be included right from the outset of R&D planning. This is a complex undertaking, that requires multilayered, coordinated interventions across various disciplines and sectors, including but not limited to pharmaceutical regulation, ethical oversight, technology transfer, intellectual property ecosystem, market dynamics, production capacity, supply systems, communities engagement etc.
Partnerships grounded in the principles of fairness, respect, care and honesty as per TRUST Code (A Global Code of Conduct for Equitable Research Partnerships), and established with a thorough comprehension of the process of decolonization of global health research, are essential pre-requisites for enabling African clinical researchers, their research centres and partners to achieve these ambitious objectives. In particular, fair and collaborative partnerships will (i) enable defining a regional and continental clinical research agenda that prioritizes the population unmet health needs, and (ii) facilitate the generation of evidence and translation of research findings into concrete access to new products to all those in need, including through rapidly-available multisource and/or biosimilar quality-assured formulations.
Once fair governance mechanisms are established, collaborations -including in the clinical research field- should be empowered to adopt a systematic approach that addresses the interconnectedness of R&D with the legal, regulatory and policy determinants of access. Such an approach should include comprehensive planning from the start, addressing provisions for, among other things, quality-assurance, surveillance, sustained supply, technology transfer and market shaping. To achieve this broad scope, from R&D to ensuring product quality, availability and affordability to all, these collaborative partnerships must not be limited to researchers alone. They should actively involve regulators and policymakers within the local pharmaceutical systems. By engaging all relevant stakeholders, we could create a more comprehensive and effective framework to achieve equitable access to healthcare products.
]]>Despite advancements in medical research worldwide, there are still gender and geographical inequities in clinical trials, with a disproportionate underrepresentation of women and marginalised groups. In order to overcome these obstacles and fill information gaps, there is a need to enhance clinical research capabilities in Africa, promoting women’s participation, and valuing diversity.
To close the knowledge gap and promote inclusivity, capacity-building efforts enable women in Africa to assume leadership roles in clinical research. The gender imbalance is exacerbated by historical prejudices, job difficulties, and cultural expectations, which prevent the progress of inclusive and diverse medical knowledge. As a result, Trials of Excellence in Southern Africa is implementing training for female PhDs aimed at nurturing a generation of skilled and knowledgeable women researchers and leaders who will drive advancements in medical research and will present it as a case study.
Initiatives to enhance capacity are essential for women to assume clinical research leadership positions. These programmes should offer skills development, leadership training, and mentoring opportunities. To achieve this, it is necessary to invest in financing, education, and infrastructure for a supportive research atmosphere.
In most African societies, cultural norms are a barrier to women in leadership positions. A more inclusive research environment should be created by raising awareness within communities of the value of women’s contributions and challenging traditional gender stereotypes. Breaking barriers calls for partnerships for capacity-building initiatives and resource sharing and expertise. Additionally, institutional support, including gender-sensitive policies and flexible work schedules, can help women succeed in research.
Beyond gender equality, empowering women to conduct clinical research is essential for expanding medical knowledge and enhancing healthcare outcomes in Africa. By addressing gender and diversity gaps in research leadership, we can bridge knowledge disparities, break barriers, and build a more inclusive and resilient healthcare system for the continent.
]]>The invaluable lessons learned from the application of pathogen genomics during the HIV and COVID-19 pandemics hold significant implications for pandemic preparedness. These insights can shape our strategies to tackle future infectious disease outbreaks and reinforce global health readiness. Firstly, the understanding of transmission dynamics gained through genomic surveillance has highlighted the importance of early detection and rapid response. By closely monitoring viral mutations and genetic diversity, public health authorities can swiftly identify emerging pathogens, track their spread, and implement containment measures.
Secondly, the successful evaluation of interventions and treatment success using genomics data emphasises the need for evidence-based decision-making. Pathogen genomics provides real-time information on the effectiveness of therapeutics and vaccines, allowing the refinement of treatment strategies. By leveraging these insights, future pandemic responses can be more agile and effective, saving lives and reducing the burden on healthcare systems.
Furthermore, the identification of SARS-CoV-2 variants and their geographic distribution has demonstrated the importance of a globally coordinated surveillance network. Early detection and characterisation of variants enable the development of region-specific public health measures and targeted vaccination campaigns. Building international collaborations and data-sharing mechanisms will be crucial in facilitating a rapid response to emerging variants in future pandemics. Moreover, the ethical considerations surrounding pathogen genomics underscore the necessity of establishing robust ethical frameworks in pandemic response
Lastly, the collaborative efforts demonstrated during the HIV and COVID-19 pandemics underscore the significance of global partnerships in pandemic preparedness which should be strengthened. International cooperation, knowledge exchange, and resource-sharing are essential in addressing global health challenges effectively.
In conclusion, lessons from HIV and COVID-19 genomics have far-reaching implications for pandemic preparedness. Integrating pathogen genomics into public health systems can revolutionise disease control efforts, optimise outbreak response, and foster a proactive approach to tackling emerging infectious threats and mitigating the impact of future pandemics.
]]>Integration of vertical programmes for the control of malaria, schistosomiasis and soil-transmitted helminthiasis has been recommended to achieve the elimination of malaria and neglected tropical diseases (NTD) by 2030. Given the dearth of studies on the acceptability of the integrated approach, we conducted this qualitative study within the context of a randomized controlled trial to explore the perceptions and views of parents/caregivers of at-risk children and healthcare providers to determine their acceptability of the integrated malaria-helminth treatment approach.
Randomly selected parents/caregivers of children enrolled in the trial, health care providers, trial staff, malaria and NTD programme managers were interviewed using purpose-designed topic guides. Transcripts obtained from the interviews were coded and common themes identified using content analysis were triangulated. Fifty-seven study participants comprising 26 parents/caregivers, 10 study children aged ≥10 years, 15 trial staff, four health care providers and two managers from the Senegal Ministry of Health were interviewed.
Thirty-eight of the participants (66.7%) were males and their ages ranged from 10–65 years. Overall, the integrated malaria-helminth treatment approach was considered acceptable but the study participants expressed concerns about the taste, smell and side effects associated with amodiaquine and praziquantel in the combination package. Reluctance to accept the medications was also observed among children aged 10–14 years, due to peer influence and gender-sensitive cultural beliefs.
Addressing concerns about the taste and smell of amodiaquine and praziquantel is needed to optimize the uptake of the integrated treatment programme. Also, culturally appropriate strategies need to be put in place to cater for the inclusion of children aged 10–14 years in this approach.
Abandoned water closets can serve as reservoir habitat for mosquitoes especially the Asian tiger mosquitoes. Botanicals larvicides are among the recommended strategies used in Integrated Vector Management (IVM) of mosquitoes. Biological potency of ashes of scent leaves (Ocimum gratissimum) and lemon grass (Cymbopogon citratus) against larvae of Aedes mosquitoes were assessed.
Aedes albopictus larvae were surveyed and marked in water closet in a university in Niger Delta region of Nigeria. Ashes from the plants were measured in 1g, 2.5g, 5g, 10g and 15g respectively and emptied into the bowl of the closet with stagnant water. Acute and Chronic toxicity were carried out and mortality recorded after 10 to 60 minutes and 6hours to 60 hours respectively. Adult emergence was also used to measure efficacy of treatment.
It was observed that larval mortality increased with time in all concentrations of test plants and chronic toxicity showed 100% mortality in all treatments. The 15g of lemon grass concentration recorded the highest mortality of larvae after 30 minutes in the acute toxicity experiment. There was 0% mortality of the larvae in the all the scent leave concentration in the acute toxicity experiment. Lethal time of 50% was 0.58 and 2.7g, and for and 95% was 2.3 and 34.1g for Scent leave and lemon grass ashes respectively (p<0.05).
These treatments are therefore considered as good materials for local treatment of abandoned water closets to reduce vector populations and chances of increased biting rates in Africa.
The University of Botswana (UB) received a grant from the European and Developing Countries Clinical Trials Partnership (EDCTP) from 2011 to 2013. The overall aim of the grant was to strengthen capacity for ethical review and promote ethical conduct of research at UB. This paper presents findings from a study that evaluated the impact associated with the implementation of the grant on the research ethics processes at UB.
Through a document review, the funded project plan, including targets, tasks and milestones, were assessed against the met deliverables, achievements and impact associated with the project.
The grant enabled the establishment of a Research Ethics Office, which is now a permanent structure, providing ethics oversight to all research conducted by the University research community. In addition, an IRB Administrative Officer was hired to coordinate the activities of the IRB and now heads the Research Ethics Unit. The grant also facilitated the acquisition of office equipment that contributed to improving the operations of the committee, including speeding up the ethics review process and communication with stakeholders. Standard Operating Procedures and guidelines on human research were developed, and several workshops held for graduate students and university staff. Furthermore, the grant facilitated IRB staff and some committee members to attend short courses on research ethics in South Africa, hence enhanced their skills and knowledge. Finally, key government stakeholders responsible for the issuance of research permits were involved in a workshop that reviewed and streamlined the review process and reduced the turnaround time for issuance of research permits.
The EDCTP grant was critical in strengthening the research ethics oversight structures at the University of Botswana. These structures and processes have the potential to serve as a best practice model for other Universities intending to establish Research Ethics units in Botswana and beyond.
We conducted a pragmatic evaluation of GeneXpert Ultra (‘Ultra’) for diagnosis of childhood tuberculosis (TB) within national public health systems in West Africa.
In this cross-sectional study, children (<15 years) with presumed pulmonary TB were consecutively recruited and evaluated at three tertiary hospitals in Benin, Ghana, and Mali. Bivariate random-effects models were used to determine the pooled sensitivity and specificity of Ultra against a microbiological reference standard ([MRS]; liquid culture) and a composite reference standard ([CRS]; culture-confirmed TB and unconfirmed TB).
Overall, we enrolled 193 children with a median (IQR) age of 3.2 (1.1 - 8.9) years, 88 (46%) were female, and HIV prevalence was 36/142 (25%). 32 (17%) children had confirmed TB, 39 (20%) had unconfirmed TB, and 122 (63%) had unlikely TB. Using MRS, the pooled sensitivity and specificity of Ultra were 55% (95% CI: 28 - 79%) and 95% (95% CI: 88 - 98%), respectively. Ultra demonstrated sensitivity and specificity of 50% (95% CI: 16 - 84%) and 95% (95% CI: 85 - 99%), respectively, using sputum, as against sensitivity of 46% (95% CI 17 - 77%) and specificity of 93% (95% CI: 87 - 97%) for gastric aspirate. Against the CRS, the pooled sensitivity and specificity of Ultra decreased to 17% (95% CI: 4 - 53%) and 93% (95% CI: 87 - 96%), respectively. Using sputum, sensitivity and specificity of Ultra were 24% (95% CI: 7 - 50%) and 94% (95% CI: 82 - 99%), respectively, compared with sensitivity of 14% (95% CI: 5 - 30%) and specificity of 91% (95% CI: 82 - 96%) using gastric aspirate.
The suboptimal sensitivity of Ultra in children with TB investigated routinely within national public health systems in West Africa constitutes a major challenge.
Funding: EDCTP-West African Networks of Excellence for TB, AIDS & Malaria.
Malaria remains a major public health concern, especially in the tropics and subtropics where disproportionately high disease burden occurs annually. The World Health Organization recommends parasitological confirmation of suspected malaria cases by either Giemsa stained microscopy or rapid diagnostic tests (RDT) before treatment. The most sensitive RDT used for malaria diagnosis targets histidine-rich protein 2 (HRP2), an antigen unique to Plasmodium falciparum. HRP2 based RDTs also detect histidine-rich protein 3 (HRP3), a structural homolog sharing multiple epitopes with HRP-2. This notwithstanding, there are reports of the deletion of the pfhrp2/pfhrp3 gene and it impact on performance. To improve on the detection of the deletion, this study aimed to investigate the prevalence of pfhrp2/pfhrp3 gene deletion using novel digital PCR (dPCR) in Southern Ghana. The dPCR assay provides absolute quantification of the target gene without a need for a calibration curve.
Community-based cross sectional study was conducted at three districts (i.e., Nkwanta South, Sekyere South and Ga South) in Southern Ghana. A total of 1134 whole blood samples were obtained from asymptomatic individuals in the aforementioned study sites.
After screening for Plasmodium falciparum with varATS multicopy gene, 304 samples were selected from Nkwanta South (54.6%, n=166), Ga South (28.3%, n=86) and Sekyere South (17.1%, n=52) and were typed for the presence/absence of the target gene using digital PCR. The assay detected deletion in pfhrp3 gene with 0.3%(n=300) of the isolates examined reported to have a deletion. Unlike pfhrp3, no deletion was observed with respect to pfhrp2.
Our findings validate the novel dPCR assay as a is high-throughput and highly sensitive tool for molecular surveillance of pfhrp2/pfhrp3 gene deletion in Ghana.
Onchocerciasis (river blindness) is still endemic in parts of Africa, causing skin, eye, and brain disease. The cornerstone intervention for onchocerciasis control is community-directed treatment with ivermectin (CDTI), but therapeutic coverage remains sub-optimal in several endemic communities. The "Slash and Clear" (S&C) vector control technique has been proposed as an environmentally-friendly alternative tool to supplement CDTI.
We conducted repeated cross-sectional entomological studies in Nachtigal, an onchocerciasis-endemic village located beside a fast-flowing segment of the Sanaga River in Cameroon. Blackfly breeding sites were mapped and monthly blackfly biting rates (BR) assessment, initiated at the Nachtigal riverbanks using the human landing-catch approach. Blackfly catching for BR measurements were done for three consecutive days (7:00 to 18:00 daily) every month, by the same two catchers, switching every hour. On March 1st 2023 (a timepoint marking the transition from dry to rainy season), we implemented the S&C intervention at the Nachtigal rapids. Physically-fit village volunteers were trained and supervised in the destruction of the breeding sites using machetes and the removal of potential substrates for blackfly breeding from the river. Post-intervention BR were assessed two weeks after the S&C, and changes in BR were calculated.
Following S&C, monthly BR went from 28,000 in February 2023 to 13,888 bites per person in March 2023 (50.4% reduction). In contrast, in the absence of S&C, BR were 31,108 in February 2022; rising to 36,053 in March 2022 (15.9% increase) with the returning rains. Therefore, compared to the natural evolution of blackfly abundance and nuisance, the S&C intervention engendered 50.4+15.9=66.3% decrease in the BR at the Nachtigal riverbanks.
Our study demonstrates the significant impact of a community-based S&C vector control approach on blackfly biting rates. Coupled with good CDTI coverage, reducing the blackfly population would break the onchocerciasis transmission cycle and accelerate its elimination.
Individuals living with HIV are susceptible to other infections due to poor or weakened immune system. Viral haemorrhagic fever caused by Lassa Virus (LASV) has been endemic in parts of West Africa. About four lineages have been discovered in Nigeria a country bordering Cameroon. The porosity of the borders and increased movement across West African countries put Cameroon at risk of LASV. Interestingly, there has not been any report of Lassa fever in Cameroon. Here we evaluated, the seroprevalence of LASV antibodies among HIV patients in Cameroon.
Serum samples obtained between December 2021 and April 2022 from 330 HIV-positive consented patients were tested for LASV IgG and/or IgM antibodies specific for LASV nucleoprotein and/or prefusion envelope glycoproteins using ReLASV® Pan-Lassa IgG/IgM ELISA Test Kit according to the manufacturer’s instructions. Data were analysed using SPSS and GraphPad.
Analysis of these samples showed that IgG and IgM antibodies were detected in 2.4% (8/330) and 1.8% (6/330) samples respectively. All the IgM positive samples were also positive for IgG. Our data showed that both IgG and IgM antibodies do not depend (p>0.05) on age, gender and duration on antiretroviral therapy (ART) though the prevalence was high in age group <25 years, males, and those who had taken ART for <5years. The mean OD of both IgG (0.06 Vs 0.03) and IgM (0.88 Vs 0.04) were significantly higher (p< 0.05) between LAVS positive and negative cases.
Our results are the first to detect LASV antibodies in Cameroon. With increase movement and porosity of the border, it is plausible that exposure to LASV is inevitable. This has direct implications for understanding the transmission risk, mitigation, and eventually the prevention and control of LASV in Cameroon. Our results indicate the urgent need to extend LASV surveillance in other part of Africa.
Lassa fever causes morbidity and mortality in Africa. An estimated 100,000 to 300,000 cases of Lassa virus infection and 5,000 fatalities occur in West Africa annually. Lassa fever accounts for 10%–16% of hospital admissions in Liberia and Sierra Leone annually. On the 6th of January 2023, the Bong County Health Team confirmed Lassa fever in a student nurse at Phebe Hospital, Liberia. Five additional cases were reported before the 15th of January 2023. We investigated the source, magnitude, identified and traced contacts, and implemented control measures.
We reviewed medical records from December 2022 in the hospital, and interviewed health workers and contacts. We modified the case definition, listed contacts, followed up for 21 days using checklist, and tested suspected cases. We performed descriptive analysis using Microsoft Excel 2016. Results were presented in frequencies, proportions, and median and displayed in tables, graphs, and maps.
A total of 15 persons were suspected and tested for the Lassa virus from January 6 - 31, 2023. Of these, 53.3% (8/15) were positive for the Lassa virus, with a case fatality rate of 25% (2/8). Fifty percent (4/8) were health workers. The median age range for the cases was 34 (6–48) years. Males accounted for 62.5% (5/8). Seventy-two contacts were listed, 4.2% (3/72) of the contacts became cases. Forty-two percent (3/7) of the additional cases were health workers linked to the index case. Fifty percent of the cases were imported from other counties. The index was a student nurse who worked in the hospital on December 12, 2022, on a missed Lassa fever case.
The outbreak was sporadic, however among the health workers it was hospital-acquired due to a missed case of Lassa fever and improper hygiene measures. We recommend training and supplies for health workers, especially affiliating students.
COVID-19 remains a public health threat globally. As part of control measures, the Zambian government integrated it into the IDSR, hence the need to regularly analyse COVID-19 data to inform decisions. This analysis was done to assess COVID-19 descriptively, and to generate hypothesis of factors associated with its mortalities in Monze district.
Between 31st October 2022 and 9th December 2022, we conducted a cross-sectional review of COVID-19 cases and mortalities for the period 1st June 2020 to 30th June 2022. Data were extracted from COVID-19 line list and analysed using EpiInfo. Results were presented in tables and graphs.
Between June 2020 and June 2022, Monze district recorded 3141 cases of COVID-19, where 54.2% (1702/3141) were females however, 66% (51/77) of males died of COVID-19 compared to females. The median age was 31 years (IQR 22 – 43) with case fatality rate of 2.5% (77/3141). Most 71.3% (2239/3141) of those who were infected reside in urban area. Majority 28.4% (891/3141) of cases were from 21 – 30 years whilst most 53.2% (41/77) of mortalities were from 71 years and above. Most 29% (912/3141) of cases and 32.5% (25/77) mortalities occurred in June 2021. Sex and age were associated with COVID-19 mortalities.
More females were infected whilst more males died from COVID-19. The most infected age group was 21 – 30 years. Higher mortalities were recorded in the age group 71 years and above. Majority of the cases were from urban areas. Most cases and mortalities occurred in June 2021. Further studies are required to determine higher reported cases among females, urban settings, 21–30 age group and deaths in the elderly.
Lassa fever, an acute viral haemorrhagic and zoonotic disease has high case-fatality among hospitalised patients. We investigated an outbreak of Lassa fever in Weija-Gbawe Municipality to determine its magnitude, trace case-contacts, identify the source, and suggest preventive and control measures.
A descriptive study involving reviews and observations was conducted within Weija-Gbawe municipality, from 1st March to 25th March 2023. Hospital and community case searches were done. Suspected case was any person with illness of gradual onset with unexplained acute fever (temp >37.5oC) with one or more of following: malaise, headache, sore throat, cough, nausea, vomiting, diarrhoea, myalgia, oedema, sudden convulsion, bleeding, spontaneous abortion following fever, chest pain, hearing loss, history of contact with excreta of rodents or epidemiological linked to a case of Lassa Fever from 13th February 2023 within the Greater Accra Region. Attack and case-fatality rates were calculated. Case-contacts were identified, line-listed, blood samples taken to confirm Lassa fever, and monitored 21 days from day of last contact with a confirmed case. A nearby market where most of the inhabitants purchase food stuffs was inspected for waste disposal and food storage. Traps were set for rodents in the market and their body fluids, excreta sent for laboratory investigation.
Of 62 cases and contacts listed, the overall attack and case-fatality rates were 11.3% (7/62) and 14.3% (1/7) respectively. Mean age of cases was 33.5 years (± 7.1). Majority, 71.4% (5/7) were female. Waste and food stuff were poorly kept and accessible to rodents in the market. Laboratory investigation on rodents was negative for Lassa fever.
The outbreak was contained with low mortality. Health workers and community were sensitized on Lassa fever, its mode of transmission and preventive measures. The municipal health director should disinfect homes of confirmed cases and the health facility.
In low and middle incomes countries such as sub-Saharan Africa, the management of febrile diseases remains challenging given the lack of practical diagnostic tools to screen the real cause of fever and the limits of malaria rapid diagnostic tests. In order to improve the management of febrile diseases in children under 5 years, this study has been conducted.
The study was conducted at the Field Station of Sigle, set-up by the Clinical Research Unit of Nanoro. All patients from 6–59 months attending the outpatient clinic of the health facility of Bologho in the health district of Nanoro, with documented fever or history of fever within the pass 7 days were invited to participate to the study. Participants were randomized either the intervention package (e-Algorithm or RDT-decisional algorithm arm(RDT-DA)) or routine system. The intervention package was constituted by the following PoC tests: two-step malaria RDT detection PfHRP2 and pLDH, CRP, white blood cells (WBC) count, oximetry, Group A Streptococcus, and Salmonella/Shigella.
Antimalarial prescription was 42.05% (164/390) in e-Algorithm arm, 43.65% (172/394) in RDT-DA and 52.30% (232/392) in standard practice system [risk difference (RD): -10.25% (p p<0.001) for e-Algorithm and -8.65% (p<0.001) for RDT-DA). Antibiotics were prescribed in 46.92% (183/390) in e-Algorithm arm, 50.25% (198/394) in RDT-DA arm and 76.28% (299/392) in routine system [RD: -29.36% (p<0.001) for e-Algorithm and -26.03% (p<0.001) for RDT-DA]. The reduction of antibiotic prescription greater in children without malaria [RD:-64.79% (p<0.001) for e-Algorithm arm and -61.62% (p<0.001) for RDT-DA algorithm arm].
Implementation of two-step malaria RDT and PoC tests for bacterial infections has potential to improve the management of febrile diseases in children under 5 years and reduce inappropriate prescription of antibiotics. Nevertheless, the use of CRP test is not suitable differentiate bacterial to non-bacterial infections in children with malaria.
The movement of people contributes to the propagation of COVID-19 between and across communities. In Cameroon like in many other countries, the movement of population is mainly by public bus transports. Due to their hypothetically key role in disease transmission, recommendations for the prevention of COVID-19 in travel agencies were included in the response plan. This study was conducted with funding from FIND to map the knowledge of COVID-19 prevention measures in travel agencies and their practices regarding the implementation of these measures.
This was a cross sectional descriptive study targeting travel agencies in main cities of the West region that include Bafoussam, Dschang, Mbouda, Bangangte, Foumban and Foumbot. Data were collected in June 2022 by a semi-structured questionnaire from heads of travel agencies by trained surveyors. Data were collected to assess the awareness of heads of travel agencies regarding COVID-19 preventive measures and the application of these measures.
Of the 61 travel agencies reached, 55 (90.2%) consented to participate. Most of the respondents were heads of travel agencies. All travel agencies were aware of the existence of recommendations on COVID-19 preventive measures, 46 (83.6%) were informed via the local authorities and 35 (63.6%) via media. The most known preventive measures were the obligation of facemask wearing by travelers (54 [98.2%]) and the setting up of a hand washing or disinfection station in travel agencies (53 [96.4%]). Of the travel agencies, 27 (49.1%) implemented at least one of the recommended COVID-19 preventive measures with 18 (66.7%) applying the recommendation on setting up of a hand washing or disinfection station in their travel agency.
During the pandemic, the implementation of the recommendations to limit the transmission of the disease was not fully implemented by travel agencies. A monitoring system should be set up to ensure appropriate implementation of recommendations during epidemics.
Low peripheral parasitemia caused by sequestration of Plasmodium falciparum in the placenta hampers the diagnosis of malaria in pregnant women, leading to microscopy or conventional rapid diagnostic tests (co-RDTs) false-negative results. Although mainly asymptomatic, maternal malaria remains harmful to pregnant women and their offspring in endemic settings and must be adequately diagnosed. Ultra-sensitive RDTs (uRDTs) are thought to be more sensitive than co-RDTs, and their diagnostic performance was assessed in the present study in pregnant women living in Kinshasa, a stable malaria transmission area in the Democratic Republic Congo.
To assess and compare the performances of both co-RDTs and uRDTs, 497 peripheral blood samples were tested using microscopy and quantitative polymerase chain reaction (qPCR) as the index and the reference tests respectively. The agreement between uRDT, co-RDT, microscopy and qPCR was determined by Cohen’s Kappa test.
The median parasite density by qPCR was 292 p/μL of blood [IQR 292 (49.7–1,137)]. Using qPCR as the reference diagnostic test, microscopy was the least sensitive test [55.7% (95% CI: 47.6–63.6)], followed by co-RDT [81.7% (95%CI:74.7–87.3)] and uRDT [88% (95% CI:81.9–92.6)]. The corresponding specificity was respectively: 98.5% (95% CI:96.6–99.5), 95.2% (95% CI:92.5–97.2) and 94.4% (95% CI:91.4–96.6). The agreement between qPCR and uRDT was almost perfect (kappa=0.82). For parasite density (qPCR) below 100p/µL, the sensitivity of co-RDT was 62% (95%CI:47.1–75.3) compared to 68% (95%CI:53.3–80.4). Between 100 and 200p/µL, the sensitivity of co-RDT tended to be lower compared to uRDT: 89.4%(95%CI:66.8–98.7) versus 100%(95%CI:82.3–100) for uRDT. In both cases, microscopy was lower, with 20% (95%CI:10–33.7) and 47.3% (95%CI:24.4–71.1) respectively.
uRDT tended to be more sensitive than co-RDT in the detection of malaria in pregnant women. Therefore, it has the potential to improve malaria management in pregnant women. Microscopy shows poor performance for the diagnosis of malaria in pregnancy.
Mycobacterium tuberculosis (Mtb) transmission among households contributes significantly to the tuberculosis (TB) burden. Understanding TB risks and the prevalence of Mtb infection in affected households may help designing strategies for case-finding and targeted prevention. The EDCTP-funded ERASE-TB study aims to validate new diagnostic tests in a cohort of household contacts (HHCs) of adults with infectious pulmonary TB.
2,101 HHCs ≥10 years of age were enrolled across three sites in Mozambique, Tanzania and Zimbabwe and are being followed up for 24 months. Enrolled HHCs undergo 6-monthly symptom screening, physical examinations and chest X-ray (CXR). HHCs with symptoms presumptive of TB and/or a CXR suggestive of TB undergo sputum-based tests, i.e., Xpert MTB/Rif Ultra/culture. At each visit, novel diagnostics, e.g. TAM-TB and Xpert Host Response (Cepheid), are conducted and blood and urine samples stored in a biorepository. The biorepository will be used for future investigations of new diagnostics applying a case-control design. Testing for Mtb infection is done at baseline using interferon-gamma release assays (IGRA; SD Biosensor).
An average of 2.4 contacts per household were recruited. The median age was 26.7, 62% were females, 321 (15%) were living with HIV, and 44 (14%)of these were newly diagnosed. One-quarter of the enrolled HHCs were children aged 10–18 years. At baseline, 355 (17%) had TB-related symptoms and 5% CXRs suggestive of TB. The prevalence of pulmonary TB was 0.7% while the prevalence of Mtb infection was 54%. Follow-up of study participants is ongoing.
Despite COVID-19 related interruptions, the targeted enrolment size of 2100 HHC was achieved. While a considerable proportion of HHC had Mtb infection at baseline or had symptoms and/or CXR findings suggestive of TB, less than 1% were diagnosed with TB. This is a relatively high HIV prevalence, albeit mostly known and on treatment.
Targeted mass drug administration (MDA) of single-dose albendazole to the at-risk population as preventive chemotherapy or deworming is recommended by WHO to halt transmission of soil-transmitted helminth (STH) in endemic countries. We assessed the effectiveness of single-dose albendazole distributed through a school-based MDA program against hookworm, ascaris lumbricoides, and trichuris trichiura STH infection.
984 STH-positive school children from two rural woredas in southern Ethiopia were enrolled. Stool samples were examined before MDA and at weeks 4 and 8 post-MDA. Efficacy was assessed using cure rate (CR) and egg reduction rate (ERR).
The proportion of children who were cured of any STH parasite at week 4 and week 8 of post-MDA were 46% and 43.3%. The CR was 97.2%, 71.5%, and 49.5% for hookworm, ascaris lumbricoides, and trichuris trichiura respectively at week 4 post-MDA. The ERR at week 4 was 98.8%, 84.5%, and 68.3% for hookworm, ascaris lumbricoides and trichuris trichiura respectively. The observed CR (97.2%) and ERR (98.8%) for hookworm were above the WHO efficacy threshold (CR ≥95%, ERR ≥90%). However, CR (71.5%) and ERR (84.5%) for ascaris lumbricoides were lower than the WHO efficacy threshold (>95%) indicating a reduced efficacy. The CR (49.5%) for trichuris trichiura was below the WHO efficacy threshold (>50%) but the ERR (68.3%) was above the WHO efficacy threshold (>50%). The CR of ascaris lumbricoides in younger children was significantly lower compared to the older children (64.4% versus 74.2%, p=0.006).
We found a reduced efficacy of single-dose albendazole against ascaris lumbricoides and doubtful for trichuris trichiura but efficacious in treating hookworm. Therefore, alternative treatment options are needed for the effective elimination of STH as a public health problem by 2030.
Funding: This study was supported by the EDCTP2 program as part of the PROFORMA project (Grant number CSA2016S-1618).
The increasing number of clinical trials in developing countries providing solutions to the high burden of diseases leads to the vulnerability of study participants and their communities and access to the trial results. In CIOMS, Post-trial access (PTA) is defined as the obligation of sponsors, researchers, host government and other relevant stakeholders, including the community and the research ethics committees to make any intervention or product developed, and knowledge generated, for the study participants or community available as soon as possible. This study explores the stakeholders’ perspectives on post-trial access and how PTA arrangements could be feasibly and sustainably incorporated into clinical trials in Ethiopia.
A qualitative study was conducted on stakeholders involving principal investigators, institutional review board (IRB) members; regional ethics review committee (RERC) members; national ethics review committee (NEC), regulatory agency members, and funding organization using face-to-face in-depth interviews and thematically analysed.
Our analysis shows that the majority of the study participants do not know about PTA and its implementations, responded lack of binding regulations/laws, the weak collaboration between different stakeholders, and the lack of follow-up of clinical trials. Moreover, most participants pointed out the possibility of study participants and their community exploitation because of PTA statements in the current clinical trial approval and authorization processes.
Therefore, we recommend revising the available working documents/guidelines by including PTA, capacity building at different levels, and establishments of independent bodies facilitating the arrangements of PTA and follow-up of its implementations.
Serological tests play a crucial role to diagnose gambiense human African trypanosomiasis (HAT) by preselecting individuals for microscopic examination, and, in the near future, by directly identifying patients for treatment. Variability in reported specificities, the introduction of new rapid diagnostic tests (RDT) and the hypothesis that malaria decreases RDT specificity, led us to evaluate the specificity of 5 HAT screening tests.
Venous blood samples from 1095 individuals from Côte d’Ivoire and Guinea were tested with commercial (Bioline HAT 2.0, HAT Sero-K-SeT, CATT/T.b. gambiense) and experimental (HAT Sero-K-SeT 2.0, DCN) HAT screening tests and with a malaria RDT. Individuals negative with all 5 HAT tests were considered HAT free, while positives underwent microscopy. HAT case definition was based on trypanosome detection by microscopy.
One HAT case was detected. Test specificities (n=1094) were: CATT/T.b. gambiense [98.9% (98.1–99.4%), p<0.0001] > HAT Sero-K-SeT [86.7% (84.5–88.5%), p<0.002] > Bioline HAT 2.0 [82.1% (79.7–84.2%), p=0.0113] > HAT Sero-K-SeT 2.0 [78.5% (76.0–80.9%)] and DCN [78.2% (75.7–80.6%)]. Bioline HAT 2.0 and DCN include 2 test lines, and specificities of line 1 [respectively 83.7% (81.4–85.8%) and 80.6% (78.2–82.9%)], corresponding to ISG-65, were significantly lower (p&t;0.0001) than with line 2 [respectively 95.8% (94.4–96.8%) and 94.5% (93.0–95.7%)]. The ISG-65 line therefore significantly decreased overall test specificity. Although all the HAT tests were less specific in malaria positive than in malaria negative individuals, differences (p values >0.08) were not significant.
CATT/T.b. gambiense is more specific than HAT RDTs. The HAT Sero-K-SeT is more specific than second generation RDTs which all contain ISG-65, either as a separate test line (Bioline HAT 2.0 and DCN) or within a single "mixed antigen" test line (HAT Sero-K-SeT 2.0). To improve specificity, removing ISG-65 from experimental RDTs or ignoring the ISG-65 line should be considered, if test sensitivity is not significantly impacted.
Low-income countries bear 90% of the worldwide burden of disease yet there is underrepresentation of research addressing priority issues for low-income countries. Lack of research skills exacerbate the problem. While calls support locally driven research, investigators initiating RCTs in low-income countries encounter barriers, preventing RCT execution. We use our investigator self-initiated trial to provide some of our experiences, in executing a trial in a low-income country.
We are conducting a large RCT to determine the effect of text messaging plus motivational interviewing on sustaining breastfeeding, among 275 women living with HIV.
We first assessed the feasibility of the large trial. We submitted multiple grant applications for the pilot trial and secured enough funds within three years. Some awarded funds were returned due to grant timeframe conditions. The pilot trial capitalized on existing research infrastructure. In 2020, we secured the EDCTP2 grant for the large trial. Lack of infrastructural support negatively affected the budget. The pilot trial was exempted from ethics fee. The large trial was approved by ethics before the EDCTP action period, due to tight funding timeframe. We secured funds elsewhere for ethics fee. Each study was approved within three months. The Western Cape Government, Department of Health (WCDH) has a National Health Research Database assisting researchers with applications submission for review by the Provincial Health Research Committee granting access to provincial healthcare facilities. WCDH approved each study within six months. We recruited from a healthcare facility, serving a small pool of our target population which prolonged pilot trial recruitment. We use Research Electronic Data Capture at no cost.
Enabling environments improve efficiency of trial execution. Leveraging on existing research infrastructure optimize use of available resources. Small research grants should consider flexible funding timeframes. Collaboration with stakeholders in routine healthcare facilitates facility access for research.
A consortium of African and European Universities, National Institutes of Public Health and Research Centers proposed a project to implement a Master’s in Field Epidemiology via blended-learning platforms based at University of Cape Verde. The field training is implemented with the National Institutes of Public Health of each country where strengthening of the local health systems in perspective. Thus, the presentation will describe the experience of implementing a blended-learning advanced field epidemiology training, the defining strategies for the internship and the first outputs produced by Epi Fellows.
The overall project will be described as well as processes in developing the curriculum and its accreditation at different levels and the establishment of International Steering Committee. We describe the recruitment of students, how sites for training were selected as well as the outputs of the first student internships.
A total of 55 applications were received and 15 students were selected (6 from Cape Verde, 6 from Guinea-Bissau and 3 from São Tomé & Príncipe). Through a consultative process and field visits, tutors were identified for each student in their country of origin as well as field training sites considered relevant to enhance experiences and capacity of trainees in health surveillance and outbreak response at ministerial, municipality/district and hospital/health facility levels. The expected outputs from field training were defined and the 3 products of the first internships, focusing on the evaluation of the national health information systems of each country, the epidemiological surveillance from a one health perspective, the focus on antimicrobial resistance and outbreak investigations are critically described.
The practical training in the countries of origin complemented with theoretical training offered online will allow better insertion and retention of the trained cadres in their countries of origin and contribute for health system strengthening.
Although the Alere Filariasis Test Strip (FTS) is recommended for surveillance and monitoring of Wuchereria bancrofti infection, the performance characteristics of this tool in post-treatment settings have not been established. To determine the accuracy of the FTS in effectively monitoring treatment of bancroftian infection, we investigated the sensitivity of the test in detecting different subgroups of asymptomatic adult worm-infected individuals at pre-treatment and post-treatment and the specificity of the test in detecting treatment success following therapy.
Plasma samples obtained from the same cohort of individuals (n = 143) with known adult worm and microfilariae (Mf) burdens at pre-treatment and 24 months post-treatment were used. The sensitivity of the FTS was assessed for the detection of microfilaremic and amicrofilaremic subgroups of adult worm-infected individuals at both time points. The post-treatment specificity of the test was assessed in those who cleared both adult worm and Mf burdens 24 months following doxycycline treatment. Seventy-one samples from W. bancrofti-uninfected individuals living in the same endemic areas were also analyzed.
The FTS showed significantly greater sensitivity for the detection of microfilaremic adult worm-infected individuals (pre-treatment = 100%; 24 months post-treatment = 95.8%) than amicrofilaremic adult worm-infected individuals (pre-treatment = 65.8%; 24 months post-treatment = 52.2%). The FTS’s specificity for successfully treated individuals at 24 months post-treatment was 73.0% (CI = 62.58–81.90), which was significantly less than the specificity of the test for uninfected individuals (95.8%, CI = 88.14–99.12).
From our results, the FTS does not satisfy the WHO’s minimum diagnostic requirements of 85% sensitivity and 98.8% specificity for identifying amicrofilaremic adult worm-infected individuals and successfully treated individuals at 24 months post-treatment, respectively. Our study highlights the need for high-quality diagnostic tools to provide a more precise endpoint infection threshold and accelerate the achievement of the global elimination target for 2030.
Six sub-Saharan African nations are in the top 10 globally for losing over 50% of their medical graduates to work abroad. Insufficient training and career advancement options hinder retention, harming sustainable development. Evidence-based research training is needed to improve research capacity and retention.
The Global Health Network (TGHN) and the UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR) collaborated to create an Evidence-led Essential Research Skills Training Curriculum (EERSTC). The study surveyed 7,176 individuals from 153 countries worldwide, with 54% of respondents from Africa. The EERSTC showed effectiveness in developing research skills among novices. The curriculum recommends specific modules for clinical research training programs.
TASK Research Academy used selective modules from the EERSTC to develop a training course that uses storytelling, simulations, and interactive case studies to teach core competencies. Since its launch in August 2022 the course has enrolled 127 novices, with 82 having completed it. 98% of students believe the course improved their confidence in their ability to work in clinical trials, while 90% indicated that it helped them create career opportunities. The academy plans to further develop bi-chronous clinical research career pathway programs for research-naive individuals. These role-focused career pathway programs will be based on the suggested EERSTC modules and will use the latest digital technologies to create simulation-based training. By providing industry-ready training that emphasizes practical application, graduates will be prepared to start working immediately.
To achieve the Sustainable Development Goals by 2030, Africa requires research capacity building to attract sponsors and promote clinical research. Lack of research experience is a significant barrier to entry. Training that aligns with industry needs and core competencies can equip the next generation of researchers and support and African research culture, easing entry barriers and combatting workforce deficiencies.
The objective of this study was to evaluate the effect of CYP2B6 and CYP3A4 polymorphisms on the virological and immunologic responses of patients receiving an efavirenz-containing regimen. A total of 153 HIV-positive patients were enlisted for the current study.
Viral load and median CD4 T cell counts were evaluated at baseline and month 6 (M6). Single nucleotide polymorphisms (SNPs) in CYP2B6 and CYP3A4 genes were genotyped using TaqMan genotyping assays.
Interestingly, the AG genotype in CYP2B6 rs2279343 was associated with viral load suppression (VLS) compared to the homozygous AA (OR 2.6; 95% CI 1.3–5.3). Moreover, in the overdominant model, the AG genotype was associated with VLS compared to AA/GG (OR 2.05; 95% CI 1.3–2.9). The AG genotype in CYP2B6 rs2279343 was associated with an increase in CD4 cell count between baseline and M6 (p = 0.01). In CYP2B6 rs3745274, CD4 cell count at M6 was higher than that of baseline for GG carriers (p = 0.04) and for GT carriers (p = 0.013). In contrast, the TT mutant displayed no difference in CD4 cell count at M6 and baseline (p = 0.3). In CYP3A4 rs2740574, the TC carriers showed a higher median CD4 count at M6 compared to that of the baseline count (p = 0.024), similar trend was noted for CC carriers (p = 0.004). In contrast, the TT genotype showed no trend (p = 0.8). The best genotypes combination associated with CD4 cell count improvement were AA/AG in SNP rs2279343 (p = 0.003) and GG/GT in SNP rs3745274 (p = 0.002).
Our findings support the fact that CYP2B6 rs2279343 could help in the prediction of VLS and both SNPs rs3745274 and rs2279343 in CYP2B6 and CYP3A4 rs2740574 were associated with immune recovery in Malian HIV-positive patients.
Africa experiences great mental illness burden due to highly prevalent impoverished living conditions and a double burden of disease, exacerbated by COVID-19’s socioeconomic decline and systematic inequalities augmentation, rendering mental healthcare inaccessible. Mental health in Africa is under-researched, accounting for 2% of global research, mirroring gaps in mental healthcare with 84% fewer specialized providers than the global average. The WHO reports that only 45% of African States have a mental health policy complying with international human rights. Stereotypes such as witchcraft are attributed to mental illnesses, increasing stigma and discrimination. Currently, no mental health research review guidelines specific to sociocultural and gender aspects exist. High rates of gender and social inequalities in Africa necessitate their inclusion when evaluating research. Ethics committees are strategically positioned to ensure the scientific and ethical rigour of mental health research.
Thirteen tools evaluating mental health research, programmes, policies and sex- and gender-sensitive considerations were systematically reviewed. Data extracted and adapted to the African context yielded a 54-item assessment tool.
A 54-item assessment tool, created categorized into Research governance, Background and justification, Methodology and Ethical impact of the research. It will guide the process of mental health research protocol evaluation taking into account ethical, gender, and sociocultural factors in Africa.
This will enhance health equity in Africa, bridge gaps in mental health research, prevent discrimination, facilitate the achievement of the 3rd and 5th SDGs, and guarantee the African Charter on Human and Peoples’ Rights 16th Article, entitling humans to the highest attainable mental health state. The tool applies to mental health research protocols review and explores various dimensions such as team competency, cultural congruency of the methodology, perpetual respect for participant dignity, autonomy, and rights, gender and intersectionalities- based sensitivity of data collection, analysis, and dissemination.
Funding: EDCTP funded project - BCA-WA-ETHICS II
Ivermectin and Albendazole (IA) are drug combinations used in mass drug administration (MDA) to halt transmission of lymphatic filariasis (LF) in endemic communities. Safety data on haematological and biochemical changing patterns following MDA is limited. We investigated changes in such parameters among individuals exposed to IA during MDA in rural Tanzania.
An analytical cross-sectional study was conducted amongst 498 individuals whose blood samples were collected before and after MDA. Complete blood count, renal and liver function tests were done at day 0 and 7. Wilcoxon signed rank and McNemar tests were used to compare the median and proportion of individuals with abnormal values respectively, before and after MDA.
The overall findings indicate changes in some parameters after IA intake. The median values of haematological parameters to include RBC, Hb, and HCT decreased and MCH and MCHC increased significantly in both FTS positive and negative individuals following MDA (p<0.05). Platelet counts to include PDW, MPV and PLCR all increased after drug intake in both groups (p<0.05). Biochemical parameters to include ALT and BilD decreased in both groups whilst AST increased in FTS positive (from 24.4 U/L to 25.35 U/L, p=0.01) and decreased in FTS negative individuals (from 24.95 U/L to 24.55 U/L, p=0.04). A significant proportion of individuals had haematological parameters below reference range (RBC 8.2%, p=0.01; Hb 23.5%, p=0.002; HCT 32.9% p<0.001; MCH 9.8%, p<0.001; and MCHC 0.5%, p<0.001). Sex was the only predictor of low Hb levels with females at a higher risk of experiencing low Hb than males (aOR: 3.16, 95% CI= 1.29–7.76, p=0.01).
Our findings demonstrate that haematological changes may occur following IA MDA. No significant changes in biochemical (kidney and liver function test) parameters were observed after drug use. Overall, the observed abnormalities were minor with minimal clinically relevant safety concerns.
Schistosomiasis remains one of the most prevalent neglected tropical diseases, especially in Nigeria which has the greatest number of infected people worldwide. School-aged children are the most vulnerable, as they participate in water contact activities that expose them to free-swimming cercariae released by infected snail species in freshwater; hence most studies target this age group. A cross-sectional study was conducted among 466 participants from two communities in South-west Nigeria to investigate the risk factors associated with high prevalence of the two human schistosome infection.
Urine and stool samples were collected from consenting school children in Ilie and Ore communities of Osun State, Nigeria. Schistosoma haematobium eggs were detected in the urine using the urine filtration technique, while S. mansoni eggs were detected in stool using the Kato-Katz thick smear technique.
The overall prevalence of schistosomiasis was 40% (185/466), with 31% and 10% infected with S. haematobium and S. mansoni, respectively. The multiple logistic regression analysis revealed that water contact activities i.e washing and fishing (X2 =7.52; p< 0.06; X2 =19.54, p =0.000) knowledge of schistosomiasis (X2 =12.7; p= 0.00) blood in the urine (X2 =37.8; p< 0.00) were the significant risk factors associated with schistosomiasis in these communities.
This study revealed that schistosomiasis is still prevalent in endemic communities of southern Nigeria. Factors predicting schistosomiasis were related to water contact activities (fishing and washing) knowledge of schistosomiasis, previous infection, and blood in the urine. These findings highlight the need for mass drug administration, health education, and community mobilization to significantly reduce the prevalence and morbidity of schistosomiasis in these communities.
Funding source: This work does not receive any funding
Artemisinin resistance is a major limitation against malaria control. Routine monitoring of the efficacy of artemisinin-based combination (ACT) treatment is required to ensure early detection and response to drug resistance. This research evaluated therapeutic response to directly observed treatment with artemether-lumefantrine (AL) in participants infected with uncomplicated falciparum malaria.
The study was conducted in Ijede, a sentinel site in southwestern Nigeria. Microscopy, rapid diagnostic test and 18S ribosomal ribonucleic acid (rRNA) polymerase chain reaction (PCR) methods were used to diagnose Plasmodium falciparum. Primary outcomes were clinical and parasitological cure rates at day 28. Secondary outcomes included patterns of fever and parasite clearance. Parasite genotyping using merozoite surface proteins 1 and 2 markers was performed at baseline and at the time of recurrence of parasitaemia to differentiate between recrudescence and new infections.
Of the 79 participants enrolled, 58 completed the follow-up to day 28. Clinical observations and microscopy showed no early treatment failure whereas 18S rRNA PCR analysis identified parasite DNA in 37% (23/62) of participants followed up on day 3. However, this did not correspond to treatment failure in subsequent follow-up days. Based on Kaplan-Meier survival estimate, day 28 cumulative incidence of success of AL treatment was 96.6%.
This finding demonstrates sustained in vivo efficacy of AL as first-line treatment of uncomplicated malaria in the study area. Investigations are underway for ex vivo genotyping of resistance markers to validate the efficacy status of ACT in this population.
Malaria/HIV co-infection (MHC) is a public health challenge which may present with worse health outcomes due to interactions. Coadministration of artemether lumefantrine (ALU) and antiretroviral therapy may have potential drug-drug interactions that can affect the course of treatment for both diseases. Generic ALU medications are used in Ghana for malaria treatment after RDT or microscopy diagnosis. ALU is metabolized by the enzymes CYP2B6, CYP3A4/5, CYP2A6 and UGTs which can be affected by pharmacogenetics. A better understanding of the effects of MHC on ALU drugs could help prompt treatment, and control of malarial parasites among HIV-infected patients. This study evaluated effects of MHC on ALU drugs used in antimalarial treatment and pharmacogenetic influences on their efficacy.
To compare metabolite profiles and treatment outcome in patients on generic ALU for uncomplicated malaria and MHC, this study has recruited about 218 participants. However, we currently have complete preliminary metabolite and genomic data on 52 participants. Blood was taken for microscopy, genotyping using iPLEX Gold microarray and PCR-RFLP, and metabolite analysis using LC-MS/MS.
Median parasite density was 2119.42/uL, 760.10/uL, 0/uL and 0/uL on days 1,2,3 and 7 for malaria-only participants and 7322.52/uL, 3928.60/uL, 0/uL and 0/uL for MHC participants. Plasma concentrations of dihydroartemisinin (DHA) ranged from 3.30–35.85ng/ml. Desbutyl-lumefantrine (DBL) concentrations ranged from 7.8ng/ml-40.44ng/ml on days 3 and 7. Decreased concentrations of lumefantrine, DBL and DHA were observed across CYP2B6 *1/*1, CYP2B6 *1/*18/*1/*6, CYP3A5 *1/* and CYP3A5 *1/*3/*1/*6/1*/*7 carriers for MHC participants. However, MHC carriers of non-functional haplotypes CYP2B6*6/*6 or *6/*18 or *18/*18 showed increase in lumefantrine, DBL, artemether and DHA concentrations.
Pharmacogenetic variations affected ALU plasma concentrations although blood parasites were eliminated by day 3 in malaria monoinfected and MHC participants. This however shows there is potential drug-drug interactions between ALU-ART components which can influence the progression of either disease.
Despite a worldwide decrease, sub-Saharan Africa (sSA) still has high incidence and the highest percentage of under 5 deaths (55%) in the world. This is due to several causes, including high incidence of infectious disease, often neglected or underreported, lacking effective treatments or vaccines. During our activities on Typhoid fever, Sclavo Vaccines Association (SVA) and Fondazione Achille Sclavo (FAS) came across increasing evidences in sSA of marked morbidity and mortality due to an unreported disease in children and HIV patients: invasive Non-Typhoidal Salmonellosis (iNTS)
SVA and FAS, two nonprofit Italian institutions devoted to supporting development of vaccines for LICs, committed to catalyze funds and a group of institutions to fight this disease of the most vulnerable. The institutions applied for national and European funding, receiving first a validation at the local level, followed by funding from the EC and EDCTP. This stepwise approach created the necessary know-how to prepare solid projects, supporting a valid candidate vaccine fit for use in LICs. The projects synergistically address reasons why this disease is neglected: low epidemiology knowledge and disease awareness, lack of candidate vaccines and financial commitments.
Two projects were rejected at the national and EU level: finally a grant was obtained in Italy from the Tuscany Region (S-Afrivac) concentrating on epidemiology, disease modeling and vaccine and assay development. The successful conclusion of this project worked to open doors for two EU grants: the H2020 EC Vacc-iNTS and the EDCTP Pedvac-iNTS projects. Within 4 years, these projects multiplied tenfold the funds devoted in the EU to iNTS vaccine development.
The validation of targeted projects against neglected diseases at the national level followed by synergistic submission to European Agencies in appropriate calls addressing all causes of neglection may significantly increase success in fighting these modern plagues of LMICs
Research is an essential component of the response to health challenges such as weak health care systems and high disease burden that Africa faces. In addition to these challenges, the advent of health emergencies has led to a significant increase in the number of protocols for review by Research Ethics Committees (RECs). The majority of RECs in Africa still use paper-based review systems with long lead times for authorization. Regarding the major role assigned and the desired efficiency of the CERs, the digitization of the protocol ethics review process is a necessity for scientific development.
We conducted a literature review using key words related to the digitization of RECs in Africa and used the experiences of RECs in Benin that are in the process of digitization through to the AMELIORER Project (2021–2023) entitled "Enhancing Research Ethics and Regulatory Capacities in Benin" and funded by EDCTP (CSA2020ERC-3086).
The digitization of committees on the continent has brought light to their operations by facilitating dynamic and efficient ethics review. It has contributed to improving the quality of review through standardization and harmonization of ethics review procedures and reduction administrative workload and costs. However, RECs are facing digital learning challenges and technological capacity (availability of computer equipment and quality connectivity).
For a more effective and dynamic research framework in Africa, it is essential to support RECs to implement and overcome the challenges inherent in the digitization process.
The funding source: CSA2020ERC-3086
In Kenya Mass Drug Administration (MDA) intervention with single dose of Diethylcarbamazine Citrate (DEC) and Albendazole (ABC) commonly referred to as DA. has been in use since 2002 the control of Lymphatic Filariasis(LF), however no safety surveillance has been conducted before. Recently, the Neglected Tropical Disease (NTD) Program, piloted the use of Ivermectin (IVM), Diethylcarbamazine and Albendazole known as IDA triple therapy in two highly endemic counties.
This was a longitudinal community-based cohort event monitoring 10,010 and 10, 411 eligible participants in Kilifi and Mombasa Counties respectively. Adverse event monitoring and grading was actively done at 24 hours, 48 hours and at day 7 following mass drug administrations. The collected data was analysed for incidence, types, and predictors of adverse events.
A total of 5807 and 3102 AEs were reported by 2839 and 1621 individuals in the IDA and DA groups, respectively. The incidence of experiencing one or more AEs was significantly higher (p<0.0001) in IDA (27.3%; 95%CI, 26.4%-28.2%) compared to DA (16.2%;95%CI, 15.5–16.9%) group. The three most AEs reported among those who took IDA were dizziness (15.9%), drowsiness (10.10%) and headache (6.5%), compared to DA that reports dizziness (5.9%), headache (5.6%) and loss of appetite (3.3%). Female sex, taking ≥ 3 tablets of DEC or IVM, older age, taking concurrent medications, ≥3 tablets of DEC, and type of meal taken before MDA were significant predictors of AEs. The AEs were systemic, mild to moderate and transient.
Both the dual Therapy with DA and triple therapy with IDA were generally safe and well as MDA regimens for Elimination of LF. The incidence of experiencing one or more type AEs is about two-fold higher with IDA than with DA. The integration of safety monitoring during MDA is critical for the timely detection and management of reported AEs.
Spirometry testing in respiratory disease research, diagnosis, and management relies on reference equations. The Global Lung Function Initiative (GLI) reference equations are based on data from 26 countries, but sub-Saharan African populations are largely under-represented. This study assessed the appropriateness of GLI equations (African-American, southeast Asian, others/mixed, Caucasian, and northeast Asian) in healthy Gambian children.
Healthy children were recruited for spirometry tests using a hand-held spirometer. We compared mean z-scores of forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) obtained from each GLI reference equation with a value of 0 using one-sample t-tests. We assumed that if the GLI predictions were optimal, the measured z-scores of the healthy Gambian children would have an average value of 0 and a standard deviation of 1.
Out of 91 children, 86 (94.5%) had valid spirometry results per ATS/ERS criteria. The median age (IQR) for participants with valid results was 11.3 years (8.1–13.7), with 34 females and 52 males. Mean z-scores for FEV1 and FVC were closest to 0 with the African-American reference equation (FEV1: -0.91±0.87; FVC: -0.97±0.93) and lowest with the northeast Asian reference equation (FEV1: -2.43±1.21; FVC: -2.80±1.39). The proportion of children with FEV1 and FVC z-scores below -1.64 (LLN) was lowest with the African-American reference equation (FEV1: 18.6%; FVC: 23.3%) and highest with the northeast Asian reference equation (FEV1: 75.6%; FVC: 79.1%). Mean z-scores for FEV1 and FVC were significantly lower than 0 for all GLI reference equations.
African-American GLI reference equation showed best fit, while the northeast Asian equation was the worst in this study. However, none of the GLI equations adequately represented Gambian children’s lung function. Locally derived reference equations are needed.
Funding: EDCTP2 Career Development Fellowship (grant number: TMA2020CDF-3197) and Wellcome Trust Institutional Strategic Support Fund (grant no PS3456_WMNP).
Perinatally acquired HIV is a treatable chronic condition such that through antiretroviral therapy (ART), children with HIV (CWH) are now surviving to adulthood. However, CWH often exhibit impaired growth. We aimed to identify the height growth patterns among CWH and determine age at peak-height-velocity (PHV).
This is a secondary analysis of data collected prospectively in the ongoing VITALITY randomised controlled trial in Zimbabwe (EDCTP: VITALITY-RIA2018CO-2512). The trial has recruited 840 CWH (11–19 years) established on ART for at least 6 months, to determine whether vitamin-D3/calcium supplementation improves bone mass and strength with follow-up to 96 weeks. Height is measured at 12-week intervals with currently (31-March-2023) 135 participants having completed 96-weeks of follow-up. Weight and height for age were calculated using 1990-UK-reference values, with Z-score≤-2 classifying those underweight and stunted. Analysis of height trajectories was performed using the Superimposition by translation and rotation (SITAR) adjusting for size, pubertal-timing and growth-rate and fitting the mean and velocity curves by sex.
We recruited 447(53.2%) females and 393(46.8%) males and followed them up for 1.37(IQR:1.15–1.1.61) years; at baseline median (IQR) age was 15(13–17) years and 30.0%(n=252) were stunted. CHW were taking ART for median (IQR) 9.8(6.3–12.3) years of their lives and 81.9%(n=688) were on an ART regimen containing tenofovir-disoproxil-fumarate. Lifetime fracture prevalence was 5.9%(n=50). At baseline (n=840), mean (SD) height-for-age was -1.70(1.06) and -1.22(1.05) for males and females respectively. Over 48-weeks (n=780), median (IQR) height gains were 3.3(1.1–5.9) cm and 1.2(0.3–3.5) cm for males and females separately. Age at PHV was 15.0 years (PHV:8.2cm/year) and 13.2 years (PHV:5.6cm/year) for males and females respectively.
There is a high prevalence of stunting among CWH in Zimbabwe. Both males and females showed delayed PHV compared to regional estimates (females:11.8, males:14.4 years), raising concerns for persistent height deficits in adulthood known to impact human capital and function in later life.
Tuberculosis is a leading infectious disease killer. It primarily affects the lung, accompanied by tissue damage from excessive host inflammation. Neutrophils are implicated as primary mediators of this tissue destruction. This study aims to access neutrophils and their soluble mediators in relation to TB-induced tissue damage.
Fifty-three (53) patients with confirmed TB were recruited. Neutrophil numbers in sputum and blood were assessed using microscopy and automated counting. Soluble mediators were analysed in sputum and plasma by ELISA. Participants were classified as having mild (n=24) or severe (n=29) lung pathology at baseline based on a median chest X-ray Ralph score of 70%. Lung recovery was also assessed at 6 months of TB therapy with 14 participants classified as having good recovery and 15 having poor recovery based on overall change in Ralph score.
Plasma MMP9 levels at baseline were significantly higher in patients with severe [median (IQR) = 404548 (272166 - 465789) pg/ml] compared to mild [median (IQR) = 94461 (43194 – 168716) pg/ml] lung pathology (p=0.0277). Plasma MPO levels in both groups decreased significantly by week 2 (p=0.0287) and week 8 (p=0.0110) treatment respectively. Patients with severe lung pathology at baseline had significantly higher levels of circulating MPO compared to those with mild pathology [median (IQR) = 208913 (146125 - 239403) pg/ml and 106366 (69207 - 146633) pg/ml] (p=0.0432). No difference was seen in analytes between good and poor lung recovery patients.
Severe lung pathology was associated with high plasma MMP-9 and plasma MPO at baseline. No difference was seen in good and poor lung recovery groups at 6 months but should be assessed at later time-points. Understanding how neutrophils and their associated protein markers drive lung pathology and subsequent long term post-TB lung disease could inform, whether and which HDT may support better treatment outcome.
Although "Slash and Clear" has proven effective in reducing blackfly densities in low transmission foci, the impact of this strategy in high transmission settings with large rivers and important vector densities remains to be demonstrated.
A controlled before-and-after community-based intervention comprising two arms (Bayomen as control site and Biatsota as intervention site) was carried out in the Mbam Valley (Centre Region, Cameroon). In each arm, baseline blackfly densities were collected over one year using the human landing method. The intervention consisted of destroying the trailing vegetation where blackflies breed. Blackfly densities were collected post-intervention to assess the impact of the intervention. Before the intervention, a total of 36,273 and 29,041 blackflies were collected in Bayomen and Biatsota, respectively.
After the intervention period, the total blackfly density in the intervention site decreased from 29,041 to 20,011 (31.1% reduction), while an increase of 2·7% was observed in the control site (from 36,273 to 37,248). The Poisson mixed regression model shows that the reduction was significantly greater in the intervention site than in the control site (p<0.0005).
This study showed that "Slash and Clear" approach is feasible and has a significant impact on vector densities in a high transmission setting. Further studies are needed to investigate the long-term impact of this vector control approach, and how this promising strategy can be scaled-up and sustained until elimination of onchocerciasis.
Campylobacteriosis is the lexicon used to denote the group of infectious diseases caused by several species of Campylobacter. A form of Campylobacteriosis of significant public health importance is Campylobacter enteritis. Campylobacter species are increasingly being recognized as leading agents of gastroenteritis. In South Africa, it has been suspected that Campylobacter infection could be endemic. Freshwater environments are under pressure from climate change and consequent drought, change in conditions and migration of new species into these systems. Environmental management and managing environmental risk factors will control and prevent the epidemic or at least could significantly reduce the vulnerability of communities to Campylobacteriosis. This study provides knowledge-based recommendations for controlling and preventing Campylobacteriosis in South Africa.
Collection of secondary data of at least five years of culture-confirmed cases of Campylobacter infection in two Municipalities in the Eastern Cape was conducted to establish community infection and infection rates. River water samples were also collected and analysed for Campylobacter spp. In addition, this study utilized a literature review and interviews of residents to identify local environmental risk factors of Campylobacteriosis in the two populations.
Campylobacter infection could be endemic in the Eastern Cape region of South Africa. Direct contact and consumption of surface waters faecal-contaminated local rivers are likely risk factors for Campylobacteriosis. Also, protecting surface water from access by animals is critical to interrupting the transmission of Campylobacter from animals to humans in these rivers.
Campylobacteriosis in South Africa may be environmentally mediated. Rivers in South Africa are platforms for transmission of Campylobacter spp., and so prevention of Campylobacteriosis can be achieved by reducing their Campylobacter burden by protecting these platforms from contamination. The findings of this study are policy levers to mitigate Campylobacteriosis risk in South Africa.
Crimean-Congo hemorrhagic fever (CCHF) is a zoonotic arboviral illness and a geographically widespread tick-borne viral infection. On February 13, 2023, the National Viral Hemorrhagic Fever Laboratory at the Uganda Virus Research Institute received an alert for a suspect VHF case in a 4-year-old male who presented with VHF-compatible signs and symptoms at Kawepe Regional Referral Hospital in Kampala.
By using RT-PCR, a blood sample from the suspected patient was examined for CCHF and found to be positive. Increased anti-CCHFV IgM antibody titers on successive blood samples taken from this patient during serological testing confirmed a recent infection. Following the initial RT-PCR positive result, an epidemiological outbreak investigation was started to find any other suspected patients.
From the outbreak, three further CCHF patients were identified following field investigations. One confirmed case person died, (Case Fatality Rate = 25%). The clinical presentation of symptoms was general body weakness (100%), fever (100%), and spontaneous bleeding through the gastrointestinal tract (bloody diarrhea) (75%). By the time of this report, no animal samples or ticks had been collected from the neighborhood as part of the environmental investigation.
This is one of the CCHF outbreaks that have been reported in Uganda in recent months. The results indicate that CCHF is endemic in Uganda, with sporadic outbreaks occurring throughout the country. The findings also demonstrate that tick exposure increases the likelihood of human infection. In a developing nation like Uganda, these findings further highlight the significance of having a well-established national Viral Hemorrhagic Fever (VHF) surveillance system and diagnostic capability to quickly respond to secondary cases and identify the first cases of VHF outbreaks. We advocate for improved awareness and education about the disease and its transmission among the public, healthcare professionals, and individuals at high risk of exposure.
This research highlights the role of natural, cultural and structural gaps which shape sickness experiences and social stigma of women with manifestations of female genital schistosomiasis (FGS), a neglected gynaecological condition resulting after untreated infection with urogenital schistosomiasis. We focus on using women’s shared experiences without them emerging as victims, but as voices for change, all activists and collaborators in the quest of their human rights, good health, and representation. Women take ownership and present their own interpretations capturing expressive, and symbolic aspects as persons living with a neglected tropical disease.
Focusing on ethnography and specific case studies of women manifesting symptoms of FGS within endemic rural fishing communities in Cameroon, we present illness experiences of women affected by FGS, drawing from a narrative method, and information on health service provision around FGS, to show the role of women and their histories in research on health, a frequently neglected angle.
Our results show how gendered power dynamics in decision making, and gendered experiences such as the need to manage menstrual health; as well as structural gaps, combine to bring an FGS mental health toll. Sub-fertility brings a heavy psychosocial toll from external blame and rejection, exacerbating the burden affected women experience of internalized stigma and the mental challenge of not being able to fulfill cultural standards, leading to exclusion.
Gender-analysis is used to highlight missing gaps, and context embedded understanding which could be used to address neglected tropical diseases and their related psychosocial burden. With context-specific experiences portraying co-morbidity with mental ill-health and FGS as a neglected tropical disease, there is a need to prioritize women’s voices and mental-health management at policy level through a person-centred approach.
Funding: "Projet Lutte Contre Les Maladies Tropicales Négligées en Afrique Centrale" (MTN) [grant numbers BMZ-Nr 2015.69.227, BMZ 2016.68.797].
Tuberculosis (TB) disease remains undiagnosed or unreported in approximately 4.2 million people annually. To address these "missing millions", we assessed the feasibility and impact of a scalable model for transmission-interrupting, community-based active case finding (ACF) in major cities of four African countries: Cape Town, South Africa, Lusaka, Zambia, Harare, Zimbabwe, and Maputo, Mozambique.
In peri-urban informal settlements using a 1:1 randomised controlled trial (stratified by country), we performed ACF using a low-cost mobile clinic fitted with a portable 2-module Xpert system and compared a point-of-care (POC) Xpert to a standard-of-care centralised laboratory Xpert with sputum culture used as a reference standard. At the Cape Town site, those with microbiologically confirmed TB received infectiousness studies, including smear microscopy, chest x-ray (CXR) and cough aerosol sampling (CASS).
Of 4193 rapidly screened individuals, 1977 were identified as at risk for TB and received targeted screening and randomisation to either POC Xpert (n=988) or centralised Xpert (n=988). Across all sites, 97 (4.9%) of 1977 participants had microbiological confirmation of TB; 53/531 at the Cape Town site (10.0% TB positivity rate; 29/53 [54.7%] culture-positive). Xpert identified 75% (22/29) of all culture-positive samples. 40/53 participants had all infectiousness studies performed, and 26/40 were identified as probably infectious (defined as cavities on CXR [n=26] and/or smear-positivity [n=9] and/or CASS-positivity [n=3]). Xpert identified almost all probably infectious cases (25/26 [96.1%]).
Community-based active case-finding using portable molecular-based diagnostic tools reliably detects probably infectious, minimally symptomatic TB patients. These data inform key elements of ACF strategies needed to bridge the gap to find, treat and end TB.
In Benin, as of April 12, 2023, 28,014 cases and 163 deaths of coronavirus disease (COVID-19) had been notified. COVID-19 disease has been associated with an increased risk of preterm birth, caesarean delivery and maternal morbidity. However, few studies have evaluated the extent of SARS-CoV-2 infection among pregnant women in sub-Saharan African countries. In this EDCTP-funded COVID-19 surveillance project, we aimed to determine SARS-CoV-2 seroprevalence and identify factors associated with seropositivity among pregnant women in Benin.
A cross-sectional study was carried out between April and June 2022 in Allada, a middle-size city in southern Benin, and Natitingou, a city located 500 kilometres North. Pregnant women in their third trimester of pregnancy were recruited at study antenatal care clinics. A rapid diagnostic test for detection of IgG/IgM against the receptor binding domain of SARS-CoV-2 spike protein was performed, and socio-demographic and clinical characteristics of the participants were recorded.
A total of 861 women were included in the study. Mean age of study participants was 26.4 years, and their mean gestational age was 35.0 weeks. SARS-CoV-2 antibodies were detected in 75.7% (95%CI 75.6%-78.6%) of non-vaccinated participants. Only 6.7% (95%CI 5.15–8.62%) of the participants reported to had been vaccinated against COVID-19. Unvaccinated participants from Allada who had at least one previous morbidity had an almost three-fold increased risk of presenting SARS-CoV-2 antibodies (OR=2.89 [1.19–7.00]). None of the participants had been diagnosed/tested for COVID-19 during their pregnancy.
The SARS-CoV-2 virus has circulated greatly among pregnant women from Benin. Despite none of the participants had been diagnosed with COVID-19, three out of four participants presented SARS-CoV-2 antibodies, suggesting that COVID-19 cases were asymptomatic or remained undetected by the national surveillance systems.
Lassa fever is an acute viral hemorrhagic zoonotic disease. The epicentre of Lassa in Nigeria is Ondo and Edo but recently, there has been an upsurge in Benue State. This is in addition to an emerging pattern of all year transmission representing a drift from peak period of November-April. In this study, we described the epidemiology of Lassa fever in Benue State from January-December 2022.
We conducted a secondary analyses of Lassa fever data obtained from Surveillance outbreak response management analysis system (SORMAS), Benue State, Nigeria over a 12 month period (January-December). Data on total reported cases, tested positive, mortality and sociodemographic characteristics was extracted and analysed.
A total of 264 suspected cases were reported within the study period; of these, 34 (12.9%) were confirmed by laboratory diagnosis with 11 deaths and case fatality rate (CFR) of 32.4%. Of the total confirmed cases, 22 (64.7%) were male while the median age range 30–39 years had the highest number, 78 (29.5%) of confirmed cases. Majority, 29 (85.3%) of the confirmed cases within the study period occurred in Makurdi, the State capital. The seasonal trend of Lassa fever from epi-curve was propagated with peak from January to February.
There was a very high burden and endemicity of Lassa fever in Benue State with an unprecedented highest CFR ever recorded among the 36 States of Nigeria which has become the new hotspot in the country especially Makurdi the State capital and young active working population more affected. Lassa fever transmission occurs all year-round with peak from January-February. There is need to develop preparedness plans and define thresholds for Lassa fever epidemic.
4 million tuberculosis (TB) cases are undiagnosed annually. A global host biosignature to distinguish TB from other respiratory diseases (ORD) is required to develop a point-of-care (POC) triage test for TB. Our aim was to identify a global host biosignature for TB in sputum samples.
Sputum samples from HIV negative confirmed TB patients (n=221) or patients with other respiratory disease (ORD) (n=414) were analysed from South Africa, Peru, Vietnam and The Gambia. Cryopreserved native sputum samples from all countries were digested with sputolysin for 15 minutes at room temperature, centrifuged, and supernatants stored at -80oC until analysis. Multiplex cytokine arrays were used to analyse 64 host markers. Analyte levels from sputum digested after freezing were compared with those from paired freshly digested supernatants (n=45) in the Gambian cohort.
Levels of TNF-α (p<0.0001), MMP-2 (p<0.0001), IL-1β (p=0.0002), IL-22 (p=0.0004) and LIGHT/TNFSF14 (p=0.0007) were all significantly higher in sputum from TB compared to ORD patients. A global signature consisting of 12 analytes resulted in an AUC of 0.93, Sensitivity of 81% and Specificity of 91% while a reduced performance was seen for a 7-marker signature (AUC 0.81, Sensitivity 73% and Specificity 76%). A 4-marker signature consisting of GCSF, IL19, IL2 and MMP1 from South Africa and Gambia combined resulted in an AUC of 0.84, Sensitivity of 82% and Specificity of 70%. Fresh samples had significantly higher levels of analytes compared to post-hoc digested sputum.
We identified a global signature that reached WHO TPP for a triage test but could not reduce from 12 markers with all countries combined. A 4-marker signature from Gambia and South Africa performed well but did not reach the TPP for a Triage test. Freshly digested sputum was superior to post-hoc digestion, indicating that use of frozen samples was a limitation in this study.
Affordable medicines facility-malaria (AMFm) program and subsequently Co-payment mechanism were developed to help increase access to quality assured Artemisinin Combination Therapies (ACTs) in seven countries in sub-Saharan Africa. We explored through a qualitative study, experience of healthcare personnel on Co-payment mechanism and the implication on access and availability of ACTs in private drug outlets in Uganda.
In each drug outlet, data was collected from pharmacists through key informant interview. The interview covered, (i) awareness of the co-payment mechanism, (ii) Knowledge of quality assured artemisinin combination therapies (QAACT), (iii) stocking of QAACTs, (iv) dispensing price of QAACTs), and (v) determinants of dispensing price of QAACTs. Data was managed using Atlas.ti and analysed using framework methodology.
From 25 key informant interviews, five themes emerged, (i) considerations taken while stocking antimalarial agents, (ii) access and purchasing behaviour of clients, (iii) antimalarial dispensing, (iv) awareness of QAACT, and (v) awareness of Co-payment mechanism. None of the respondents was aware of Co-payment mechanism and QAACT (green leaf ACT). Duocotecin brand of ACTs (non-QAACT) was the most stocked antimalarial agent. Every seven in ten drug outlet clients request to purchase ACTs without a prescription and preferred buying cheaper brands. Drug outlets stocked and sold both ACT and non-ACT antimalarial agents. Most drug outlet clients cannot afford buying a full dose of an ACT. None of the respondents considered using Co-payment mechanism while stocking ACTs.
There is lack of awareness of Co-payment mechanism and QAACT among pharmacists. There was reportedly no difference in the dispensing price between QAACT and non-QAACT. The dispensing of less than a full dose of ACTs to drug outlet clients is a common practice. The Ministry of Health needs to create awareness through public campaigns on the Co-payment mechanism in the country.
Detection delay is defined as the period between onset of first signs and symptoms of leprosy and the time of diagnosis, comprising of a ‘patient delay’ and a ‘health-system delay’ and reliability refers to the consistency of a measure. Three types of consistency are considered: over time (test-retest reliability), across items (internal consistency), and across different researchers (interrater reliability). For the case detection delay (CDD) two are applicable: test-retest reliability and interrater reliability.
The study was conducted in Ethiopia, Mozambique and Tanzania. The CDD questionnaire was administered to 79 leprosy patients. One month later, another researcher re-administered the CDD questionnaire with these same patients. Interrater reliability was assessed using the intra class correlation coefficient (ICC). The test-retest reliability was assessed among 69 leprosy patients by determining the CDD at one month difference, both times using the same rater, and then we determined the reliability by looking at the Pearson correlation between the two sets of CDD data.
Results from 79 leprosy patients show that, 3 (3.8%) were children under 15 years of age and 25 (31.6%) were women. Interrater reliability: the first interviews led to a mean CDD of 24.0 months (95% CI =17.1 - 30.9). The second interviews, also led to a mean CDD of 24.0 months (95% CI =17.7 - 30.3). For the test-retest reliability, the mean CDD of the first and second interviews were 16.5 (95% CI =13.6 - 19.5) and 16.9 (95% CI =13.8 - 20.1) respectively: the interrater reliability measured with ICC was 0.89 (95% CI of 0.84 - 0.93). Test-retest repeatability coefficient was 0.90 (p = 0.01).
The PEP4LEP CDD tool to determine the case detection delay of newly diagnosed leprosy patients, was validated in the three African countries showing that both test-retest and interrater reliability measurements demonstrated good reliability of the instrument.
Mycobacterium tuberculosis, the causative agent of Tuberculosis (TB) is a notorious pathogen that is responsible for the highest mortalities from a single bacterial pathogen worldwide. Many studies have revealed that cholesterol contribute to M. tuberculosis pathogenesis with unique transcriptome changes implicated to cholesterol metabolism in genetically diverse clinical strains of M. tuberculosis complex (MTBC). Hence, the current study was aimed at investigating epigenetic changes associated with cholesterol metabolism since these changes may provide novel targets for development of TB treatments.
The laboratory M. tuberculosis strain, H37Rv together with the recently identified Lineage 8 clinical strain were cultured in 7H9 broth and minimal media supplemented with cholesterol as the main carbon source. DNA was extracted using the Cetyltrimethylammonium bromide method followed by clean-up using Zymo DNA concentrator kit. Long read whole genome sequencing was performed in a PacBio SMART sequencer for complete methylome characterization using the RS Modification and Motif Analysis protocol and annotated further using DistAMo by selecting methylated genes with a significant z score (≥2 or ≤-2).
The highest significantly methylated motifs, CTCCAG, CTGGAG and VNCYGVNYR coding for Rv2060, rseA and Rv1175 genes, respectively, were detected in H37Rv grown in normal 7H9 broth while an additional CYGVNYR motif was detected during growth in cholesterol-rich media. This was in contrast to RNCYGVNYR motif detected in the Rv3632 gene for Lineage 8 strain during grown in 7H9 broth compared to CBBV, CTACCCGVC, GATNNNNRTAC, GNCTACSCA, GTAYNNNNATC, GVGGYMVCR and CACGCAGHNH motifs detected for pks8, Rv2459, PE_PGRS16, vapC22, fadD2, sseA, ackA genes, respectively.
These findings suggest "unique" epigenetic regulation in clinical strains of MTBC compared to the laboratory H37Rv, which may explain their virulence traits. The precise characterization of MTBC methylation profiles in cholesterol-rich environments could open new avenues for the development of treatments since cholesterol is essential during M. tuberculosis pathogenesis.
Funding: EDCTP
Global expansion of Arboviral diseases transmitted by Aedes mosquitoes is alarming. As seen by the frequent reports of the emergence and re-emergence of dengue, zika and chikununya infection.
There is a growing interest in the use of biomarkers for exposure to mosquito bite, including Aedes Nterm-34 kDa, as a proxy for Aedes-borne diseases risk. The objective of this study was to assess whether IgG antibodies against Nterm-34 kDa peptide was associated with the level of human exposure to Aedes mosquito bites and risk of dengue infection.
Three longitudinal surveys were conducted during rainy season (June 2021), dry season (September 2021) and short rainy (January 2022) in three villages in Bondo, Tanga. The study included children aged between 2–10 years and adolescents/adults aged 11–70 years. Face-to-face interviews were conducted. A pre-tested questionnaire was used to collect information regarding demographic characteristics and mosquito bite prevention measures. The developed questionnaire was uploaded in the system and data was collected electronically using Open Data Kit (ODK) application. Collected blood samples were tested for the presence of IgG antibodies against Aedes Nterm-34kDa using ELISA test.
Results showed that the medians of specific IgG antibodies levels were significantly different in three seasons (p=0.009; Kruskal-Wallis test). Dengue positive participants presented a higher level of anti-salivary IgG compared with dengue negatives (p=0.02; non-parametric Mann-Whitney test).
Anti-Nterm-34kDa IgG antibodies is important correlate of human exposure to mosquito bite, thus the antibodies are important indicator to measure the risk of dengue infection.
Funding: This study is part of the EDCTP2 program supported by the European Union (grant number TMA2019PF-2694-SABOT).
The COVID-19 pandemic placed healthcare workers worldwide under significant physical and psychological stress due to increased workplace demands causing fatigue and burnout. In addition, shortages in personal protective equipment (PPE) were commonly, leading to fears for their own personal safety. The pandemic also renewed ethical questions about how to reconcile healthcare workers{acute} duty to care with concern for their personal health, safety, and well-being. Our study aimed to explore this dynamic from the perspectives of frontline healthcare workers.
We conducted a mixed-methods, descriptive study in which we carried out semi-structured, in-depth interviews in April-June 2022, with frontline healthcare workers at four hospitals in Maputo Province, Mozambique. Qualitative interviews were audio-recorded, transcribed and entered into Microsoft Excel for content analysis. Quantitative data was entered in REDCap with descriptive analysis in SPSS.
We interviewed 53 frontline workers (physicians, nurses and assistants). When asked about their ethical responsibility to provide care during a pandemic, 20 (38%) respondents affirmed that, despite the risk, they had an obligation to care for patients with COVID-19, even without PPE, due to their professional commitment. Eighteen participants (34%) stated that they were not obligated to provide patient care, without PPE, due to the risk of contracting the virus. The remaining 15 (28%) said that they would take care of patients in rare situations. Thirteen (25%) respondents reported first-hand knowledge of examples during the pandemic in which patients were discriminated against in the health care setting, received poor care, or had health workers who refused to provide them care all together.
Our findings show that frontline healthcare workers in Mozambique were divided as to the limits of their professional responsibility to care for patients with COVID-19. Risk management strategies for highly infectious diseases like COVID-19 must be reformulated to improve service delivery while safeguarding providers.
Due to diagnostic challenges in childhood tuberculosis (TB), the World Health Organization (WHO) has recommended the use of non-sputum-based samples, including stool. This study evaluated the feasibility and acceptability of different TB diagnostic sampling procedures.
In a prospective observational cohort study, we collected clinical data from children presenting with presumptive pulmonary tuberculosis (PTB). At enrolment, collection of TB diagnostics samples included respiratory samples (gastric aspirate, induced sputum and expectorated sputum), blood, urine and stool. Questionnaires on the acceptability and feasibility were collected from caregivers and healthcare workers (HCWs). A social scientist observed the collection of samples and performed qualitative interviews with HCWs.
We conducted 59 diagnostic and acceptability questionnaires of children’s experiences of TB diagnostic sample collection. Sample collection was successful in 59% for urine, 36% for stool, 74% for blood and 72% for any respiratory sample. Overall, more than half of the caregivers felt that stool (86%), urine (75%), blood samples (67%) and respiratory samples (57%) were convenient for their children.
We observed sample collection in 32 children. HCWs had specific challenges with collecting urine samples from young girls due to the leaking urine bags. Children of all ages were resistant when collecting respiratory samples. In children aged 7–12 years, HCWs faced difficulties with collecting stool samples. These children felt embarrassed providing stool samples due to increased self-awareness. HCWs found blood samples easiest to collect, followed by respiratory samples, urine and stool. Even though blood sample collection was observed to cause more discomfort and pain.
Although urine and stool samples seem a good non-invasive alternative sample for TB diagnosis in children, remaining challenges hamper the feasibility and acceptability of these specimens, which will need to be considered for future studies.
Adherence to antiretroviral treatment (ART) among HIV-positive pregnant and breastfeeding women is influenced by various context-specific factor. This study aimed to investigate clinic experience and adherence among pregnant and breastfeeding women living with HIV. This cross-sectional study was conducted among pregnant and breastfeeding women living with HIV who were receiving care at selected health facilities in Kilimanjaro region.
Data were collected through face-to-face interviews using a semi-structured questionnaire. We analyzed data using descriptive statistics to describe levels of adherence. Differences in adherence rates between pregnant and breastfeeding women were assessed using chi-square tests.
The study included 100 breastfeeding women and 42 pregnant women. Self-reported adherence to antiretroviral therapy (ART) among pregnant and breastfeeding women was 94%, while pharmacy refill data indicated adherence rates of 57%. Although not statistically significant, pregnant women were found to be more adherent compared to breastfeeding women by 57.14%, (p = 0.987). Women who were satisfied with clinic care also tended to be more adherent, with a rate of 57.45%, (p = 0.248), compared to those who were not satisfied. Fifteen percent of the participants reported having to travel a long distance to access the clinic, despite other facilities nearby. This was attributed to concerns about stigma, lack of comfort, and unfriendly healthcare workers. Eighty percent of the women understood the importance of adhering to ART. However, only 37% had attended workshops or training sessions at the clinic on adherence to ART and medications.
This study highlights the importance of ensuring access to healthcare services for pregnant and breastfeeding women living with HIV. Despite the high level of understanding of the importance of adherence to ART, only few women had attended workshops or training sessions on adherence to ART. Efforts should be made to increase participation in training and education programs to improve adherence to ART.
The detection of schistosome-derived antigens in urine is a highly effective diagnostic approach for controlling schistosomiasis. It offers greater sensitivity compared to parasitological methods and involves a more convenient, user-friendly lab-based method. This diagnostic approach is particularly advantageous for pregnant women and young children, as early detection of active infections can lead to prompt treatment with Praziquantel (PZQ). The freeBILy clinical trial in Gabon (NCT03779347) evaluated the accuracy of the circulating anodic antigen (CAA) test for detecting Schistosoma haematobium (Sh) infections in pregnant women as well as an endpoint measure for PZQ efficacy.
The accuracy of the upconverting particle lateral flow (UCP-LF) CAA urine test was comprehensively evaluated using a cross-sectional design and comparing it against urine filtration (UF) and PCR. Subsequently, Sh-positive pregnant women were enrolled in sub-study and received a single dose of PZQ either immediately (intervention) or after delivery (control) to assess the safety of PZQ use during pregnancy and to monitor the kinetics of CAA levels following PZQ administration. Finally, in an observational, longitudinal study mothers and their newborns were followed to determine the incidence of schistosomiasis in infants with accurate diagnostics.
A total of 733 pregnant women were enrolled in this study with mean age 25.3 years. The prevalence of schistosomiasis measured by the respective tests was 18% (UF), 19% (UCP-LF CAA), and 12% (PCR). Compared to the composite reference standard, the sensitivity of UCP-LF CAA was 71.8%, with 64% and 68% for UF and PCR, resp.
Preliminary data show a high prevalence of schistosomiasis among pregnant women. Furthermore, the UCP-LF-CAA test was more sensitive than conventional microscopy, which contributed to the improved health of pregnant women as they were treated during pregnancy. PZQ treatment had no deleterious effects on mother nor child, and administrating it to pregnant women can be considered to be safe.
The virostatic effect of antiretroviral therapies (ART) infers viral persistence in sanctuaries, with a high likelihood of reactivation off-treatment. This systematic review and meta-analysis aimed at estimating the global burden of archived drug resistance mutations (ADRMs), the size of reservoirs and their determinants in paediatrics.
Were included, randomized and non-randomized trials, cohorts and cross-sectional studies of HIV reservoirs in vertically-infected participants, published in English/French between 2002–2022. As primary outcomes, we evaluated the prevalence of ADRMs and estimated the size of reservoirs (HIV-1 DNA copies/10 6 cells) in paediatrics. Subgroup analysis were performed to further characterize the data and the meta-analysis was done through random effect models.
Overall, 50 studies from 17 countries worldwide were included encompassing 2569 vertically infected participants (aged 2-days to 19-years; 52.81% females). There were limited data on the quantitative characterization of viral reservoirs in SSA, and sensitive tool as ddPCR for characterizing viral reservoirs were not implemented in the most sub-Saharan Africa (SSA) countries. Overall prevalence of ADRMs was 37.80% [95%CI: 13.89–65.17], with 48.79 [95%CI: 0–100] in Africa, 42.08% [6.68–82.71] in America, 23.88% [95%CI: 14.34–34.90] in Asia, and 20.00% [95%CI: 10.72–31.17] in Europe; without any difference between infants and adolescents (p=0.656). Starting ART before 2 months of age limited the size of HIV-1 DNA (p=0.054). Participants with long suppressed viremia (>5years) had lower rates of HIV-1 DNA (p=0.027) whereas pre-/post-ART CD4 ≤29% and pre-/post-ART viremia ≥5Log were all found associated with higher rates of HIV-1 DNA (p=0.038, p=0.047, p=0.041 and 0.035 respectively).
Our findings underscore high levels of ADRMs in paediatrics worldwide, with a higher reservoir driven by delayed ART initiation, shorter period of viral suppression and immuno-virological failures. Thus, strategies for paediatric HIV functional cure should target adolescents/children with very early ART initiation, high immunity and long-term viral suppression.
New emerging and re-emerging infectious diseases continue to cause loss of life around the world. For a rapid, effective, and robust response to these outbreaks, a multidisciplinary public-private consortium "ONE HEALTH", PANDORA-ID-NET-1 of 22 partner institutions (13 African and 9 European) led by Fondation Congolaise pour la Recherche Médicale was created following an EDCTP (2016) call.
PANDORA-ID-NET-1 implements its activities by area and by transversal activities through 4 regional hubs (West, East, Central, and South Africa) for the development of intervention teams with rapid, mobile laboratory services, capable of responding to epidemics of emerging and re-emerging infectious diseases, and of carrying out inter- and intra-epidemic actions.
Expected impact: Global visibility of this essential network that provides accelerated evidence for the optimal clinical management of patients and guides the public health response to any serious infectious epidemic. Medium-term impact: Improved capacities for the detection and epidemiological surveillance of new or re-emerging infectious disease threats originating in Africa or elsewhere.
Long-term impact: Capacities of the 4 regions to develop and conduct high-quality clinical trials and research on emerging infectious diseases.
PANDORA-ID-NET-1 had an impact on research in many African countries of 4 regional hubs. He has been an important tool for improving capacity to respond to outbreaks of emerging and re-emerging diseases for public authorities and aims to support the Africa CDC in its action. Through its many activities, workshops, capacity building, interventions in response to Lassa Fever in Sierra Leone, Chikungunya outbreak in Republic of Congo, Arenavirus surveillance in Zambia, Monkeypox studies in Nigeria, Europe’s response largest Monkeypox outbreak and currently against Covid-19 pandemic in Sub-Saharan Africa, the Global Response or epidemiological, genomic surveillance in Congo and in antimicrobial resistance and, has made more 222 publications, more 20 in The Lancet (https://www.pandora-id.net/) and joining different initiatives.
Vaccination is one of the most successful public health interventions for preventing infectious diseases. A successful vaccination program depends on high coverage, and health care workers (HCWs) play a pivotal role in ensuring high uptake of vaccines in the population. COVID-19 vaccines have been proven to be efficacious, and vaccination campaigns have been ongoing, however there is a perceived high vaccine hesitancy even among health care workers in Uganda.
This study aimed at describing the facilitators, barriers to and level of uptake of COVID 19 vaccines among healthcare workers in primary healthcare facilities in an urban setting in Uganda.
We conducted an online cross-sectional survey among healthcare workers in private and public healthcare facilities in Entebbe municipality between July 2021 and August 2021. Data was collected using an online questionnaire. Uptake of the vaccines among healthcare workers was analysed as proportions, and logistic regression was used to analyse barriers and facilitators to uptake of COVID 19 vaccines.
The study enrolled 360 participants, with 61.7% (n=222) females. A total of 236 (65.6%) healthcare workers had received at least one dose of COVID 19 vaccine with higher uptake among females 64%(n=151). Age above 40 years (OR 4.29), participating in COVID 19 vaccine related activities (OR 4.18) and having had a negative SARS-COV-2 test result (OR 1.79) increased the odds of having been vaccinated. Working in either a private for profit (OR 0.23) or a private not for profit (OR 0.19) reduced the odds of having been vaccinated. History of having cared for a COVID 19 patient and having a positive SARS-COV-2 test result did not influence the uptake of the vaccines in the study population.
Vaccine uptake among healthcare workers was close to the World Health Organisation (WHO) recommended uptake of 70% by mid-2022.
The greater efficacy of antiretroviral drugs has directed focus towards improving the lifestyle and longevity of people living with HIV/AIDS (PLWHA). Malnutrition impacts the immune system and is influenced by HIV infection and drugs. The aim of this study was to investigate the effect of malnutrition on the immune status of PLWHA in the study population.
A cross sectional study was conducted among 610 HIV positive participants between the months of May 2019 to November 2020 in HIV treatment centres in Fako Division. A questionnaire was used to collect lifestyle data. BMI was used to classify nutritional status. Venous blood was analysed for haemoglobin levels, some macro- and micro-nutrients (Albumin, total cholesterol, triglycerides, iron, calcium, magnesium and Vitamin D), CD4+ cell count, viral load and some inflammatory cytokines (IL-1, IL-6 and TNF-α).
Based on BMI results, 316 (52.8%) participants were malnourished, with 39 (6.5%) being undernourished and 277 (46%) were over nourished (overweight and obese). The majority of the patients were deficient in Vitamin D (74.8%) and serum iron (82.4%). Albumin revealed a positive relationship with CD4 cell count (r = 0.208, P = 0.009) and a negative relationship with viral load (r = -0.229, P = 0.010). There was a positive correlation between serum iron and CD4 cell count (r = 0.250, P = 0.044). Albumin correlated negatively with IL-6 (r = -0.109, P = 0.035) and TNF (r = -0.121, P = 0.014). Total cholesterol correlated negatively with TNF-α (r = -0.269, P<0.001) while calcium and magnesium correlation positively with TNF (r = 0.108, P = 0.029) and IL-1 (r = 0.105, P = 0037) respectively.
It could be concluded that macro- and micronutrients may considerably modulate the immune recovery of PLWHA, thus affecting the quality of life.
Study received funding from CANTAM (Ref: 2517/FCRM/D/DR/08–18)
A key objective of the EDCTP SAVING Consortium was to build Institutional and Individual capacity in Implementation Research (IR). The aim was to equip institutions along the Access and Delivery Value Chain to identify and address bottlenecks hindering delivery of new medical interventions including vaccines using IR.
A Capacity Needs Assessment was carried out and results used to plan the capacity building approach. All trainees were enrolled and undertook a specialized Massive Open Online Course (MOOC) on IR. The MOOC was adapted to suit availability needs of trainees. Trainees were then taken through three in-person 5-day residential IR workshops. The workshops covered proposal development, preparation of documentation for ethical approval, and Report/manuscript writing. The workshops involved presentations by experienced facilitator/investigators within the consortium with supportive sessions where trainees put into practice what they had learnt. Each workshop was interspersed with a period of six weeks during which the trainees completed the required outputs. A unique feature adapted from an earlier TDR funded study included embedding of Research Scientists in each of the teams to provide on-going support during and in between workshops. Senior Consortium Investigators provided back-up support.
The needs assessment showed that 64.1% of 78 respondents considered themselves beginners with regards to experience in IR. By the end of workshop 1, four proposals addressing bottlenecks identified had been successfully drafted by three teams from stakeholder institutions. After workshop 2, three proposals were submitted for ethical review and approvals obtained. All three teams are currently at various stages of data collection and analysis.
This hands-on model for Institutional training in IR is effective as it ensures that trainees obtain needed support as their capacity is being built. They "learn by in doing" in real time, while capacity and confidence is built in a sustained manner.
Tuberculosis (TB) is a major public health issue in resource-limited settings, including Gabon, which it is one of the top 30 countries worldwide with a high burden of the disease. Managing multidrug-resistant TB (MDR-TB) in these settings is challenging due to limited access to rapid diagnostics and drug susceptibility testing. Early detection of drug-resistant TB is crucial to controlling transmission of resistant strains and initiating appropriate treatment. The study aimed to determine the proportion and resistance patterns of pre-extensively drug-resistant (Pre-XDR) and extensively drug-resistant (XDR) TB among MDR-TB patients in Gabon and to identify the distribution of their lineages.
In this cross-sectional study, we collected 92 TB isolates from rifampicin-resistant (RR) patients based on Genexpert. We performed BD MGIT liquid culture and whole-genome sequencing using the MinION according to standard procedures.
Our findings showed that the HIV-TB co-infection rate was 14.1%, and the mean age of the participants was 31.94 years. We observed that 65.2% of patients had MDR-TB, 19.6% had Pre-XDR, 14.1% had RR-TB, and 1.1% had XDR-TB. We identified three main lineages, with Lineage 4 being the most common (81.52%), followed by Lineage 5 (14.13%) and Lineage 2 (3.26%). The dominant genotypes were Cameroon, LAM, Harleem, West Africa 1b, and Beijing, accounting for 47.82%, 19.56%, 17.39%, 6.5%, and 4.3% of cases, respectively.
Our study reveals a high proportion of Pre-XDR patients, underscoring the need to enhance laboratory capacities to monitor Pre-XDR and XDR-TB patients. This is the first detection of Lineage 2, the most virulent TB strain in Gabon, Further studies are needed to investigate the transmission dynamics of the Lineage 2 TB strain in Gabon. TB programs should prioritize the effective and rational use of second-line drugs for newly diagnosed MDR-TB patients to prevent the emergence of Pre-XDR/XDR-TB strains.
Only 1.3% of the sub-Saharan African diagnostic laboratories are performing clinical bacteriology. To improve this, diagnostic tools in LRS should be simple, affordable and maintenance-friendly, in contrast with the expensive machinery used in high-income countries, such as mass spectrometer for identification. Lensfree imaging is a label-free identification technique that can be performed directly on colonies growing on agar plates, with low-cost instrumentation.
We report here the very first clinical assay of a wide-field lensfree imaging device, namely 24mm x 36mm, for identification down to species. Considering this large field of view, several hundreds of colonies can be analysed simultaneously. A database of over 250 clinical bacterial isolates was collected at LHUB-ULB, gathering respiratory (20% of isolates), urine/genital tract (20%) and skin/wound (20%) samples, as well as positive blood cultures (40%). Partially coherent light emitting diodes (wavelengths 550nm and 940nm) illuminated microbial cultures growing on Mueller Hinton agar at 36°C. Clinical isolates were labelled through MALDI-TOF mass spectroscopy. To optimize supervised learning, various deep learning models, pre-trained or not, were developed and compared.
Over 11.000 colonies were collected in the database that focused on 5 species (Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus, Staphylococcus epidermidis). From these, different deep learning models were trained with at least 1800 samples per species. As a result, the algorithms yielded unambiguous identification of each species, with at least 90% accuracy.
This very first database paves the way towards a future imaging device for the diagnosis of bloodstream infections in LRS, within the SIMBLE project. As a second stage, a second database is to be acquired, in Africa, on positive blood cultures.
Non-tuberculous mycobacteria are increasingly recognised as causative agents of opportunistic and device-associated infections in humans. In Gabon, data is scarce, as species identification and drug susceptibility are not performed in most laboratories. The objectives of our study were to identify the relative frequencies of non-tuberculous mycobacteria species circulating and to determine their genotypic susceptibility pattern regarding the antibiotics most commonly used to treat NTM infections among presumptive tuberculosis patients.
This cross-sectional prospective study was conducted at the CERMEL TB laboratory from January 2020 to December 2022 to generate drug susceptibility data on NTM species identified from presumptive TB patient specimen sent to the National TB Reference Laboratory. The drug susceptibility to macrolides and aminoglycosides and the NTM subspecies identification were performed using the genotype NTM-DR kit.
Among 524 culture-positive specimen, 146 (28%) were NTM. The predominant group was Mycobacterium avium complex, MAC 80/146 (54.8%), of which M. intracellular 53/146 (36.3%) and M. avium 27/146 (18.5%)); followed by Mycobacterium abscessus complex, MABC 38/146 (26.0%), of which M. abscessus subsp. abscessus 20/146 (13.6%); M. abscessus subsp. massiliense 10/146 (7.0%); and M. abscessus subsp. bolletii 8/146 (5.4%)). All MAC were genotypically fully susceptible to macrolides and aminoglycosides. All five isolates of MABC showed polymorphisms both of the erm (41) and rrl genes, both coding for macrolide resistance.
All MAC isolates were fully susceptible to macrolides and aminoglycosides, thus confirming their role in NTM treatment. However, resistance-conferring polymorphisms indicate limited susceptibility of M. abscessus complex isolates against both drug classes; requiring further investigation to comprehensively determine M. abscessus drug susceptibility. The study results presented here shall guide clinicians to better manage treatment. Routine susceptibility testing is not available.
Disclosure of research results may impose undesirable responsibilities and consequences on the participants. Locally and culturally applicable guidelines for protection of research participants from negative consequences of genomic research results disclosure have been not enunciated in many developing countries. Establishment of such guidelines needs to be guided by preferences of the indigenous research participants. This study therefore attempts to determine potential research participants understanding and expectations of disclosure of genomic research results and its implications to participants in genomic research in Nigeria.
In a cross sectional descriptive study 150 participants were selected by systematic sampling from patients attending the laboratory of Adeoyo Maternity Hospital in Ibadan. Information was collected on socio-demographic characteristics of participants, awareness of genomic research studies, preferences on the mode of disclosure of their result and the recipients of such disclosure. Data were analysed using the SPSS version 17 and presented with the tables of frequencies.
Most participants were aware of genomic identification of diseases (68%). The main advantage expected from undergoing genomic testing is awareness of health status (58.7%) and main disadvantage is psychological trauma (71.0%). Respondents (94%) preferred genomic research results be communicated to the study participants and certain third parties (86.7%), mostly next of kins (30.7%) and spouses (20%). Reason for seeking disclosure is to obtain social (37.3%) and medical (22%) support. Participants suggested withholding result on account of mental health status of the recipient (10.7%), incurability of the disease (8.7%) and negative social consequence of the disease (8.7%).
This study suggests that research participants welcomes disclosure of genomic research results specifically to certain third parties due to the expected benefits. However the consequences of disclosure should be considered before its undertaking. Genomic research undertakings therefore should consider and document research participants’ preferences for disclosure while participants consent is being obtained.
Female Genital Schistosomiasis (FGS) remains one of the most critical and neglected topics in Neglected Tropical Diseases (NTDs) and the health of women and girls worldwide. Health workers’ knowledge of FGS is vital to the prevention and management of the disease. This study, therefore, conducted implementation research to identify and address the FGS knowledge gap among health workers in Ghana.
This study was a 3-year (2020 -2022) implementation research study applying a pragmatic uncontrolled quasi-experimental study design. The study involved a baseline assessment, an intervention phase involving the training of health workers about FGS and an endline assessment. A mixed-method approach was applied to data collection. The qualitative data involved 20 In-depth Interviews while the quantitative data involved 116 health workers. NVIVO 12 and STATA 14 were used for qualitative and quantitative data analysis, respectively.
Before the intervention, there was little knowledge about FGS among health workers as most participants only understood FGS as merely urogenital schistosomiasis in females. Based on the baseline assessments, an FGS education intervention in the form of training of health workers and distribution of FGS educational materials was carried out. The impact of this intervention enhanced health workers’ awareness and management of FGS. However, access (availability and affordability) to praziquantel (the main drug used in treating and preventing schistosomiasis) was cited as a challenge.
The FGS intervention has improved health workers’ awareness and understanding of FGS. However, there is a need to improve access to praziquantel to facilitate FGS management. In addition, a holistic strategy encompassing all stakeholders at the individual, community, and health-system levels is required to improve the general knowledge and management of FGS.
The PregnAnZI-2 trial was conducted in The Gambia and in Burkina Faso to evaluate the efficacy of intrapartum azithromycin (AZI) to reduce neonatal sepsis and mortality and maternal infections. Overall, 11,983 birthing parents and their newborns (6,735 participants for Gambia Site) were recruited into the study and randomized at a 1:1 ratio to receive either AZI or placebo. The independent trial monitoring was conducted by the Clinical Trials Unit of the Medical Research Council Unit The Gambia at LSHTM and we report here the main quality measures implemented in the trial and the subsequent protocol deviations observed in The Gambia site.
As part of quality control measures, the trial implemented frequent retraining of trial staff on study procedures, electronic data capture systems with integrated real-time eligibility and data quality checks, and pre-prepared drug blisters numbered similarly as the randomization list and envelopes. We conducted a total of 20 monitoring visits (a site initiation visit, 18 interim monitoring visits and close out visit) and captured all the protocol deviations identified in a purposively developed database.
Overall, there were 55 protocol deviations (PDs) identified in The Gambian site among the 6,735 women enrolled, giving a PD rate of 0,82% per participant. The most common PDs were delayed safety reporting of serious adverse events (SAEs) to ethics and sponsor (30.9% [17/55]), wrong sequence in treatment allocation (13% [7/55]) and delayed/out of window visit (7.3% [4/55]). PDs related to inappropriate consenting, and inclusion of ineligible participants represented 18% [10/55] and all other deviations 30.9% [17/55].
With robust quality control measures, frequent onsite monitoring, and by tapping into the potential of electronic data capture systems, research teams can efficiently implement large clinical trials of high quality with very few protocol deviations in resource-limited settings.
Antimalarial drug resistance represents an increasing public health concern in Africa. Indeed, since the introduction of IPTp-SP and SMC in moderate-to-high transmission settings, the prevalence of Sulfadoxine-Pyrimethamine and Amodiaquine resistance markers are increasing. This calls into question the effectiveness of these preventive strategies in the future. In this project, we aim to evaluate how NGS tools may contribute to the molecular surveillance of malaria drug resistance markers in target populations in Burkina Faso.
The study will be conducted in Nanoro Health District in Burkina Faso. A retrospective analysis of archived samples collected in 2015 from pregnant women receiving IPTp-SP and in 2016 from their children within the ‘’COSMIC’’ trial. Archived samples collected in 2020 from children participating in a study known as ‘’In-Host’’ project will be included as well. In addition, prospective cross-sectional studies will be conducted in 2023 and 2025 in children and pregnant women, respectively. The identification of P. falciparum infections will be performed by microscopy and qPCR. Resistance markers will be investigated using the AmpliSeq Assay and a sequencer machine (MiSeq, Illumina, USA). The multiple nucleotide sequence alignments method will be used to identify the resistance markers.
The expected results include the impacts of IPTp-SP and SMC on the evolution of targeted resistance markers in pregnant women in a 10 year-time and in children under 5 years in a 6 year-time. In addition, the level of P. falciparum resistance to Artemisinin-based combination therapies will be known in the two study groups.
Regarding the pressure of antimalarial drugs on the selection of resistance markers, it is necessary to use NGS techniques to monitor these markers and assess current strategies for target populations in order to inform and guide the national malaria control programs.
The EDCTP_STOP project is a multicentric clinical trial (ALIVE trial ct.gov: NCT05124691) that aims to interrupt the transmission of soil-transmitted helminths using novel treatment regimens. While cure rate measured by microscopy is the primary efficacy outcome, limitations in sensitivity after successful treatment pose a challenge. Nucleic acid amplification tests are a promising alternative. One objective in the EDCTP_STOP project is to assess real-time polymerase chain reaction (qPCR) as a secondary efficacy outcome, which necessitates implementing an external quality assessment scheme (EQAS).
The Helminth External Molecular Quality Assessment Scheme (HEMQAS), provided by the Dutch Foundation for Quality Assessment in Medical Laboratories (SKML), was implemented in the study. The sample distribution consists of blinded ethanol-preserved stool samples to assess DNA extraction, and purified DNA samples in stabilizing buffer to assess the amplification technique. Four consortium partners participated in the 2022 assessment. LUMC scored 99% (91/92 targets correctly identified). KEMRI scored 74% (68/92 targets). CISM scored 99% (75/76) and ULE scored 100% (62/62 targets).
For stool samples, the outcomes demonstrated that ineffective DNA extraction caused multiple false negative outcomes, particularly for Trichuris trichiura. Pipetting-error during DNA extraction may explain false positive outcomes. For DNA samples, false negative outcomes most likely resulted from handling errors. Systematic errors such as qPCR channels used to detect targets may account for false positive outcomes as spectral overlap in a multiplex qPCR may cause incorrect data interpretation. The use of validated positive control DNA elucidated which primer and probe pairs required optimization.
These outcomes facilitated targeted molecular optimization per trial site prior to testing trial samples. Participating in an EQAS facilitates capacity building by identifying training and laboratory validation needs, and ensures reliable reproducible results.
Diabetes mellitus (DM) maybe a risk factor for tuberculosis (TB) and negatively affect outcome of treatment. We investigated the impact of DM on TB treatment outcome in a longitudinal study.
The diabetic status of all microbiologically confirmed TB patients was determined at baseline (t0). The DM group consisted of known DM and on anti-diabetics (TBDMt) and newly diagnosed DM patients who were monitored by clinicians for three months without DM treatment (TBDMnt). Bacterial clearance at days 0, 7, 14, 28 and 56 were analysed by molecular bacterial load assay (MBLA) and HbA1c levels at three (t1), and six (t2) months during TB treatment, and 3 months post-treatment (t3). Clinical examination including X-ray was done.
A total of 559 TB patients were followed, 49 (8.8%) were diabetic with 36 (6.4%) TBDMt and 13 (2.4%) TBDMnt. The HbA1c of the TBDMt showed significant decrease in median-HbA1c from t0 to t3 (p=0.029) but still hyperglycemic. The TBDMnt cohort showed a significant decline in median-HbA1c from t0 to t1 (p=0.006), and remained normoglycemic. The TBDMt cohort had more infiltrations in the lower lung fields than the TB-only cohort (p=0.02). Analysis of 354 serial sputa collected from 59 cases (42 TB-only and 17 TBDMt cases) showed that the average bacterial load of the TB-only cohort at diagnosis was significantly higher than TBDMt cohort (p=0.03). However, after 56 days of TB treatment, the bacillary load of TBDMt cohort was significantly higher (p=0.04) using TB-MBLA. Time of sputum conversion from positive to negative as measured by TB-MBLA was shorter in TB-only participants (66 days) than TBDMt participants (88 days). Genotyping of mycobacterial isolates showed that Mycobacterium africanum Lineage 6 was associated with TBDMt cohort (p=0.023).
Our findings suggest delayed mycobacterial clearance among DM cohorts and DM may predispose individuals to TB caused by distinct lineages.
The EDCTP SAVING Consortium aimed to build Institutional and individual capacity in Implementation Research (IR). This was to enable Stakeholder Institutions along the Access and Delivery value chain identify and address implementation bottlenecks hindering delivery of new medical interventions such as vaccine. As a first step in the capacity building, there was a need to tailor the Massive Open Online Course on IR to the availability needs of the target institutions.
Initial consultations were held with trainees to agree on the mode of training that would be most impactful. Extensive consultations were held with local organizers of the MOOC to discuss adapting the mode of training to suit the Consortium. A variety of approaches were considered based on earlier experience with other institutions. The MOOC was held weekly over a 5-week period with 3 to 4 hours at each sitting. This was alternated with a free week to enable members see to their other duties at their institutions. Two modules were taken at each sitting. During each training session, members watched the videos together with onsite facilitators who were Senior Investigators in the Consortium and who were IR trainers. Each video was followed by an interactive session during which facilitators clarified any unclear areas providing practical examples. Trainees took the assessments immediately. Outstanding assessments were completed before the next in-person session. All 5 models were completed in three sessions over a 5-week period.
By the end of the 5-week period, out of the total of 53 participants who enrolled, 41 successfully completed the MOOC and gained TDR certificates of completion by the end of the period.
This model for undertaking the MOOC is a good choice for participants who require IR training but who have very busy work schedules like participants in our setting.
Adherence to treatment is a challenge to people living with HIV (PLHIV). Therefore, interventions are highly needed to assist PLHIV in adhering well to medication. Digital adherence tools (DAT) that offer real-time intervention are promising due to their ability to timely detect non-adherence and provide an opportunity for counselling. We tested DAT to understand the need for tailored adherence feedback among children and adolescents living with HIV (CALHIV) in Kilimanjaro, Tanzania.
We conducted a mixed methods study among CALHIV with their caregivers. Participants completed a survey at study entry to collect disease, treatment, and adherence background information. Then, they used the DAT for one month. The DAT included (1) using Wisepill box that records lid opening as medication intake, (2) receiving reminder SMS and (3) receiving adherence feedback after one month based on reports generated by the DAT. The feedback sessions lasted for maximum 30 minutes and focused on identifying possible solutions to the non-adherence patterns. After that, we conducted exit interviews, in-depth interviews and focus group discussions. We did descriptive and thematic content analysis.
We included 20 children (0–14 years) and 20 adolescents (15–19 years). Median adherence measured with DAT was 98.5% among children and 72% among adolescents. Most participants understood the feedback graph, liked the feedback content and thought receiving adherence feedback and counselling would improve their future adherence. Participants explained that feedback reports provided great accuracy in discussing adherence behaviour with counsellors and nurses. However, 25% of adolescents did not agree with the feedback as it indicated they did not open the pillbox while they had. This was mostly due to technical and connectivity challenges.
DAT with personalized feedback on adherence is a promising intervention to improve counselling and disease management among CALHIV. Our upcoming randomized clinical trial will assess in detail its effectiveness in improving adherence.
Women are under-represented in academic careers, particularly in research. The challenges they face include difficulties in balancing family/life responsibilities and work, lack of adequate mentors, financial challenges, and bias in the provision of opportunities. In sub-Saharan Africa, the proportion of women scientists is even smaller. The Capacity Building for Female Scientists in East Africa (CaFe-SEA) program is funded by EDCTP through the Partner States’ Initiated Activity. It aims to equip female scientists from under-represented countries with knowledge and skills for research in infectious diseases.
The program is delivered by the Eastern Africa Consortium for Clinical Research (EACCR) through universities within the region. Scholars were selected through a competitive process, and each was attached to an EACCR partner institution. CaFe-SEA is multidisciplinary program delivered through five tracks including laboratory sciences, an interface between non-communicable diseases and communicable diseases, maternal and child health and health-behavioural sciences. The scholars receive training in cross-cutting courses like epidemiology and biostatistics, bioethics, research management, and leadership, GCP-ICH, GCLP and scientific writing.
The project enrolled 8 female scholars from South Sudan, Burundi, Ethiopia, Rwanda, Zanzibar, Uganda, Kenya, and Tanzania. All scholars are registered at universities in their home countries except the South Sudan scholar who has registered in Uganda. All scholars have been attached to EACCR mentors working with their university supervisors. They have developed their proposals and are in the process of obtaining ethics approval before initiating field activities. The main challenges faced are managing family and PhD studies by some of the scholars and learning English for the scholars from Burundi and South Sudan.
The early achievements the CaFe SEA project demonstrate the possibilities of supporting African female scholars to become distinguished scientists.
Funding: CaFE Sea is funded by the EDCTP through grant number PSIA2020AGDG-3318
Long-acting injectable PrEP (LAI-PrEP) is a new, appealing substitute for oral PrEP especially among individuals for whom daily medication adherence is challenging. However, there are no available data on willingness to use LAI-PrEP among young women in Uganda. Therefore, this study aims at assessing the level and factors associated with willingness to use LAI-PrEP among high-risk young women in Kampala, Uganda
We conducted a cross-sectional study that analyzed data from a cohort of 14–24-year- old high-risk young women enrolled between January and October 2019. Participants were given an overview of the attributes of LAI-PrEP including its dosage and administration. Willingness to use LAI-PrEP was defined as whether an individual was willing to adopt injectable PrEP as an HIV prevention method. The complementary log-log model was used to assess factors independently associated with willingness to use LAI-PrEP.
We enrolled and analyzed data for 285 participants with mean age of 19 years, 65.1% reported heavy episodic drinking of alcohol (consuming 6 or more drinks on an occasion as per the AUDIT tool), 68.8% had multiple sexual partners in the past 3 months and only 3.9% were aware of LAI-PrEP at baseline. Overall, 199 (69.8%) participants expressed their willingness to use LAI-PrEP with the most commonly cited advantage being the injection’s longer lasting HIV protection. Participants that were divorced/separated (aOR 1.74,95%CI 1.02–2.94) and those with multiple sexual partners (aOR 2.12, 95%CI 1.46–3.09) had higher odds of willingness to use LAI-PrEP while those that were screened as heavy episodic drinkers had lower odds of willingness to use LAI-PrEP (aOR 0.61,95%CI 0.42–0.89).
Our findings suggest that LAI PrEP, as an alternative to daily oral PrEP, may be used to supplement current evidence-based HIV prevention programs. Therefore, programs for scaling-up LAI-PrEP for AGYW should integrate HIV testing services with sensitization to create awareness of its potential.
The COVID-19 pandemic has more than ever demonstrated the urgent need to train more skilled epidemiologists and biostatisticians in Sub-Sahara Africa to reverse the deficiency of reliable epidemiological data while efficiently monitoring, analyzing, and interpreting these data to inform public health policy and decision-making. The project "Training Epidemiologists and Biostatisticians for enhanced response to disease outbreak and epidemic in West Africa" (TEBWA, 2021–2024), supported by EDCTP2, aims to enhance West Africa’s research capacity in epidemiology and biostatistics to respond efficiently towards diseases outbreaks and emerging (and re-emerging) infectious diseases. Specifically, the project aims to (i) train fifteen skilled postgraduate biostatisticians and infectious disease epidemiologists in West Africa; (ii) strengthen the ability of young scientists from West African countries to manage epidemic disease outbreaks, and (iii) strengthen regional and international cooperation in Biostatistical and epidemiological research. The project is coordinated by the University of Abomey-Calavi (Benin) in partnership with the London School of Hygiene and Tropical Medicine (LSHTM, UK) and the Benin National Agency for Primary Health Care (Benin). Fifteen young Africans (7 women and eight men) from eight countries (Benin, Ghana, Togo, Mali, Liberia, Guinea, Niger, and Cote d’Ivoire) have been recruited. They are currently following a master’s degree in either Biostatistics or Epidemiology and public health interventions. They are further taking online courses with the LSHTM. The project TEBWA also provides its fellows with a special mentoring program where fellows benefit from the rich and extensive experiences and networks of their mentors (from Africa and Europe). This mentorship program is key for their career development after the end of the project. The fellows are also supported in subscribing to several scholars and practitioners’ societies. The fellows are currently doing their research on various topics related to diseases such as COVID-19, Lassa Fever, Malaria, Cholera, Measles, Ebola, etc.
]]>The genetic complexity of Plasmodium falciparum is a contributory factor to the emergence of drug-resistant parasites. WHO recommends intermittent preventive treatment of malaria in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) to reduce the deleterious effects of maternal and neonatal malaria in high transmission settings. However, asymptomatic malaria still persists in areas of endemicity despite IPTp-SP regimen. The study evaluated the allelic profiles of Plasmodium falciparum merozoite surface proteins (Pfmsp-1, Pfmsp-2), glutamate-rich protein (Pfglurp) and multidrug resistance-1 gene (Pfmdr-1) in pregnant women on IPTp-SP regimen from southwest Nigeria.
100 PCR-confirmed Plasmodium falciparum isolates, comprising visit 1 (V1) (n = 52), Delivery (n = 31) and Cord blood (n = 17) were randomly selected from EDCTP2 funded study (Trial no. 98867 IPTp-SP resistance in Nigeria TMA 2015 CDF – 973). Genomic DNA was genotyped using nested PCR. The Pfmdr-1 gene was further evaluated using restriction fragment length polymorphism (RLFP) at codon 86 with Apo1 restriction-digestion enzyme. Allelic frequencies, proportions and multiplicity of infection was calculated. Statistical significance was considered at p ≤ 0.05.
Isolates from V1 confers 21.2% (Pfmsp-1), 32.7% (Pfmsp-2) and 9.6% (Pfglurp) distinct alleles, while delivery samples had 45.2% (Pfmsp-1), 32.3% (Pfmsp-2) and 6.5% (Pfglurp) allelic types. Cord isolates recorded the highest alleles; 70.6% (Pfmsp-1), 58.0% (Pfmsp-2) and 5.9% (Pfglurp). The MOI for V1 was 2.7, 2.1 and 1.1 for Pfmsp-1, Pfmsp-2 and Pfglurp. Delivery and cord isolates recorded 3.2, 1.9 and 2.7, 1.9 for Pfmsp-1 and Pfmsp-2 respectively; but had monoclonal Pfglurp alleles. The Pfmdr-1 wild/mutant allelic combination (N86Y) was present in 11.8% (V1), 61.3% (Delivery) and 58.8% (Cord blood) p ≤ 0.05. Single point mutation (86Y) was only present in 5.9% cord isolates.
Antigenic falciparum strains with N86Y Pfmdr-1 mutations may limit the efficacy of intermittent sulfadoxine-pyrimethamine prophylaxis of malaria during pregnancy in southwest Nigeria.
Participant information sheets and consent forms (PIS&C) in paediatric/adolescent clinical research are predominantly produced by adults. They are long and complex, meeting ethics, regulatory, and where applicable, pharmaceutical industry requirements, rather than the target audience. Young people report they do not understand much of the information provided, so do not read it, and rely on conversations with trusted Healthcare Providers. LATA (NCT05154747) being conducted by the BREATHER Plus Consortium, is the largest randomised trial of long-acting injectable antiretroviral therapy in virologically suppressed adolescents aged 12–19 years living with HIV-1 (ALWH). LATA has ‘Youth Trials Boards (YTB)’ in the participant countries (Kenya/South Africa/Uganda/Zimbabwe) that consist of supported, structured groups of ALWH who are active partners in the development and delivery of LATA, which started enrolment in May 2023.
YTB members attended a global digital meeting to explore what information their peers need to give proper informed consent/assent and what medium would best deliver this.
The group agreed a short, engaging video would provide core information on how the medicine works, the injection experience and trial requirements. Youth engagement specialists worked with animators to develop a concept and provisional script. The process included ongoing ‘science and youth’ checks. YTB members lent their voices to ensure the video was in local languages. The final video was 5–6 minutes long (u-tube link to follow). All the national ethics committees have approved the video.
The LATA video compliments the traditional PIS&C and was made through genuine youth engagement. The process allowed the young people to decide the format and content, whilst ensuring it correctly represented the trial. While this video is an adjunct to the PIC&S, in future, videos such as this could replace much of the lengthy complex language provided to trial participants, this merits further discussion with ethics committees and regulators.
Conducting vaccine studies in resource-poor settings comes with challenges. These challenges could include lack of infrastructure for cold chain management, accessibility of vaccination centres, the community’s behaviour towards researchers, and political interference. In a pandemic situation e.g., during the Covid-19 peak, overcoming these barriers was difficult. To ensure more than 80% coverage during the field implementation of a Typhoid Conjugate vaccine (TCV) Trial in Ghana (TyVEGHA), we developed strategies to overcome these challenges.
The study team identified the strength and weaknesses of the community and established a community advisory committee to help guide the conduct of the trial. This committee included chiefs and prominent members of the community, religious leaders, local health administrators, and community activists many of whom were employed as field workers. Communication was done in many forms, i.e., through the local media, fieldworkers moving from home to home, using communication vans at the marketplaces, and mounting platforms of religious groups. Five satellite sites were identified and integrated into the strategy for the primary campaign. Personnel from these sites were recruited, and sheds were built for the study to bring the vaccination closer to hard-to-reach communities. Vaccines were deployed daily from the main trial centre in cool boxes with thermometers and additional cooling elements. Small community durbars with queen mothers as ambassadors led the discussion on the importance of the typhoid vaccine and the need for participation in the study.
With support from the community an average of 500 children were screened daily. 20,052 (87.2% of eligible children) were vaccinated, with less than 10% of those screened, hesitant to receive the vaccine. No major vaccine related issues occurred during primary vaccination.
Good communication strategies and community participation with a sense of community ownership was the primary force for the successful vaccination campaign.
Funding: EDCTP
Deployment of large-scale surveillance in low-income settings can be challenging. Meanwhile, the inclusion of pharmacists, health centres, over-the-counter medicine sellers (OTC), and herbal clinic practitioners as referral agents for health programs has the potential to improve access to healthcare services, increase enrolment in surveillance programs, and improve patient outcomes. We report here the participation of these important players in a large-scale vaccine deployment: Typhoid Vaccine in Ghana (TyVEGHA) programme in a rural setting in Ghana.
We published elsewhere the concept of the severe typhoid fever programme (SETAPlus). In brief, we trained pharmacists, OTC agents, and herbal medicine sellers within the catchment area of the TyVEGHA study to support referral of eligible participants to Agogo Presbyterian Hospital-Trial Site. Facilitated (through incentives and community-sensitization) Participatory Training (FPT) was conducted to support the partnership and understanding of referral processes for eligible participants. The owners/caretakers were trained in the use of digital thermometers, bench aids and logs for referral and enrolment. Refresher training was conducted every six-months to ensure sustained knowledge/skills. We assigned study members to supervise their activities and facilitate referral process. Finally, we conducted monitoring activities twice-a-week to certify compliance with good clinical practice and adherence to protocol.
Prior to the use of FPT in July-2022, the number of providers identified was 36. This number increased to 48 as of April 2023 (within a period of nine month), with 137 participants being referred for enrolment, blood draw, and subsequent follow-up. However, only 79% of the total facilities identified are currently referring participants due to challenges including inconsistent operation of OTCs, unrealistic incentive expectations and proxy drug purchases.
FPT using health agents and community sensitization increased referral for participation in the TyVEGHA study. The study highlights the potential advantages of including these as referral points for health programs.
Anemia is a serious global health problem particularly in malaria and Soil-transmitted helminths (STH) co-endemic areas, where those parasitic infections can influence the anemia severity. The present analysis aimed to assess the prevalence and associated risk factors of anemia in malaria and STH co-endemic areas.
We conducted a cross-sectional survey between October 2020 and January 2021 in the Bata district. Venous blood was collected for hemoglobin levels assessment using the HemoCue Hb201. Anemia was defined based on the WHO threshold. Plasmodium infection was diagnosed using the microscopy technique and the Kato-Katz technique was used for STH egg identification in stool samples. Multiple logistic regression analysis was performed to assess factors associated with anemia.
A total of 339 participants were included in this analysis, with a mean age of 24.4 (SD=23.7) and 64 (19%) aged less than 5 years. A total of 187 (55%) participants were female, while 119 (35.1%) and 79 (23.3%) of them lived in peri-urban and rural areas, respectively. The prevalence of anemia was 77% (95%CI: 72 – 82). Among the anemic population, severe anemia represents 6% (17/262), while moderate and mild anemia represents 60% (157/262) and 34% (88/262), respectively. Anemia was associated with age (p<0.001) and locality (p=0.03). Compared to participants aged 1–5 years, those aged 6–14 years (aOR=0.39; 95%CI: 0.14 – 0.95, p-value=0.048) and those aged more than 14 years (aOR=0.18; 95%CI: 0.06 – 0.41, p-value<0.001) had a lower odd of anemia. Compared to urban areas, peri-urban areas had a high odd of anemia (aOR:1.15; 95%CI:1.24 – 4.87, p-value=0.01).
Anemia prevalence is high in the Bata district calling for more research on the determinants of the disease in the country. Our results indicate old age and peri-urban areas as the main factors associated with anemia in the Bata district.
WHO recommended the RTS,S/AS01 malaria vaccine for widespread use for children in regions with moderate to high plasmodium falciparum malaria transmission after data from a pilot study revealed the vaccine was safe, significantly reduces severe life-threatening malaria, and can be administered effectively in real-life childhood vaccination settings. This study is consistent with the work of the SAVING Consortium, which builds on the Access and Delivery Partnership value chain framework and emphasizes the importance of high-quality implementation and delivery research as a crucial tenet for the efficient distribution of new medications. Factors that influence primary caregivers’(PCGs) adherence to the RTS,S vaccination schedules as well as health professionals’ access to and administration of the RTS,S vaccine were explored.
The larger study "Dynamics of Healthcare Utilization in the Context of RTS,S/AS01 Vaccine Implementation in Ghana" provided the secondary data for this study. Completed transcripts of 45 PCGs and 24 health professionals were imported into NVivo 12 for theme categorization and analysis.
Facilitators of adherence were benefits of RTS,S vaccine and trust in the health system and health workers. Barriers to adherence were social activities and other engagements. PCGs preferred fewer vaccination visits with more vaccines because frequent visits disrupt their daily activities. Health workers perceived that the phased introduction of the pilot and delay in its start affected the initial implementation and fuelled rumours. These rumours, though widespread, did not have much effect on uptake after reinforced education.
Education and sensitization increased trust and promoted adherence to the RTS,S vaccination schedules. PCGs preference for less vaccination visits should be considered. Future introduction of new vaccines such as the R21/Matrix-M vaccine as well as subsequent roll-out of RTS,S vaccine should leverage on these enablers for implementation success.
Tuberculosis (TB) is one of the leading causes of death from a single infectious agent with approximately 1.4 million deaths annually. Efforts to eradicate TB are threatened by diabetes mellitus (DM), which confers a greater than a 3-fold TB disease risk. Both TB and DM are accompanied by marked immunologic changes, however, changes in Mtb-specific T-cell functional responses remain poorly characterised. We compared Mtb-specific CD4+ and CD8+ T-cell functional responses among patients with LTBI-DM (21), DM (16), ATB (19) and ATB-DM (04).
Peripheral blood mononuclear cells were stimulated with ESTA-6/CFP-10 peptide pools or PHA, and characterised Mtb-specific CD4+ and CD8+ T cell functional memory (CD45RA/CCR7), activation (HLA-DR), exhaustion (PD-1) and apoptosis (Bcl-2) profiles by flow cytometry. Data were analysed using FlowJo v.10.8.2 and Prism v.8.4.
Central memory CD4+/CD8+ T cells were decreased in ATB [median (IQR): 30.80 (20.70–34.80)] compared to DM [41.35(36.63–57.13)] (P<0.0001)/(P=0.0388) and LTBI-DM [45.60(38.75–50.40)] (P<0.0001)/(P=0.0028) patients. Effector memory CD8+ T cells were decreased in DM [21.50(15.18–30.28)] compared to LTBI-DM [32.00(23.45–43.80)] (P=0.0193) patients. TEMRA CD4+ phenotypes were decreased in ATB [1.17(0.88–2.83)] compared to LTBI-DM [0.70(0.30–1.26)] (P=0.0040) and DM [0.99(0.41–1.34)] (P=0.0057) patients. CD4+ T cell HLA-DR expression was upregulated in ATB [2.49(1.12–3.49)] compared to LTBI-DM [1.16(0.89–1.43)] (P=0.0016) and DM [1.63(0.99–2.33)] (P=0.0235) patients. CD4+/CD8+ T cell PD-1 expression was upregulated in LTBI-DM [1.77(1.49–2.94)] compared to DM [1.63(0.95–2.07)] (P=0.0499) and ATB-DM [0.62(0.33–0.94)] (P=0.0381) patients. Finally, CD4+ T cell Bcl-2 expression was increased in ATB [4.17(2.99–5.87)] compared to LTBI-DM [2.08(1.44–3.71)] (P=0.0077) patients.
ATB decreases CD4+/CD8+ T-cell central memory while DM decreases CD8+ T-cell effector memory compromising immune surveillance and production of effector cytokines against TB. DM upregulates TEMRA, cells less protective against Mtb. CD4+/CD8+ T cells are exhausted possibly due to persistent inflammation and Mtb-exposure but remain anti-apoptotic. Loss of PD-1 mediated inhibition in DM could promote severe TB disease.
The Covid-19 pandemic led to severe health systems collapse, as well as logistics and supply delivery shortages across sectors. For example, delivery of PCR related healthcare supplies was massively delayed during the COVID crises. A rapid and accessible SARS-CoV-2 molecular detection method in low resource settings offers many advantages. The aim in this study was to validate a novel isothermal amplification method for rapid detection of SARS-CoV-2 across seven sub-Sharan African countries and build capacity onsite.
In this multi-country phase 2 diagnostic study, 3,231 clinical samples at seven African sites were tested with two reverse transcription Recombinase-Aided Amplification (RT-RAA) assays targeting the SARS-CoV-2 Nucleocapsid (N) and RNA-dependent RNA polymerase (RdRP) genes. Testing was performed in a mobile suitcase laboratory within 15 minutes. All results were compared to reference real-time RT-PCR.
All sites passed the initial quality control before screening the clinical samples in a single-blinded clinical trial. Four sites demonstrated good to excellent agreement between RT-RAA and PCR, while three sites showed fair to moderate results. The sensitivities for RdRP varied depending on Ct and study site (Ct values <30 ranged 60.5 – 100%; Ct values 30–35 ranged 23–90%; Ct values >35 ranged 3.6- 46.3%). Various factors regarding the setting and test operator were shown to have an effect on the test accuracy.
Overall, the RdRP based RT-RAA test showed the best assay accuracy. Lessons learned from this study to assure test accuracy across various sites include the implementation of standardized operation procedure, in-person continuous training for staff, and enhanced quality control measures.
Roughly 1.3 million infants are exposed and 150,000 newly diagnosed with Human Immunodeficiency Virus (HIV) annually. Estimates of Vertical HIV transmission (VHT) rates vary by setting. In this study, we assessed the risk factors for VHT among infants born to women living with HIV in Tanzania and Mozambique.
Between October 2019 and August 2021, data was collected from pregnant women living with HIV who participated in the LIFE study [RIA2016MC] at 28 obstetric health facilities in Tanzania and Mozambique. VHT was assessed up to month 3 of age in all infants. At baseline, demographics and clinical characteristics were collected to assess risk factors for VHT. Mixed effects models adjusted for health facility clustering were used to calculate risk ratios.
In total, 6,509 women living with HIV and their 6,605 exposed infants were included in the study. VHT up to month 3 of life was 2.69% (95% CI: 2.21, 3.24) in Mozambique, significantly higher than the 0.62% (95% CI: 0.35, 1.00) observed in Tanzania (RR: 4.45, 95% CI: 2.63, 7.99). On average, Tanzanian women were significantly older, attended antenatal care more frequently, and had been on antiretroviral treatment for a longer period. After adjusting for these factors, virologic non-suppression at delivery was the principal risk factor for transmission (RR: 35.7, 95% CI: 19.2, 73.1). In Mozambique, 31.0% of all mothers were not suppressed at delivery compared to 8.1% in Tanzania; only 8.9% (11/124) infants who acquired HIV by month 3 had mothers who were virally suppressed at delivery.
We observed a striking difference in VHT between countries. Lack of viral suppression at delivery was the main risk factor for VHT, highlighting the need for better understanding the individual, community, and health system factors associated with lack of viral suppression in pregnant and lactating women living with HIV.
The proportion of virologically suppressed (83%) people living with HIV (PLHIV) in Tanzania is below the 95%-target. Enhanced adherence counselling (EAC) is given when the viral load (VL) is >1000 copies/ml. Centralised laboratory VL monitoring hinders reaching the 95%-target due to challenges like long turn-around times. Point-of-care (POC) tests may overcome this. The aim was to assess the feasibility of POC monitoring.
We assessed pre-feasibility during preparations of the EAPOC-study, a cluster randomised trial on the effectiveness, acceptability, and feasibility of POC-VL monitoring using m-PIMA in East Africa. M-PIMA gives results within 70 minutes, displayed as <800 copies/ml, or if above 800, an actual number. We used the ‘Measurement Instrument for Determinants of Innovations’ (MIDI) framework to determine feasibility comprising determinants of (1) the innovation, (2) the end-users, (3) the organisation, and (4) the socio-political context. We deployed the MIDI on narratives from meeting minutes, informal conversations, emails, and WhatsApp conversations. We did a thematic framework analysis to identify themes.
Considering the innovation, POC was expected to be complex, and there was unclarity in the need for centrifuges. Regarding end-users, nurse counsellors think they can give results rapidly, have beliefs about better treatment outcomes, understand the process and need training. Themes related to the organisation included time availability, re-arrangement of clinic staff to use POC inside the counselling room, counsellors’ self-efficacy, and cartridges’ availability. A central socio-political theme was a change of standard care in study sites whereby EAC was done at VL>50 copies/ml.
We identified challenges that may hinder the feasibility of POC for viral load monitoring. We recommend having good manuals and thorough training of staff, well-defined staff duties and available time and a good supply of cartridges. In addition, we advocate for POC devices that display VL copies as low as 50 copies/ml.
The Ghana-based SAVING consortium aims to identify and address implementation challenges for the delivery of new medical interventions, such as RTS,S, the malaria vaccine introduced in Ghana in 2019. Inoculation is at 6, 7, 9 and 24 months of age. The lifesaving potential of the vaccine can be limited by its effectiveness and implementation issues.
In November 2022, a qualitative study, employing in-depth interviews of five managers, three health workers and two community health volunteers was performed on: steps and challenges in introducing RTS,S; acceptability of RTS,S among health workers and community members; vaccine coverage.
There was a cascade training approach on RTS,S in the 10 districts that received RTS,S; the national centre trained staff at regional level. The region then trained the districts, which then trained the frontline healthcare workers and widely informed the population about RTS,S. In general, the training was perceived as adequate and well deployed. Acceptance of RTS,S by the healthcare workers and the population was good in spite of some misconceptions and a low perceived need for the vaccination. Awareness among the population and one health worker about the low level of effectiveness of the vaccine was limited. Vaccination coverage for the 4th dose of RTS,S was 40.1% among the eligible children (as of June 2022). A large drop-out rate between dose 3 and 4 was observed.
Use of the Med Safety Mobile App: the Regional Health Administration/Directorate introduced this MedApp in collaboration with the Food and Drug Authority. The motivation of the health delivery system to make full use of the MedApp was limited. In the visited district hospital, the MedApp was not being used.
The encountered challenges are common to other vaccines, including COVID-19 vaccines. Governments and stakeholders should take note of the existing evidence to anticipate these issues.
Severe malaria is a life-threatening disease with intravenous artesunate as the only recommended first line therapy. Global annual incidence of severe malaria is ~2 million cases with a case fatality rate >5% (despite antimalarial treatment) in endemic regions. Children under 5 years of age account for ~80% of all malaria deaths. Consequently, early evaluation of efficacy and safety in children <5 years of age is of paramount importance for the development of severe malaria therapies. KAE609 (Cipargamin) is a potent and fast-acting schizonticidal drug. Data are presented here from nonclinical juvenile toxicity studies with Cipargamin that supports early inclusion of paediatric patients in Phase II studies.
Repeated-dose toxicity studies in juvenile animals were conducted to support enrolment of paediatric patients from 6 months to 12 years of age. The rat is a sensitive toxicological species, and parenteral administration was used for ease of administration to young animals and to maximize systemic exposure. Effects from birth through to sexual maturation were assessed by administration on days 4 to 11 or days 20 to 27 of age with ~3 months of recovery. Endpoints included clinical observations, assessments of sexual maturation, oestrous cycling and reproductive capacity, clinical pathology, toxicokinetic analyses and histopathology.
Toxicological findings for Cipargamin in juvenile rats were comparable with earlier toxicity studies in adult animals. No indication of developmental or reproductive risks were observed that preclude use of Cipargamin in paediatric patients.
The juvenile toxicity studies fully assessed the nonclinical safety profile of Cipargamin and enable inclusion of the planned paediatric population in Phase II studies.
Funding: This project is part of the EDCTP2 program supported by the Wellcome Trust.
There is a high prevalence of infections and sepsis in pregnancy in Malawi, with evidence of a rising incidence of antimicrobial resistance. Lack of resources to inform the organism-specific therapy of maternal infections results in a significant proportion of maternal deaths being due to infections and sepsis. Through the implementation of a microbiology services for obstetrics patients, we aimed to describe the epidemiology and antimicrobial resistance profile of maternal infections in a tertiary hospital in Blantyre, Malawi, and investigate the impact of maternal infections surveillance platform on pregnancy outcomes.
Data on pregnant women from a maternal infections surveillance project serving a tertiary hospital in Blantyre, Malawi from 1 February 2021 to 30 March 2023 was used for the analysis. Descriptive statistics were used to describe the prevalence of infection and antimicrobial resistance. The association between infection from different samples and adverse delivery outcomes (a composite created through theory-driven grouping of a priori defined variables) was tested using multivariate logistics regression.
Preliminary analysis on urine sample data for 347 patients shows the prevalence of infections in urine in this population was 41.2% (95% CI of 36.0% to 46.4%), with up to two-thirds (57.3%) of the patients being on at least one empirical antibiotic on admission. 29.2% of the cultures grew Escherichia coli, and 8.2% grew Klebsiella pneumoniae. There were high levels of antimicrobial resistance demonstrated by the commonest isolates, especially Pseudomonas aeruginosa. Infection in urine was associated with adverse delivery outcomes 1.95 (95% CI 1.24 to 3.10, p=0.004). Having a culture result significantly informed the choice of antibiotic prescribed to a patient.
These results suggest that having an infection in urine is associated with a greater prevalence of adverse delivery outcomes. Additional studies of a prospective nature are required to rigorously investigate this association.
Regional Referral Hospitals (RRHs) are mandated by MoH to conduct research to provide evidence-based care to patients, however most lack the knowledge and skills. These provide mostly tertiary care to patients and serve as referrals for several districts under their catchment. Eastern Africa Consortium for Clinical Research (EACCR) through its HIV work package builds capacity for conducting ICH-GCP complaint research in the region.
Two RRHs from two regions in Uganda with high volumes of patients were considered: Masaka RRH and Jinja RRH located in Central and Eastern Uganda respectively.
The needs assessment done to identify the research capacity gaps, showed that the hospitals lacked Institutional review board (IRBs) to guide and evaluate research protocols. Memorandum of understanding were signed between Masaka and Jinja RRHs and the EACCR HIV work package. The parties agreed to train and build capacity of the members of the IRBs to review protocols and establish IRB offices in Masaka and Jinja RRHs.
Over 10 staff from each of the two hospitals were trained in good clinical practice, Research management, protocol reviews and research bioethics during pandemics. Masaka RRH had their IRB office refurbished with lockable cabins, a computer, and a printer scanner. The administrators received a one-weeks mentorship attachment to the IRB office at UVRI to learn IRB office operations. The IRB in Masaka and Jinja were guided to develop Standard Operational procedures (SOPs) as reference documents for operations. The IRB Office in Jinja had their office renovated and lockable -movable cabins were installed. All these RRHs are in the process getting accreditation from Uganda National Council of Science and Technology (UNCST). UVRI IRB continues to provide peer mentorship to these two IRBs.
When accredited, the two hospitals will use the patients and cohorts’ data for health research to answer research questions affecting communities in Uganda.
Antimalarial drug resistance threatens global malaria control efforts. Critical resistance-mediating mutations include those in the targets for sulfadoxine-pyrimethamine, transporter proteins and propeller domain of P. falciparum Kelch-13 protein that are associated with artemisinin partial resistance.
To gain insight into antimalarial drug resistance trends, we surveyed vital P. falciparum polymorphisms from 10–16 health facilities across Uganda from 2016–22. We further assessed for evidence of evolutionary selection of resistant isolates by evaluating diversity in genomic regions flanking resistance loci.
Five mutations in the targets of sulfadoxine (PfDHPS 437G, 540E) and pyrimethamine (PfDHFR 51I, 59R, 108N) were prevalent (80–100%). The prevalence of PfDHFR 164L and PfDHPS 581G mutations, which mediate higher level antifolate resistance, varied between sites and over time. The PfDHFR 164L mutation was most common in southwestern and central Uganda (>20–75%), with increasing prevalences from 2016–17 to 2022, and increases were also seen in other parts of the country. The PfDHPS 581G mutation was also most common in the four sites in southwestern and central Uganda, although significant changes were not detected. Mutations in PfCRT and PfMDR1, associated with aminoquinoline resistance, were increasingly uncommon. The PfCRT 76T allele was detected in western Uganda bordering the Democratic Republic of Congo. The PfMDR1 86Y mutation, which was previously very common, was absent from 2018–2022. The 1246D mutation decreased, with 0% prevalence in 2022. Four PfK13 mutations (675V, 469Y, 469F and 561H), remain highly prevalent by 2022, compared to our earlier reports. Regarding evolutionary selection, isolates with antifolate and aminoquinoline resistance-associated alleles showed similar diversity to wild-type isolates, in genomic regions flanking the resistance loci.
These results suggest limited evidence of recent selection of antifolate resistance, consistent with stable transmission of resistant isolates; and continued recovery of aminoquinoline sensitivity in Uganda.
The devastating effect of malaria in pregnancy (MIP) is mitigated by periodical administration of intermittent preventive treatment in pregnancy with sulfadoxine-pyrimethamine (IPTp-SP). Possibility of emergence of Plasmodium parasites resistant to SP portends a threat to pregnant women living in malaria endemic regions. This was an EDTCP2 funded study to assess the effect and prevalence of Plasmodia resistance to SP in selected Nigerian communities.
Consenting pregnant, gestational age 16–29 weeks, having met the inclusion/exclusion criteria were enrolled into one of the 5 study centres within Ikenne and Remo North LGA, Ogun State. Subjects were screened for malaria using microscopy, RDT and PCR, from enrolment to delivery. Positive malaria parasite samples were further analysed for Plasmodium falciparum dihydrofolate-reductase (Pfdhfr) and Plasmodium falciparum dihydropteroate-synthase (Pfdhps) mutations. All result were entered into REDCap® database and statistical analysis done using Microsoft Excel® 2019 and Stata 17®.
A total of 520 women, mean gestational age of 21 weeks were enrolled. Participants had average of 4 visits and 4 doses of SP before delivery. The prevalence of malaria parasitaemia was 2.9%, 4.8% and 35.5% using microscopy, RDT and PCR analysis respectively. There were 87 (19.4%) clinical malaria and 361 (80.6%) asymptomatic cases during the study. A total of 114 malaria positive samples were analysed for mutations. 51.8% were positive for mutations, while 4-points mutations were most prevalent (14.0%) and 4.4% had all 10-points mutations for Pfdhfr and Pfdhps. There were significantly more Pfdhfr mutations than Pfdhps and significantly higher mutations at enrolment.
The prevalence of clinical malaria was low considering Nigeria is endemic for the disease, but high asymptomatic cases. Higher Pfdhfr/Pfdhps mutations were seen at enrolment. This study is the first to report the use of 6 doses of IPT-SP and all 10-points mutations for Pfdhfr/Pfdhps, which are definitive markers for SP resistance.
Clinical trial knowledge and skills significantly influence the quality of clinical trial conduct. This article assesses the confidence of the ClinOps study coordinators’ training program trainees in the various clinical trial knowledge and skill domains.
Eighty-nine participants from 19 countries in Africa and South Korea participated in this cross-sectional study before commencing the training program for study coordinators. We assessed their confidence in several domains, such as clinical trial phases, regulations, ethics, data management, informed consent, project and financial management, internal and external team management, investigational product management, investigational site files (ISF), safety reporting, and patient recruitment and retention on five scales from "1" (Not Confident) to "5" (Extremely Confident). We compared the differences in confidence on various domains using the Kruskal Wallis test and pairwise Wilcoxon rank test with Bonferroni p-value adjustment. We also assessed factors associated with the baseline confidence of the trainees and the contribution of baseline confidence to a successful course completion using logistic regression, and Fisher’s exact test, respectively.
Confidence in conducting a trial complying with ethical principles, informed consent process, securing approval, and managing ISF were relatively high among the trainees. However, the confidence of participants in financial, project, and external partner management, as well as closing out a trial was low. The differences in confidence in the various domains were statistically significant. After the training, the trainees’ confidence was significantly increased in all the domains, though the confidence in the four domains remained relatively low.
Training efforts aiming to augment the knowledge and skills of study coordinators should give better attention to financial, project, and external partner management, as well as closing out a trial to ensure study coordinators with holistic clinical trial knowledge and skills.
Sub-Saharan Africa is the region with the highest burden of malaria and HIV worldwide, being pregnant women the most vulnerable populations. Mefloquine (MQ) for intermittent preventive treatment (IPTp) of malaria in pregnancy has shown to significantly reduce malaria-related adverse maternal outcomes. However, while effective in HIV-uninfected pregnant women, results from an EDCTP-funded placebo-controlled trial assessing the safety and efficacy of IPTp-MQ among HIV-infected pregnant women showed that MQ recipients had a two-fold increased risk of HIV mother-to-child transmission (MTCT) compared to the control group. In this analysis we aimed to determine the antiretroviral (ARV) drug levels among a sub-sample of pregnant women participating in the aforementioned trial by treatment arm.
ARV drug levels were determined by UPLC/MS/MS methodology (LLQ 2.5ng/mL, for all drugs) in venous and cord blood samples of 249 pregnant women enrolled from 2010 to 2012 in Manhica, Southern Mozambique.
No significant differences in the maternal and foetal levels of nevirapine (NVP), lamivudine (3TC) and zidovudine (AZT) were found across groups. However, maternal levels of NVP tended to be decreased in MQ recipients compared to the placebo one among the subset of women transmitting the HIV to their infants (344.64 [558.99] vs 926.4 [619.67], p=0.054).
Our findings suggest potential pharmacological interactions between MQ and NVP that warrant caution in the administration of antimalarial drugs to HIV-infected women on ARV treatment.
The cervicovaginal mucosa is inhabited by an ecosystem of bacteria, fungi and viruses, which likely interact with each other. The vaginal virome may influence vaginal immunity directly, or though modulation of the bacterial component via bacterial-phage dynamics. These interactions may play an important role in sexual and reproductive health outcomes. However, it is predicted that over 60% of the human DNA virome has not yet been identified, and the RNA virome is even less explored, nor has the impact of HIV on the vaginal virome composition been described.
We optimised viral particle extraction from vaginal swabs. We then optimised a Sequence Independent Single Primer Amplification (SISPA) approach to enable deep sequencing of the viral metagenome that decreases the GC and genome size bias introduced by commonly used methods such as Multiple Displacement Amplification and Rolling Circle Amplification, while also yielding a greater diversity of near-complete metagenome-assembled genomes.
SISPA was able to recapitulate almost exactly the relative abundance of a viral mock community. Storing swabs in universal transport media (UTM) directly after collection and treating the sample with a 18G needle prior to viral particle extraction resulted in the greatest yield of viral nucleic acid and subsequent read depth, over storing swabs dry or in a 1:1 dilution of UTM and SM buffer. We have applied this method to vaginal swabs from Sub-Saharan African women with and without HIV.
This work lays the ground work for project TMA2020CDF-3192, which will assess the interaction of vaginal virome and bacteriome in pregnant women with HIV in sub-Saharan Africa and risk of preterm birth.
5-flucytosine (5FC) is used for the treatment of cryptococcal meningoencephalitis (CM) in patients with advanced HIV. The current dosing is four times a day involving high risks of low adherence and not adapted for severely ill patients. To address this, a sustained release (SR) pellet formulation was developed. Two PK studies in healthy subjects were performed, evaluating the immediate release (IR) and SR formulations. To estimate the SR formulation exposure of 5FC in patients, PBPK modelling was applied.
A healthy population was generated in PK-Sim [3,4] and modified to include the following disease components: 1) increased (20%) intestinal permeability as a consequence of "leaky" intestine, 2) decreased (20%) intestinal permeability as a consequence of damaged microvilli intestine, 3) diarrhoea due to faster transit time in small intestine (20%) and large intestine (50%), 4) diarrhoea due to higher water volume in large intestine (50%) and 5) severe malnutrition.
The main risk in exposure with the SR formulation compared to IR formulation is for diarrhoea caused by fast transit time, resulting in a 10% lower ratio (SR/IR) exposure compared to a healthy population. This can be explained by the shorter time available for absorption in diarrhoea, affecting the SR formulation to a greater extent than the IR formulation.
Switching from an IR to SR formulation for the treatment of CM is not predicted to impact exposure in a patient population, except for patients with fast transit diarrhoea.
Funding: This project is funded by the EDCTP2 programme supported by the EU, with additional funding from the Swiss Agency for Development and Cooperation (SDC), MSF International, and other private foundations and individuals. The findings and conclusions contained herein are those of the authors and do not necessarily reflect positions or policies of the aforementioned funding bodies.
To fight neglected tropical diseases (NTD), clinical trials implemented in endemic settings are crucial. This requires high standards of Good Clinical Practice (GCP) to ensure participant safety and reliable data. Yet, the local implementation can be challenging due to limited resources, remote study sites, or inexperienced staff. This study aims at assessing barriers and facilitators to implement GCP in limited resources contexts through the example of the clinical trial freeBILy.
A mixed-methods design was used: quantitative data to measure frequencies and extent of GCP nonconformities were extracted from the trial database, while qualitative data were collected among trial staff (n=30) through in-depth interviews and focus group discussions. A closed questionnaire captured background information of the staff. Statistical analysis with R® includes classification of nonconformities by error type and severity, as well as regression analysis of sociocultural factors associated with nonconformities. Qualitative data are being analyzed following a thematic approach. Triangulation of the data will be performed.
From a random sample of 500 study IDs of enrolled women, a total of 331,349 data entries have been retrieved from the database and organized to proceed with the regression analysis. The informed consents of the same 500 women were manually reviewed. A total of 30 nurses and midwives with a median age of 30 years (IQR: 29, 34) were qualitatively interviewed. The majority were female (77%) with a university degree (100%), fluent in French (86%), and had received GCP training in the last 2 years (97%).
Our preliminary data show that the involved staff were well educated and regularly attended GCP trainings, challenging the stereotype of inexperienced staff in SSA. Further analysis will assess association of specific factors with frequencies and type of nonconformities in order to inform implementation strategies of future trials.
ID93_GLA_LSQ is one of the adjuvanted-recombinant protein vaccines that are in clinical development for the prevention of pulmonary TB. The current composition comprised of two vials, one containing the antigen and one containing an adjuvant, which is‘ bedside mixed’ immediately prior to immunization. Hence, this study developed a strategy for the presentation of the vaccine as a single vial through conjugation and lyophilization. The study also evaluated the field-stability of these samples stored at room temperature in five health facilities in Nigeria.
Lyophilization process was developed to have a single vial of co-mixed(coVL) and conjugate(ConjVL). The physicochemical stability and biological activity stability were evaluated for three months at 4°C and 37°C. The parameters evaluated include cake quality and melting point for the powder, while the reconstituted liposomes were assessed for liposome reformation, particle size, GLA and QS21 concentration and the integrity of ID93. The samples were stored in five health centres to assess the stability of the formulation outside cold chain for nine months.
The assessment of the stability parameters for coVL and ConjVL, showed that they were stable at 4°C and 37°C. Moreover, the two formulations maintained their biological activity at the two storage conditions for three months, however, the conjugated formulation still maintained higher memory T cell cytokine recall response in the in vitro whole blood assay as observed with the liquid formulation. The two formulations stored at average daily room temperature of 29.3–30.7°C in five health centres across South -Western geopolitical zone of Nigeria maintained the cake quality and melting points for the nine months with less than 20% reduction in GLA and QS21 across the sites and the particle size growth was also less than 50%.
This work presents development of thermostable adjuvant-containing subunit tuberculosis vaccine in developing country.
Funding: This work received funding support from EDCTP
Fc gamma receptors (FcR) are cell surface glycoproteins that bind to the Fc portions of immunoglobulin IgG antibodies to elicit diverse effector functions. Polymorphisms in different FcR genes have been associated with HIV infection and vaccine trial outcomes. Some studies have suggested that FcRIIa may be a marker of latent reservoir size, however, this remains controversial. Hence whether FcRIIa and other Fc receptors have functional consequences on the size or reactivation capacity of the reservoir needs to be investigated.
In this pilot study, single-nucleotide polymorphisms (SNPs) in FcRIIIa, FcRIIa, and FcRIIb genes were determined by Sanger sequencing in 50 HIV-infected ART-suppressed individuals. HIV reservoir size was determined by quantifying total HIV DNA (vDNA) and cell-associated unspliced (US) HIV RNA by qPCR. Association analysis was performed using three coding SNPs, one per gene (FcRIIIa-rs396991, FcRIIa-rs1801274, and FcRIIb-rs1050501).
The median reservoir size as estimated by vDNA copy number was 116 (range, 1 - 5798) copies/million cells and US RNA was detectable in 15 out of the 50 samples. Our analysis found the median reservoir size was almost 3 times larger in males compared to females who are suppressed (p=0.038).
Reservoir size was observed to be larger in younger patients compared to those older, however, not statistically significant. However, there was no significant associations between the FcR SNPs and HIV vDNA or US RNA. Studies in larger cohorts are necessary to explore associations between FcR polymorphisms and HIV reservoir.
Funding: EDCTP-AREF TMA2018PF-2535
Current programs to control schistosomiasis mainly target school-aged children and rely on mass drug administration centered on primary schools. Alternative drug distribution platforms need to be identified to ensure equitable access to the potential new treatment option for pre-school aged children, once registered.
The Paediatric Praziquantel Consortium has developed an operational research program with the aim to identify and describe robust yet flexible drug distribution platforms and delivery modalities that can easily be adapted to different settings. Called ADOPT program, the approach includes a rigorous acceptability and perception assessment as basis for small-scale pilot studies to evaluate and compare potential delivery platforms and access strategies in terms of feasibility, costs and coverage. Insights and lessons learnt from this phase will inform and guide the roll-out of the most promising approaches.
Working with partners in three countries, social science studies were already conducted to establish a baseline of acceptability and perception of paediatric schistosomiasis and its potential new treatment, and to inform the social mobilization strategy. Following the systematic assessment of a range of potential distribution platforms, a restricted number per country has been prioritized. Standard protocols for the pilot studies are currently under development and will be submitted to ethics review committees to start the pilots soon after obtaining a positive opinion from regulatory authorities. Practical aspects including the determination of the correct drug dose in settings without access to scales, drug administration to small children, and training needs are also explored.
High geographic and population coverage will only be achieved if the social mobilization is effective, the drug distribution platform has universal reach, and staff are adequately trained. A toolbox with a selection of tested protocols and guidance documents for their adaptation will facilitate rapid expansion both inside study countries and by other interested partners.
Albendazole (ALB) is used safely for the reduction of Loa (L.) loa microfilaremia. However, there is no official recommendation. ALB could be used routinely in onchocerciasis outbreaks in case of coendemicity with loiasis, in order to make hypermicrofilaremia carriers eligible for mass treatment with ivermectin. The purpose of this study is to compare the efficacy and safety of two ALB treatment regimens in the management of hypermicrofilaremic loiasis.
The study was conducted in the Woleu-Ntem region of northern Gabon. Clinical, haematological and parasitological data were collected. Patients were divided into 3 groups: 2 groups of hypermicrofilaremia (≥8000 mf/mL) treated with 400 mg and 800 mg for 30 days and a control group consisting of patients with low microfilaremia (<8000 mf/mL) treated with ALB 400 mg for 30 days. Microfilaremia and adverse events were investigated and monitored weekly until day 30.
In total, 72 patients were included and followed for 30 days on daily ALB administration. The control group had 38 patients. In the two experimental groups, 16 received ALB 400 mg and 18, ALB 800 mg. L. loa microfilaremia and eosinophilia were measured at day (D) 0, 2, 7, 14, and D30. Clinical data were monitored daily before each ALB dose administration. Microfilaremia decreased at D30 in 82.3% of hypermicrofilaremic subjects to below 8000 mf/mL. No serious adverse events were recorded; 30.0% had clinical manifestations after ALB, and for 20.0%, the main adverse event recorded was pruritus. No difference between the two groups of hypermicrofilaremic patients was observed in the reduction of microfilaremia and the occurrence of clinical manifestations. Eosinophilia decreased in all groups with no difference between two experimental groups.
ALB 400 mg/800 mg for 30 days, decreased significantly reduces microfilaremia/eosinophilia/symptoms and can be used for eligibility of microfilariae carriers for mass treatment with ivermectin.
Sexually transmitted infections (STIs) and bacterial vaginosis (BV) are highly prevalent risk factors for HIV infection, partly driven by genital inflammation. We have developed a novel true point-of-care inflammation lateral flow assay called the Genital InFlammation Test (GIFT). GIFT detects the presence of elevated genital inflammatory cytokines to screen for asymptomatic STIs/BV cases that are missed in settings where syndromic management is practiced. Novel point-of-care tests (like GIFT) must benchmark their performance against the guidelines specified by the WHO’s REASSURED criteria, which includes being equipment-free. This study compared the performance of human eye reading of the GIFT device to an automated device reader.
Bio-banked lateral vaginal wall swabs collected from 10 women were tested for the presence of inflammation biomarker bands (IL-1alpha, IL-1beta) on GIFT devices, which were visually assessed by two independent researchers for band intensity (using G-scores between 0–10). Visual inspection of G-score band intensity was benchmarked against cytokine concentrations measured by commercial ELISA. G-score visual assessments were compared with band intensity measurements using an automated device reader (AXXIN-AX-2X-S™).
Significant concordance was observed between visual (G-scores) for IL-1alpha and IL-1beta and automated reader intensities (rho=0.96, p<0.0001 and rho=0.89, p=0.0003, respectively). However the automated reader enabled test line detection at lower cytokine concentrations (<300pg/ml) than visual inspection. A three-country field study of the GIFT device in 675 women is currently being conducted in South Africa, Zimbabwe and Madagascar. Data from real world use of the GIFT device will confirm the value of including an automated reader in result interpretation.
This laboratory evaluation of the GIFT device performance, assessed visually or using an automated reader suggests that the reader may offer a sensitivity benefit over visual reading at lower vaginal cytokine concentrations, while accuracy will be comparable at higher concentrations.
Timely and appropriate diagnosis and treatment are key to reduce tuberculosis (TB) mortality, morbidity and prevent transmission. However, almost half (4.3 million) of the 10 million annual TB cases remain undiagnosed. Incorporating patients’ preferences when implementing of a point-of-care (POC) strategy for TB diagnosis may facilitate scale-up and impact. This qualitative study explores the values and preferences of patients, healthcare providers and decision makers regarding a POC TB diagnostic strategy using the Molbio TrueLab platform in Mozambique and Tanzania.
We conducted semi-structured interviews with patients (20–24/country), professional users (laboratory staff, nurses, clinicians, 10/country) and decision makers (3/country). Direct observations of the testing procedures and usability surveys in staff operating the platform were also conducted.
Preliminary findings show that Molbio TrueLab platform and TB assays are easy to use (System Usability Scale score= 82.5/100). During observations, the most frequently error was forgetting to check for internal control line of the cartridge (n=6/9). Providers appreciated the possibility of identifying TB and rifampicin resistance on site, without having to transport samples for centralized testing. Patients preferred the same-day results and fast initiation of treatment when samples were investigated by Molbio. However, some view waiting longer time for the results as an acceptable trade-off if results are more accurate. While some patients described difficulties producing the sputum sample, most thought that sputum was the only samples which could be investigated for TB. In terms of the diagnostic process, patients valued the support and counselling from staff. Fears of being stigmatized after diagnosis were common.
The Molbio platform and TB assays were perceived as easy to use by health providers, and an alternative for TB diagnosis at the POC that was not just acceptable but also preferred by patients in Mozambique and Tanzania.
Vitamin D deficiency (VDD) and malaria are conditions of public health importance whose burden is still rising among children globally and in sub-Saharan Africa (SSA). Animal studies have found evidence of the association between VDD and various outcomes, including malaria. However, few observational studies quantifying the effect of VDD or vitamin D insufficiency (VDI) on malaria in humans exist. This study aimed to examine the effect of vitamin D on malaria risk among children in SSA.
This analysis utilised data from a prospective birth cohort in Entebbe, Uganda and a community-based cohort in Kilifi, Kenya. Univariate and multivariable Poisson regression with robust standard errors, logistic, and linear regression models were used to estimate the effect of vitamin D on malaria (incidence/risk/antibodies), respectively.
Of the 2493 children analysed, 42.0% had VDD/VDI (25(OH)D levels<75nmol/L). After adjusting for age, sex, iron deficiency (ID) and country, there was some evidence of an association between VDD/VDI and malaria incidence at 6 months following vitamin D measurement (ARR:1.18;95%CI:0.98–1.42;p=0.072). Malaria risk and incidence results were similar. After adjusting for age, sex, ID, inflammation, and cohort, there was strong evidence of an association between VDD/VDI and higher log anti-AMA-1 (Adjusted β:0.25;95%CI:0.08,0.43;p-value=0.004). Some differences in the relationship between VDD/VDI and malaria antibody levels were seen between cohorts.
Low vitamin D levels are associated with increased malaria incidence and P.falciparum antibodies. The results of this analysis were consistent with the evidence from animal studies and did not support the clues found in some existing observational studies. These results suggest that VDD/VDI may play a role in advancing malaria infection, but the malaria antibody results could be due to reverse causality. Further research is warranted to confirm the malaria incidence/risk results and address the direction of causality between VDD/VDI and malaria antibodies using Mendelian randomisation.
Funding: EDCTP
The safety of iron and folate supplementation in young women living in malarious areas, before and during their first pregnancy, is uncertain as both nutrients can alter malaria risk.
Folate biomarkers were assayed by ELISA in sera of 541 never pregnant women (mostly adolescent) enrolled in a periconceptional controlled trial of weekly iron/folic acid supplementation in rural Burkina Faso (Funded by AREF-EDCTP). Of these 315 become pregnant during the trial, with 226 remaining non-pregnant.
For paired samples mean homocysteine and folic acid concentrations increased between both baseline and early pregnancy (p<0.0001), and baseline and late pregnancy (p<0.0001), although B12 concentration only increased by late pregnancy. In those remaining non-pregnant with paired samples (n=133), homocysteine and folic acid decreased between baseline and end of study (respectively 59.0±24.0 versus 56.5±25.8, (p=0.001; and 39.9±8.3 vs 33.7±7.00 nmol/L, p=0.0001, [(t test]). Vitamin B12 concentrations did not change between enrolment and end assessment (189.32±32.83 vs 189.45±32.95 pmol/L, p=0.97, [t test]). Malaria parasitaemia prevalence was 54.0% in pregnant women in early pregnancy and 41.8% in women remaining non-pregnant women at end assessment. In pregnant women mean B12 concentration was lower in those with parasitaemia (170.9± 25.4 vs 181.1± 25.8 pmol/L, p<0.01). In non-pregnant women these values were 34.0 ±6.4 vs 33.2±7.0 nmol/L (p=0.56) for folic acid; 193.5±31.8 vs 189.9±30.9 pmol/L (p= 0.57) for B12, and 53.6±24.4 vs 58.1±28.0 µmol/L, p=0.40, [t tests]) for homocysteine. In pregnant or non-pregnant women folic acid and homocysteine concentrations did not differ by malaria status.
In conclusion, concentrations of folate biomarkers increase from early in pregnancy, with a negative association of malaria parasitaemia with vitamin B12 concentration. In non-pregnant women folic acid and homocysteine decrease at end of study with no association of malaria.
Proteins such as cytokines, chemokines and growth factors play critical roles in biological processes. These act as disease biomarkers in the study of various infectious diseases. Dysfunction or dysregulation of these biomarkers may cause a variety of pathophysiological conditions. Consequently, biomarker profiling and related technologies are essential for biological studies, disease diagnosis, monitoring of treatment response and drug discovery. Many multiplexing platforms are available for the detection of these biomarkers. There is limited independently published information about the reliability of most of the platforms available in the market. The objectives of this study were to assess the abilities of the Luminex, Meso Scale Discovery (MSD) and the Curiox Drop-Array system in the detection of biomarkers in spiked sera.
We assessed the abilities of three multiplex technologies; Luminex, MSD and the Curiox Drop-Array system in the detection of five cytokines, interleukin (IL)-2, IL-6, IL-10, Tumour necrosis factor alpha (TNF-α) and Interferon gamma (IFNg), in the same set of spiked serum samples. Experiments on each platform were performed as recommended by the kit manufacturer. We assessed the concentration of each analyte detected by each platform Vs. the expected actual concentrations.
For samples with known low and high cytokine concentrations, all platforms were able to discriminate between low Vs. high expression, however, the actual concentration for each cytokine varied greatly amongst the three platforms. Our data revealed MSD as the most sensitive amongst the platforms compared, and Curiox as the most suitable for high-throughput multiplexing, when employed alongside a Luminex platform.
Although quantitative differences were found between the platforms assessed, the relative concentrations detected were comparable, showing that all three platforms were suitable for analyzing trends in multiple cytokine profiles. Further studies, including comparison with ELISA are ongoing.
Whole-blood-based transcriptomic methods have limitations, including in the amount of blood required for standard RNA blood collection tubes. This is particularly relevant to individuals with difficulty in providing large volumes of blood, such as children. Furthermore, the cold chain required for storing blood tubes is problematic in field applications and in remote settings. It is therefore important to optimise RNA extraction techniques to allow for the isolation of high quantity and quality RNA from small blood volumes, and samples that are easier to collect and store under field conditions. Thus, the aim was to evaluate the quantity and quality of RNA extracted from small volumes of whole blood including dried blood spots (DBS) using three commercial extraction kits, to determine suitability for future use in RT-PCR-based experiments.
Total RNA was extracted from small blood volumes (500μl, 100μl, 50μl) and DBS samples using the GenElute™ Total RNA Purification, PureLink® RNA Mini, and Tempus™ Spin RNA Isolation Kits. The yield, purity and integrity of the resulting RNA was assessed with fluorometry, spectrophotometry and agarose gel electrophoresis respectively.
An average of 2321 ± 456.30 ng and 336.3 ± 113.6 ng RNA was obtained from 500 μl of blood with the Tempus™and PureLink® kits respectively. Overall, the RNA isolated with both kits were intact and of high quality. RNA isolated from lower blood volumes (100 μl, 50 μl and DBS) using all three kits, was not of sufficient quantity or quality.
Preliminary findings indicate that the quantity and quality of RNA isolated from 500μl of blood using either the PureLink® or Tempus™ kits may be sufficient for downstream transcriptomic analysis. Upon completion, our findings may be valuable in future studies that are conducted in individuals with difficulty in providing large volumes of blood such as children.
Emerging artemisinin resistance threatens the effort to eliminate malaria; artemisinin resistance investigation emphasizes parasites’ genetic modification as the leading cause of treatment failure. But CYP2B6*6 is vital in determining Artemisinin pharmacokinetics hence treatment outcome. Interindividual variability may mediate variable responses to artemisinin therapy among malaria patients.
We recruited 100 symptomatic malaria patients aged five and above; who had P. falciparum infection and prescribed Artemether-Lumefantrine. We established their parasite load change during a 3-day treatment using the quantitative Polymerase Chain Reaction (qPCR) technique. We determined the prevalence of CYP2B6*6 Single Nucleotide Polymorphism among the patients and assessed the relationship with parasitological outcome.
63% of patients had detectable parasites by qPCR, 54% had slow parasite load reduction, and 24% had parasite fold reduction of <100, while 5% of the individuals had > 10000 parasites/µL at day 3. Genotype frequency for CYP2B6*6 was 43% GG, 17%TT and 40% GT. Heterozygosity was associated with slow parasite clearance; P=0.02. The majority of the males were heterozygous.
Most patients had delayed parasite reduction after Artemether-Lumefantrine therapy; this is more prevalent among CYP2B6*6 heterozygous individuals. Delayed parasite load reduction could be due to the slow activation of artemisinin to its active metabolite by CYP2B6*6 heterozygous patients. Such patients will have subtherapeutic levels of the active drug, unable to clear the parasite in the required treatment duration at the recommended dosage of artemisinin. The difference in treatment outcomes between different genotypes indicated that host genetic variability could determine treatment outcomes or confer selection pressure against artemisinin and the partner drug.
Funding: EDCTP2 under Pfkelch13 emergence (TMA2019CDF-2662) through MSc Scholarship.
Schistosomiasis, highly prevalent in tropical regions, affects over 240 million people. Praziquantel (PZQ) is considered the standard-of-care treatment. However, around 50 million preschool-aged children (PSAC) remain untreated in public health programs, mainly due to the lack of a child-friendly formulation. In 2012, the Pediatric Praziquantel Consortium was established to provide a treatment tailored for PSAC.
This work has resulted in the development of arpraziquantel: a novel (oro)dispersible tablet containing L-PZQ, the biologically active PZQ enantiomer. The 150 mg tablets are small, allow precise dosing and have improved taste properties.
The new formulation was developed by Astellas (Japan) and Merck KGaA, Darmstadt, Germany. Farmanguinhos (Brazil) has established drug product production while Universal (Kenya) is preparing for local manufacturing. Phase I, II and III clinical trials have been completed. The latter was conducted in Côte d’Ivoire and Kenya in PSAC (3 months to 6 years) infected with Schistosoma mansoni or Schistosoma haematobium. 288 PSAC were treated with a single dose of arpraziquantel or PZQ. The primary endpoint was clinical cure at week 3.
High cure rates close to or above 90% were achieved in Schistosoma mansoni-infected children at a dose of 50 mg/kg, and in Schistosoma haematobium-infected children at 60 mg/kg. Egg reduction rates were very high (~99%) across all groups. The safety profiles of arpraziquantel and PZQ were similar, and no new safety issues were identified.
Phase III results indicate that arpraziquantel is efficacious, well-tolerated, and shows improved palatability among PSAC. Through Merck KGaA, the Consortium has applied for a scientific opinion from the European Medicines Agency under the EU-M4all procedure for high-priority medicines intended for markets outside the European Union. A positive opinion would facilitate the inclusion of arpraziquantel in the WHO list of prequalified medicinal products as well as regulatory approvals in endemic countries.
Mpox disease formally known as Monkeypox is an ongoing public health emergency of international concern associated with high morbidity/mortality with current global burden of 88122 cases, 1,211 probable cases with 148 deaths and CFR =0.17%. In Nigeria, Bayelsa State reported the first mpox case in 2017. However, there is limited information on the epidemiology of mpox in the State. This study therefore aimed to explore the overall prevalence, trends of mpox disease in Bayelsa State.
We reviewed surveillance data on mpox cases from the Bayelsa State Ministry of Health, between November 2017 to March 2023. Data was cleaned and analysed using Stata (v15.0) while results were presented with Descriptive statistic and charts.
A total of 242 Mpox cases were reported in eight local government areas (LGA) of Bayelsa State, with majority (64.9%) being males, and below age twenty (34.6%) and from Yenagoa (64.2%), the state capital. The mean age (±SD) was 24.4 (±14.7). Meanwhile, 97.9% of patients did not travel out of their LGA in the two weeks preceding symptom onset. The proportion of mpox cases was markedly reduced consistently from 47.8% in 2017 to 6.6% in 2018 and 4.1% in 2020, with an upsurge of 50.0% in 2022. Out of the 242 cases, 43.4% were classified as discarded case, 35.1% confirmed cases, 21.5% suspected cases with 1 death and CFR =1.2%. Most of the cases (84.6%) had primary or no education, and 46.5% were pupil/student engaged in low-income occupations. The disease is symptomatic in majority (86.8%) of the cases, 10.8% of affected patient presented with Cutaneous eruption.
The findings suggest local transmission dynamics propel Mpox mostly among those with low income and limited education. Strengthening laboratory diagnostics and outbreak response capacity is therefore recommended.
Soil transmitted helminthiasis (STH) remains a major public health problem worldwide. WHO has recommended a number of strategies for the control of STH, but due to logistical and financial constraints, only school-based deworming using Albendazole/Mebendazole is frequently used. However, this does not take into consideration other age groups who share similar risk and rate of infection, and the drugs used showed reduced efficacy on certain species of soil-transmitted helminths. Some trials have demonstrated that the combination of Albendazole/Mebendazole and Ivermectin a better potential for the interruption of transmission of STH. However, the introduction of ivermectin in the treatment regimen presents a high risk of occurrence of potentially fatal serious adverse events (SAEs) occurring after administration of ivermectin among individuals heavily infected with loiasis. This study aimed to investigate the proportion of individuals coinfected with STH and loiasis, in order to determine which proportion of the population would be at-risk of SAEs if the regimen including ivermectin was used.
A cross-sectional survey was conducted in 2022 in three health districts (Awae, Akonolinga and Okola) in the Centre Region of Cameroon. Capillary blood and stool samples were collected for the diagnosis of loiasis and STH, respectively. Calibrated thick blood smears were prepared for the enumeration of Loa loa microfilariae in the blood, and stool samples were analyzed by the Mini-FLOTAC and Kato-Katz methods.
Overall, 660 individuals were tested for both loiasis and STH in the three health districts, of which 23 (3.5%; 95%CI: 2.3–5.2) were coinfected. The overall coinfection rate was 5.3% (95% CI: 2.3–11.7) in Okola, 3.9% (95%CI: 2.3–6.5) in Akonolinga and 2.2% (95%CI:0.9–5) in Awae. Of the coinfected individuals, 69.5% (95%CI: 49.1–84.4) had light L. loa infection while 26.1% (95%CI: 12.5–46.5) had moderate infection and 0.04% (95%CI: 0.007–21) had heavy infection.
The risk of developing SAEs remains in the population.
Africa bears the highest double-burden of HIV and malaria worldwide. In 2022, 25.6 million people were living with HIV (PLHIV) and 228 million malaria cases were diagnosed in Africa. Malaria patients co-infected with HIV are considered at a higher risk of failing malaria treatment according to the WHO. This review aims to assess the treatment outcomes following artemisinin combination therapies (ACTs) in PLHIV.
The literature search was conducted up to April 2022 in the following databases: MEDLINE, EMBASE, Web of Science, Cochrane Central, WHO Global Index Medicus and Clinicaltrials.gov. Studies describing any malaria treatment outcomes or antimalarial drug exposure (area under the curve, concentration) in PLHIV treated for falciparum malaria infection were eligible for inclusion.
A total of 26 eligible articles were screened of which 19 studies (2003–2017) from six countries were included in this review; this represented >3,000 malaria episodes in PLHIV across various transmission settings. Antimalarial treatments studied were artemether-lumefantrine [AL] (n=16), dihydroartemisinin-piperaquine (n=7), and artesunate-amodiaquine (n=1); PLHIV were treated with efavirenz (EFV, n=11), nevirapine (NVP, n=9), atazanavir-ritonavir (n=1), trimethoprim-sulfamethoxazole (n=6), lopinavir/ritonavir (LPV/r, n=4), or were untreated (n=3). Compared with no HIV patients, EFV reduced exposure to all antimalarial components (n=2), LPV/r increased lumefantrine exposure (n=1); NVP reduced artemether exposure only (n=2). There was no evidence of increased risk of recrudescence in PLHIV compared to patients without HIV (n=7), but for AL, PLHIV receiving LPV/r appear to have a lower risk of recurrence when compared to no HIV (n=1), or PLHIV on NVP or EFV (n=2).
Limited data on ACT treatment outcomes or drug exposure in PLHIV exist, and the effect of antivirals appears inconsistent in the literature. Considering the heterogeneity in study designs, our findings support conducting an individual patient data meta-analysis to explore the impact of ARVs on antimalarial treatment.
Several host blood transcriptomic signatures have shown promise as tuberculosis (TB) diagnostic candidates, supporting the use of such biomarkers in prototype RNA-based point-of-care tests. Further validation of these signatures across different clinical and endemic settings in relevant patient cohorts is required to ascertain their global applicability. We aimed to evaluate the accuracies of published TB transcriptomic signatures in discriminating TB disease from lower respiratory tract infections (LRI) and latent tuberculosis infection (LTBI) in a low-burden hospital setting.
We evaluated the accuracy of 20 candidate blood transcriptomic TB signatures in diagnosing TB in 86 individuals (18 TB, 19 LRI, and 49 LTBI) recruited at Oslo University Hospital, Norway. Gene expression was measured using the fluidigm microfluidic qRT-PCR platform on Paxgene blood RNA samples collected at inclusion. The diagnostic performance of the signatures was assessed by area under the receiver operating characteristic curve (AUC-ROC).
When a head-to-head comparison of the accuracies of the signatures was made between the study groups (TB vs LRI and TB vs LTBI) similar diagnostic performance was observed for the Sweeney 3-, Francisco 2-, Gjøen 7-, and Roe 3- gene signatures (AUC between 0.78 and 0.89). GBP1 and GBP5 were the most accurate individual genes (AUC ≥ 0.80), differentiating TB patients from individuals with LRI and LTBI. However, new 3- and 5-gene combinations, improved the accuracy in distinguishing TB from LRI (AUC=1.00, Sensitivity and specificity of 100%) and TB from LTBI (AUC=0.99, Sensitivity = 93.3%, Specificity = 97.9%), respectively.
Host blood transcriptomic TB signatures primarily identified in studies from high TB-burden settings showed equivalent diagnostic potential in a low-burden hospital setting. New combinations of transcripts with improved diagnostic accuracy, met the minimal WHO target product profile thresholds for non-sputum-based triage TB tests, and warrant further investigation in larger, prospective, and diverse patient cohorts.
Long-acting therapies combining second generation non-nucleoside reverse transcriptase inhibitors (2Gen-NNRTI) with integrase inhibitor (INSTIs) such as cabotegravir, have demonstrated potent activity in treatment-experienced HIV-infected patients. In our context it has already been shown that less than 1% of patients are resistant to INSTI. However, there is not data on cross-resistance events between first (EFV and NVP) and 2Gen-NNRTI (Etravirine, Rilpivirine,Doravirine). This study aimed to evaluate 2Gen-NNRTI resistance and their susceptibility in patients failing antiretroviral treatment (ART) in Cameroon.
An observational study was conducted at the Chantal BIYA International Reference Centre among patients failing ART from 2020–2023. Genotypic resistance testing was interpreted using Stanford HIVdb; penalty scores of drug resistance were ≥60 (high-resistance), 30–59(intermediate-resistance), <30(susceptible). Acceptable threshold for potential drug-efficacy was set at >50% at population-level.
A total of 670 patients were enrolled including 366 failing first-line (1stGen-NNRTI based) and 304 second-line (protease-inhibitors) regimens. Median viremia was 54889 [9,867–231,470] copies/ml and ART-duration was 17[15–25] months. Prevailing 2Gen-NNRTI mutations were: Y181C (22.24;149/670%) and G190A (18%;120/670). Overall rate of resistance to NNRTI was 88.81% [ with 91% (334/366) failing first-line and 85% (261/304) failing second-line; p=0.03]. Drug susceptibility was 54.93% (Etravirine); 46.87% (Rilpivirine), 40.60% (Doravirine). Following susceptibility profile, patients failing on Efavirenz-based regimens were more susceptible to 2Gen-NNRTI (OR=0.42[0.21–0.84]; p=0.004), while those failing after receiving EFV and NVP were less-susceptible to 2Gen-NNRTI (OR=4.4[1.16–14.81]; p=0.02). CRF02_AG was the prevailing subtype (68.31%), without any significant effect on any 2Gen-NNRTI susceptibility.
After ART-failure in Cameroon, there is a high-level of cross-resistance to 2Gen-NNRTI. However, etravirine retains residual efficacy in half of the population. Etravirine represents the most suitable 2NNRTI for combination with INSTI as part of long-acting ART, pending a stratified approach to identify eligible patients in RLS.
Transitioning to dolutegravir-based therapy in Cameroon has improved viral suppression (VS) rates, known as low-level viremia (LLV) <1000copies/ml. However, there is a growing number of patients experiencing VS with detectable LLV, indicating risk of virological failure. This study aimed to characterize the distribution of LLV and associated factors in the Cameroonian context.
A laboratory-based study was conducted among treatment-experienced patients monitored for HIV plasma viral load (PVL) from January 2020 through April 2022 at the Chantal BIYA International Reference Centre (CIRCB), Yaoundé-Cameroon. PVL was measured using the Abbott m2000RT-PCR. Among patients with LLV, levels of PVL were stratified into 4 cut-points: <50, 50–200, 201–500, and 501–999 copies/ml, with p<0.05 considered statistically significant.
Overall, 14970 patients were enrolled: 72.5% were female; 14219 adults, 466 adolescents, 285 children. By ART-regimens, 3411 were on NNRTI-based, 505 on PI/r-based and 11054 on DTG-based ART. Median [IQR] duration on ART was 36[27–39] months. Overall VS (<1000 copies/ml) rate was 88.8% (13291/14970) (95% CI: 88.2–89.3), and stratification in this population showed 1.5% (207/13291) with 501–999 copies/ml, 3.3% (445/13291) with 200–500 copies/ml, 10.8% (1439/13291) had 50–200 copies/ml, and 84.2% (11200/13291) with <50 copies/ml, p<0.0001. By ART-regimens, detectable LLV (50–999copies/ml) was 13.9% (1540/11054) with DTG-containing versus 14.1% (551/3916) with other ART-regimens, p=0.81. By age, detectable LLV was 13.8% among adults versus 16.9% mchildren/adolescents, p=0.01. Most importantly, the trend overtime of detectable LLV between 50–200 copies/ml increased significantly from 65.2% (534/819) in 2020, 70.7% (678/958) in 2021 and 72.2% (227/314) in 2022, p=0.001.
Even though VS rate appears encouraging, there is a significant increasing proportion of patients with detectable LLV in this DTG-era. Of note, LLV with 50–200 copies appears highly predominant, suggesting a revision of threshold for VS at a maximum of 200 copies/ml in resource-limited settings like Cameroon.
The novel Coronavirus 2019 pandemic brings about overwhelming demographic, social, and economic damage worldwide. Evidence on disease progression (COVID-19) and viral clearance time remain limited in resource limited settings. Such understanding is crucial for public health control measures at both individual and community-levels. We evaluated the viral clearance of SARS-CoV-2 infection and factors associated with positivity duration in COVID-19 cases in Cameroon.
A prospective cohort-study of SARS-CoV-2 positive cases was conducted from March 2020-October 2021 in Yaounde-Cameroon (representing the first-three waves). RT-PCR was carried out on the participants using nasopharyngeal swabs. SARS-CoV-2 positivity duration was evaluated from the first to last positive PCR-test before a negative result. Epi-info V.7.0 and Graphpad Prism Version 6 was used for data analyses with p<0.05 considered statistically significant.
A total of 282 participants were enrolled; mean age was 41±14 years, 62.1% were males, and 15.6% (42/282) symptomatic cases with 59.0% (25/42) having cough. The overall median of positivity duration was 15 [IQR: 9–23] days. Positivity duration was significantly higher in males (16 versus 14 days, p=0.03) and people aged >40 years (15 versus 14 days, p=0.02). Positivity duration was not affected by presence or absence of symptoms (p=0.80) and so significant correlation was found with viral load (r=0.03; p=0.61). Considering baseline (24.7±7.2Ct) and last viral load (29.3±5.9 Ct), the Ct (4.6±1.3) and positivity duration (15 days) revealed a kinetic in viral decay of 0.3±0.087 Ct/day.
In this African setting, the positivity duration of 15 days is in accordance with viral clearance around 2 weeks for optimal confinement at community-level, with men and/or the elderly experiencing prolonged infection. Given the viral decay (0.3 Ct daily), we suggest personalized control periods in accordance with baseline viral loads.
Vaccinated persons are still prone to SARS-CoV-2 breakthrough infection since vaccines do not offer 100% protection. Thus, quick decision-making on identifying high-risk persons prone to COVID-19 breakthrough infection is essential for effective medical care and cost saving. We explore how one can use Explainable Artificial Intelligence (XAI) to create a decision-making tool that can aid medical professionals in detecting patients prone of SARS-CoV-2 breakthrough in South Africa and beyond.
A dataset obtained from an intervention study on volunteers with cardiovascular disease (CVD) risk factors conducted in Cape Town, South Africa, comprising symptoms and feedback from 257 persons — 203 were vaccinated and 54 not — was used for the investigation. Two machine learning algorithms: Deep Multilayer Perceptron (Deep MLP) and the XGBoost classifier were trained on the dataset. The Shapley Additive Explanations (SHAP) was used to investigate the most critical variables influencing breakthrough infection from the ML models’ results. Lastly, a decision-support tool for detecting patients prone to breakthrough infection that leverages the ML model with the best results was created.
The results show that the XGBoost model performed better (F1= 0.86; AUC = 0.74; G-Mean=0.71; MCC=0.49). Body temperature, total cholesterol, glucose level, blood pressure, waist circumference, body weight, body mass index (BMI), haemoglobin level, and physical activity per week are the most critical variables influencing breakthrough infection.
We established threshold values for each of them so that we could classify every new value as either high or low, and used these to construct an XAI model that combines machine learning and rule-based reasoning to predict if a patient is prone to breakthrough and provide a rationale/justification for the prediction made.
Funding: This research was partially supported by a grant from the South African Medical Research Council (SAMRC).
Although all vaccines used in National Immunization Programmes are safe and effective, no vaccine is completely risk-free and adverse events occasionally occur after an immunization. Failure to report adverse events following immunization (AEFI) can lead to death and misconceptions about vaccine safety hence vaccine hesitancy. Alleged vaccine quality and safety issues must be dealt with rapidly and effectively. This study assessed level of knowledge and reporting of AEFI among healthcare workers and caregivers at Mengo Hospital, Kampala.
A health facility-based mixed-methods cross-sectional study design was used. Eligible participants were caregivers of children and healthcare workers. Qualitative data were collected through self-administered questionnaires. Focus group discussions (FGDs) among caregivers and Key informant interviews (KII) among healthcare workers collected data on knowledge and reporting procedures of AEFIs. Level of knowledge of AEFI was assessed using the Likert scale and logistic regression was used to analyse the association of different factors with reporting of AEFI. Qualitative data were analysed manually into themes.
A total of 388 participants enrolled with mean age (SD) of 28.75 (5.65) years and 51.8% were female. Over two-thirds (61.3%) had poor knowledge about AEFIs. Less than half (41.8%) had ever reported an AEFI to the hospital. Unemployment (OR= 1.628), good knowledge of AEFI (OR=1.572), and parity less than four (OR= 2.070) were found to increase odds of reporting of AEFIs. From the 7 KII and 6 FGDs, we found that most healthcare workers and caregivers had good knowledge of AEFIs but the majority had never reported nor knew the procedure for reporting of AEFI.
The reporting of AEFIs was low among caregivers in Kampala. There is need to sensitize caregivers about the necessity to report AEFIs.
Funding: The study was sponsored by EACRR2 which was funded by EDCTP2, Grant number: RegNet2015–1104-EACCR2.
Growing resistance of Plasmodium falciparum to Sulfadoxine-Pyrimethamine threatens the effectiveness of the intermittent preventive treatment during pregnancy with Sulfadoxine-Pyrimethamine (IPTp-SP) in malaria endemic areas. WHO recommends discontinuation in case of ineffectiveness as determined by over 95% and 10% prevalence of K540E and A581G mutants respectively. The objective of this study was to determine the prevalence of molecular markers of P.falciparum resistance to SP in the parasite population circulating in the south of Brazzaville and beyond, in the Republic of Congo.
Two parallel surveys including hospital and community based cross sectional studies were carried out in the south of Brazzaville and beyond (urban, rural areas) between February 2021 and September 2022, to characterize the molecular markers of P.falciparum resistance to SP (dhfr and dhps). Restriction Fragment Length Polymorphism was used for the detection of single nucleotide mutation within the dhfr and dhps genes of the parasite, and detected mutations were further confirmed using Oxford nanopore sequencing platform.
High prevalence of mutations was reported for dhfr gene: N51I (100%), C59R (79.9%), S108N (100%), N164L (0.9%), and dhps gene: A437G (89.5%), K540E (42.4%), A581G (42.1%). The prevalence of the quintuple mutant (N51I+ C59R + S108N + A437G + K540E) and sextuple mutant (N51I+ C59R + S108N + A437G + K540E + A581G) were reported for 32.9% (111/337) and 20.8% (70/337) of the participants respectively while all the seven investigated mutations were reported in only one participant (0.3%). dhfr and dhps mutations were more prevalent in rural compared to the urban areas.
These results indicate high prevalence of mutations within the dhfr and dhps genes of P. falciparum in south of Brazzaville and beyond in the Republic of Congo, which might threaten the effectiveness of IPT-SP in this area.
Monitoring indicators for prevention of mother-to-child transmission of HIV programs (PMTCT) is key to assessing the progress toward elimination of mother-to-child transmission (MTCT) of HIV. Using a patient-orientated innovative strategy based on the second visit in the expanded program on immunization (EPI-2) visit at 6–8 weeks, we assessed PMTCT indicators in Burkina Faso and Zambia.
From December 2019 to September 2021, the PROMISE-EPI study (Clinical Trial: NCT03870438) assessed women attending EPI-2 at primary health care facilities in Burkina Faso and Zambia with their children about their exposure to PMTCT interventions. Women living with HIV viral load was measured using GeneXpert® HIV RNA, and their children were tested for HIV using GeneXpert® HIV Qual.
Overall, 25093 were enrolled from Burkina Faso and 8961 women from Zambia. Almost, all women attended at least one antenatal care visit, the median number of visits was 4 (IQR: 3–5) in both countries. Among Women diagnosed with HIV at EPI-2, 4.5% and 1.7% were not aware of their HIV status, in Burkina Faso and Zambia, respectively. Among those aware of their HIV positive status, 95.8% and 99.2% were on ART in Burkina Faso and Zambia respectively. Among WLHIV on ART, 75% and 79.2% achieved a viral load suppression (Viral load < 1000 copies/mL) in Burkina Faso and Zambia respectively. Infant post-natal prophylaxis was administered from birth until EPI-2 to 60.9% and 89.7% of HIV exposed children in Burkina Faso and Zambia, respectively. In Burkina Faso, only 60/192 (31.3%) of HIV exposed children were sampled for early infant diagnosis and 3 (1.6%) received a result by EPI-2. In Zambia, these figures were 879/1465 (64.0%) and 9.9% (145/1465) respectively.
This evaluation strategy could strengthen program monitoring and help identifying gaps to be addressed on the last mile towards elimination of MTCT of HIV.
Malaria Mass Drug Administration (MDA) is recommended to reduce malaria in low transmission settings, with a target coverage of ≥80%. This study assesses the feasibility of a programmatic MDA (pMDA) pilot implementation in southern Mozambique.
The National Malaria Control Programme implemented pMDA in Chidenguele (Gaza Province), where the estimated population is 59,271. Two rounds of door-to-door distribution (using satellite maps with previously enumerated households (Reveal® platform)) with fixed points were conducted between December 2022 and February 2023. Household coverage was estimated with both district census data and satellite number of expected households. All eligible individuals ≥6 months received a full therapeutic 3-day-course of dihydroartemisinin-piperaquine. Individual data collection was conducted during round 1 (R1), which was changed to aggregated data at the household level in round 2 (R2). Community engagement and human resources were also strengthened between the two rounds. The target number of households to be reached by team/day was 25/30 in R1 and 15 in R2.
When using census data, household coverage (households reached over targeted) increased from 59.4% (8799/14818) in R1 to 94.3% (13972/14818) in R2, while with the satellite estimates, it increased from 62.5% (8799/14075) to 99.3% (13972/14075). Population programmatic coverage (individuals treated over total population) increased from 40.9% (24237/59271) to 69.8% (41347/59271). Treatment rate among present individuals (operational coverage) decreased from 91.3% (24237/26541) to 85.1% (41347/48588).
Collecting aggregated data, decreasing the household target per day per team and using fixed-points at the end as a recovery strategy helped improve operational performance. However, reaching an 80% programmatic coverage is challenging even with high rates of household visitation and operational coverage, mainly due to absences and exclusions.
Funding: This project is funded by the EDCTP2 Programme.
The design of this study was intended to evaluate the use of saliva as a reliable non-invasive tool for the genomic and immunological surveillance of SARS-CoV-2 infection in the Republic of Congo.
During this cross-sectional study, the active infection was determined by detecting SARS-CoV-2 RNA using RT-PCR in 220 paired saliva and oropharyngeal samples (OPS), and by sequencing SARS-CoV-2 genome using the Oxford nanopore technology. The detection of anti-SARS-CoV-2 IgG antibody was done in 148 pair saliva and plasma samples using an in-house developed ELISA, and the reproductivity of the assay based on Saliva were assessed in two independent laboratories.
Overall, saliva (22/220) and OPS (23/220) showed similar rates of viral detection (p= 1.00). The sensitivity and specificity of detecting SARS-COV-2 active infection in saliva were 95.7% (95%CI: 79.0–99.8%) and 100% (95%CI: 98.1–100%) respectively, with the mean cycle threshold values similar to those of oropharyngeal samples (p>0.05). The genome sequencing revealed a mean coverage of 95.5 ± 2.8%, finding omicron as the main variant. The anti-SARS-COV-2 antibody detection in saliva showed a sensitivity of 92.0% (95%CI: 85.0–96.0%) and specificity of 93.3% (95%CI: 78.0–99.2%) compared to plasma. There was a high agreement in antibody detection results between FCRM and ITM laboratories (Cohen’s kappa 0,94; p = 0.0001).
These findings demonstrate that saliva can be used as a surrogate to Oropharyngeal or plasma for surveillance of SARS-COV-2 infection in the Republic of Congo.
Mass Drug Administration for malaria consists of administering antimalarial drugs to the whole population in a defined area, irrespective of infection status. The World Health Organization recommends it to reduce transmission in low transmission settings. To ensure that MDA is effective, at least 80% of the target population should be reached.
Between December 2022 and February 2023, two rounds of programmatic MDA (pMDA) were implemented by the Mozambican National Malaria Control Program in the administrative post of Chidenguele (Manjacaze district, Gaza province), where the estimated population is around 59,000. To evaluate the coverage, adherence, acceptability, adoption and appropriateness of the pMDA delivery strategy, a cross-sectional community survey and a survey to the health staff involved in the implementation were conducted.
Data routinely-collected during the pMDA show that population programmatic coverage (individuals treated over total population) was 69.8% (41347/59271), while according to the cross-sectional survey, 73.9% (569/770) of respondents reported having taken the medication. 84.2% (648/770) of community respondents thought that the campaign could help decrease malaria in the community, and 91.3% (703/770) thought that taking the medication regardless of malaria infection was acceptable. Among community respondents that were aware of the pMDA campaign (686/770), 76.5% (525/686) stated they knew about its objectives. 88% (22/25) of surveyed health staff reported to be very willing to collaborate and comply with procedures and with the intervention prior to the start of the implementation and 73.1% (19/26) agreed that the designed intervention was adequate to meet the objectives of the program.
Overall, the pMDA delivery strategy was accepted by both the community and the implementers. Community and stakeholder engagement were essential to ensure a successful campaign implementation.
Funding: This project is funded by the EDCTP2 Programme.
Plasmodium infection remains a public health issue in endemic areas, with anaemia being one of the main indicators of disease morbidity. In areas co-endemic for helminths, both infections very often occur in the same individual and interactions have been reported. The present analysis aimed to assess the effect of helminth infections on haemoglobin concentration in Plasmodium infection in a population of children and young adults living in rural areas of Gabon.
The study was longitudinal where participants were followed for six months. Urogenital schistosomiasis (UGS), soil-transmitted helminths (STH), and filariasis were assessed by microscopy at baseline and at month six. Plasmodium infection status and haemoglobin concentration were assessed at month six, only. Anaemia was defined using the recommendation of the WHO.
A total of 217 participants were included in this analysis. Of them, 73% (160, 95%CI: 67–79) were anaemic. Anaemia was associated with Plasmodium infection (p-value=0.04), but not with UGS (p-value=0.12), STH infection (p-value=0.16), and filariasis (p-value=0.59). Adjusted to age, sex, ascariasis, and UGS, participants with Plasmodium infection had an odds of 2.44 (95%CI: 1.07–6.13) of anaemia, compared to those without Plasmodium infection. In the stratified analysis on STH and adjusted to age and sex, participants with Plasmodium infection had a significant decrease in haemoglobin concentration as compared to those without (β= -0.90, 95%CI: -1.36 – -0.43, p-value<0.001) among participants infected with STH, while no difference was observed between both groups among participants negative for STH (p-value=0.051).
Our results reveal a high prevalence of anaemia making it a serious public health issue in our community. We found Plasmodium infection as the main parasitic infection associated with anaemia in our community, with STH infections showing a protective effect on the reduction of haemoglobin concentration in Plasmodium infection.
Funding source: Deutsche Forschungsge-meinschaft (DFG), grant number: MO 1071/12–1.
Few early-career researchers are working on rights-based knowledge production in sexual and reproductive health (SRH) in francophone Africa. To accelerate the generation and dissemination of evidence in the field of SRH and rights, young researchers need support. One form of support is the setting up of a mentorship program embedded in a researchers’ network.
We designed and implemented a mentorship program aiming to produce six original articles in SRH with a right-based perspective. Articles accepted were published in a special edition of a specialized peer review journal. The process included design and strategic dissemination of call for applications, three-stages selection process of mentees, identification of mentors according to the research topic of the mentees and building of six mentor-mentee dyads. It was completed by competency-based trainings on scientific writing and advocacy (in-person workshop and webinars), in-person/remote meetings and email exchanges between each mentee-mentor dyad and internal peer-review of manuscripts before submission to the journal.
We selected six mentees (four women and two men) with medical, midwifery, demography and social sciences background. Their mean age was 35.2 and only two published a paper as first author. The addressed topics were related to identity effects of differential gender socialization on first child and marriage aspirations of adolescents, delivery experience, modern contraception use among adolescents and abortion. All the manuscripts are currently in the peer-review process for publication. The research results will be used to support advocacy activities in each context.
This mentorship program provides early-career researchers with research and advocacy skills. The network set up is an enabler for the continuous production of knowledge and its effective use to drive change for the benefit of the region’s communities.
Despite various efforts to control malaria among children, the disease remains a leading cause of morbidity and mortality worldwide. In the Sahel region, including Burkina Faso, seasonal malaria chemoprevention (SMC) using Sulfadoxine-Pyrimethamine (SP) and Amodiaquine has been implemented since 2014. However, introducing this new strategy may lead to the spread of Plasmodium falciparum resistance to SP. This study analyses the mutations in SP resistance genes, dihydrofolate reductase (Pfdhfr) and dihydropteroate synthase (Pfdhps) before and after adopting SMC in Burkina Faso.
Dried blood spots obtained from previous studies conducted in Nanoro from 2010 to 2020 were randomly selected. Out of this selection, 769 Plasmodium falciparum isolates were retained, with 299 collected between 2010–2012 before the SMC adoption and 470 collected between 2018–2020 after the SMC implementation in 2014. The Pfdhps and Pfdhfr genes were amplified using nested PCR, and mutations that confer resistance were identified by sequencing the resulting products.
The prevalence of Pfdhfr triple mutations (CIRNI) increased from 44.4% before the adoption of SMC to 84.4% following its implementation (p<0.0001). There were no mutations at codon Pfdhps 540; those at Pfdhps 581 remained rare and were reported exclusively after the SMC implementation (2.8%). The prevalence of haplotypes observed for the Pfdhps gene did not differ significantly over time. However, the Pfdhps haplotype quadruple mutant VAAKGS recently reported in Nigeria was found only in 2020 (1.4%). The combined Pfdhfr/Pfdhps quadruple mutant IRN/AAKA was the most common and increased following SMC implementation (44.9% vs 16.5%; p<0.0001).
After the SMC implementation, the prevalence of Pyrimethamine resistance markers increased significantly, while no difference was observed for Sulfadoxine resistance markers. Nevertheless, the detection in 2020 of the emerging Pfdhps haplotypes highlights the need to monitor SP resistance continuously.
Funding: PAMAFRICA/EDCTP
Developing a vaccine to prevent Lassa Fever (LF), caused by Lassa virus (LASV), is a World Health Organization priority. We describe preliminary findings of a LASV epidemiologic study in Nigeria to inform preparation for CEPI/EDCTP funded phase 2 LF vaccine trial.
We conducted a community-based cross-sectional study at 10 randomly-selected primary healthcare centers in Abuja Municipal Area Council (n=6) and Ikorodu (n=4). A total of 630 participants aged ≥ 18 years were enrolled between February-September 2022. Socio-demographics, willingness to participate in a future LF vaccine trial, and knowledge of LF were assessed in questionnaires. Blood and urine samples were collected for laboratory analyses, including LASV antibody assays using Zalgen ReLASV Pan-Lassa Combo NP/Prefusion GP IgG/IgM ELISA kits.
Of 630 participants, 434 (69%) were female and the median age was 38 years (interquartile range 28–50). LASV IgG seropositivity was detected in 51 of 176 (29.0%) participants so far tested; further testing is underway. Most participants (87%) were knowledgeable about LF and radio/television was the most commonly reported source of information (63%). Willingness to participate in a future LF vaccine trial was affirmed by 580 (93%) participants and 99.7% (574/576) were willing to provide biological samples. Potential protection from LF was the most common reason for willingness to participate (78%). Among 22 (4%) unwilling participants, the most common reason was fear of harm by the vaccine (36%).
Our findings suggest substantial LASV exposure and eagerness to participate in a LF vaccine trial in two Nigerian locations with previously limited epidemiologic data. Radio and television-based messaging that emphasizes the safety of vaccine trial participation and the potential protective value of a licensed LF vaccine may improve recruitment for the imminent phase 2a LF vaccine trial in Abuja, Nigeria.
In the same month the WHO declared COVID-19 a pandemic (March 2020), the first case was reported in Mozambique, and by April 2023 the country had seen four waves of COVID-19 233,334 with cumulative positive cases and 2,242 deaths. We conducted community-based serosurveys in the Manhica district to assess the evolution of exposure after successive COVID waves.
Four seroepidemiology surveys separated by ~3 months were conducted between May 2021 and June 2022. In each, 1,200 individuals residing in Manhica District were randomly selected from the Demographic Surveillance System, stratified equitably into four age groups (0–19, 20–39, 40–49, ≥60 years). Blood samples were collected and analyzed by commercial Elisa kit (Wantai) for the detection of total antibodies (IgM and IgG).
Overall, 4,579 participants had blood samples collected, of which 3,346 were tested. The prevalence of SARS-CoV-2 antibodies increased over time from 27.6% (184/666) in serosurvey one to 63.6% (595/936) (p: <0·001) in serosurvey two, reaching 91.2% (700/768) (p: <0·001) and 91.1% (1017/1117) (p: 0·941), in the third and fourth serosurveys, respectively. Higher antibodies detection was observed among individuals aged 20–39 years in serosurveys one, three, and four (32%, 96.1% and 94.3% respectively), but age group 40 – 59 years during serosurvey two (66.8%). A high seroprevalence (85.7%; 156/182) was still observed among individuals who had not been vaccinated at the time they were enrolled in serosurvey 4. The pattern of increasing seroprevalence was related to the occurrence of COVID-19 waves.
Our data demonstrate increased seroprevalence levels after each serosurvey from 27% to 91%, showing universal exposure to SARS-CoV-2 of the general population residing in the Manhica District after four COVID-19 waves. High seroprevalence were also observed among unvaccinated and vaccine ineligible (<18 years) individuals reaching over 90% at the last serosurvey.
High burden of Tuberculosis (TB) in Africa justify continued need for development of safe, efficacious, accessible and affordable anti-TB. Paradoxically, the continent contributes <3% of global clinical trial outputs. Lack of appropriate trainings has been cited as important factor. Therefore, this project aimed to strengthen capacity of the fellow and peers in clinical trial designs, operational planning, conducting, management and reporting.
EDCTP funded and linked the fellow to Pan-African Consortium for Evaluation of Antituberculosis Antibiotics (PanACEA) at University of St. Andrews. The fellow and supervisors developed 12 months training plan with five objectives fitting precisely into the ongoing SimpliciTB-OptiRiMoxTB trial to evaluate short treatment regimen for drug-susceptible TB. Intensive field work activities have been conducted at Kibong’oto Infectious Diseases Hospital-Tanzania, followed by National Health Services (NHS) Scotland, Helse-Nord TB-Initiative (HNTI)-Malawi and other PanACEA sites. The fellow attended meetings including PanACEA Annual 2022 meeting and The Union World Conference on Lung Health.
Skills of clinical trial designing and operational planning were imparted during development of OptiRiMoxTB protocol version 1.0. Developed drug management plan provided skills on handling of investigational medicinal products to ensure quality, safety and efficacy. Obtained ethical and regulatory approvals and reflective report on community engagement during clinical trials transformed the fellow on ethical consideration and safety. Reflective report from experiential visits at NHS and HNTI, in-person Good Clinical Trial training and developed Manual of Procedures have imparted clinical trial conducting and management skills. Developed manuscript of OptiRiMoxTB protocol has strengthen fellow’s scientific reporting skills during clinical trials.
The acquired transformative skills prepared the fellow for further sustaining chain reaction-like model of expanding human capital with clinical trial skills for TB and other poverty related diseases through short course trainings of almost 100 peers and personal career development hence increasing clinical trials leadership in Africa.
Inadequate sampling poses challenges in the COVID-19 diagnostic cycle. Nasopharyngeal swabs are gold-standard but often associated with patient discomfort, require trained healthcare workers (HCW), and are resource intensive. The saline gargle (SG) method has proven to be acceptable for respiratory pathogen detection. We performed a prospective cross-sectional study to evaluate the SG method against the nasopharyngeal and oropharyngeal (NO/OP) method in the molecular detection and next generation sequencing (NGS) of SARS-CoV-2 in Botswana.
Eligible participants aged ≥5 years, who were close contacts of a positive case, and/or presented with clinical symptoms of COVID-19, were recruited December 2021- January 2022, and July-September 2022. NP/OP samples were HCW-collected followed by SG collection where participants swished and gargled 5ml sterile 0.9% saline for 20 seconds. Samples collected December 2021-January 2022 underwent nucleic acid extraction and RT-PCR while samples collected July-September 2022 were tested with GeneXpert SARS-CoV-2 Assay. McNemar exact test was used to analyze comparability of testing with significance set as P<0.05.
Post-recruitment, random sampling of 10 lab-confirmed SARS-Cov-2 positive stored sample pairs underwent NGS.
Of 127 pairs, 25 matched samples tested positive for SARS-CoV-2 on both sampling methods. Additionally, SG had 6 false negatives and one sample which was positive but negative with NP/OP. Statistical analysis revealed some evidence of a difference in the detection of SARS-CoV-2 between SG and NP/OP samples (p=0.031). SG showed an overall sensitivity of 81.25% (95%CI 68.8%-96.0%).
NGS was successful in 16 samples, 10 SG and 6 NP/OP. The 5 matched successful pairs revealed similar genomic strains (73–100% relatedness). All samples had mutations of high affinity to ACE2 receptor in the Spike gene suggesting circulation of Omicron variant.
The SG method is a reliable and logistically easier alternative for SAR-CoV-2 detection and NGS to contribute toward efforts of COVID-19 surveillance in Botswana.
Menstrual health (MH) is a public health issue in low- and middle-income countries impacting adolescent girls’ education. This study aims to measure MH self-efficacy and its association with school attendance among girls in Wakiso and Kalungu districts of Uganda.
Participants were Secondary 2 girls enrolled in the ongoing MENISCUS cluster-randomized trial evaluating the impact of a multi-component MH intervention on education, health, and well-being outcomes in 60 secondary schools. Baseline data on demographic and socioeconomic status (SES) was collected through a self-administered questionnaire in March-June 2022. School attendance was measured as a girl missing 2 or more school days during the term due to menstruation, MH self-efficacy was measured using the 26-item Self-efficacy in Addressing Menstrual Needs Scale (SAMNS) with scores categorized into tertiles. Logistic regression was used to assess the association.
There were 3,673 girls with a median age of 16 years, of which 2,123 (55.8%) were day scholars, as opposed to boarding students, and 762 (20.0%) were of the lowest SES. The prevalence of missing 2 or more days in term due to menstruation was 830 (22.6%). Missing school due to menstruation was associated with lower SES (OR=1.93, 95%CI: 1.57, 2.36), being a day student (OR 1.53, 95%CI:1.31, 1.70), being older than 15 years (OR = 1.62, 95%CI:1.38, 1.89), and attending government school (OR = 1.27, 95%CI:1.08, 1.49). Missing school for 2 or more days due to menstruation was strongly associated with being in lower menstrual health efficacy after controlling for SES, age, student type (day/boarding), household size, and school ownership (Government/Private) (OR=1.68, 95%CI:1.39, 2.04, P=0.0053).
Results indicate that lower MH self-efficacy significantly affects girls’ school attendance. Missing school results in underperformance in the curriculum and decelerates education for the girl child. Supporting these girls through menstruation could improve self-esteem and promote school completion.
In low-resource settings, blood culture bottles (BCBs) are often visually inspected for signs of growth. We developed a "Turbidimeter" to objectively assess growth based on the presence of broth turbidity. The first generation Turbidimeter detected growth in four out of ten bacterial species (i.e. three Enterobacterales and one Streptococcus sp.) in simulated blood cultures inoculated with spiked horse blood. Here, we present the results of the second generation Turbidimeter.
Home-made BCBs (30 ml Tryptone Soy Broth with 0.3 mg/ml sodium-polyanethole sulphate) were inoculated with 2 ml of fresh human blood spiked with 20 different microorganisms (i.e. five Enterobacterales, three non-fermenting Gram-negative bacteria, two staphylococci, one Enterococcus sp., four streptococci, two fastidious organisms and three yeast spp). The BCBs were incubated in Turbidimeter modules inside a conventional incubator for 20–96 hours; measurements were done every 30 seconds. Growth detection was based on the decrease of transmitted and increase of scattered light. We compared growth detection between the first and second turbidimeter generation (improved design with new LED and detector).
Growth was detected in 80% of 118 BCBs tested, showing full detection of all enterococci, streptococci, and non-fermenting Gram-negative bacteria (100%), and partial detection of Enterobacterales (84%), staphylococci (88%), fastidious organisms (17%) and yeast (67%). Compared with the first prototype, growth detection improved considerably. Six microorganisms that remained undetected before, were now (partially) detected: 100% growth detection of BCBs with Staphylococcus aureus, Burkholderia cepacia and Pseudomonas aeruginosa and 17% of BCBs with Candida albicans, Haemophilus influenzae and Neisseria subflava.
The second generation Turbidimeter showed improved growth detection (17–100% of BCBs) compared with the first prototype. Field testing will be conducted within the EDCTP2-funded SIMBLE project from May 2023 until end of 2024 in Benin and Burkina Faso, to evaluate performance and ease-of-use for future implementation in field laboratories.
Global efforts to scale-up malaria control interventions are gaining steam. These include the use of LLINs, IRS, Intermittent Preventive Treatment and Test, Treat and Track. Despite these, the drive for malaria elimination is far from being realistic in endemic communities in Africa. This is partly because asymptomatic parasite carriage, not specifically targeted by most interventions fuel transmission. There is a need to use alternative strategies that target asymptomatic parasitaemia. We report the impact of malaria mass testing, treatment and tracking (MTTT) on prevalence of asymptomatic parasitaemia over a two-year period in Ghana.
5800 individuals in 7 communities in the Pakro sub-district of Ghana participated in this study. Community-based health volunteers moved from house-to-house testing participants using RDTs and treating positive cases with ACTs quarterly.
In the intervention arm, the prevalence of asymptomatic parasitaemia significantly decreased from 22.9% (95% CI: 19.8, 26.1) in March 2020 to 6.5% (95% CI 5.9, 7.0) in March 2022 among all the participants. Also, a significant reduction in parasitaemia was observed during the July season 2020 to 2021 (P<0.001). Interestingly, there was no significant decline in asymptomatic malaria during the season of November between 2020 and 2022. In the control arm, the parasitaemia increased from 30.3% (95% CI: 24.1, 36.5) in March 2020 to 41.4% (95% CI: 32.8, 50.0) in March 2022. Similar trends were observed for participants ≤15 years and ≥15 years. In the intervention arm the prevalence of moderate anaemia reduced from 4.2% in March 2020 to 1.2% in March 2022.
This study suggests that implementing MTTT could reduce the prevalence of asymptomatic parasitaemia in children under 15 years of age over time. However, care should be taken when planning MTTT as the asymptomatic parasitaemia prevalence varies across season. There is a need to reduce the times interval between interventions.
Setting up a robust typhoid demographic surveillance system (DSS) in low-resource areas will help in characterizing, and defining priorities and strategies for typhoid control activities such as the deployment of new conjugate typhoid vaccines. The study describes the DSS methodology, data, strengths and use in achieving high vaccine coverage.
Enumeration areas (EAs) were used as the clusters for the Typhoid Conjugate Vaccine Trial in Ghana (TyVEGHA) study. The existing EA maps had two main limitations: they did not capture the structures and the boundaries were not clearly defined. We employed drones to take spatial pictures of the study area and generated GIS maps with well-defined boundaries. With the GIS maps, enumerators located and enumerated every participant in each structure within a cluster. A census form, developed on Commcare running on tablets, was used to capture the demographic, socio-economic and WASH attribute information of participants and households. For purposes of the mass vaccination, each participant in the study area was given a census identification (ID) card.
Overall, demographics of 73,625 individuals (i.e., 55,881 during baseline and 17,744 during the first update) from 15,029 households (13,266 for baseline and 1,764 for first update) were recorded. It was observed that 1,125(1.95%) birth, 343(0.59%) death, 2,219(3.84%) in-migration and 1,101(1.91%) out-migration occurred in the TyVEGHA catchment area between the baseline and first update. The eligible participants for the TyVEGHA trial during the baseline was 22,539/55,881 (40.33%). Due to the robust DSS, we observed a high vaccine coverage rate of 88.36% (20,323) including screen failures. Overall, 4.7% (961 per 20,323) queries were detected and quality control guidelines were used to resolve all queries weekly.
Setting-up robust demographic surveillance in low-resource areas is necessary for improving the dearth of reliable data for planning health and socio-economic interventions and achieving high vaccine coverage rates.
Even though 92% of people receiving antiretroviral treatment (ART) have achieved viral suppression (VS) globally, adolescents with perinatal HIV-infection (APHI) have challenges in sustaining VS, probably due to HIV-1 archived drug resistance mutations (ADRMs). Our objective was to investigate on ADRMs among APHI on VS in Cameroon.
An analytical study was conducted in 2021 among 38 consenting APHI on VS at the Chantal BIYA International Reference Centre (CIRCB) in Yaoundé-Cameroon. Proviral-HIV-1 DNA was extracted from buffy coat, DNA extracts were amplified, purified and sequenced by capillary electrophoresis. Generated proviral sequences were used to analyse ADRMs on HIVdb.v9.0. Molecular phylogeny was performed with MEGA v10x and data were analysed with a significance threshold of 5%.
A total of 30 samples were successfully amplified, of which 28 sequences were obtained and one sequence was excluded due to APOBEC3G mutations. Sex ratio M/F was 3/4; median age was 14 years [IQR: 13–16.5]. Regarding ART, twelve (42.9%) were on first line, and the most common regimens were TDF+3TC+EFV and TDF+3TC+ATV/r; and 64.3% (18/28) were fully adherent. Regarding ART response, 92.9% were at WHO clinical stages 1/2; median CD4 was 642 [IQR: 421–769] cells/mm3; 32.1% (09/28) had undetectable viraemia. The prevalence of ADRMs was 59.2% (16/27), of which main DRMs by class were M184MV/I (25%), T215Y/IL/FS (15.9%) for nucleoside reverse transcriptase inhibitors (NRTIs); K103K/N (25.7%), A98A/G (14.3%) for non-NRTIs; I54V and V82VA (3.7% each) for PI/r. Second line of ART were associated with ADRMs (p=0.001). ADRMs were found in detectable (66.6% i.e. 12/18) versus undetectable viraemia (44.4% i.e. 04/09), p=0.58. Seven HIV-1clades were found, with CRF02_AG being prevalent (67.8%).
Despite VS, APHI harbour ADRMs, which underscore high risks of subsequent ART failure, even with undetectable viraemia. Limiting emerging ADRMs suggest targeting APHI on second-line ART, after previous exposure to NRTI-containing regimens.
Tuberculosis (TB) is the #1 bacterial killer worldwide. Despite of successful antibiotic treatment, exacerbated patients did not regain sufficient lung capacity and develop postTB lung disease (PTLD). We hypothesized, that neutrophils play an important role in disease exacerbation and associated marker can be used for early detection of PTLD.
25 confirmed MDR-TB Patients were recruited, sputum samples were taken over 6 months and analyzed for neutrophil associated proteins by ELISA. TB severity was assessed at baseline and month 6 using spirometry (lung function) and x-ray (lung pathology). Patients were categorized in mild and severe diseased by using Ralph score (threshold 40 pts) or spirometry (threshold FVC<0.85*LLN.FVC or gli.FEV1.zscore<-2).
16 patients (64%) had a stable severe impairment in lung function and no improvement after 6 month was observed. In contrast, x-ray pathology was improving in 10 patients (40%) and remained stable severe in 10 patients (40%). Ralph scores were significantly higher in patients with impaired lung function. Neutrophil associated marker significantly declined under antibiotic treatment. Patients with stable severe impairment have significantly increased MMP8 sputum concentrations at baseline (p = 0.017) and increased concentrations of Calprotectin (p = 0.008), MPO (p = 0.034), ELA2 (p =0.031) and NGAL (p = 0.01) at week 2. In addition, Calprotectin (p = 0.005), MMP8 (p = 0.011) and NGAL (p = 0.03) concentrations were increased in males at month 4, while no sex differences in x-ray pathology was observed.
Early postTB lung impairment was associated with neutrophil proteins in acute TB and elucidate the impact of neutrophils on disease progression and immune pathology. These proteins will be further analyzed as targets for Host Directed Therapies to reduce oxidative stress, tissue degradation, as well as immune modulators to prevent PTLD.
Funding: Funded by German Center for Infection Research
According to WHO only 25% of women in the health workforce are in senior positions. Underrepresentation of women in leadership positions in biomedical research has contributed to gender bias in research questions, study designs, and outcomes. In 2019 IAVI published a report on factors inhibiting women’s careers in STEM in Africa with the Academy of Sciences and developed a framework to enhance gender transformative processes in HIV biomedical research.
Building on its previous work, IAVI conducted an operational study across nine of its partner clinical research centers (CRCs) in Africa to understand the barriers and enablers for growth in leadership in 2022. A gaps assessment was conducted through a cross-sectional survey and key informant interviews of male and female staff from nine African partner CRCs in Kenya, Uganda, South Africa and Zambia.
Out of the 58 respondents, 65.6% agreed that recruitment at their institutions demonstrate gender parity, but the distribution across disciplines does not necessarily represent gender balance. According to 50%, leadership positions at their institutions are representative of institutional gender make-up. 75.8% agreed that their institution would benefit from additional resources and training for on gender equity and inclusion issues. Key influences women researchers’ career choices associated growth in leadership included family responsibilities, socio-cultural biases casting women in supportive roles, unawareness of networking opportunities, and personal perceptions on leadership abilities.
Recommendations from the needs assessment are being used to develop targeted strategies to address structural, institutional, and individual mindsets and promote a gender transformative environment within IAVI’s CRC partner network under the leadership of a technical working group. The strategies will include awareness creation and sensitization in the workplace, targeted programs including coaching, mentorship and peer learning, as well as targeted support to women enhance women’s participation in networking and learning opportunities.
Dolutegravir (DTG) containing antiretroviral regimen (ART) has been rollout for pregnant and breastfeeding women in Ethiopia since April 2020. However, no data was reported on the new regimen’s pregnancy and birth outcome safety.
A retrospective cohort study was conducted in 14 hospitals across Ethiopia. Data were collected from the routine prevention of mother-to-child HIV transmission recording charts and participant medical charts. Eligible participants were HIV Positive pregnant women enrolled in the PMTCT care and later their infants. The primary outcomes were any adverse pregnancy outcome (abortion, intrauterine fetal death, preterm birth, and maternal death) and any adverse birth outcome (stillbirth, early neonatal death, low birth weight, infant death).
A total of 2653 pregnant women enrolled in the PMTCT care. Among these, 38 (1.5%) of the pregnancies end up with abortion, 10 (0.4%) intrauterine fetal death and 20 (0.8%) gave birth to a dead fetus. Among the live births, 5 (0.2%) newborns died before one month of age, and 8 (0.4%) died after one month. There were two maternal deaths, one before and one after birth, due to obstetric complications. 87(4.9%) and 80(4.7%) of the women gave birth before 37 weeks of gestation and <2500 gm birth weight, respectively. 55.6% and 29.3% of the women used DTG and efavirenz-containing ART regimens for PMTCT, respectively. The remaining 15.1% used other ART regimens. The rate of adverse pregnancy outcome was significantly lower (p<0.002) among women who received a DTG-based ART regimen (2.2%) than efavirenz based (4.7%) or other ART regimens (9.4%). The rate of adverse birth outcome was lowest (p=0.059) for DTG (4.7%) compared to efavirenz- based (5.1%) or other ART regimens (6.5%).
DTG-containing ART regimens for pregnant women has a better pregnancy and birth outcome safety profile than efavirenz-based or other ART regimens.
It is acknowledged that Human Infection Studies (HIS) can accelerate discovery of promising therapies, but this particular research design presents significant ethical, social and cultural challenges, particularly on LMICs. Over the last eight years, embedded social science and ethics research on ongoing malaria HIS examine some of these contextually sensitive challenges. We conducted an embedded social science study in an ongoing malaria vaccine efficacy trial within a HIS in coastal Kenya to further document how experience of participation varied across different malaria HIS.
We conducted 3 focus group discussions and 20 interviews, with 38 male and female HIS participants after vaccination, and during residency, between October 2022 and February 2023. Voice recordings were transcribed, translated, and analyzed using thematic analysis.
HIS volunteers reported a range of previous benefits and burdens of study participation. In general [during the in-patient stay], there was raised anxiety around COVID-19 testing, where positivity was an exclusion criteria, considering the need to observe and mitigate for prevention measures such as physical distancing and exit from study participation. Although weekly payments were preferred, their disbursement had logistical and administrative delays and requirements that resulted in strained relationships between participants, family members and the study team. Similar to previous studies participants appreciated using funds from the financial compensation for immediate household needs during the in-patient stay, access to medical screening and general care during in-patient stay.
In this preliminary analysis, we highlight the need for HIS teams to carefully consider, striking a balance between potential burdens vs benefits, in the design and conduct of studies, while also being proactive in documenting and responding to unanticipated issues emerging during the study that could affect study participants wellbeing.
Antiretroviral therapy (ART) has improved the survival of people living with HIV (PLWH). With improved lifespan, there is increased risk of Non-communicable diseases (NCDs), notably Chronic kidney disease (CKD). This study aims to determine CKD’s prevalence and associated factors among ART-naïve PLWH in Nigeria.
This is a secondary data analysis of ART naïve PLWH enrolled over six years (2014 – 2019) at a large treatment center in Lagos. Data collected include sociodemographic characteristics, weight, height, concurrent co-morbidities (hypertension, diabetes mellitus, and tuberculosis), and HIV-specific factors (WHO clinical stage, viral load, and CD4 counts). CKD was defined as an estimated glomerular filtration rate less than 60ml/min/m2 using the three equations [Body surface area corrected Cockcroft Gault (BSA-CG), Modification of Diet in Renal Disease (MDRD), and Chronic kidney disease Epidemiology Collaboration (CKD-EPI)]. Ethical approval was obtained before the study commencement.
A total of 2782 PLWH were included in the study, with a mean age of 37.9 (± 9.8) years. A significant proportion of study participants were females (62.2%), had at least secondary school education (58.8%), were married (54.8%), employed (85.7%), and did not consume alcohol (76.6%). Hypertension (21.1%) and tuberculosis (6.1%) were the predominant co-morbidities. A significant proportion of participants were in WHO stages 1 or 2 (55.5%), had CD4 counts less than 500 cells/mm3 (75%), and were virally suppressed (71.7%). The age-standardized prevalence of CKD was 10.0% (8.6 – 11.4), 17.2% (15.4 – 19.0), and 13.1% (11.5 – 14.7) using the BSA-CG, MDRD, and CKD-EPI equations, respectively. Increasing age and anaemia were found to predict the presence of CKD, irrespective of the equation used.
The prevalence of CKD is relatively high, and age and anaemia were significant predictors. Therefore, comprehensive care is needed to ensure close monitoring of PLWH for CKD and associated predictive factors.
Lassa fever (LF) is a viral haemorrhagic fever responsible of 5000 deaths per year in West Africa, with in-hospital mortality at 12%. Ribavirin is the only treatment available with worrying toxicity, questionable efficacy and low access because of its high cost. Consequently, there is an urgent need for new drugs to treat LF patients.
The INTEGRATE study is a platform, multinational, multicentre, sequential, seamless phase II-III, controlled, randomised, superiority trial in open-label parallel arms. Its primary objective is to compare the efficacy of each Investigational Medical Product (IMP) to Standard of Care Drug (SCD) to prevent death or organ failure in hospitalized patients with confirmed LF. The primary endpoint is the proportion of patients presenting no clinical aggravation between D0 and D14. All hospitalized patients, including pregnant women, are eligible for enrolment. The total follow-up period is 28 days. Three interim analyses are planned, with a total study population of 218 patients per arm. A co-sponsorship will be assumed by ANRS-MIE and the Irrua Specialist Teaching Hospital (ISTH).
Trial inclusions will begin in Nigeria in April 2024 at the Federal Medical Centre Owo and at ISTH. Other West African sites (Liberia, Benin, Guinea and Nigeria) will join the platform as they complete a site preparedness program currently undergoing. The first IMP to be evaluated will be the repurposed drug Favipiravir, compared to the SCD Ribavirin. The second IMP will probably be the antiviral ARN 75039, which has shown promising results in pre-clinical phases and is currently in phase I evaluation.
The ribavirin treatment for LF is still debated in term of safety, efficacy and affordability. The INTEGRATE study will provide evidence on new drugs efficacy in order to treat patients and reduce the burden of LF.
Funding: Acknowledgment to EDCTP for funding this study.
Early HIV testing and treatment is crucial to the survival and long-term well-being of children and adolescents living with HIV. In Sub-Saharan Africa, the risk of HIV transmission and infection among children and adolescents, especially young girls is high. Tanzania adopted the test and treat, where all children and adolescents who tested positive for HIV are initiated into care, though adherence to medication and viral suppression is challenging. Strategies to overcome adherence challenges include education provisions at the clinics. In this study, we assessed the educational content provided, the needs of children and adolescents, and its impact on viral load suppression (VLS).
A cross-sectional study was conducted among 286 children and adolescents living with HIV on ART in Kilimanjaro, Tanzania. Socio-demographic characteristics, clinic educational contents, and viral load results were collected using semi-structured questionnaires. Numerical and categorical variables were summarized using descriptive statistics. We compared the educational contents and adherence with VLS using chi-square tests to find the difference between groups.
Among 286 participants recruited: 142 (33.3%) were children and 143 (33.4%) were adolescents. Their median age was 9 (7–12) and 18(16–18), and there were 145 males and 141 females. Among 101 who received education content at the clinics, 68(67%) received education on the importance of taking medication and improving adherence. Of those who received adherence education 48(71%) had VLS while 22(69%) of those who never received adherence education were suppressed(P=0.852). Other 141 children and adolescents reported needing educational seminars at the clinics on adherence, safe sex practices, reproductive health education, and entrepreneurship.
Continuous education provision at clinics is vital to improve health and adherence among children and adolescents. Further strategies to incorporate health education in clinics should be implemented even with little evidence of improving VLS from this study.
Recently, WHO has recommended expansion of the malaria preventive chemotherapies to include intermittent preventive treatment of school children (IPTsc). However, there is concern due to the emergence and spread of partial artemisinin resistance based on PfKelch13 mutations in Eastern Africa. This study was conducted to determine the baseline prevalence of molecular markers of artemisinin-based combination therapies (ACTs) and Sulfadoxine-Pyrimethamine (SP) resistance prior to implementation of IPTsc intervention in a highly malaria endemic area.
Pre-intervention assessment of the prevalence of molecular markers of artemisinin, partner drugs, SP resistance and Histidine Rich Protein 2/3 (HRP 2/3) genes deletion was conducted in Handeni and Kilindi districts from July 2020-December 2021. The districts implemented programmatic IPTsc trial using Dihydroartemisinin-Piperaquine. Dried Blood Spot were collected from children (5–15 years). DNA was extracted from malaria positive samples using commercial kits. NGS sequencing was used for the analysis of molecular markers.
Out of the SNPs detected at low frequency in the Pfkelch13 gene (A578S, K568T, N489Y), none have been validated as molecular markers of artemisinin partial resistance, majority 95.5% (340/356) was the wildtype. The majority of Pfcrt haplotype (n=356) was CVMNKTHFIMCGI (75.5%), other occurred at low frequency, CVIETTHFIMCGI (11.8%), CVIETTHFIMCGT (7%), SVMNTTHFIMCGI (0.8%), SVMNTTHFIMCGT(2.2%). Pfmdr1 haplotypes (n=355) NYSND (71.5%) and NFSND (20.6%) were predominant; others were at low frequency. Quintuple Pfdhfr-Pfdhps haplotypes (n=134) was at high frequency (70.1%). Parasites with HRP2 and 3 gene deletion was detected in 4.5% (15/335) and 20.9% (70/335), respectively.
The lack of validated artemisinin resistance markers is reassuring and confirms targeted areas are suitable for malaria chemoprevention implementation. The baseline assessment is essential in implementing drug resistance monitoring during scaling up of the IPTsc intervention.
Funding: EDCTP-TMA2018CDF-2398 and co-supported by Global Fund, French Government, French Parasitology Alliance for Health Care (ANR-11–15 LABX-0024-PARAFRAP) and University of Strasbourg (IdEX 2022).
Schistosomiasis is a waterborne disease with high morbidity in Sub-Saharan Africa countries, including Madagascar. Mass drug administration is the main public health control strategy for the disease. Even though recently recommended to all age groups and pregnant women, school-aged children are most targeted due to a lack of prevalence data on other vulnerable populations, including pregnant women. This study has the objective to estimate the prevalence of Schistosome’s infection in pregnant women in the highlands of Madagascar to inform the control strategies in the country.
This cross-sectional study was conducted using baseline data on pregnant women enrolled in a cluster randomized controlled trial freeBILy (fast and reliable easy-to-use-diagnostics for eliminating bilharzia in young children and mothers). Women were recruited between April 2019 and February 2020 at one of the 42 included Primary Health Care Centers when attending routine antenatal care services during the second or third pregnancy trimester. The urine-based UCP-LF-CAA (Up-Converting Phosphor – Lateral Flow) test was used for the detection of Schistosome infections. The prevalence was estimated for the overall sample and stratified by women characteristics.
A total of 4328 urine samples were collected. Of these, 55.9% [CI95%:53.6–58.2] were positive for Schistosome’s infection. The prevalence of Schistosome’s infection was 55.0% [CI95%:52.9%-57.0%] among pregnant women living in rural settings, 62.2% [CI95%:53.3–70.4] among those with no formal education, and 54.4% [CI95%:52.2–56.6] among those working as farmers. The prevalence increased with age, ranging from 51.6% (CI95%:48.7–54.4) among 16–19 years old to 62.3% (CI95%: 59.4–65.1) among 30–49 years old.
Our study shows a high prevalence of Schistosome’s infection among pregnant women in the rural highlands of Madagascar. Public health interventions including pregnant women are urgent to progress toward the elimination of schistosomiasis as a public health problem by 2030.
BK-SE36/CpG is a lyophilized formulation of recombinant Plasmodium falciparum serine repeat antigen 5 adsorbed to aluminium hydroxide gel and reconstituted with the TLR9 adjuvant, CpG-ODN (K3). In the primary study in malaria-exposed adults and children living in Burkina Faso, the vaccine showed acceptable safety and immunogenicity profile. The 5–10 years old cohort was chosen for a follow-up study to evaluate the long-term persistency of the immune response.
In the primary trial, participants were randomized to receive three doses of either BK-SE36/CpG or the control vaccine at 0, Week 4 and 16. The trial was completed in January 2020 (Day 365). The follow-up study consisted of a single visit conducted 3 years after enrolment (~24 months following D365). All children who participated in the 5–10 years-old cohort were invited for a short medical examination and a blood sample was collected for parasitological and immunogenicity measurement.
44 children out the 45 in the primary trial provided consent for the follow-up study. The proportion of children with detectable anti-SE36 IgG titres in the BK-SE36/CpG arm as compared to the control arm remained high (82.8% vs. 46.7% in control group). The differences in the geometric mean of anti-SE36 IgG titers were statistically significant for vaccine arms at any timepoint: D140 (4 weeks after Dose 3: p<0.001), D365 (p<0.001) and Year 3 (p=0.039). Compared to baseline, antibody titres were 60 and 3.6 times higher at D140 and Year 3, respectively.
BK-SE36/CpG induced high level of antibody responses in 5–10 years-old. The antibody response persisted/or remained high at Year 3. There were some indications that the antibody response can be boosted by natural infection, which may explain the sustained level of antibody titres obtained in this follow-up study.
Cervical cancer is the commonest cancer of women in Uganda. Over 80% of women diagnosed in Mulago a national outpatient and teaching hospital have advanced diseases. Pap smear screening, on an opportunistic rather than systematic basis, is offered free in the gynecological outpatients’ clinic and the postnatal/family planning clinic. One of the objectives of the study was to obtain women’s knowledge, acceptance and willingness to use self-sampling before the development of the cervical cancer screening intervention with a self-sampling device.
The study employed a qualitative approach. This was conducted among women and community representatives through Focus Group Discussions. This study was conducted in the districts of Kampala, Mukono, and Wakiso in Uganda to obtain women’s input before starting the development of cervical cancer screening intervention with a self-sampling device.
The majority of the women expressed positive responses towards a self-sampling device as a very good initiative and were willing to use it if proved effective. Women share perceived benefits as promoting privacy, saving time spent at the clinic, preventing stigma, and solving transport concerns hence promoting cervical cancer screening. Women further preferred self-sampling over standard practices because of no embarrassment and not seem painful. The preferred ways to inform women about the results of self-sampling included designated counselling rooms at health facilities, on the phone if the results are negative, and one-on-one.
Self-sampling is a crucial initiative and will be welcomed by women however, there is a need to engage, sensitize and involve the target population like policymakers, health workers, politicians, local leaders, policymakers, women leaders (groups), and any other key influential individuals at the community level on the benefits and how to use it before it is rolled out for buy-in.
Women are disproportionately affected by HIV/AIDS in Sub-Saharan Africa. Women’s participation in HIV prevention research is associated with men/spousal influence. The willingness of women to participate in HIV prevention research is challenged by negative influences from the male fraternity as primary decision-makers. The UVRI-IAVI HIV Vaccine Program (UVRI-IAVI) engaged both low and high-risk women in HIV vaccine trials and epidemiological preparedness studies. We document experiences of engaging women in HIV prevention research among fishing communities in Uganda.
From 2002–2022, Good Participatory Practices (GPP) plans provided a framework of activities that aimed at enhancing male support for women’s participation in research. Community gate keepers and male targeted platforms of engagement were implemented. Women supported disclosure packages, community based male champions of women’s participation, and spousal invitations for HIV risk reduction and appreciation at the research site were conducted. Games and sports activities involving men were organized as advocacy platforms with free treatment extended to spouses and children. Tokens of appreciation benefitting families were offered to female participants at different milestones in studies. Myths and misconceptions surrounding women participation were addressed in communities.
Between 2002–2022, improved trends in women enrolment and retention were registered when their spouses were involved. Community based structures for male champions promoting advocacy for women participation in research have been established. General community appreciation for women HIV risk and vulnerability assessment form a basis for their consent to women participation in research with emerging trends in adult advocacy for women’s participation in HIV prevention research.
Advancing women participation in research greatly contributes to the global HIV research efforts for new HIV prevention options.
Monitoring HIV infection rates is needed to guide health interventions and assess their impact, especially in highly vulnerable groups to the infection such as pregnant women. This study describes the trends of HIV infection over 10 years in pregnant women attending antenatal care (ANC) clinics in southern Mozambique.
Data collected as part of three studies undertaken between 2010 and 2021 in HIV-infected pregnant women attending the ANC clinic were analysed. HIV incidence was estimated between prevalence points using two validated methods, one based on mortality rates and the other on survival information after HIV infection. Trends over time were obtained by fitting a second-order orthogonal polynomial regression model.
Overall, 10392 pregnant women attending their first ANC visit were included in the analysis. There was a decrease of the HIV prevalence from 33.9% (95% CI: 30.9–36.9%) in 2010 to 21.4% (95% CI: 19.6–23.2%) in 2021, after a peak of 35.3% (95% CI: 30.1–40.8%) in 2016. Regarding maternal age, prevalence of infection was highest in women aged 20–25 in 2010 progressively increasing in older women being the highest in 35–40 year old women in 2021. HIV infection incidence increased from 3.7 per 100 person-years during 2010–2016 to 10.1 per 100 person-years in 2018–2019, decreased to 6.2 per 100 person-years in 2020–2021.
In the last decade, there was an initial increase of the prevalence and incidence of HIV followed by a downward trend, in this area of southern Mozambique. This encouraging trend may be attributable to the massive expansion of antiretroviral therapy during 2010–2021 in Mozambique. However, the burden HIV remains unacceptably high in this particularly vulnerable group, calling for a need to strengthen HIV preventive strategies to ending HIV/AIDs in the country.
A package of care reduces mortality from advanced HIV disease (AHD) but is poorly implemented. We are assessing feasibility of its implementation, using point-of-care Omega VISITECT CD4 (VISITECT) to identify CD4>200cells/µL or ≤200cells/µL, within two TB-triage studies in South Africa and Lesotho. During near-facility passive case-finding (TB TRIAGE+ ACCURACY, n=1,392), implementers found AHD package implementation feasible, despite challenges. Here, we report feasibility and outcomes during community-based active case-finding within the ongoing TB TRIAGE+ TRIAL (current n=3,304).
All people living with HIV (PLHIV) are offered VISITECT testing, and if CD4≤200cells/µL a urine Alere Determine tuberculosis lipoarabinomannan (TB-LAM) and Immy cryptococcal antigen (CrAg) test. Same-day community initiation of anti-retrovirals, cotrimoxazole and TB-preventive therapy is provided. We assessed procedural compliance and have conducted one group discussion with implementers in South Africa.
Between September 2022-April 2023, in South Africa and Lesotho respectively, 416/1306 (31.9%) and 439/1998(22.0%) of enrolled participants were PLHIV, among whom 16/416 (3.8%) and 20/439 (4.6%) newly diagnosed. In South Africa and Lesotho respectively, 331 (79.6%) and 368 (83.8%) among PLHIV received VISITECT, and in 23 (6.9%) and 32 (8.3%) VISITECT indicated CD4≤200cells/µL. In South Africa and Lesotho respectively, TB-LAM was performed in 23/23 (100%) and 32/32 (100%), and CrAg in 23/23 (100%) and 30/32 (93.8%). TB-LAM and CrAg were positive in 1 (4.3%) person in South Africa. Since April 2023, VISITECT testing was interrupted following batch recall due to suboptimal specificity. The main challenges reported (long procedural duration and results reading of VISITECT) reflected findings from facility-based implementation. However, implementers did not recommend the package after the recall.
During community-based provision of the AHD care package, compliance with most procedures was good. The principal barrier was VISITECT inaccuracy, leading to overreporting of CD4≤200cells/µL and interruption of testing. An accurate, rapid, user-friendly point-of-care CD4-test is necessary for community implementation of this package.
Funding: EDCTP2 grant number: RIA2018D-2498; TB TRIAGE+
The laboratory diagnosis of P. jirovecii pneumonia (PCP) is typically based on microscopic observation of cysts and trophic forms on deep respiratory specimens. In low-income countries, access to bronchoalveolar lavage is limited, particularly for children, and PCP is usually a clinical diagnosis in HIV-positive infants. The use of different laboratory tests on more easily-obtained upper respiratory and venous blood samples could enhance laboratory-confirmed PCP diagnosis.
PCP-PED is an ongoing ancillary-study of the EMPIRICAL trial (#NCT03915366), supported by the EDCTP2 Program and the European Union (TMA2020CDF-3217), which recruits HIV-positive infants hospitalized with severe pneumonia from 8 hospitals in Mozambique. Nasopharyngeal aspirates are processed for direct immunofluorescence microscopy (IFM) to detect P. jirovecii cysts and for quantitative polymerase chain reaction (qPCR) targeting kex-1 gene (Genesig real-time PCR kit). Plasma samples will be used for serologic quantification of (1–3)-β-D-glucan (BG) and Human Krebs Von Den Lungen-6 (KL-6) antigens.
In interim analysis as of March 2023, 61/151 (40.4%) participants recruited have qPCR and IFM results. Median age was 4.0 [IQR, 3.1–6.3] months and 47.5% (29/61) were female. Median HIV viral load and CD4% were 6.0 logs cp/mL [IQR, 5.9 -6.9] and 13.5% [IQR, 10.0–19.6], respectively. qPCR was positive in 45.9% (28/61) and 39.3% (11/28) were on cotrimoxazole prophylaxis prior to hospitalization. The median P. jirovecii fungal load on positive samples was 13,304 copies/mL [IQR, 3,975–61,484]. Among participants with positive qPCR, 25% (7/28) were IFM positive. All participants with negative qPCR results were IFM negative; no participants with positive IFM had negative qPCR results.
Positivity rates for qPCR were higher than for IFM, suggesting superior sensitivity for P. jirovecii detection. Future analysis will focus on qPCR/IFM correlation, BG and KL-6 results, and P. jirovecii PCR fungal loads to attempt to differentiate colonization and infection.
Emergence and spread of P.falciparum strains resistant to artemisinin-based combination therapies (ACTs), poses a significant threat to global malaria control efforts. Therefore, the close monitoring of molecular markers is essential as an early warning system to detect the emergence and spread of resistance. This study aims to assess the prevalence of haplotypes of the Pfcrt, Pfmdr1 and PfK13 resistance markers in isolates from the south of Brazzaville and beyond, in the Republic of Congo.
Between March and October 2021, a cross-sectional study was conducted in rural and urban areas of the south of Brazzaville and beyond in individuals aged 1–83 years with microscopic P. falciparum infection. Parasite DNA was extracted using Qiagen kit and all samples were screened to confirm P. falciparum infection by nested PCR. Restriction Fragment Length Polymorphism was used for the detection of single nucleotide mutation within the Pfcrt, Pfmdr1 genes of the parasite, and detected mutations were further confirmed using Oxford nanopore sequencing platform, while PfK13 gene mutations were investigated by sequencing.
Among 329 samples with confirmed P. falciparum infection, the overall prevalence of the 76T (Pfcrt), 86Y (Pfmdr1) and 184F (Pfmdr1) mutations were 26.7%, 5.3% and 23.9% respectively. The Pfk13 wild type was found in 98.3% isolates while, 1.7% isolates had a mutation in the Pfk13 domain (4 synonymous mutations and 1 non-synonymous mutation, A578S). No significant difference was observed between rural and urban data.
These results indicate low prevalence of mutations within the Pfcrt, Pfmdr1 genes of P. falciparum and no validated Pfk13 mutation associated with artemisinin drug resistance in this study setting, suggesting that ACTs remain effective in the area, but required continuous surveillance.
The Manhica Health Research Center (CISM)is a well-established research center with a strong and consolidated research capacity into communicable diseases prevalent in Mozambique, with particular focus on the main causes of morbidity and mortality. Since its creation, CISM has grown within the framework of a bilateral cooperation programme between the Mozambican and Spanish governments and with support from the Hospital Clinic (HC) and the University of Barcelona (UB) to fight diseases and protect the health of vulnerable populations through research, healthcare and training.
In 2008 the Manhica Foundation was created representing one of the most important events in the development of the Centre because it entitled CISM to a Mozambican legal framework, which facilitates its sustainability and long-term autonomy. In 2010, as part of this strategy for integration and country ownership, the Foundation for Community Development and Eduardo Mondlane University joined as partners. And in 2015, the Barcelona Institute for Global Health replaced the HC and the UB.
One of the key strategies of this partnership to build CISM’s research environment has been the training of staff through the joint development of capacity building and strengthening activities. After 27 years of successful collaboration, a Training Fellowship Programme has been established to train young African graduates wishing to develop their career as researchers; the program provides hands-on training within research projects implemented at CISM. Many training courses and workshops have been developed to train clinical researchers, technicians, data managers, etc.; and networks with other Sub-Saharan African countries have been established to strengthen research capacities (e.g., TESA). All these efforts succeeded in awarding 114 postgraduate degrees in collaboration with North and South universities all over the world for both African and international students: 63 doctorates and 47 master; more than 140 research and training internships; and more than 10 funded collaborative projects.
]]>Pneumonia in children is common worldwide and is associated with significant morbidity and mortality. PediCAP is an ambitious randomised controlled trial (ISRCTN63115131) with the aim of determining the optimal duration and formulation of amoxicillin and co-amoxiclav for children aged 2 months to 6 years with severe community acquired pneumonia in sub-saharan Africa.
Recruitment occurred across thirteen sites in Uganda, Zambia, Zimbabwe, South Africa and Mozambique. Virtual monitoring of recruitment was led by the Medical Research Council Clinical Trials Unit (MRC-CTU). The recruitment target was set to 1100 in the main trial, PediCAP-A, and 120 in the pharmacokinetic substudy, PediCAP-B.
A total of 987 patients were recruited to the main trial between December 2020 and May 2023 (2 in 2020, 216 in 2021, 528 in 2022 and 241 in 2023). Recruitment is currently ongoing. Several external factors affected recruitment speed over this period. The SARS-CoV-2 pandemic led to staff redeployment, local lockdowns which affected patterns of respiratory disease and delayed ethical approval timelines. An Ebola epidemic further exacerbated these challenges in some sites. Changes in national empirical antibiotic guidelines to a non-protocol antibiotic caused a significant reduction in children eligible for recruitment in South African sites. Constant communication between the MRC-CTU and the sites was needed in order to respond to these barriers to recruitment. Additional virtual meetings and updates were scheduled to maintain trial safety during concomitant outbreaks of infectious diseases. Decisions to close sites affected by changing empirical guidelines was made when recruitment was thought to be permanently affected, given that other sites were recruiting well.
Unforeseeable challenges are inevitable in global RCTs. Pragmatic responses to these challenges allows recruitment to trials like PediCAP to continue safely while maximizing the chance of reaching the recruitment target, therefore enabling more impactful results.
Tuberculosis (TB) diagnosis is challenging in children, particularly in infants, contributing to high TB-related mortality. Up to 30% of infants with pulmonary TB have concurrent extrapulmonary disease, with findings that can frequently be detected with ultrasound. A protocol of focused assessment with sonography for HIV-associated TB (FASH) at six abdominal and thoracic positions has shown promise for diagnosis in children and adults, but few infants have been included in published studies.
EMPIRICAL (#NCT03915366) is a randomized, controlled trial funded by EDCTP (RIA2017MC-2013) recruiting HIV-positive infants <12 months hospitalized with severe pneumonia without current/past TB diagnosis or exposure. All participants have Xpert Ultra (stool, nasopharyngeal aspirate) and urine LAM testing, and in an ongoing blinded diagnostic ancillary study at 5 hospitals in Mozambique, FASH is performed. An interim descriptive analysis was done for participants no longer active in the trial as of April 2023.
For the 39 participants included, the median age was 3 months (IQR:3.17–5.13), 48.7% were female, and the median CD4% was 13% (IQR:9.90–17.55). There was ≥1 positive FASH finding in 10/39 (25.6%); all had pericardial effusion 10/39 (25.6%), with focal splenic lesions and ascites also noted in 2/39 (5.1%) and 1/39 (2.6%), respectively. No participants had pleural effusion, focal liver lesions, or abdominal lymphadenopathy. In participants with laboratory-confirmed TB, 42.9% (3/7) had ≥1 positive FASH finding. There were 2 positive FASH findings in 7.6% (3/39) participants, of whom 66.7% (2/3) had laboratory-confirmed TB.
Positive FASH findings were frequent in HIV-positive infants hospitalized with severe pneumonia and even more common in the subset of participants with laboratory-confirmed TB, with pericardial effusion noted on all positive FASH exams. Future analysis will attempt to define which abnormalities on FASH exam are most predictive of TB disease and assess the use of FASH to monitor TB treatment response.
Sexually transmitted infections (STIs) and bacterial vaginosis (BV) are major risk factors for HIV infection and reproductive complications in women living in sub-Saharan Africa, in part because of inflammation associated with these conditions. In women, most STIs and BV are asymptomatic, and therefore not diagnosed in low and middle income countries (LMICs), where etiologic testing is not common and infections are treated based on presence of signs or symptoms (syndromic management). To improve STI/BV case finding in LMICs, we have been developing a true point-of-care low cost lateral flow test based on inflammation biomarkers – called the Genital Inflammation Test (GIFT) – to screen women who would benefit from further etiologic testing.
Through an EDCTP2 RIA2020I funding mechanism, the first version of the GIFT device has been developed in South Africa and is currently being evaluated in three parallel clinical studies in South Africa, Zimbabwe and Madagascar. Field testing is intended to inform optimisation of the final prototype device.
The GIFT-Africa consortium (www.GIFT-Africa.org.za) includes a cross-disciplinary team of experts, including those working on design, optimisation, manufacture and laboratory validation of the first in field GIFT device, clinical performance in each region compared to inflammation biomarkers measured by ELISA, STIs measured using NAATs, and BV measured by Nugent. In addition to assessing sensitivity/specificity in different LMIC settings, implementation of the GIFT device into reproductive health services will be evaluated using: in-depth interviews with patients and healthcare professionals (user experience); discrete choice experiments with end-users; cost, budget impact and cost-effectiveness analyses, and; a DELPHI survey to evaluate key stakeholder recommendations for implementation.
The GIFT device is positioned to cost-effectively increase STI/BV case-finding, but also to improve STI/BV management for women in LMICs, who are at high risk of HIV infection and reproductive complications.
The combination of bedaquiline, pretomanid, moxifloxacin, and pyrazinamide (BPaMZ) provides the shortest duration of treatment required to sterilize mice in relapsing mouse models. SimpliciTB was an open-label study to evaluate the safety and efficacy of 4-months BPaMZ (4BPaMZ) compared to standard therapy (4HRZE/2HR) in DS-TB participants. The trial also included a cohort of DR-TB participants who received 6-months BPaMZ (6BPaMZ). The primary efficacy endpoint was time to culture negative status through 8 weeks; the key secondary endpoint was relapse-free cure at week 52.
The proportions of patients with culture conversion by 8 weeks and of favorable outcome at week 52 (MITT analysis) for 4HRZE/2HR, 4BPaMZ and 6BPaMZ were 47.3%, 84.1%, 85.7% and 93.1%, 85.3%, 83.1%, respectively. The lower rates of favorable outcomes in BPaMZ arms were largely due to higher rates of hepatotoxicity-related trial discontinuations, in which PZA may have contributed.
Using Kaplan-Meier (KM) and Cox PH models adjusting for socio-demographic and clinical factors, we explored the effect on outcome of baseline resistance to pyrazinamide (BRZ) in the DR-TB group of participants.
55 of 152 (36.2%) participants in the DR-TB cohort had BRZ based on phenotypic and genotypic drug susceptibility testing. Time to negative sputum culture for patients with and without BRZ was not statistically significantly different (aHR=0.79, 95% CI (0.54,1.15) p= 0.22). Relapse-free cure was documented in 42/51 (82%) participants with and 68/79 (86%) participants without BRZ (unadjusted Chi-sq test p=0.57).
PZA resistance at baseline did not impact outcomes at week 8 or week 52 in DR-TB patients treated with BPaMZ. A regimen of pretomanid, moxifloxacin with a potent diarylquinoline could present an efficacious and better tolerated therapeutic alternative for DS- and DR-TB patients and should also be explored as a therapeutic option for DS-TB.
An estimated 40% of Nosocomial infections have been attributed to cross-infection via the healthcare personnels’ hands, which could result either directly and/or indirectly from touching contaminated surfaces and patient contact. The COVID-19 pandemic has been a stark reminder of the importance of basic infection prevention measures (hand washing, disinfection/decontamination, Personal Protective Equipment use) when providing patient care. Hence, illustrates the importance of establishing the prevalence of nosocomial contaminants found on fomites from March to August 2020 at the Biology, Emergency Departments and Disposal site of a hospital in Yaounde.
In a cross-sectional study, 736 swabs were collected from trash bins (infectious and non-infectious) and surfaces (tables, sinks, chairs, countertops, desks, patient beds and bed stands) of all aforementioned sites. Inoculated on Mueller-Hinton agar, contaminants were isolated and, identified using Gram staining, classical biochemical tests (oxidase, catalase, coagulase, germ tube and Kligler Iron Agar) and grown on specific media (Hektoen Enteric Agar, Mannitol Salt Agar and Potatoes Dextrose Agar).
There was a high prevalence of surface contaminants (78.9%) especially for non-infectious bins (90.3%). Their mean frequencies were significant for sampled surfaces of the Biology Department, and only sampled beds of the Emergency ward indicating their equal potential to cause infections. In addition, highly touched surfaces were prone to S. aureus contamination (22.4%), a constituent of the human hand microbiota which suggests that the staff’ hands could be the main vector of surface contamination in analysed units. In May, contaminants’ frequencies dropped (24.9%) due to increase in the awareness of basic infection control measures amongst staff, staff rotations, changes in work hour schedules and hospitalisation beds’ availability.
The concept of environmental bacterial reservoir is a reality. Improvement strategies include interventions to reduce/contain the shedding of pathogens and, improving the efficacy of cleaning/disinfection of hospital surfaces and hand hygiene.
BK-SE36/CpG is a recombinant Plasmodium falciparum vaccine candidate targeting blood-stage parasites. The P. falciparum SE36 protein was expressed in E. coli, adsorbed to aluminium hydroxide gel, and reconstituted with CpG adjuvant. An acceptable safety profile of the BK-SE36/CpG vaccine was previously showed in healthy malaria-naïve Japanese adults. The aim of the Phase Ib study reported here was to assess the safety and immunogenicity in healthy malaria-exposed African adults and children.
A double-blind, randomized, controlled, age de-escalating, clinical trial was conducted in an urban area of Ouagadougou, Burkina Faso. One hundred and thirty-five healthy participants aged 21–45 years, 5–10 years, and 12–24 months were randomized 2:1 to receive three vaccine doses of BK-SE36/CpG (BK) or rabies vaccine. Subjects were monitored within 7 and 28 days following each vaccination for solicited and unsolicited adverse events. Severe and serious adverse events were collected throughout the study duration (12 months). Immune responses were measured at baseline, 28 days after each vaccination, and at trial end.
Of the one hundred thirty-five subjects enrolled, one hundred thirty-four received all three scheduled vaccine doses. Five Grade 3 events unrelated to vaccination were reported in three subjects (3%) in the BK arm. Five SAEs reported, all due to severe malaria, were judged unrelated to the study vaccine. BK induced higher mean anti-SE36 antibody titers compared to control, with higher titers post-Dose3 compared to post-Dose2. A stronger immune response was observed in younger cohorts (12–24-month-old > 5–10-year-old > 21–45-year-old). In all cohorts, epitope mapping of sera from BK vaccinees showed predominant reactivity with the synthetic peptides that are lied into intrinsically unstructured regions.
The BK-SE36/CpG vaccine was well-tolerated and immunogenic in all age groups. These results pave the way for further proof-of-concept studies with larger cohorts to demonstrate the efficacy of the vaccine.
Intermittent Preventive Treatment of malaria in infants (IPTi) is a malaria control strategy consisting of the administration of sulfadoxine-pyrimethamine alongside routine immunizations. IPTi has been renamed as Perennial Malaria Chemoprevention (PMC), accounting for its recently recommended expansion into the second year of life. Before starting a pilot implementation on PMC, the currently implemented strategy was assessed in children in selected areas of Sierra Leone.
A cross-sectional, community-based, multi-stage cluster survey was conducted in 2021 in three districts in Northern and northwestern provinces of Sierra Leone among 10- 23 months old children. IPTi coverage was calculated using percentages and 95% confidence intervals weighted for the sampling design and adjusted for non-response within clusters. Factors associated with iPTi coverage including malaria RDT were assessed.
A total of 720 children were recruited. Coverage of three IPTi doses was 50.57% (368/707; 95% CI 45.38 – 55.75). Adjusted for all other studied covariates, older children (OR per month increase 1.07, 95% CI 1.02–1.11, P-value 0.0056), those who slept under a mosquito net the previous night (OR 1.76, 95% CI 1.22–2.53, P-value 0.0029) and those whose caretaker was paid-employed (OR 2.74, 95%CI 1.11, 6.74, P-value 0.0290) were more likely to have received the complete three IPTi doses. Children whose caretakers were males (OR 0.50, 95% CI 0.28–0.91, P-value 0.0251), residing in Port Loko district (OR 0.40, 95% CI 0.19–0.87, P-value 0.0212) and those with a positive RDT result (OR 0.57, 95% CI 0.39–0.82, P-value 0.0035), were less likely to have received complete three doses of IPTi.
In this survey, IPTi coverage was around 50%. A positive health behaviour possibly explains the association with use of mosquito nets. This implies that positive health behaviour messaging is key in improving coverage of IPTi, a key malaria prevention strategy.
Live attenuated, including viral vector, vaccines may be transmitted to others. Benefits of secondary transmission include increased vaccine coverage and accelerated achievement of herd immunity. In contrast, risks include vaccine evolution to wild-type pathogens e.g., oral polio vaccine and risks of adverse events in vulnerable populations.
Recently, we reported the shedding of the rVSVG-ZEBOV-GP vaccine in children’s saliva, suggesting potential secondary transmission to relatives. In this phase 2 vaccine trial, we investigate the secondary transmission of the rVSVG-ZEBOV-GP vaccine to the vaccinees’ relatives in Gabon.
One hundred sixty-three relatives of our study vaccinees (Gabonese children aged 1–12 years old) were enrolled to assess the transmission of the rVSVG-ZEBOV-GP vaccine, compared to another live attenuated vaccine containing the Oka strain of the varicella-zoster virus. They were followed up on days 0, 2 or 3, 7, 14, 21, 28, and 56 post-vaccination. Clinical symptoms and signs were observed, and samples were collected during the study visits. Relative plasma and saliva were tested by RT-PCR for presence of rVSV RNA, alongside antibody titers’ determination.
Quantifiable rVSV RNA was detected in plasma in a low proportion of relatives on days 2 or 3; there was no detection in the saliva of relatives at any visit. These data will be aligned with titers of anti -ZEBOV-GP and further interpreted. No adverse event was observed in the relatives.
rVSVG-ZEBOV-GP vaccine virus is transmissible to relatives or close contacts of vaccinees, based on the RT-PCR Ct values, favoured by virus shedding in vaccinated individuals. The implications of this finding require further consideration.
Funding: IMI, VSV-EBOPLUS consortium
Universidade Eduardo Mondlane (UEM) and Hospital Central de Maputo (HCM) were invited to join a consortium of established pediatric research groups from 5 other sub-Saharan Africa countries in a proposal for the EMPIRICAL trial, which received EDCTP funding in 2019 (RIA2017MC-2013). At that time, HCM and UEM did not have an active pediatric research team, nor a history of collaboration on a pediatric clinical trial.
A research office was established on the HCM pediatric wards. Procurement and laboratory cooperation was established with another Mozambique recruiting site, Centro de Investigacão em Saúde de Manhica. Dedicated and part-time staff were hired, including an HCM pediatrician and nurse. Comprehensive research training was conducted, and the first EMPIRICAL patient was recruited in May 2020. Due to slow recruitment across the consortium, UEM agreed to extend to an additional 3 hospitals in Maputo, again including Ministry of Health staff at each new site. Recruitment was similarly extended to the principal referral/academic hospitals in the other regions of Mozambique with inclusion of Hospital Central de Beira in 2020 and Hospital Central de Nampula in 2021, in partnership with Universidade Católica de Mocambique and Universidade Lúrio. This network has led recruitment in EMPIRICAL, is participating in four pharmacokinetic substudies and an autopsy substudy, and has 2 local ancillary studies, one with EDCTP Career Development Fellowship support (TMA2020CDF-3217).
The infrastructure and capacity established through EMPIRICAL has been leveraged for additional pediatric inpatient research opportunties, with UEM leading 4 hospitals participating in the EDCTP-funded PediCAP trial (RIA2017MC-2023), and 2 hospitals in the UNITED-meningitis diagnostic study.
A successful pediatric inpatient research network was quickly established in Mozambique with donor support that facilitated capacity building, and a model that prioritized inclusion of Ministry of Health hospital staff in research teams with inter-institutional collaboration to achieve national coverage.
Malaria remains a major global health challenge, with millions of people affected annually. Traditional methods for predicting malaria outbreaks are limited by factors such as cost, availability, and accuracy. The application of machine learning techniques has emerged as a promising alternative for modeling and predicting malaria outbreaks. This systematic review aims to evaluate the current state of research on machine learning-based modeling of malaria.
A comprehensive search was conducted in several databases, including PubMed, google scholar, and Web of Science, to identify relevant articles published between 1992 and 2022. The search terms included "machine learning," "predicting," and "modeling" in combination with "malaria," We included studies that focused on machine learning techniques for predicting malaria outbreaks and assessed the strengths and weaknesses of the models.
Preliminary analyses showed that studies used different machine learning techniques, including artificial neural networks, decision trees, linear regression, random forest, and support vector machines to predict malaria outbreaks and identify the main factors that determine outbreaks. Most of the studies used a combination of environmental and socio-economic factors, such as temperature, rainfall, and population density, to predict malaria outbreaks. The prediction accuracy of the models ranged from 80% to 95%, depending on the machine learning technique used and the dataset.
Machine Learning techniques have shown promise in predicting malaria outbreaks by incorporating environmental and socio-economic factors. The strengths of the models included high accuracy and the ability to predict outbreaks before they occur. However, the limitations of the models include the need for extensive data and the difficulty of generalizing the models to other settings. Further research is needed to address these limitations and to optimize the machine learning-based models for predicting malaria outbreaks.
Capacity Development of Applied Epidemiologists (CDAE, 36-months programme, seeks to create a networked cohort of highly competent professional with master’s degree in Epidemiology or Biostatistics (EPI fellows) and strengthens the supervision capacity of targeted universities to effectively deliver programmes in Epidemiology or Biostatistics. In this paper, we describe the progress made, challenges encountered, and lessons learned.
The African Population and Health Research Center leads the programme in partnership with Amref International University (private university) and Jaramogi Oginga Odinga University of Science and Technology (public university), both in Kenya, and Lund University in Sweden. We conducted a highly competitive and rigorous recruitment process which attracted highly qualified applicants from diverse backgrounds.
We received 706 applications from 21 countries from which 15 EPI fellows were admitted. They completed their course work and participated in two Joint Seminars, designed their research proposals, defended, and received ethical approval (collection of data is ongoing). Concurrently, 20 supervisors were trained on quality supervision for two weeks to ensure EPI fellows received adequate support and guidance throughout the programme. The programme however encountered several challenges including: high number of qualified applicants but limited funding, adherence to timelines, unequal learning conditions, and difficulty in reaching out to other stakeholders. Some lessons included: high demand for the programme in Sub-Saharan Africa (SSA), concurrent training of EPI fellows and supervisors provides interaction opportunity, expansion need for the programme, and greater synergy in collaborations (academia and industry).
CDAE is critical for strengthening public health systems in SSA. This programme provides a blueprint for other countries seeking to build the capacity of their public health workforce. As we draw near the end of the programme, "what next" discussions are ongoing. Our programme demonstrates the importance of public-private partnerships and drawing synergies from various institutions to deliver seasoned epidemiologist.
Malaria is one of the significant health problems in the world, and the greatest burden of the disease is concentrated in Africa, which accounts for about 95% of cases. The World Health Organization indicates that early seeking for treatment is crucial to avoid worsening the disease and, consequently, death. This work evaluated the factors that influence early health care-seeking (EHCS) behaviour in children under five years old and the effect of EHCS on hospitalisations.
We conducted a health facility-based observational longitudinal study over 5 years, starting in January 2015 where confirmed P. falciparum (Pf) malaria cases were identified in an ongoing morbidity surveillance system established in Manhica district hospital and 5 referral health centres by Manhica Health Research Centre. Using the first visit for all children that visited a Health Facility (HF) with fever or history of fever in the previous 24 hours and confirmed Pf malaria, we defined EHCS as a visit to an HF within 48h after the onset of fever. We used multilevel logistic regression to identify the factors related to EHCS and the association between EHCS and hospitalisation.
Of 66620 under 15 years old children screened only 1603 meet all inclusion criteria. A kilometre increase in the distance to a health facility reduced the odds of EHCS by 11% (aOR=0.89; CI: [0.83–0.95]; p=0.001). EHCS reduced the odds of hospitalization (aOR=0.56; 95% CI: [0.34 -0.93]; 0.024) and year increase in the year of the visit increased the odds of hospitalization by 66% (aOR = 1.66; 95% CI: [1.41–1.93]; p<0.001).
Increasing the distance to HF reduced the likelihood of EHCS, whereas EHCS reduced the risk of hospitalisation. Maulana and Calanga lead the hospitalisation cases in the study area in children with malaria and cases of delay in health care seeking.
The Covid-19 pandemic and other emerging diseases increased the need to conduct clinical trials (CTs) to investigate appropriate treatments or prevention measures. One of the main barriers for conducting CTs in Africa is delays in regulatory and ethics reviews. Furthermore, existence of inadequate regulatory inspections of CTs to evaluate the integrity of data submitted to health authorities, protect patient safety, and assess the adequacy of site/sponsor quality systems to achieve the same. To this end, the ASCEND project assessed the level of competency and training needs for evaluating clinical trial applications (CTAs) and conducting clinical inspections in Tanzania. Moreover, to recommend interventions to bridge the gap.
A descriptive cross-sectional study was conducted from February to June 2021 using an online survey to collect information on training needs and competencies. The population was 130 respondents from research, regulatory and academic institutions.
Out of 130 approached respondents, only 69.2% (90/130) participated. The most common qualification of the respondents was a master’s degree (59%). Bachelor degree and PhD holders stood at 21% and 20%, respectively. The findings indicated that 94% of the respondents needed training on assessment of clinical data, 92.2% on product quality, 92.6% on statistical data, and 81.2% on understanding and using the checklist for Good Clinical Practice (GCP) inspection.
These findings were used to develop two accredited short courses 70-hours (7-credits) each. The courses were CTAs assessment and GCP inspection. Consequently, 2-weeks short courses were conducted. Pre- and Post- course tests were administered to assess the training impact.
A pool of proficient assessors is important for quality reviews of CTAs and in timelines reduction. The short courses conducted were successful, and increased a pool of competent assessors and GCP inspectors in Tanzania. For further strengthening the regulatory capacity, additional training is recommended.
Salmonella are a group of facultative anaerobic bacteria that belong to the family of Enterobacteriaceae. The common serovars are Salmonella enterica subsp. enterica serovar Typhi which causes typhoid fever and the non-typhoidal Salmonellae (NTS) which are associated with gastroenteritis. Data on the epidemiology and genomic characteristics of Salmonellae in sub-Saharan African countries are limited.
This study describes the epidemiology and genomic characterization of Salmonellae in Ghana.
A prospective incidental hospital-based surveillance study among patients presenting with febrile illness from May, 2016 to April, 2023 was conducted in the Asante Akyem District of Ghana and Komfo Anokye Teaching Hospital. Blood cultures were processed for identification of Salmonella using standard bacteriological techniques. A subset of Salmonella isolates were confirmed using real-time-PCR amplification targets for S.Typhi and invasive NTS. The concentration of DNA were quantified using nanodrop and shipped to Eurofins Genomics for illumina based sequencing. Raw reads were assembled and analysed using Pathogenwatch web tool.
The study enrolled 6,557 participants between the ages of 1 and 95 years of which 51.7% were males. The prevalence of Salmonella Typhi and NTS were 0.14% (95%CI: 0.096 – 1.5) and 0.33% (95%CI: 0.21% - 0.5%) respectively. Male gender (adj OR; 95%CI = 1.6; 0.93–2.75) and age group below 15 years (Adj OR; 95%CI=3.94; 1.67–9.3) had higher odds of infection with Salmonella Typhi. A subset of 42 Salmonella Typhi isolates sequenced, identified the predominant genotype as 2.3.2 (54.1%) followed by 3.1.1 (42.9%). Of 17 iNTS isolates sequenced, Typhimurium (10; 62.5%), Enteritidis (5; 31.3%), Poona (1; 6.2%) and Saintpaul (1; 6.2%) were identified. Common resistance markers identified were chloramphenicol resistance (catA1; 10/50), sulphonamides resistance (sul1; 10/50), beta-lactam (9/10) and trimethoprim (dfrA; 10/50).
The increasing rate of resistance and endemicity of infections emphasize the need for the introduction of vaccines to reduce disease burden.
Heterologous immunity is the induction of an immune response to an unrelated pathogen upon exposure to a different pathogen, involving memory T cells and B cells response. Studies showed that BCG-immunization would induce resistance to Listeria infection and increase B cells and T cells responses. Viral vectored vaccine are promising and vaccine platform that favour the induction of cellular immune responses beyond potent humoral immune responses. We investigate the potential of the rVSV-EBOV-GP vaccine to induce heterologous immunity through immune mechanisms involving cellular immune responses and a network of cytokines.
We investigate the effect of the vaccination with rVSV-EBOV-GP on the childhood vaccines, including TB, Polio 1,2,3 serotypes, Diphtheria, Bordetella pertussis, Hepatitis B, Yellow fever, Measles, Influenza type B, which are part of the expanded program on immunization in Gabon. We analyzed samples of 120 children enrolled in Phase 1/2, a randomized, controlled, open-label trial. Among them, 80 received the rVSV-EBOV-GP vaccine, and 40 received the Varicella-Zoster vaccine.
Antibody titers or cellular immune responses against TB, Polio 1,2,3 serotypes, Diphtheria, Bordetella pertussis, Hepatitis B, Yellow fever, Measles and Influenza type B are being evaluated before vaccination and at days 7, 28, 56, 180 and 365 after vaccination. We also measured adaptive cytokines IFN, IL-5, IL-12, IL-13, IL-10, IL-17A, IL-22 at the corresponding time points.
Cellular and cytokines immune responses are reliable biomarkers that could be used to assess vaccine candidate efficacity and vaccine heterologous induced-immune response.
Deadly emerging infectious pathogens pose an unprecedented challenge to health systems worldwide, especially in the Republic of Congo, where health care infrastructure is limited. Thus the COVID-19 pandemic has been an opportunity to improve the national genomic platform that could be expand to all circulating pathogens serving surveillance, prevention and response actions. This work aimed to establish the genomic platform for the effective control of infectious pathogens in the Republic of Congo.
By 2021, we established the Oxford Nanopore Technology platform for the first time in the Republic of Congo to respond firstly to the COVID-19 pandemic and secondly to other pathogens like Plasmodium falciparum, Mycobacterium tuberculosis, HIV and others. Between April 2020 and August 2022, a total of 1200 oropharyngeal samples were tested positive for SARS-CoV-2 by RT-PCR. Of these samples, 589 with Ct< 28 were selected for sequencing by ONT next generation sequencing (NGS). All the complete sequenced genomes were submitted on GISAID for publication, and variants were identified using Pangolin and Nextclade nomenclature.
A total of 381 SARS-CoV-2 whole genomes were successfully sequenced and submitted on GISAID. Our results revealed the circulation of 21 SARS-CoV-2 variants in the Republic of Congo during the study period, with the presence of variants of concern such as alpha (B.1.1.7), delta (B.1.617.2) and Omicron (B.1.1.519). Four waves of the virus epidemics were observed during this study period. The B.1.640.1 variant was reported for the first time in the Republic of Congo through this study, and was observed to be spreading locally and regionally.
This work contributed to monitor in a daily basis the spread of SARS-CoV-2 in the country to support the national containment strategies of the pandemic. This established platform is serving for the identification of other pathogens that could represent a threat of public health.
Spinal tuberculosis (TB) is a potentially severe form of TB that accounts for 50% of all musculoskeletal TB cases. The condition presents with non-specific symptoms often resulting in delayed diagnosis. Therefore, there is an urgent need for new tools that can aid early diagnosis. Host transcriptomic biosignatures have shown promise in the diagnosis of pulmonary TB and may be useful in spinal TB. We aimed to evaluate the utility of selected published host transcriptomic signatures for the diagnosis of spinal TB and monitoring of treatment response.
The study was conducted at a tertiary hospital in the Western Cape, South Africa. A total of 26 genes were evaluated in participants with confirmed spinal TB (n=24) and mechanical back pain (n=17) using qRT-PCR on RNA extracted from Paxgene blood. Receiver Operating Characteristic (ROC) curves and General Discriminant Analysis were used to evaluate the diagnostic potential of individual genes, as well as gene combinations.
Preliminary analysis of four individual genes (GBP5, DUSP3, BATF2 and SERPING1) indicated their potential as diagnostic candidates with areas under the ROC curve (AUCs) ranging from 0.83 to 0.87. The four-gene signature (GBP5+DUSP3+SERPING1+BAFT2) was able to diagnose spinal TB with a sensitivity of 87.5% (95% CI, 67.6%-97.3%) and a specificity of 66.7% (95% CI, 29.9%-92.5%) in a resubstitution classification matrix. However, after leave-one-out cross validation, the sensitivity was 79.2% (95% CI, 57.8–92.9%) while the specificity was 66.7% (CI, 29.9–92.5). A significant difference (p≤0.05) was observed in the expression of all four genes at baseline and 12 months of treatment.
Our preliminary results highlight the potential of the selected genes as candidate biomarkers for spinal TB diagnosis and monitoring of treatment response however, further investigation is warranted to validate these findings.
UPTAKE is a programme to accelerate access and facilitate adherence to effective and innovative long-acting technologies to prevent HIV and unintended pregnancy among Adolescent Girls and Young Women (AGYW) and Female Sex Workers (FSW) through behavioural science in Kenya and Uganda. We identified characteristics which predict the use of HIV and pregnancy prevention products and measured the strength of preferences.
A quantitative survey was administered to 326 AGYW and 334 FSW in both countries. Descriptive, inferential, and segmentation analysis was applied to reveal user-preferences, behavioural patterns and the predicting factors of product uptake.
Product usage, particularly for HIV prevention, was lower among AGYW than FSW. Although awareness of long-acting prevention products including implants and intra-uterine devices (IUDs) was high among both groups, uptake remained low, primarily due to perceived side effects. For pregnancy prevention, the male condom was most used among both AGYW and FSW, followed by injectables. For HIV prevention, male condoms were most used, followed by oral pre-exposure prophylaxis (PrEP). Effectiveness and easy accessibility were the most highly valued product features.
The influential factors driving and predicting uptake varied by product. At the 0.05 significance level, risk preference, stigma, Intimate Partner Violence (IPV), locus of control, peer influence, subjective risk, country, and age appeared significant in influencing uptake of various products. Segmentation was only found influential for the uptake of implants and male condoms among AGYW.
More than half of participants are aware of long-acting contraceptive products, though only 17% of AGYW and 22% of FSW used implants, and less than 2% used IUDs. Furthermore, very few recognised the ring as a HIV prevention method, and none used it. Behavioural interventions should be tailored by product and respond to the key influential factors to increase awareness and bridge the gap between awareness and uptake.
The African Vaccine Regulatory Forum (AVAREF) is a network of African national regulatory authorities (NRAs) and ethics committees (NECs) with an objective of improving access to medicines by reducing and standardizing review and approval times for clinical trial applications, while also optimizing quality of regulatory processes across sub-Saharan Africa (SSA)¹. It utilizes joint reviews and parallel CTA submissions to NRAs, NECs and Institutional Review Boards (IRBs).
Novartis piloted use of the AVAREF procedure for a Phase 2 clinical study in malaria patients involving 7 countries/13 sites in SSA.
A letter of intent for a scientific advice meeting was submitted to AVAREF to trigger the procedure start. The meeting occurred 2 months later with participation of experts from SSA. One NEC identified for inclusion in the procedure did not agree to participate.
The timetable was agreed by all parties, which facilitated CTA parallel submissions. However, differences in understanding of the procedure emerged. Despite scheduling of a face to face joint review meeting including all parties to discuss questions on the CTA, two NEC approvals were received prior to the joint review. Validation questions requesting sequential approvals by IRBs/ECs were also received. The procedure is currently ongoing, and the pilot will inform the path for future EC/HA submissions in SSA.
AVAREF procedure holds promise to reduce lengthy sequential NEC and NRA approval timelines in SSA. It also provides a forum for open discussion of study-related questions and for scientific advice in SSA. Attention is warranted to further clarify the review process and expectations for NECs, in particular.
Post-TB lung disease (PTLD) is a neglected chronic lung condition that occurs despite successful completion of TB treatment. Statins have broad-range immune-modulatory and anti-inflammatory properties with a potential to reduce PTLD and improve symptoms.
In our ongoing StatinTB trial (RIA2017T-2004; NCT04147286), we evaluate safety and efficacy of 40 mg atorvastatin to reduce persistent lung inflammation (PLI) after TB treatment in HIV-/HIV+ adults measured by 18F-FDG-PET/CT. Here we aim to investigate the ex vivo immunomodulatory activities of atorvastatin on peripheral blood mononuclear cells (PBMCs) from treated TB patients following M. tuberculosis infection.
At the end of TB treatment, enrolled study participants were subjected to PET/CT scan and. PBMCs were collected at baseline and treated ex vivo with atorvastatin overnight followed by infection with M. tuberculosis (Mtb) HN878 strain. At 24 hours post infection, PBMCs were subjected to flow cytometry to evaluate inflammatory cell surface markers and cell populations. Confocal microscopy was performed to measure phagosome maturation (Rab-7), phagolysosome fusion (Cathepsin-D and LAMP-3) and autophagy (LC3B). CFU and Tunnel assays were conducted to measure intracellular Mtb growth and apoptosis.
Ex-vivo treatment of PBMC with atorvastatin significantly reduced the intracellular growth of Mtb as measured by CFU assay. Atorvastatin treatment significantly reduced the expression of inflammatory cell surface markers (CD11b and CD16) and decreased classical monocyte (CD14+CD16-) population measured by flow cytometry. The colocalization coefficient of Mtb with the phagosome marker (Rab-7), phagolysosome markers (Cathepsin-D and LAMP-3) and autophagy marker (LC3B) were significantly enhanced by atorvastatin as measured by confocal microscopy. Apoptosis was significantly increased by the treatment of atorvastatin.
As a host protective mechanism atorvastatin induces phagosome and phagolysosome maturation, autophagy and apoptosis in Mtb-infected PBMCs.
Factors associated with long-term TB treatment outcomes are not well understood. The aim of our study was to determine the association of mycobacterial lineage and HIV co-infection on mortality and TB recurrence five years after first-line TB treatment in Bamako, Mali.
Between 2015–2022, we conducted a longitudinal cohort study enrolling adults with smear-positive rifampicin-susceptible pulmonary TB. After diagnosis, patients were followed at 1 month (M), 2M, 5M and 6M to determine treatment outcome. Spoligotyping was used to determine baseline lineage classification (M. tuberculosis (L4), and M. africanum (L6)). After treatment completion, patients were evaluated every 6 months for five years to determine their clinical status. Univariate and multivariate logistic regression was used to identify factors associated with treatment outcome.
Of the 1,283 patients enrolled, 911 (71%) were male and 116 (9%) were co-infected with HIV. BMI <18.5 (aOR: 1.4, 95% CI: 1.1–1.9) and HIV co-infection (aOR: 2.9, 95% CI: (1.8–4.8) were associated with initial treatment failure. Among the 684 patients maintained for the entire 5-year follow-up, 72 (11%) died and 35 (5%) developed recurrent TB. Baseline L4-infected patients were not more likely to die than L6-infected patients (51% vs 26%, p=0.79) or develop recurrent TB (54% vs. 31%, p=0.58). HIV was not associated with death (p=0.58) or TB recurrence (p=0.32). Among all recurrences, 8 (23%) recurred within 1 year after treatment completion, 25 (71%) within 18 months, and 28 (80%) within 2 years. We were not able to obtain a recurrent TB sputum sample.
Neither HIV co-infection nor mycobacterial lineage was associated with 5-year mortality or TB recurrence. Only half of the patients completed follow up and we were limited by the inability to differentiate TB relapse from reinfection. Future analyses that can differentiate relapse from reinfection may be helpful.
P. falciparum parasite genotyping in longitudinal studies was described as a suitable manner for measuring outcomes of interventions and to estimate the force of the infection.
This study was designed to compare the force and multiplicity of infection (FOI and MOI) in children on SMC (<5 years) or not (5 to 12 years) in Banfora, an area of intense malaria transmission in Burkina Faso. Both groups received supervised curative doses of artesunate (AS) or dihydroartemisinin-piperaquine (DHA-PQ) to eliminate existing parasites. Parasite DNA was extracted and then analyzed by nested PCR to detect and genotype P. falciparum parasites. Both active (biweekly sampling at home) and passive (sampling at health center visits) case detection were used to ensure that a high proportion of infections were captured.
A total of 458 PCR-detected P. falciparum positive samples were collected and 87.99% were positive for msp2 gene. There were no differences in MOI (p=0.80) and FOI (p=0.09) between the two DHA-PQ and AS treatment cohorts. The mean values of FOI and MOI were 2.00 [1.82–2.18] and 2.98 [2.83–3.14] respectively. In comparison, there was no statistically significant difference (p=0.92) between the mean values of the FOI of subjects on SMC (1.98 [1.57–2.39]) and those who were not (2.00 [1.82–2.21]). The same was true (p=0.75) between the MOI of subjects on SMC (3.03 [2.69–3.38]) and the other group (2.97 [2.79–3.15]). With a fever and parasitemia >5000 trophozoites/µL, the value of the polyclonality in passive detection was 57.69% [43.26–70.99] and the difference with that in active detection (2.28% [1.06–4.62]) was statistically significant (p<0.01).
Both FOI and MOI were not age-dependent, despite current malaria control methods that target children under five years. This would suggest that the SMC did not provide specific protection on these children living in an area of very high transmission.
Treatment for Multi-Drug Resistant Tuberculosis (MDR-TB) is long and costly. Currently, there are limited effective and affordable treatment response monitoring tools. We set to evaluate the performance of alternative bacteriological measures of response to therapy during the initial 16 weeks of MDR-TB treatment.
In a prospective study of MDR/RR-TB in Uganda, all smear-positive participants were enrolled for treatment response monitoring using Concentrated Fluorescent Microscopy (CFM), Fluorescein-di-acetate (FDA) AFB vital smear microscopy, and 16S rRNA-based assay in a Molecular bacterial load assay (TBMBLA) and Mycobacterial Growth Indicator Tube (MGIT) as alternative bacteriological measures. Pooled early morning and spot sputum samples were processed at weeks 0 (pre-treatment), 2, 4, 6, 8, 12, and 16. Solid culture, Middle Brook 7H11 selective (MB7H11S) colony-forming units were used as the standard measure of treatment response. Bacteriological conversion to negative by the alternative tests was assessed against MB7H11 at weeks 12 and 16 of treatment.
A total of 59 participants were enrolled, of whom 58 provided sputum samples at baseline. Participants were; 64% male, median age (IQR) 33 (28.6–37.4), 44% HIV-positive, and 78% on ART. The underweight (BMI<18.5kg/m2) was 61% and the median BMI (IQR) was 18.1 (17.3–18.6). Bacteriological positive at baseline were n (%); CFM 49 (84.5), FDA 40 (69.0), TB-MBLA 32 (60.4), MGIT 51 (87.9), and MB7H11S was 47 (81.0). Bacteriological conversion to negative at week 12 and week 16 respectively were CFM 92% and 98%, FDA 98% and 98%, TB-MBLA 98% and 100%, MGIT 95% and 93%, MB7H11S 96% and 98%.
Our data show that concentrated fluorescent smear microscopy, fluorescein-di-acetate smear microscopy, TBMBLA, and MGIT culture as suitable alternative measures of response to therapy among MDR-TB patients. Efforts should be made to make such methods available for the timely monitoring of patients on MDR-TB regimens.
The prevalence of Non-communicable Diseases (NCDs) in countries where Tuberculosis (TB) and HIV/AIDS are still major challenges rises concerns for public health. Mozambique faces an epidemiological transition and the overlap of TB, HIV and NCDs may have implications for the control of the three diseases.
The objectives of this study were to determine the prevalence of diabetes, obesity and arterial hypertension and the associated risk factors in patients with pulmonary tuberculosis in the city and province of Maputo, south Mozambique.
A cross-sectional study was conducted in four Health Centers from March 2021 to July 2022. All new cases of pulmonary tuberculosis confirmed by bacilloscopy (BK) or GenExpert, and with or without HIV, were recruited and tested for diabetes by measuring glycosylated haemoglobin (Hb1Ac). The arterial blood pressure and body mass index (BMI) were measured, and socio-demographic variables were collected through a questionnaire. The data were entered into the REDcap platform and analysed using the SPSS version 20.
Of the 402 patients TB subjects, 62.2% were male, with a mean age of 38 years. The prevalence of Diabetes (HbA1c > 6.5%) was 12.7%. Regarding hypertension, systolic hypertension (SBP>140 mm Hg) was 16.9%, and diastolic hypertension (DBP >110mm Hg) was 29, 9%. The Obesity (BMI > 25) was 13.7%. In overall subjects, HIV was positive in 41.3%. Regarding the risk factors for chronic diseases, 11.7% had a family history of Diabetes, 50.7% had alcohol habits, 19.9% had smoking habits and 74.6% did not practice physical activity.
Of the HIV positive patients, 30.7% had systolic hypertension and 19.3% diastolic hypertension, 16.3% diabetes and 14.5% obesity.
The prevalence of diabetes and arterial hypertension in TB patient is high compared to other African countries. Thus, is recommended to establish an integrative screening service for NCDs screening in patients with Pulmonary Tuberculosis.
The diabetes burden in sub-Saharan Africa is high, but data on the relative importance of insulin resistance and beta-cell dysfunction there is scarce. We investigated the association between dietary patterns with insulin resistance and beta-cell dysfunction among HIV-infected and HIV-uninfected adults in Mwanza, Tanzania.
In a cross-sectional study, insulin resistance and beta-cell function were measured from plasma insulin and glucose during an oral glucose tolerance test. Diet data were collected using a validated food frequency questionnaire, and dietary patterns were derived by principal component analysis and reduced rank regression. Socio-demographics, smoking, alcohol taking, and physical inactivity data were collected using structured questionnaires. Logistic regression analysis was used to assess the association between insulin resistance, and beta-cell dysfunction with dietary patterns adjusting for potential confounders.
Of 462 participants, the mean age was 42 (±12) years, 58% were females, and 60% were HIV-infected. The proportion with insulin resistance was 43% and 35% by the Matsuda index and HOMA-IR, respectively. Beta-cell dysfunction was present in 37%, 43%, and 43.3% by the insulinogenic index, HOMA-β, and oral disposition index, respectively. Higher adherence to a carbohydrates-dense diet pattern was associated with more insulin resistance by HOMA-IR (aOR 3.7, 95% CI 2.2; 6.3) and Matsuda index (aOR 6.2 3.4; 11.2), and less beta-cell dysfunction by HOMA-β (aOR 0.4 0.2; 0.6) and insulinogenic index (aOR 0.5 0.3; 0.9). Higher adherence to the vegetable-rich pattern was associated with insulin resistance by the Matsuda index (aOR 2.2 1.3; 3.7). Conclusion Carbohydrate-dense pattern increases the risk of insulin resistance but decreases beta-cell dysfunction. Higher adherence to a vegetable-rich pattern increases the risk of insulin resistance. Further studies to look at glucose metabolism and why a vegetable-rich pattern has an odd effect in sub-Saharan Africa are warranted.
Funding: EDCTP-2 program, grant agreement number: TMA2017GSF-1965-REEHAD
Rheumatic diseases, including juvenile idiopathic arthritis, are chronic inflammatory conditions affecting children. There have been concerns regarding the potential role of live attenuated viral vaccines in triggering rheumatic diseases. This phase 2 trial aimed to investigate the association between two live attenuated viral vaccines and the development of rheumatic diseases in children.
A randomized, controlled open-label trial was conducted involving children aged 1–12 years who were eligible to receive live attenuated viral vaccines for heterologous rVSV-ZEBOV-GP Ebola or varicella. Participants were randomly assigned to receive the vaccine. A muscle-skeleton examination, FBCs, ESR, CRP, HLA-B27, lgM, RF, and ANA were accessed on Days 0,1,2/3, 7, 14, 21, 28, 58, 180, and 365 routinely. The primary outcome was the development of rheumatic diseases, within the follow-up period.
120 children were enrolled in the trial, with 80 in the rVSV-ZEBOV-GP group and 40 in the varicella group. The mean age at enrolment was 6.46 years, and the study population consisted of an equal distribution of gender. The follow-up period, days 1, 2/3, 7, 14, 21, 28, 58, 180, and 365 showed no significant differences in the incidence of rheumatic diseases between the two vaccines clinically. Some participants complained of arthralgia (1.9%), however, it was associated with plasmodium falciparum. For the rest of the inflammatory markers, analysis has been completed and will be available timely.
In this phase 2 trial, there was no evidence to suggest that administering two live attenuated rVSV-ZEBOV Ebola and Varicella, was associated with a risk of rheumatic diseases in children. The noted pseudo-signs of rheumatic diseases like arthralgia and body ache were strongly linked to Malaria infection. These findings provide reassurance regarding the safety profile of rVSV-ZEBOV-GP Ebola and varicella concerning rheumatic diseases in children.
The END TB strategy recommends scaling up of research training and capacity by growing the workforce of scientists in tuberculosis (TB) endemic settings skilled in "development and rapid uptake of new TB tools and "interventions" and "research to optimise implementation and impact". The SimpliciTB consortium aimed to develop the skills, confidence and international competitiveness of African research leaders engaging in TB while extending network of African sites capable of performing high quality clinical trials in TB.
Through co-leadership and partnership with St Andrews University, University College London from United Kingdom; Radboud University Medical Center-The Netherlands and TB Alliance-United States mentorship was provided to the senior clinical research fellow and clinical research & development fellow based at Kibong’oto Infectious Diseases Hospital in Tanzania to execute sponsor and trial management responsibilities for a new clinical trial of anti-TB therapy to be delivered in four African countries: Gabon, Malawi, Mozambique and Tanzania.
From January 2022- April 2023, achievement in capacity development include design of the potential regimen for a phase III TB clinical trial, and development of the protocol titled: "A pragmatic trial with optimized dose of rifampicin and moxifloxacin for the treatment of drug susceptible pulmonary tuberculosis (OptiRiMoxTB)". The Operational team meeting was successfully formulated comprising of two categories i) sponsor category with international principal investigators as co-chairs, trial manager and associated core groups including biostatistics and data management, pharmacy and drug management, microbiology and biomarkers, finance and administration and ii) Trial sites each bringing at least the site PI, and site coordinators. Trial-governance including the data safety monitoring and steering committees are set. All sites have submitted ethical and regulatory clearance to their respective bodies and authorities.
Despite challenges, the preparatory phase has completed and enrolment of participants expects to start in the second quarter of 2023.
Despite the availability of anti-TB treatment, successfully treated TB patients remain with persisting lung inflammation regardless of HIV status. Lung inflammation has been linked with robust or imbalanced host immune responses which exacerbate tissue necrosis. Soluble host biomarkers have been shown to correlate with the development of lung inflammation at different stages of anti-TB treatment which further affect sputum conversion in these patients.
In our ongoing StatinTB trial (RIA2017T-2004; NCT04147286), we evaluate safety and efficacy of 40 mg atorvastatin to reduce persistent lung inflammation after TB treatment in HIV-/HIV+ adults measured by 18F-FDG-PET/CT. Here we aim to explore the expression profile of host serum biomarkers from successfully treated TB patients with or without persisting lung inflammation.
Study participants were screened for sputum conversion at month-4 and month-6 of anti-TB treatment. Enrolled participants were subjected to PET/CT scan, where Arm A=TLG<50SUVbw*ml (minimal lung inflammation) and Arm B=TLG≥50SUVbw*ml (persisting lung inflammation). A total of 71 participants (Arm A=42, Arm B=29) were evaluated in this study. Serum samples were collected after 1-week washout period following completion of anti-TB treatment. A panel of 48 biomarkers were evaluated using Luminex multiplex platform (Bioplex200).
Twenty soluble biomarkers were differentially expressed between Arm A (TLG<50SUVbw*ml) and B (TLG≥50SUVbw*ml). These included 9 pro-inflammatory biomarkers,1 anti-inflammatory cytokine, 5 growth factors, 2 pleiotropic mediators and 3 chemokines. Using ROC curve, 14 biomarkers were identified as potential individual candidates to distinguish between Arm A and Arm B with AUC ranging between 0.702–0.833 where sensitivity ranged between 58.6–69.0% and specificity ranged between 71.4–81.0% at specific cut-off values.
This study highlights that successfully treated TB patients remain with persisting lung inflammation. These patients further present with different soluble biomarker profiles which may be driven by lung inflammation.
The diagnosis of childhood tuberculosis is still a challenge in the world because children are generally paucibacillary moreover obtaining sputum is very difficult. Most of the existing diagnostic tests for tuberculosis are based on sputum sampling in symptomatic tuberculosis patients. The objective of this work was to detect mycobacteria by Gene Xpert MTB/RIF Ultra in the stools of children samples.
We conducted a cross-sectional study between January 2022 and June 2022on the diagnosis of tuberculosis by the Xpert MTB/RIF Ultra test from the stools. All Children under 15 years suspected of having tuberculosis from the pediatric department were included in the study. Stools samples have been collected and tested by xpert in the P3 laboratory of tuberculosis and hemorrhagic fevers of UCRC. In addition, sputum samples were also collected for Xpert MTB/RIF Ultra. The variable diagnostic performance was calculated.
We enrolled twenty-two (22) children suspected of tuberculosis. The average age of the children was 21.72 ±21.93 months. The sex ratio was sex (3,4) in favor of the male and 14% (3/22) of the patients had positive HIV status. After carrying out the Xpert MTB/RIF Ultra test from stools and sputum, 45% (10/22) of stools were positive and among the sputum 40% (9/22) were positive. The positive predictive value (PPV) and the negative predictive value (NPV) of the test Xpert MTB/RIF Ultra stool and sputum were 47,62% and 47,83%) and for sputum 45,83% and 45.45% respectively.
Considering these results, the Xpert MTB/RIF Ultra test performed on stool may be an alternative for the diagnosis of childhood TB in the absence of a good sputum sample.
Tuberculosis (TB), HIV and Helminths are serious overlapping public health problems in sub-Saharan Africa. This triple burden may lead to accelerated disease progression. Although HIV is integrated in TB programs in Cameroon, data on TB-helminth co-infection still remains limited. This study was aimed at determining the prevalence of helminths and their associated factors among pulmonary tuberculosis patients at Jamot hospital in Yaoundé, Cameroon.
This was a cross sectional study conducted at the Jamot hospital in Yaoundé, Cameroon from April 2022 to March 2023 with participants aged 18 years and above. A well designed questionnaire was used to capture sociodemographic data, clinical history and risk factors for TB, HIV and helminth infections. Sputum, stool and blood samples were collected from each consenting participant. Sputum was examined using auramine microscopy. Stool was examined using the kato-katz and Mini-FLOTAC techniques. Blood was used for HIV serology according to guidelines. TB-uninfected healthy controls were also recruited and their blood and stool samples similarly analysed.
A total of 321 sputum smear-positive TB patients (72% males and 28% females) and 65 healthy controls (54% males and 46% females) were included in this study. The prevalence of TB-HIV co-infection was 13.4% (43/321). The prevalence of any helminth infection among TB patients was 13.5% (37/274) and 7.7% (5/65) among controls. The most prevalent helminth species in this study was Ascaris lumbricoides (62%, 23/37), followed by Trichuris trichuria (19%, 7/37), Strongyloides stercoralis (5.4%, 2/37), and hookworm (2,7%, 1/37). TB-HIV-Helminth triple co-infection was found in 3 cases.
The prevalence of TB-HIV and TB-Helminth co-infection is similar. This emphasizes the fact that diagnosis and treatment of helminth infections should be integrated in TB control programs in Cameroon for a better management of the disease.
Despite evidence of its safety and efficacy in preventing infant malaria, Sierra Leone is the only country worldwide to have deployed the WHO-recommended Perennial Malaria Chemoprevention (PMC) strategy at the country level. The MULTIPLY project is evaluating extending PMC into the second year of life and strengthening PMC delivery through outreach services. We aimed to assess the acceptability and feasibility of this pilot approach among Health Care Workers (HCWs).
This was a cross-sectional mixed methods study conducted from January-February 2022 in three districts (Bombali, Port Loko and Tonkolili). A self-administered questionnaire was used among 144 HCWs and 42 CHWs actively involved in under-5 care in selected facilities (n=25). In addition, in 9 selected facilities of Bombali district, structured observations were conducted, 9 facility in-charges responded to a semi-structured individual interview as well as 13 HCWs and 4 key informants. Descriptive analysis was performed on the quantitative data, qualitative data was analyzed thematically, followed by a mixed methods analysis.
Respondents had good knowledge (score 16.4 out of 21) of the causes, symptoms and prevention of malaria. Most (93.5%) perceived PMC as an effective strategy. PMC integration alongside routine immunization was perceived as reducing HCW and caregiver costs and time-associated burden. HCWs trusted that PMC expansion through increased doses would lead to improved health outcomes. However, several existing logistical and structural barriers were documented, including stock-outs of drugs and vaccines, unavailability of supplies for PMC administration, transportation for caregivers accessing facilities and HCWs delivering outreach services, and the anticipated increase in workload due to additional reporting tools.
HCWs reported positive experiences and perceptions of PMC integrated alongside routine immunisations and the overall anticipated acceptability of the pilot strategy. Findings suggest that innovative implementation strategies will be key to overcoming the feasibility barriers identified.
Since 2014, Burkina Faso has adopted the new policy of intermittent preventive treatment of malaria in pregnancy with sulfadoxine-pyrimethamine (IPTp-SP). We assessed the effect of the 3-dose strategy of IPTp-SP on reducing the prevalence of malarial infection, low birth weight (LBW) and maternal anaemia at delivery, as well as associated risks factors in the health district of Yako, 5 years after the update of the national policy.
A cross-sectional study was carried out among recently delivered women in health facilities of Yako from July to December 2019. Sociodemographic characteristics, medical and gynaeco-obstetrics history were collected using a standardized questionnaire. We performed a microscopy and measured the haemoglobin level (Hb) by HemoCue. A multivariate logistic analysis was conducted with a significance of p <0.05.
Overall, 614 women were included. The average age was 25 ± 6 years and the majority of women (74.59%) were married, illiterate (53.83%) and housewives (69.56%). Over 92% of them said they slept under an insecticide-treated bet net (ITNs). The prevalence of malaria infection was 10.93%. The average birth weight was 2942.2 ± 462.28 grams and 11.06% were born with LBW (birth weight < 2500 grams). The use of the ITNs significantly reduced the risk of LBW, unlike the maternal age (<20 years), hypertension and the female sex of the new-born. Anaemia (Hb < 11.0 g/dl) was found in 54.77% of women, and this anaemia was severe (Hb < 8.0 g/dl) in 5.92% of cases. Young maternal age, maternal fever, malaria infection as well as a history of stillbirth were significantly associated with the risk of severe anaemia. There was no association between the number of doses of SP received and the risk of LBW.
The coverage of the IPTp strategy seems to have been improved. Studies on parasite drug resistance are needed.
Intermittent Preventive Treatment in infants (IPTi) is a strategy to prevent malaria in children living in moderate-to-high malaria transmission areas through administration of a full therapeutic course of sulfadoxine-pyrimethamine. MULTIPLY is a multicentric project aiming at implementing IPTi in three sub-Saharan Africa countries. Before IPTi implementation in Togo, we conducted a survey to estimate malaria and Plasmodium infection prevalence in children aged 10 to 23 months (U2).
A cross-sectional household survey was conducted in Haho district between Jan- Feb (dry season) 2022. Three-stage cluster random selection was carried out. Vaccination status, insecticide-treated bed net use, and children’s demographic characteristics were collected. Malaria infection was defined as positive malaria rapid diagnostic test and estimated with its 95% confidence interval (CI). A mixed-effects logistic regression model was used to assess factors associated with malaria infection. Survey data was weighted to reflect the sampling design.
A total of 685 children (51.8% male) were included with a mean age of 17 months. Eight out of ten slept under bed net the night before the interview. The prevalence of Plasmodium infection was 32.1% (95% CI: 28.6–35.7) of which a half had clinical symptoms. In the multivariable model, low educational level of the household head (primary: aOR=1.78 and no formal education: aOR=1.70; p=0.038; ref = secondary or above), presence of more than one under five years children in the household (aOR=1.47; p=0.031) and living at >5 km from the nearest health facility (aOR=1.52; p=0.042) were associated with malaria infection.
While the survey was conducted in the dry season, one third of U2 children had malaria infection. IPTi can be a promising strategy to reduce malaria burden in this vulnerable population. Strengthening outreach services and more targeted health communication could play an important role in protecting children against malaria.
T.b. gambiense human African trypanosomiasis (g-HAT) is a neglected tropical disease targeted by the World Health Organization (WHO) for elimination by 2030. The first all-oral treatment for g-HAT, fexinidazole (developed by DNDi), received a marketing authorization in DRC in December 2018 and was included as first-line treatment in the new WHO-HAT treatment guidelines and added to the 2019 WHO-Essential Medicines Lists. DNDi collaborated with WHO to support five HAT-endemic countries through EDCTP2.
The project focused on healthcare capacity-strengthening and coordination support for the appropriate use of fexinidazole, and fexinidazole surveillance and national pharmacovigilance systems support, including for the timely and efficient reporting of adverse reactions through the HAT Platform as a communication mechanism, trainings, and reinforced pharmacovigilance channels. Regarding fexinidazole surveillance, selected health facilities’ health workers were trained on WHO-HAT treatment guidelines and safety notification, including choice of internationally compatible software with Vigibase repository. Support to national pharmacovigilance systems was provided to five target countries (DRC, Guinea, Angola, CAR, and South Sudan) through baseline assessments, set-up, and training of five national and six regional pharmacovigilance units in the DRC coordinated with the DRC national PV team.
During the last two years of the project, 630 healthcare workers from 243 facilities were trained on the new WHO-HAT treatment guidelines, including fexinidazole, in the five target countries. 556 HAT patients were treated with fexinidazole, and notifications of adverse events were sent to WHO and national pharmacovigilance systems. In addition, the five national pharmacovigilance systems were equipped and trained.
This project enabled the reinforcement of five countries’ national pharmacovigilance systems and development of collaborative networking to extend safety surveillance to all drugs. Healthcare workers in all five countries were trained in the use of fexinidazole, and HAT patients are now being effectively diagnosed and treated.
Anti-SARS-CoV-2 vaccine remains a global health priority but there is scarcity of evidence on post-vaccine response from sub-Saharan Africa countries. Our objective was to assess the overall rate of SARS-CoV-2 immunity and its association according to vaccine-status and types of vaccines administered in the Cameroonian context.
A population-based sero-survey was conducted from February through July-2022 among individuals screened for COVID-19 at the Chantal BIYA International Reference Centre-(CIRCB) in Yaoundé-Cameroon. Socio-demographic, clinical features and vaccine status were collected; SARS-CoV-2 antibodies were tested on plasma using Ninonasal™ COVID-19 IgG/IgM assay. Statistical analyses were performed, with p<0.05 statistically significant.
Of the 1713 participants enrolled, median [IQR] age was 39 [31–48], 57.1% (978/1713) men, 1.6% (27/1713) had flu-like symptoms and 19.7% (337/1713) had previously SARS-CoV-2 positive. Regarding vaccination, 67.6% (1158/1713) had received at least one dose (48.5% Pfizer, 24.9% Johnson&Johnson, 18.0% Moderna; 7.8% AstraZeneca, 4.4% Sinopharm and 0.2% Sputnik-light), of whom 91.9% (1064/1158) fully vaccinated. Median duration post-vaccination was 5 [3–8] months (min: 1; max: 20). Overall rate of anti-SARS-CoV-2 antibodies was 83.9% (1438/1713), with 0.2% (3/1713) IgM, 80.6% (1381/1713) IgG and 3.2% (54/1713) IgM/IgG. Following univariate analysis, the presence of antibodies was associated with female gender (F/M, p=0.028), vaccination (Yes/No, p<0.0001), complete and partial vaccination (p<0.0001 and p=0.008 respectively), duration post-vaccination (≤5/>5months, p<0.0001), as well as with all COVID-190 vaccines except sinopharm and sputnik (p<0.0001, p=0.0002, p<0.0001, p=0.024, p=0.5 and p=0.94 respectively). Following multivariate analysis, being vaccinated and duration post-vaccination (≤5months) were predictors of the presence of anti-SARS-CoV-2 antibodies (aOR=3.13 [95%CI: 2.39–4.09]; p=0.0001 and aOR=2.5 [95%CI: 1.63–3.84]; p<0.0001 respectively).
The high-rate of COVID-19 antibodies suggests herd immunity at community-level in Cameroon following vaccination. However, rapid fading of antibodies (~5months) calls for strategies to adjust timing for booster-doses while phasing-out vaccines with poor immunity.
Tuberculosis (TB) treatment is long and complex. Here we summarise data from EDCTP-funded studies of the Tuberculosis Molecular Bacterial Load Assay (TB-MBLA) as a TB treatment monitoring tool.
Treatment naïve participants from four Sub-Saharan African countries were assessed for TB diagnosis and treatment response using TB-MBLA compared to liquid culture (MGIT) and other standard-of-care tests.
Diagnostic accuracy assessment using MGIT as gold standard showed TB-MBLA sensitivity, specificity, positive-and-negative-predictive values were 99%, 91%, 92% and 99% respectively among presumptive TB cases. TB-MBLA turn-around-time (clinic-laboratory-clinic) was <24h compared to 5–42 days of MGIT culture. 450 participants were assessed for treatment response across four studies. The pre-treatment bacillary load across cohorts was 5.33+1.33log10eCFU/mL which was cleared to zero in over 95% of the participants by month-6 of treatment. TB-MBLA revealed early bacillary load clearance in 7% (32/450) participants who achieved a stable negative TB-MBLA result by week-2 of treatment and was faster than MGIT to identify participants at a risk of disease relapse. High pre-treatment bacillary load =/>6log10eCFU/mL, was associated with failure to convert to negative by month-2 of treatment. Resolution of TB-MBLA-measured sputum bacillary load mirrored cough resolution, reduction of C-reactive protein levels in blood and correlated with MGIT culture time-to-positivity (Spearmans r= -0.5, p<0.0001) during treatment. Like MGIT, TB-MBLA demonstrated that regimens containing rifampicin-35mg/kg and rifampicin-20mg/kg-400mg-moxifloxacin cleared TB bacteria significantly faster than the standard-of-care regimen by month-2 of treatment, p=0.049 and p=0.008 respectively in DS-TB, and highlighted efficacy of bedaquiline-containing all oral regimen for DR-TB treatment. This work produced 5 African PhD graduates plus >500 clinical/laboratory scientists trained in principles of molecular diagnostic development and implementation globally.
The data shows that TB-MBLA is a robust assay for TB treatment response monitoring and anti-TB drug development. It has contributed to research capacity building across Africa and beyond.
Acute flaccid paralysis (AFP) is a sudden onset of paralysis or weakness in any part of the body in a child <15 years of age. It is caused by both infectious and non-infectious agents. The Wild Poliovirus is the most common infectious cause of AFP in children <5 years of age. There is no known medical treatment other than vaccination for prevention. The epidemiology of non-polio enteroviruses (NPEVs) remains largely unexplored in West Africa including the Gambia. This study aims to describe the characteristics of patients reported with AFP in Western Region One of the Gambia, between 2018 and 2022 and evaluate the AFP surveillance using the WHO-recommended indicators.
The study employed a retrospective records review of the AFP surveillance data of Western Region One from 2018 to 2022 recorded in the national AFP surveillance database. Data were analysed using SPSS version 20.
A total of 35 cases of AFP were reported within Western Region One from 2018 to 2022. 64% (23/35) were males and 43% (15/35) were below 5 years of age. The non-polio AFP reporting target (1/100,000 population aged <15 years per year) was achieved throughout the five years. All AFP cases had adequate stool samples. 8 confirmed cases of (NPEVs) were reported and 56% (20/35) of the cases had up to five doses of the Oral Polio Vaccine. The lowest (14%) number of cases was reported in 2020, during which no case was reported between February and August.
The AFP surveillance system is sensitive. All reported cases were investigated, and two stool samples were collected from each case, at least 24 hours between stool collection and within 14 days after the onset of paralysis. Active AFP searches should be strengthened to improve case detection in the region and health workers should be trained on AFP surveillance indicators.
Diabetes mellitus (DM) increases the risk of tuberculosis (TB) and will hamper global TB control due to the dramatic rise in type 2 DM in TB-endemic settings. Current guidelines don’t recommend TB preventive therapy (TPT) for people with DM due to an absence of evidence.
PROTID is the first randomized, double-blind trial to evaluate the efficacy and safety of 12 weekly doses of rifapentine/isoniazid (3HP) as TPT in people with DM who have latent tuberculosis infection (LTBI, n=3000), with a parallel cohort (n=1000) to measure TB risk in individuals with DM tested negative for LTBI. PROTID, run in Uganda and Tanzania, will also examine optimal ways of screening for active and latent TB, evaluate quality of DM and DM-TB care, establish cost-effectiveness and population impact, and archive samples for pathophysiological studies.
As of May 2023, 1890 participants have been screened, of whom 56.2% were LTBI-test positive, 8.5% HIV-infected, 0.5% diagnosed with TB disease and 4.9% reported previous TB. 740 participants (39.2%) have been enrolled in the trial, and 377 in the parallel cohort. Among those screened (mean age 55.8 years, 71.7% female), the mean duration of DM was 8.8 years; 38.2% were overweight and 32.2% obese, with 26.8% on insulin and a mean HbA1c of 9.4%. Further characterization showed hypertension (62.7%), myocardial infarction (1.0%), stroke (3.4%), foot amputations (5.0%), visual loss (60.9%), and peripheral neuropathy (76.9%).
PROTID will provide essential evidence regarding prevention of DM-associated TB, and DM care in sub-Saharan Africa. Its initial results show a high burden of TB and LTBI and common HIV co-infection among people with DM in Tanzania and Uganda. DM is characterized by inadequate glycemic control and frequent complications, underlining the need for interventions to improve access and quality of DM care.
Diarrheal diseases constitute a serious public health problem, particularly in developing countries and it is the second leading cause of child mortality. Self-medication and overuse of antibiotics due to the scarcity of complementary diagnostic systems can lead to the development of multi-resistant bacteria causing diarrhea. The objective of this work was to identify the bacteria responsible for diarrhea in children and to characterize their sensitivity to a panel of antibiotics used in Mali.
This study involved 554 children seen in outpatient visits at the Yirimadio community health center and diagnosed with diarrhea. Yirimadio is a peripheral district area of Bamako the capital city of Mali. Stool samples were collected and analyzed by stool culture and antibiotic susceptibility was determined by the disk diffusion method on agar medium.
The bacteria responsible for diarrheal were Escherichia coli (31.8%) and Salmonella (2.9%). In Escherichia coli strain, amoxicillin and cotrimoxazole were the most resistant antibiotics, 93.8% and 92.6%, respectively. The Extented Spectrum Beta Lactamase resistance phenotype accounted for 39.8% in Escherichia coli. A resistance of 12.5% to cotrimoxazole and cefoxitin was found to Salmonella strains.
This study showed that Escherichia coli is the most frequent bacteria involved in diarrhea in children under 3 years of age in Yirimadio, which are resistant to amoxicillin and co-trimoxazole, two antibiotics commonly prescribed in this setting.
CYP2C8 polymorphisms can impair the metabolism of the antimalarial amodiaquine and influence exposure to the key active metabolite desethylamodiaquine (DEAQ). CYP2C8*2 entailed to slow metabolism phenotype is the most frequent allele in Africa. Here we study the association between CYP2C8*2 carriage and DEAQ D7 drug level for repeated treatments. We conducted a retrospective study on achieved dried blood spot samples and drug level data from West African Network for Clinical Trials of Antimalarial Drugs (WANECAM I) conducted between October 2011 and December 2015 in Bougoula Hameau (Mali).
We analyzed 206 samples and the related data from patients enrolled in artesunate-amodiaquine arm and actively followed for 2 years. DNA was extracted with QIAGEN kit. CYP2C8*2 status was determined by PCR-RFLP. We used DEAQ day 7 plasma concentration data previously measured by High Performance Liquid Chromatography. The set of outliers with extremely high day 7 DEAQ levels were additionally analyzed by Real time PCR for the presence of CYP2C8*3 and *4. Finally, we analysed the association between homozygous genotype, drug level and the timeframe between episodes.
Out of 206 patients, 153 patients (74.3%), 40 patients (19.4%) and 13 patients (6.3%) patients were respectively *1/*1, *1/*2 and the *2/*2. During the first treatment, there was no difference in D7 DEAQ drug level between the *1/*1 and *2/*2 groups. However, when retreatment was required less than 35 days after the first intervention, a more intense DEAQ accumulation was observed among *2/*2 carriers, relative to the first episode levels (D7, + 67%), compared with *1/*1 subjects (D7, +16%).
We showed that repeated artesunate-amodiaquine administration inside a 35-day post-treatment frame leads to DEAQ accumulation, the effect being significantly higher in patients carrying the reduced function allele CYP2C8*2, suggesting an increased risk of overexposure and amodiaquine toxicity.
Unlike in developed countries, most infectious diseases such as tuberculosis (TB) and malaria continue to cause deaths in low-income countries. Recent studies have shown that hepatotoxicity during TB treatment may be related to the Arylamine N-Acetyltransferase (NAT2) acetylator polymorphism especially in countries with high TB incidence such as Cameroon. The aim of this study was to determine the NAT2 genetic variation associated with hepatotoxicity in TB/Malaria co-infected patients in Jamot Hospital, Yaoundé-Cameroon.
This was a prospective study from April 2018 - March 2019, aiming to evaluate the genetic variation in NAT2 coding region in TB patients with malaria. A total of 336 pulmonary TB patients with or without malaria infection, aged 15 years and above, were included. Each sputum sample was tested by the Ziehl Neelsen method. Whole blood sample was used for malaria detection using Rapid Diagnostic Test and microscopy. DNA was extracted by chelex method, hepatotoxicity by spectrophotometry, and genotyping done by Polymerase chain reaction followed by restriction fragment length polymorphism analyses with enzymes (KpnI, TaqI, BamHI).
Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) values were significantly higher among TB/malaria co-infected cases compared to TB mono infected patients (p=0.03, p=0.01 respectively). In the group of mono-infected TB patients, a significant difference was found for ALT values between day 1 and day 90 (p=0.021). Similarly, a significant association was found between the development of hepatotoxicity and the presence of a slow acetylator phenotype in TB-malaria co-infected (p=0.026).
The study suggests that TB/malaria co-infections and NAT2 variant phenotype are risk factors for hepatoxicity induction. Therefore, for a more efficient care, evaluation of NAT2 genotypes might be essential to reduce drug interactions and liver toxicity in case of coinfections.
In April 2010, East African Consortium for Clinical Research (EACCR) in partnership with the University of Oxford initiated the Reciprocal Monitoring Scheme (RMS). This is an innovative, practical and affordable monitoring scheme whose main aim is strategic quality management of health research for the 23 institutions that form the consortium. The main role of the RMS is to oversee the progress of clinical trials while ensuring that they are conducted, recorded, reported in accordance with approved Protocols, Standard Operating Procedures (SOPs), applicable local and international regulatory requirements and Good Clinical Practice. We share our experiences and lessons learnt in the past 13 years.
Each institution identified one or two experienced monitors who were paired with unexperienced monitors for mentorship and capacity building. Cross-country pairing was done and monitors were allocated studies to monitor. Physical training was periodically done to refresh skills and brainstorm on experiences.
A regional pool of 42 monitors were trained and paired from 6 Eastern Africa countries and 5 Northern countries. Seven sponsors have been supported to monitor thirty three (33) studies so far. The scheme offered an opportunity for cross-site sharing of best practices and networking at a cheaper cost compared to using conventional clinical research associates. Dedicating time for monitoring activities remains a big challenge for the study team and monitors.
Paired monitoring fostered capacity building and maximized sharing of best practices for quality management of internationally recognized health research. Cross-country monitoring visits promoted networking and dialogue between researchers, communities and other stakeholders.
We describe two contamination cases of Mycobacterium ulcerans clinically infected lesions by Rhodococcus erythropolis, a bacterium of environmental origin with rare cases of human infection.
Two lesion swabs collected from clinically characterized Buruli ulcer-like patients were submitted to molecular (IS2404-PCR) and biological (OA-decontamination + microscopy + culture) analyses for detection and in-vitro culture of Mycobacterium ulcerans (Buruli ulcer etiological agent) respectively.
Analysis of DNA extracts from crude samples revealed the presence of M. ulcerans DNA and the sample classified as positive. After 14-days of in-vitro incubation in Löwenstein-Jensen culture media, yellow colonies characteristic of M. ulcerans were observed. However, PCR analysis of culture suspensions revealed no M. ulcerans DNA, while Ziehl-Neelsen staining showed rough red colonies not characteristic of M. ulcerans. Further microbial identification and characterization by MALDI-TOF MS revealed the presence of Rhodococcus erythropolis. The identification was confirmed by whole-genome sequencing (WGS) to establish the genomic link between this originally called Mycobacterium erythropolis and M. ulcerans. Blasting of short reads from WGS confirmed the organism as R. erythropolis. Comparative analysis of whole genome sequences revealed low genomic relatedness between the two organisms with 5.72% average genome coverage using M. ulcerans Agy99 reference genome.
This cases illustrates that Buruli ulcer disease may be underdiagnosed due to lesion contamination by R. erythropolis and difficulties in M. ulcerans identification in the routine clinical diagnosis procedure.
Funding: This project was funded by the EDCTP2 programme supported by the EU [TMA2019PF-2693-AGBBU].
The WHO recommends the administration of Perennial Malaria Chemoprevention (PMC) alongside the Expanded Immunization Program (EPI) for children under two years. As part of MULTIPLY, a pilot-oriented research project, we described the context and assessed the perceived acceptability and feasibility of PMC implementation by key stakeholders and community actors in Haho district (Togo).
We conducted a pre-implementation mixed methods study (11/2021–02/2022). All district Healthcare workers (HCW) (n=188) of 27 health facilities and a sample of Community Health Workers (CHW) (n=43) were invited to respond to a self-administered questionnaire. Structured observations were conducted in 4 health facilities along with semi-structured interviews with 8 HCWs, 4 facility-in-charges, 4 district health system representatives, 2 CHWs, 16 caregivers and 10 community actors. Descriptive analysis was performed on the quantitative data; qualitative data were analysed thematically. Results will be triangulated following a mixed-methods analytical approach.
Overall HCWs and CHWs perceived PMC as relevant in the context of high malaria burden at district level. They had a good level of knowledge about malaria and its prevention (93.5% perceived bednets as effective). HCWs foresaw good community acceptability of PMC, due to its integration with the EPI. Although some HCWs poorly understood the rationale of PMC if children are not sick, they also believed PMC would be effective, given the positive perceptions of the preventive malaria treatment during pregnancy. Several structural and operational challenges were foreseen (e.g. distance barriers for accessing health facilities, lack of materials for PMC administration, or lack of dedicated human resources). Results from the community perspective will be further analysed and compared with these health-system insights to have a complete overview of PMC acceptability and feasibility pre-implementation.
At district level in Togo, pre-intervention acceptability of PMC was encouraging, overall. Potential barriers to the feasibility of the strategy were identified.
In addition to curative treatment against the pathogenic asexual stages of malaria parasites, targeting the transmissible sexual stages is essential to impede the spread of drug resistance. The present study relies on a clinical trial testing the benefits of combining Atovaquone Proguanil (AP) with Artemether-lumefantrine (AL) in the treatment of uncomplicated malaria. AP has been shown to prevent transmission after treatment by affecting parasite development in mosquito vector Atovaquone exhibits additional properties where it persists in the serum of treated patients for days and is also known for hindering parasite development during ookinete to oocyst and oocyst to sporozoite transition. We hypothesize that pre-established P. falciparum infection in mosquitoes may be affected by metabolized drugs in patients’ blood when ingested during a blood meal. We therefore tested the effect of the ingestion by mosquitoes of blood from AL versus AL+AP treated patients on pre-established P. falciparum infection.
Eight time points (between Day 0 to Day 28) plasma from 24 patients treated with either AL+placebo or AL+AP has been collected for mosquito feeding. Infectious blood meal was provided to laboratory-reared female Anopheles mosquitoes and infected mosquitoes were exposed 4 days later to a second blood meal containing the plasma from treated patients.
We will present the effect of treatment and days post-treatment in patients, measured by comparing the infection prevalence and intensity among mosquitoes after dissection of a subset of exposed mosquitoes. The effect of treatment and time on the dynamics of sporozoite detection and mosquito survival will also be analysed.
The present study will provide important data on alternative malaria treatments for their effect on vectorial transmission and will support decision-making for treatment policies.
We present baseline data from "Improving RETention and viral load outcomes for people taking Antiretroviral therapy through early IdentificatioN of missed doses (RETAIN)", a cohort study exploring detailed adherence metrics [viral load (VL), electronic adherence monitoring (EAM); tenofovir diphosphate (TDF-DP) concentrations and self-report (SR)] in people on ART, when initially flagged for reduced adherence.
ART-naïve people from three Cape Town ART clinics had adherence monitored by missed doses (EAM), missed clinic visits or by raised VL. At the time of first flagging by any measure, blood was drawn for HIV-1 VL and TDF-DP (indicating dosing over 4–8 weeks); urine collected for tenofovir rapid assay (indicating dosing over 3–5 days). SR adherence and EAM data were collected for the past 30 days. Initial adherence data at the time of first non-adherence are presented here.
Between July22 and March23, 61 of 282 people were flagged for poor ART adherence; 45(74%) by missed doses, 14(23%) by missed visits and 2(3%) by raised viral load. All self-reported good adherence (>90% doses taken in past 30 days), however EAM and TDF-DP showed reduced adherence across all groups [43–53% doses taken over past 30 days; suboptimal median (IQR) TDF-DP concentrations: 390 (191–677) fmol/punch (normal range >800fmol/punch)]. 56(92%) had tenofovir in their urine. Only those in the raised VL group had viremia at the time of the visit. Missed doses and missed visit were flagged sooner (35 and 45 days) than raised viral load (114 days).
All those flagged for reduced adherence had poor adherence confirmed by objective measures, EAM and TDF-DP concentrations, despite self-reporting near perfect dosing. Positive urine tenofovir reflects dosing near to the study visit (white-coat dosing). Poor adherence was noted most rapidly by detection of missed doses and missed visits; allowing time for adherence support before breakthrough viraemia occurs.
Ethics in research is one of the core pillars of responsible conduct of research which promotes good research practices and protects the rights of participants. Good ethical practices in the conduct of research is essential for high quality research. Research has shown a disparity in ethical review capacity in Africa with most countries not having national ethics frameworks with few or none-existing national ethics committees to oversee the conduct of research in these countries.
Since 1947, Medical Research Council Unit, The Gambia at LSHTM was the only research institution in the country conducting biomedical research. The country had one independent research ethics committee that was established in 1980 - The Gambia Government/MRCG Joint Ethics Committee. The committee is the only recognised Ethics Committee (EC) in The Gambia.
While the in-country research ecosystem is registering a significant growth, policies and procedures at national and institutional levels to support the ethical conduct of research are lacking. To fully identify the capacity needs, a situational analysis of the current ethical and regulatory review capacity in academic and research institutions was conducted through the ERC Grant. The assessment was done by administering a questionnaire to academic and research institutions conducting health research. The study also conducted a workshop for institutions that have functional ethics committees during which a focus group discussion was conducted, and a questionnaire administered to have an in depth understanding of capacity gaps that exist within the existing seven committees conducting review in country.
Results showed significant gap in the awareness of ethics and regulatory requirements required when conducting research.
The findings also showed that there is need for formal training on research ethics and the review process for ethics committees; the need to train a set of ethics administrators and establishing a national ethics secretariat.
First-line anti-tuberculosis drugs (FLTD) are the commonest cause of severe immune-mediated adverse drug reactions, including SJS/TEN and DRESS in PLHV. The mechanisms of these life-threatening reactions are poorly understood, making diagnosis and treatment challenging in patients who can ill-afford suboptimal treatment.
We aimed to identify genetic markers for FLTD-induced SJS/TEN and DRESS through HLA, ERAP and KIR typing, and used an integrated single-cell approach involving: i) CyTOF2 (n=8), and ii) ScRNA-seq (n=3) to characterise peripheral blood immune cells activated by offending drug.
Rifampicin (RIF)-associated DRESS was commonest. IFN-gamma ELISPOT, optimised for FLTDs, was most sensitive (75%) for RIF-DRESS. RIF-DRESS/SJS/TEN(ELISPOT+) cases were associated with HLA-B*44:03, and single-cell work was restricted to these cases and matched controls. HIV-related chronic immune activation drove expansion of exhausted (CD57+PD-1+TIGIT+) CD8+ T cells in cases and controls. However, a subpopulation of these CD8+ T cells in cases expressed co-stimulation (CD28+CD27+) markers. We confirmed these with ScRNA-seq, as KLRG1lowCX3CR1high CD8+ T-cells with RIF-specific proliferative and cytotoxic capabilities (IFNGhiTNFhiGNLYhiGZMBhiPerforinhi). The V-J junction and CDR3αβ analysis showed a unique TCR repertoire for each case, with predominantly CD8+ oligoclonality. GLIPH2 analysis of TCRβ sequences found eight common T-cell groups across the three cases. Differential gene expression identified the SQVP TCR-motif as having RIF-induced proliferative and cytotoxic profiles. Regulatory T-cells (CD127lowCD25hiCCR4hi) were higher in controls and produced more TGF-beta.
This study is the first detailed immunophenotyping work of RIF-DRESS in PLHV; including optimised ELISPOT to identify IFN-gamma T-cells to FLTD, with a strong association between HLA-B*44:03 and RIF-DRESS. We propose that, despite expanded, exhausted CD8+ T-cell populations characteristic of HIV-related advanced immunosuppression, RIF-DRESS patients have drug-specific cytotoxic CD8+ T cells, potentially sharing low-frequency TCR-motifs like SQVP. Increased functional regulatory T-cells may contribute to maintaining tolerance in HLAB*44:03+ controls. Future site-of-disease and in-vitro work is required to better define proposed pathogenic T-cell populations.
Over the years, the incidence of Human papillomavirus infections in Cameroon is on the rise (most prevalent in cervical cancer) with an estimate of 2770 new cases/year and 1787 deaths/year in women according to 2021 reports. In 2023, national statistics indicate that cervical cancer accounted for 20.9% of cancers affecting women while 2.9% of men were diagnosed with HPV-related infections. Vaccination against HPV is effective in reducing the burden of the HPV associated diseases, nonetheless 19% (Dhis-2) of girls aged 9years in Cameroon were immunized against HPV in 2022. In Cameroon, following introduction of vaccination against HPV in boys in January, 2023, Periodic Intensification of routine immunization was used to strengthen vaccination against HPV in girls and boys in 03 health districts of the Southwest region.
Microplans and lists of lost to follow up children were elaborated at health area level to identify areas with poor routine immunization performance prior to the intervention. There was also media sensitization, stakeholder meetings organized at health area and district level with local authorities. There after PIRI was conducted by each health district in 03 rounds using CHWs and healthcare providers accepted by the community. Study data was obtained from the district health information software and regional performance reports.
A total of 3401 girls and 2161 boys age 9years were vaccinated in which the region gained 8 points for girls and boys respectively when compared to 2 and 3 points the region gained in 2021 and 2022 through the same intervention.
Successful implementation of PIRI in 03 health districts with high level implication of community actors in the conflict affected Southwest region contributed to an improvement in HPV vaccination performance.
This activity was funded by UNICEF
High childhood disease prevalence and under-five mortality rates have been consistently reported in Nigeria. Vaccination is a cost-effective preventive strategy against childhood diseases. Therefore, this study aimed to identify the determinants of Incomplete Vaccination (IV) among children aged 12–23 months in Nigeria.
This cross-sectional design study utilized 2018 Nigeria Demographic and Health Survey (NDHS) dataset. A two-stage cluster sampling technique was used to select women of reproductive age who have children (n=5,475) aged 12–23 months. The outcome variable was IV of children against childhood diseases. Data were analyzed using Integrated Nested Laplace Approximation and Bayesian binary regression models (α0.05). Visualization of incomplete vaccination was produced using the ArcGIS software.
Children’s mean age was 15.1±3.2 months and median number of vaccines received was four. Northern regions contributed largely to the IV. The likelihood of IV was lower among women aged 25–34 years (aOR=0.67, 95%C.I=0.54–0.82, p<0.05) and 35–49 years (aOR=0.59, 95%C.I=0.46–0.77, p<0.05) compared to younger women in the age group 15–24 years. An increasing level of education reduces the risk of odds of IV. Other predictors of IV were delivery at the health facility (aOR=0.64, 95%C.I=0.53–0.76, p<0.05), and media exposure (aOR=0.63, 95%C.I=0.54–0.79, p<0.05). Mothers’ characteristics explained most of the variability in the IV, relatively to smaller overall contributions from the community and state-level factors (p<0.05).
The level of IV against childhood diseases was high in Nigeria. However, disparities exist across the regions and other socioeconomic segments of the population. More efforts are required to improve vaccination sensitization programs and campaigns in Nigeria.
ETEC and Shigella spp (ES) are the leading causes of diarrhea among children in impoverished areas of the world. Vaccine development for ES has been prioritized and accelerated in recent years. As promising vaccine candidates for ES move toward field trials in endemic areas, an improved understanding of the epidemiology of ES will be critical. A critical constraint is the complex, time constraining and expensive diagnostic methods currently required for detecting ES infections such as bacterial culture for Shigella, PCR of selected E. coli colonies for ETEC etc. These methods are not feasible outside a well-equipped laboratory to provide country-specific burden of ES, and not feasible for assessing vaccine efficacy in the resource poor settings (RPS). Thus, a simple and sensitive detection assay for ES is critical to fill this gap.
We developed a novel simple, rapid (<1hour), sensitive as qPCR, and inexpensive assay, RLDT (Rapid LAMP based Diagnostic Test) at JHU, which can detect ETEC (LT, STh and STp genes) and Shigella (ipaH gene) directly from stool. The assay is stable in ambient temperature, avoids maintaining a cold chain, and is mostly electricity-free.
We successfully implemented and evaluated the RLDT assay comparing with current diagnostic assays qPCR, PCR, and culture in several African and Asian countries. With funding from the EDCTP, the Centre for Infectious diseases, Zambia and GRAS from Burkina Faso were able to implement RLDT for surveillance of ES in ~2700 children seeking care to the hospitals with diarrhea. We are currently implementing RLDT in the primary health care facilities in the endemic countries.
Given, RLDT is simple, rapid, sensitive, specific, appropriate for RPS and easy to scale up, this assay is an ideal tool to fill the gap for ES disease surveillance, vaccine evaluation and case detection in the endemic countries.
Despite reduction of HIV-associated mortality in children with the implementation of antiretroviral treatment (ART), HIV-associated neurocognitive deficits are still of great concern. These are thought to result mainly from intra-cranial HIV-associated pathology. The contribution of extra-cranial infections like pneumonia is not well described. We compared neurocognitive function between infants living with HIV (ILHIV), with and without severe pneumonia.
This EDCTP-funded case-control study (TMA2020CDF-3198) was conducted among ILHIV with severe pneumonia enrolled in the EMPIRICAL trial (#NCT03915366) (cases), and age-matched ILHIV without severe pneumonia (controls). We assessed neurocognitive function using the Bayley’s Scales of Infant and Toddler Development-III within 3weeks of hospital discharge or recruitment among cases and controls respectively. We compared demographic and clinical characteristics as well as neurocognitive mean scaled scores between the two groups.
Among 66 infants (44 cases and 22 controls) included in the study, 36 (54.5%) were male and the median age was 6 months (IQR = 4.47 - 8.98). There was no difference in age (p = 0.83), sex distribution (p = 0.43), prematurity proportions (p = 0.16), breastfeeding (p = 0.56) proportion on ART and its duration, (p = 0.05, and p = 0.07 respectively), viral load (p = 0.28), or hemoglobin (p = 0.06). The cases had lower weight-for-height z-scores than the controls (-1.73 [IQR = -2.68 – 0.44] vs -0.08 [IQR = -1.85 - 0.85] respectively, p = 0.04). There was no difference in family care indicators between groups. Among infants with complete data, the cases (n=40) scored poorer than the controls (n=18) in all neurocognitive domains; cognitive (p = <0.01), language (p = 0.04), and motor (p = <0.01).
Severe pneumonia increases the likelihood of neurocognitive deficits among ILHIV. Interventions reducing the risk and severity of pneumonia may be beneficial in reducing neurocognitive decline in this population.
Shigellosis is a major public health problem worldwide. There is no vaccine to control shigellosis, which is the best way to control infectious diseases. To assess the true burden of shigellosis before proceeding with the evaluation of a candidate shigellosis vaccine, a longitudinal study was conducted in children under five years of age in a community setting.
A cohort of healthy children under five years of age from Ouagadougou’s peri-urban area was followed for twelve months. Stool samples were collected at scheduled follow-up visits (enrolment, 6-month, and 12-month) and during diarrhoea episodes. Conventional microbiology techniques plus the BD Phoenix M50 (Becton Dickinson) were used for Shigella strains identification. Shigella serotypes were identified using polyvalent antisera or PCR in case of non-serotypeable strains. Strains were tested for sensitivity to standard antibiotics.
From the 750 children followed, a total of 2170 stool samples were analysed, of which 236 were diarrhoeal. Shigella spp. was isolated from 64 stools. The annual incidence of diarrhoea was 321.8 per 1000 children (95% CI: 283.2, 365.7). The annual incidence of shigellosis was 87.7 per 1000 children (95% CI: 68.6, 112.0). The fraction attributable to Shigella infection in cases of moderate to severe diarrhoea was 4.7%. Shigella cases were more common in children older than 24 months. All four serogroups of Shigella spp were found and the most common serogroup was Shigella flexneri. All strains showed multidrug resistance. The most observed resistances were to trimethoprim-sulfamethoxazole (82.81%), tetracycline (81.25%), ampicillin (76.56%), nalidixic acid (25%) and chloramphenicol (17.19%).
This study determined the burden of shigellosis and confirmed its endemicity in Burkina Faso. The most frequent species was Shigella flexneri. The frequency of multi-antibiotic resistant Shigella spp. strains was very high. Complete typing of isolated strains is needed to guide the development of serotype-based vaccines.
CXCL10 has been shown to increase up to 200-fold during ZIKV infection in pregnant women and is associated with the pathogenesis of ZIKV. This research aimed to investigate the relationship between Zika virus (ZIKV) infection and overexpression of C-X-C motif chemokine 10 (CXCL10) in pregnant women.
The study investigated a total of 62 serum samples from pregnant women in Nigerian tertiary teaching hospitals who were positive for Zika virus IgM using RTqPCR.
Seven samples were confirmed by PCR for the presence of ZIKV RNA, indicating a prevalence of 11.1%. The quantity of ZIKV RNA detected in the seven serum samples ranged from 1.0 x 10² to 11.6 x 103 copies/ml. Further analysis revealed that CXCL10 was overexpressed in four out of the seven ZIKV-positive samples, with an increase of 4-, 24-, 27-, and 126-fold. These findings suggest a link between ZIKV viremia and CXCL10 overexpression in pregnant women. Additionally, the study identified age, gestational age, and ZIKV-related symptoms as risk factors for CXCL10 overexpression in pregnant women infected with ZIKV. Gene expression analysis revealed regulation values ranging from 1.0 to 126.2 among samples positive for ZIKV RNA.
The findings of the study provide new insights into the pathogenesis of ZIKV infection in pregnant women and suggest that CXCL10 may serve as a biomarker for the disease. Future studies may investigate the potential of CXCL10 as a therapeutic target for ZIKV in pregnant women. Overall, this research highlights the importance of understanding the immunological and virological factors involved in ZIKV infection during pregnancy.
Uganda is one of the 30 countries with a high burden of TB in the world. According to the 2014–2015 National TB prevalence survey, 39% of people with cough for two or more weeks did not seek treatment. Similarly, there was an estimated 1500 people (range 820–2300) with Drug resistant TB (DR TB) in 2018 but only 34% were notified. While Ankole region in South-Western Uganda detected 36 DR TB cases from April 2022 to March 2023, Kazo District, a majorly pastoral community diagnosed 2. Additionally, in 2021/2022, Kazo District had a case detection rate of 46% (Target 90%). There was need to improve TB case finding and therefore pairing Health workers and village health teams (VHT) to screen for TB in community hotspots was initiated.
Microplanning meetings were held with the District Health Team and USAID LPHS Ankole (TASO). A review of the District TB register was done. Hotspot mapping was done with community participation while prioritising areas with previously high TB notification. Buremba, Kyampangara and Nkungu were selected. In each hotspot, a professional health worker and a VHT were paired to do household health education, TB screening using MOH designed tools and sputum sample collection for 3 days. Samples were tested using Gene-Xpert. All diagnosed clients were started on respective treatment.
A total of 524 households were reached,1526 people were screened for TB. Presumptive TB was identified in 220/1526(14.4%) and 15/220 (6.8%) (8 male and 7 female) confirmed with TB. Of these, 13 (87%) were from Buremba. Out of the 13 clients,7(53.8%) (3 male and 4 female) had Rifampicin resistant TB.
Pairing Village Health Teams with Professional Health workers in community hotspot screening leads to high TB yield. These data provide a paradigm for optimal active TB case finding in hard to reach communities.
Serosurveillance is an important method to help monitor COVID-19 in the community in Mali. We previously adapted and qualified a two-antigen Enzyme-Linked Immunosorbent Assays for use in local laboratories using venous blood samples (95% CI, 73.9% (51.6–89.8) and 99.4% (97.7–99.9)) respectively as sensitivity and specificity). However, the burden of blood collection set cost can be challenging in resource limited region where alternative source of biological material will facilitate a large scale of COVID19 surveillance. In this study (funded by NIH) we assessed the of dried blood spot (DBS) samples to quantify Sars-Cov-2 antibodies by ELISA using RBD and Spike antigens.
Respectively 248, 226 and 391 volunteers were randomly selected from Sotuba (urban), Bancoumana (town) and Doneguebougou (village). Venous blood and DBS samples were collected, tested in parallel to assess concordance and the performances of the DBS samples. During the optimization phase (n=36), a promising concordance was found. This allowed us to analyze 829 additional samples on the Spike antigen.
We had (31/36) of samples that were COVID-19 seropositive (two category kappa 1.0) in both type of samples, suggesting a strong concordance. Analysis of the 829 samples showed a high correlation (Pearson r = 0.9239 p < 0.0001) with 98% concordance between venous blood ELISA and simplified DBS spike ELISA (kappa = 0.92). As performances, the DBS showed a sensitivity of 99% (95% CI, 98%-99%) and a specificity of 99% (95% CI, 93%-100%). It had 100% (95% CI, 99%-100%) as positive predictive value, 88% (95% CI, 79%-94%) as negative predictive value.
Overall, DBS elution and testing was comparable to venous blood testing in the Malian population, and this supports it use in large-scale SARS-CoV-2 serosurveillance studies as a valuable alternative to venipuncture. Our perspective is to optimize/adapt DBS serology to other viruses like Zika virus, Ebola virus, Dengue virus, hepatitis viruses.
Africa’s weaknesses in responding to public health emergencies triggered the University of Cabo Verde’s EDCTP/Africa CDC supported b-learning Field Epidemiology Program (2022–2024), after Mozambique{acute}s and Angola’s experiences. The Program targets 15 students from Cabo Verde (CV)(6), Guiné-Bissau (GB)(6) and São Tomé e Príncipe (3). Groups of three students completed their first field training, producing reports focusing on antimicrobial resistance (AMR) and/or One Health Surveillance within existing health information systems (HIS).
During field training students, supported by site supervisors and tutors, selected a HIS, described it, assessed its quality, and identified opportunities for improvements, namely on the possibility to expand its One Health scope.
In the three countries, the HIS for human health is structured around the platform District Health Information System 2 (DHIS2) complemented by population-based surveys. Clinical and public health services, disease programs and surveillance systems are supposed to feed their data into the DHIS2, mostly manually, although this does not always happen. AMR is not regularly monitored for lack of laboratory capacity for antibiograms; when done, it is mostly related to tuberculosis. GB is the only country reporting a National HIS Strategic Plan. Private care providers/services are not included in the DHIS2 data/information circuits.
Animal/plant health have separate information systems with variable degrees of sophistication. CV is the only country reporting the development of coordination structures with animal and environmental HIS.
Besides these experiences, students analyzed disease related data (diarrhoeal diseases, malaria, HIV, tuberculosis) and participated in outbreak investigations (shigella, influenza, rubella).
Key obstacles to develop One Health Information Systems are siloed structures for human, animal and environmental HIS, but also significant blind spots in human HIS, related to programs and services that do not dialogue with DHIS2, lack of capacity to obtain laboratory-based data and a private sector growing outside relevant data/information circuits.
About 99% of global maternal mortality occur in developing countries and Nigeria accounts for 20% of all maternal mortality. Major contributory factors include poverty, distance, cultural and religious beliefs, and ignorance. Mobile health technology (mHealth) is emerging in Africa. While SMS has been the most common intervention, mobile apps have not been explored for maternal care in Nigeria. This study describes the process of design, development, and testing of mobile app for pregnant women in Nigeria.
Using a user-centred design, we conducted semi-structured interviews at each stage of mobile app development with randomly selected pregnant women attending antenatal clinics in Oyo State, Nigeria. The first interview focused on need assessment or empathy, followed by alpha and beta testing of the mobile application prototype at health facilities in Ibadan, Nigeria.
The barriers to accessing perinatal care was distance to nearest facility (mean = 3.3km), lack of perinatal education, and cost. Low fidelity prototype of the mobile app was designed with five features (gamified microlearning, lifestyle tracking, clinic connection, financial planning, and chat). Alpha testing showed that 56% (n=7) of pregnant women surveyed considered lifestyle tracking and gamified microlearning as the most useful features of the mobile app. Mobile app increased the level of knowledge of preeclampsia by 179%. User feedback from alpha-testing informed the development of high-fidelity prototype for beta testing. 95.2% of pregnant women surveyed were willing to download the mobile app. The final app developed was uploaded on Google Playstore (MyBelle Pregnancy App) for free download.
mHealth apps have the potential to increase access to prenatal information and services in Nigeria and may reduce maternal and childhood mortality. This paper has described the process of development of first indigenous mobile app specifically for pregnant women in Nigeria using user-centred design thinking approach.
COVID-19, first reported in Wuhan, China in December 2019, was declared a pandemic in March 2020, causing restrictions of movement of people and goods worldwide. This affected every aspect of life, including the conduct of clinical trials. We highlight the challenges faced by the PediCAP consortium and how we navigated them.
The PediCAP consortium is composed of 14 partners (https://projectpedicap.org/the-consortium/) in Africa and Europe. The EDCTP-funded clinical trial (ISRCTN63115131) is enrolling children aged 2months to 6years with pneumonia in Mozambique, Uganda, South Africa, Zambia and Zimbabwe. Participant recruitment started in December 2020, during the COVID-19 pandemic; and by end of April 2023, 987 of the targeted 1100 participants (89.7%) had been enrolled. The challenges faced by the clinical sites, and measures taken to mitigate them, were obtained from minutes of monthly teleconferences and interviews with site staff, and summarized in themes.
The following were reported as challenges and their mitigating measures:
Delays in obtaining ethical and regulatory approvals: Ethical and regulatory bodies adopted paperless submissions, virtual review meetings, and used online tools to interact with applicants. Slow recruitment of participants resulting from reduction in numbers of patients attending hospitals, due to fear of contracting COVID-19, and lockdowns restricting movement. This was solved by adding a partner and satellite sites. Additionally, a no-cost extension of the project was made to allow for extension of the recruitment period. Site initiation, protocol training, procurement of trial drugs, and clinical trial monitoring were delayed/problematic. The sponsor adopted virtual platforms and local monitors to mitigate this. A need to protect site staff and participants from contracting COVID-19. Country specific COVID-19 risk management plans were developed and implemented.
COVID-19 impeded smooth progress of PediCAP trial activities. However, a joint and collaborative effort was key in navigating the challenges.
There is increasing attention to bio-banking in health research due to its value in providing rapid turnaround of research results. However, bio-banking in Sub-Saharan Africa is still in infancy and is wrought with many ethical and social-cultural challenges. There’s a dearth of research focusing on informed views of young people, who are likely to be the greatest consumers of health research information. At the KEMRI Wellcome Trust Research Programme (KWTRP) with nearly 1.5million biological specimens stored for over 30years, social science research investigated opinions about biobank/ing, and the ethical and social-cultural considerations from diverse stakeholders including youth.
One-day deliberative consultation workshop with 44/47 Young Persons Advisory Group members from three secondary schools in Kilifi County. This aimed at informing and seeking opinions of the youth on the ethical and social-cultural issues of biobank/ing. Activities included discussions about DNA, KWTRP biobank tour, plenary and focus group discussions. Topics discussed included views on sample storage, sharing, consent, assent, and benefits of bio-banking. Data was transcribed, translated to English, and analyzed using thematic analysis.
Participants seemed to understand health research and supported bio-banking due to its associated benefits. They emphasized strict adherence to ethical guidelines on sample sharing, especially confidentiality. They supported initial parental consent for continued storage and sharing of samples collected for research while they were minors. Tracing participants who transit to adults, and recall biases were some of the reasons given for not re-contacting minors to re-affirm consent for continued secondary sample use. They also suggested that assent age should be lowered to 9–16years [as opposed to 13–17 years].
Engaging the youth in bio-banking was regarded as an important step. Therefore, with careful considerations, youth can be engaged to demystify health research and bio-banking through well-tailored and suited engagement strategies.
Funders: Wellcome Trust, Global Health Bioethics Network and NIH Fogarty.
The EDCTP-funded PREV_PKDL project was designed to: i) advance the clinical development of a vaccine for prevention of visceral leishmaniasis (VL)/post kala azar dermal leishmaniasis (PKDL) and ii) to gain a greater understanding of the immune determinants of treatment outcome, using multidimensional, multiparameter phenotyping of patient cohorts recruited across the countries of the Leishmaniasis East Africa Platform (LEAP; Ethiopia, Kenya, Sudan and Uganda). Central to the latter objective was the establishment of a distributed Center of Excellence in Flow Cytometry across the collaborating sites (Ethiopia, Kenya, Sudan Uganda and UK).
Accomplishing the project objectives required acquisition of specialised equipment (CytoFLEX LX Cytometer), sourcing and validation of custom antibody panels, specialised training of flow cytometry managers, and renovation of space to develop a Flow Cytometry Laboratory. Study approvals were obtained for implementation at Kimalel and Chemolingot subcounty hospitals in Baringo County.
Multifaceted challenges were numerous, including delays in laboratory allocation and renovation, UK VISA issues precluding travel of the flow manager, supply chain delays occasioned by government requirements, late arrival of equipment, relocation of personnel and equipment from initial study site to current site, in-country insecurity and an ongoing curfew in the study area due to cattle rustling. Despite these challenges, the study has been initiated and high quality immunological data obtained from 24% of the target sample size. In addition, six Leishmania isolates have been obtained from splenic aspirates of VL patients enrolled as part of a nested collaboration that seeks to understand how parasite genotype affects clinical status and treatment response.
Developing the capacity to conduct in depth immune phenotyping of patients enrolled in clinical studies in East Africa faces many hurdles that can be overcome by perseverance and a common objective.
Funding: This project is part of the EDCTP2 Programme supported by the European Union (RIA2016V-1640).
National Ethics Committees (NECs) are critically required to ensure rigorous and ethically sound health research. In Francophone Africa, in spite of a rise in the bulk of clinical and biomedical research, and the fact that the region is highly vulnerable to emerging infectious diseases, NECs have not reached the institutional maturity of their counterparts in Anglophone Africa. To address these challenges, the Cameroon Bioethics Initiative (CAMBIN) received funding for strengthening the capacity of NECs in four Francophone African countries: Cameroon, Chad, Mali and Niger.
Through the project called "Strengthening National Ethics Committees in West and Central Francophone Africa (SNECFA)", CAMBIN supported NEC members (1) to write/update their Standard Operating Procedures (SOPs) for the review of research protocols during routine and emergency health situations; (2) register/renew their Federal Wide Assurance number (FWA); (3) develop and/or revise Training and Resources in Research Ethics Evaluation (TRREE) national supplement for their country; (4) disseminate the SOPs and TRREE national supplements and (5) draft a collaboration plan (Mali with Niger and Cameroon with Chad).
CAMBIN provided customized training programmes for NEC members. The four NECs have developed their SOPs following the WHO guidelines and are currently using them for the review of research protocols. They all have an active FWA registration – improving their international visibility. The NECs are developing and/or updating their TRREE national supplements. Finally, a groundwork for knowledge sharing, exchange of ideas and good practice between the NECs has been created through the development of two (Mali/Niger and Cameroon/Chad) collaboration plans.
The capacity of NECs in Cameroon, Chad, Mali and Niger is being strengthened. The dissemination of the SOPs and the TRREE national supplements within the scientific community will further boost their national and international visibility. Collaboration plans will be implemented in the coming months.
Malaria in pregnancy remains a major public health problem in endemic areas of the sub-Saharan African (SSA) region. However, there is limited understanding of the role of women empowerment in using Sulfadoxine-Pyrimethamine for intermittent preventive treatment of malaria during pregnancy (IPTp-SP) in the SSA region. This study examines the association between women empowerment indicators and optimal uptake of IPTp-SP (3 or more doses) in the Lake endemic region of Kenya.
We used data from a cross-sectional baseline survey of 3154 women aged 15–49 years in Kisumu and Migori Counties who had a live birth in the last two years prior to the study. Data were collected between June to August 2021. We conducted a descriptive analysis to show the distribution of respondents by key background characteristics, and bivariate and multivariate logistic regression to examine statistically significant associations between women empowerment measures (decision-making power, control of assets, education, and employment status) and optimal uptake of IPTp-SP.
Of the 3154 surveyed women, 1505 (47.7%) received optimal IPTp-SP dose during their last pregnancy. The Odds for optimal use of IPTp-SP increased among women who had: high decision-making autonomy (AOR=1.31; CI=1.10 – 1.58); 4 or more ANC visits (AOR=3.18; CI=2.64 – 3.84); interacted with a healthcare provider about IPTp (AOR=1.47; CI=1.27 – 1.71); and high knowledge of approaches to prevent malaria in pregnancy (AOR=1.99; CI=1.62 – 2.45).
The study findings suggest that maternal health interventions should focus on less empowered women (i.e. women with less decision-making autonomy), women with limited ANC visits and interaction with a healthcare provider, and those with limited knowledge of approaches to prevent malaria in pregnancy because they are less likely to achieve optimal use of IPTp-SP dose during pregnancy.
Bed nets are the main tools used in vector control of malaria. However, insecticide resistance is a looming threat on their efficacy and the gains obtained over the years. Thus, a better understanding of the resistance profile of vectors is a prerequisite towards the implementation of vector control measures adapted to local settings. We therefore aimed to evaluate the resistance of mosquitoes to various insecticides and the effect of the synergist piperonyl butoxide (PBO) on pyrethroid resistance.
Anopheles gambiae s.l larvae were collected in Lambaréné and reared until adult emergence. The susceptibility of adult mosquitoes to deltamethrin, permethrin, bendiocarb and malathion was tested using the WHO protocol with additional testing performed for permethrin and deltamethrin with mosquitoes pre-exposed to PBO.
An. gambiae s.l. mosquitoes were resistant to permethrin 0.75% and deltamethrin 0.05% with mortalities of 11% and 72% respectively, after 24 hours. Resistance to permethrin was of high intensity with mortality of 47% with permethrin 3.75% and 88% with permethrin 7.5%. The combination PBO+permethrin 0.75% resulted in a 4-fold increase in mortality to 44%. The intensity of resistance to deltamethrin is considered moderate with a mortality with deltamethrin 2.5% of 86% in the tests performed. The combination PBO+deltamethrin 0.05% resulted in a complete recovery of susceptibility with a mortality of 100%. Finally, mosquitoes were resistant to bendiocarb and susceptible to malathion with mortalities of 75% and 100% respectively.
The results obtained in this study confirm the high intensity of resistance of Anopheles to pyrethroids. However, the improvements observed with the use of PBO in terms of mortality rates suggest that second generation bed nets which are impregnated with PBO could be useful tools for vector control. These results also allow us to consider the use of malathion in combination with other insecticides to mitigate resistance.
Babies born to mothers with active TB (ATB) are at risk of poor clinical outcomes like low birth weight however, little is known about their vaccine responses. We hypothesised that these babies have reduced responses to vaccines compared to babies born to TB-free mothers.
The objectives of this study were i) to determine IgG responses to: BCG, measles, tetanus, and diphtheria vaccines and ii) to determine TB-specific cytokine responses using QuantiFERON (QFT) plasma.
A longitudinal case-control study; baby-cases (born to mothers with bacteriologically confirmed ATB) and baby-controls (born to mothers without ATB). Quantitative IgG-specific BCG, diphtheria, tetanus, and measles ELISA assays were performed on infant plasma harvested from heparinised venous blood collected on first encounter after birth (month 0), at month 3 and month 6 following immunisation as per the Uganda routine immunisation schedule for children under 1 year. Luminex (5-plex) assay for TB-specific cytokines: IL-17/IL17A, IFN-, TNF-α, IL-2 and GM-CSF was also performed on baby QFT plasma. Prism was used for statistical analysis, and P<0.05 was considered statistically significant after performing the Mann-Whitney U-test. Data was expressed as medians and interquartile ranges. Fold changes were computed by dividing medians of cases by medians of controls.
Fold change analysis revealed that cases had a 0.15-fold decrease in diphtheria antibodies and a 0.69-fold decrease in tetanus antibodies compared to controls (p=0.0281)/(p=0.0122) respectively. No significant difference in BCG and measles antibodies was observed among cases and controls (p=0.9999/p=0.6568) respectively. Also, a 1.23-fold increase in IL-17/IL-17A cytokine response among cases was observed compared to controls (p=0.0142). Finally, no significant difference in IFN-, TNF-α, IL-2 and GM-CSF cytokine responses was observed (p=0.4811/p=0.8064/p=0.1668/p=0.3881) respectively.
Maternal ATB reduces infant diphtheria and tetanus vaccine responses and causes a 1.23-fold increase in IL-17/IL-17A cytokine responses among exposed infants. Further studies are required to determine the later life response outcomes.
Schistosomiasis is a parasitic disease responsible of important morbidity and mortality in sub-Saharan endemic countries. In Senegal, national schistosomiasis control and elimination program has initiated since 2012, annual repeated praziquantel (PZQ) mass drug administration (MDA) in endemic regions in the Senegal River basin (SRB). The impact of annual MDAs is assessed at the health district level. However, considering the focal characteristic of the disease transmission, huge disparities exist at the lowest levels, such as village or contamination site.
This study consisted in following the Schistosoma haematobium infection using microscopic method in a cohort of school-age children in five villages in the SRB. Baseline prevalence was evaluated in August 2020 then 40 mg/kg of PZQ was administered. Six month after, the prevalence and reinfection were evaluated and a second treatment was administered in March 2021 following by a second prevalence and reinfection evaluation six months after.
At the baseline, very high prevalence was observed in the villages of Guia (91.2%) and Khodit (90.6%) with Human frequenting irrigation canal while moderate prevalence was noted in the village of Ndiawara (45%), and Dioundou (49%) with Human frequenting the river and also in the village of Mbane (43.1%) near the Lac de Guiers. After two six-months interval treatment, prevalence of Schistosoma haematobium was reduced in all the villages with the lowest reinfection rates noted in children frequenting the Senegal river (25.5%) and the lac de Guiers (36%), while the villages near the irrigation canal, remain hotspots with higher rates of reinfection in children (58%).
This study suggests to adept the periodicity of the MDA in the SRB at a 6-month interval in the villages near the irrigation canals, while maintaining the annual treatment in the other villages in accordance with the WHO guideline on control and elimination of schistosomiasis.
Childhood tuberculosis (TB) accounts for 12% of the 10.6 million incident cases of TB globally, and 16% of all TB-related mortality. The majority of childhood TB cases and deaths occur in TB-endemic countries where difficulties with confirming TB diagnosis with conventional sputum-based approaches contribute to poor outcomes. We present the methodological approaches and progress report from a study investigating the added value of non-sputum-based approaches for the diagnosis of TB in children in West Africa.
This is a multi-country study recruiting children (age <15 years) with presumptive pulmonary TB at study sites in The Gambia, Ghana, and Benin. Participants undergo standardised conventional clinical, radiologic and microbiological investigations for TB diagnosis. In addition, early morning stool samples are simultaneously collected for testing with Xpert Ultra (‘stool Xpert’), while Computer-aided Detection for TB-version 7 (’CAD4TBv7’; Delft Imaging, Netherlands) abnormality score are derived for their digital chest radiographs (CXR). Bayesian latent class analysis will be used to determine the added value of the non-sputum-based tests in term of relative increases in sensitivity and specificity by combining CAD4TBv7 and stool Xpert results with conventional methods.
Recruitment and investigation of eligible study participant have commenced at the three study sites, with more than 100 children enrolled from January 2023 till date. The CAD4TBv7 system has been set up at the Gambia study site. Digital CXR from the two other study sites are de-identified and transferred electronically to The Gambia, using an encrypted internet-based file transfer software, for CAD4TBv7 scoring. A blinded senior radiologist also provides independent assessment of the likelihood of TB on each CXR.
This study presents an opportunity to objectively determine how many additional childhood TB cases can be detected if CAD4TBv7 abnormality score and stool Xpert are combined with conventional diagnostic tests.
Funding: EDCTP-TALENT PhD Fellowship (Ref: PSIA2020AGDG-3317-TALENT)
Laboratory Quality Management Systems (LQMS), antimicrobial resistance (AMR) surveillance and stewardship (AMS) are important for quality patients’ care and safety. Through collaboration between Deutsche Gesellschaft für Internationale Zusammenarbeit (GIZ) and Liberia’s Ministry of Health (MOH); Health Focus GmbH (www.health-focus.de) and Integrated Quality Laboratory Services (www.iqls.net) implemented LQMS, AMR surveillance and AMS in hospitals in southeast Liberia
LQMS implementation started April 2021 with baseline assessment of five hospital laboratories, using WHO’s Stepwise Laboratory Quality Improvement Process Towards Accreditation (SLIPTA) check-list. Training topics and Quality Improvement (QI) action plans were developed to address identified gaps. Internal audit of the laboratories was conducted in April 2023, while the final SLIPTA audit is scheduled for July 2023.
For AMR surveillance and AMS, a central bacteriology laboratory was established at the JJ Dossen hospital, Harper, Maryland County; and staff were trained to perform sample analysis (bacteria ID and AST) using standard methods. Steering Committee members in each hospital perform regular AMS ward rounds. Quality indicators of antimicrobial use (i.e. correct compounds, dosage and duration) were assessed before and after AMS ward rounds.
At baseline, only the JJ Dossen laboratory reached 1-star SLIPTA threshold; and guidelines for good clinical laboratory practice and quality management were grossly inadequate. Internal audit conducted in April 2023 showed marked improvement in LQMS, with all the laboratories making overall increases in their SLIPTA points. Similarly, there was significant improvement in the antibiotic treatment guideline (due to incorporation of local antibiogram data); completeness of microbiological diagnostics; and clinical outcome.
Despite persistent systemic challenges (institutional and human), good collaboration between local and international partners, regular coaching, mentoring and supervision accounted for the successes achieved in this remote, difficult-to-reach part of Liberia. Critical stakeholders were integrated in the project to ensure continuous improvement and sustainability beyond current GIZ funding.
Among participants with PCR confirmed BU, we examined the relationship between clinical and microbiologic characteristics and wound healing as assessed using three methods for the determination of rate of healing (RoH).
Participants were grouped as fast healers and slow healers based on healing status at 8 weeks. Lesion measurements were obtained with acetate sheet tracings (2D) or Aranz software (3D) fortnightly. RoH was determined using the absolute area (AA), percentage area reduction (PAR) and linear (LM) methods at 4 weeks post-antibiotic treatment. Predicted time to healing was compared to the actual healing time. Baseline clinical and microbiological characteristics were assessed for associations with healing.
All three methods for calculating the RoH significantly distinguished between fast and slow healers (p<0.0001). The predicted healing time using the LM was comparable to the actual healing time for fast healers (p=0.34). Fast healers had shorter median time to healing [6, IQR (4,12)] compared to [24, IQR (20,33)] (p<0.0001) for slow healers. More slow healers had positive AFB (121/197(61%) at baseline, positive culture growth [52(46%), higher bacterial load at baseline (median IS404 cps/ml [500 IQR (500,1750) vs (500 IQR (250–2000; p=0.038]) and viable Mu 16srRNA (median (IQR) cps/ml [500 (500-,500) vs 0(0,500), (p=0.003)]) than fast healers. Slow healing was strongly associated with large (category II and III), plaque, oedematous lesions, longer time to clearance of viable M. ulcerans and development of paradoxical reactions.
LM predicted healing time is comparable to actual healing time. Baseline characteristics associated with healing can be considered as markers for healing to facilitate improved disease management to reduce patient and caregiver anxiety.
Funding: The work funded by WHO, MRC-UK, EDCTP, is part of the PhD work for the presenting Author who is being supported by the Senior Fellowship Grant under EDCTP2 Program for Prof. Richard Phillips.
Monitoring the safety of vaccines is a global priority and has been a major focus for the WHO. Detecting, notifying, reporting, and investigating adverse events following immunization (AEFIs) requires well-functioning reporting systems. There is substantial variation in the tracking and detection of AEFIs and many countries still report a lower share than would be expected. The global rollout of COVID-19 vaccines has been remarkably successful, with over six billion doses administered. Nigeria has modified its routine vaccine systems for tracking AEFIs related to COVID-19 and began reporting AEFIs related to the COVID-19 vaccination in 2021. Here we present the findings on the COVID-19 AEFI surveillance in the most populous state of Nigeria.
Kano is a northern Nigerian state with an estimated population of over 16 million; 40% live in urban areas while 60% live in rural communities. Line listing of AEFIs by vaccine type detected and reported following COVID-19 vaccination were collected by the Integrated Disease Surveillance and Response (IDSR) team from March 2021 to April 2023.
Out of the 19,507,819 total COVID-19 vaccine doses used, 9,321 AEFIs were reported. Majority (31%) of the vaccine doses used were Moderna with 1,514 AEFIs reported. A total of 5,307,312 were Pfizer vaccine doses (27.2%) and 1,282 AEFIs were reported. About 2,260,900 Astrazeneca vaccine doses were used while 30% (5,891,215) of the vaccine doses were Johnson and Johnson with 1,982 and 4,543 AEFIs reported respectively.
The highest AEFIs reported were from Johnson and Johnson vaccines. There is need for strengthening and continuous monitoring of AEFIs due to COVID-19 vaccines through robust safety monitoring systems. This will provide timely information helpful in building public trust about the safety of the novel vaccines which will improve COVID-19 vaccine acceptability and coverage in Nigeria, Sub-saharan Africa and globally.
Natural killer (NK) cells respond to pathogen-infected and neoplastic cells by directly killing target cells and secreting immunoregulatory cytokines. Our understanding of the role of NK cells in tuberculosis (TB) pathogenesis remains incomplete.
To gain a better understanding of peripheral blood NK cell functional changes that occur during progression to TB disease, NK cells were characterised using a CyTOF-based intracellular cytokine staining (ICS) assay in a cohort of Mycobacterium tuberculosis-exposed adolescents who were followed up over two years. To explore NK cell characteristics in human tissues, NK cells were also characterised in postmortem cohorts of TB patients who succumbed to disease, and non-TB controls who died from trauma. We characterised NK cell phenotypes and cytotoxic potential in postmortem samples from the lung, hilar lymph nodes, bronchoalveolar lavage (BAL), spleen, and peripheral blood mononuclear cells (PBMC).
Functionality scores (using Combinatorial Polyfunctionality analysis of Antigen-Specific Subsets – COMPASS) of peripheral blood NK cells were lower at distal timepoints from TB diagnosis in progressors relative to controllers. However, NK cell functionality scores of progressors increased significantly above controllers at timepoints closer to TB diagnosis. A cytokine neutralization assay suggested that peripheral NK cell cytokine and cytotoxic marker expression during TB disease were dependent on T cell bystander activation via IL-2. NK cells in peripheral blood of TB patients displayed mature, activated phenotypes, expressing higher levels of cytotoxic molecules than non-TB controls. In contrast, NK cells in tissues were phenotypically immature, and were particularly enriched in the lung of TB cases relative to non-TB controls.
We observed marked differences and between peripheral blood and tissue NK cells, where enrichment of phenotypically immature and hypo-cytotoxic (expressing low levels of cytotoxic molecules) NK cells in the lung of TB cases potentially reflects a cause and/or consequence of disease pathogenesis, which requires further investigation.
The RTS,S/AS01 malaria vaccine was introduced in Ghana, Kenya, and Malawi in 2019. Evaluation includes case-control studies designed to monitor individual-level safety and effectiveness to complement population-level estimates derived from the MVPE. Here, we discuss design and practical considerations for conducting case-control studies to measure vaccine effectiveness against severe malaria, the need for a 4th dose, and for assessment of safety outcomes.
For the severe malaria study we aimed to estimate the effectiveness of the primary 3 doses, and of the 4th dose. We also aimed to estimate rebound, if any, in children who received only the primary 3 doses. Cases were patients with severe malaria admitted to a study hospital, residing in an RTS,S/AS01 implementation area, and eligible to have received the 3rd or 4th dose of the vaccine. The case patient’s home is visited to collect data on vaccination status and other details. Four controls are then recruited from the same community, matched closely on date of birth. Vaccination status is determined from home-based records, and from clinic registers. Similar approaches were used for studies of safety outcomes.
We share preliminary results and discuss the challenges encountered and lessons learned about implementing a multi-centre case control study for a malaria vaccine, and approaches to data collection which have proved effective, including establishing surveillance, the use of specific case definitions standardized across centres, recruiting closely age-matched community controls, and obtaining reliable information from both cases and controls on potential confounding factors which may be associated with both risk of the outcome and with access to vaccination.
Case control studies are an efficient means of monitoring vaccine effectiveness and safety, but require care in design and implementation. The lessons learned from the malaria vaccine pilots will be useful for countries planning introduction of a malaria vaccine.
More than eight in ten of the world’s 1.65 million adolescents living with HIV live in sub-Saharan Africa. Despite the availability of antiretroviral therapy (ART), there is limited robust data on adherence to ART levels among adolescents, as this group is often neglected in HIV research.
Objective
Our study aimed to estimate and compare adherence levels, based on self-reporting, pharmacy-refill counts and electronic monitoring using a digital adherence tool (DAT) among adolescents living with HIV in Tanzania.
We used three measures to assess adherence levels among adolescents aged 15 to 19 years, residing in Kilimanjaro region, in Tanzania. Median adherence levels were calculated, and optimal adherence was defined as > 95% of pills taken. Adolescents used the DAT, the Wisepill dispenser (RT2000), for one month and were followed-up with a short semi-structured exit-interview. Thereafter, adolescents were interviewed about their experiences with using the Wisepill® device.
Median adherence levels were respectively 100% (IQR 93 – 100%), 97% (IQR 85 – 98%) and 72% (IQR 24 – 91%), based on self-report, pharmacy-refill counts and on results from the DAT. Strikingly, out of the twenty participants, the proportion of adolescents achieving 95% pill intake were 70%, 55% and 20% of adolescents respectively.
Even based on self-reported adherence, only less than three-quarters of adolescents achieved sufficient adherence to treatment. Therefore, interventions to improve adherence to ART regimen are urgently needed among HIV-positive adolescents, especially in resource-limited settings.
Ritonavir-boosted atazanavir (ATV/r) and rifampicin are mainstays of second-line antiretroviral and multiple anti-TB regimens, respectively. Rifampicin is a strong inducer of CYP3A4, the main enzyme involved in atazanavir metabolism, causing drug-drug interaction (DDI) in those co-infected with HIV and TB, which might be exaggerated in pregnancy. We employed physiologically-based pharmacokinetic (PBPK) modelling to investigate atazanavir pharmacokinetics during coadministration of rifampicin and ATV/r in pregnancy.
A pregnancy PBPK model was developed from a published adult PBPK model by incorporating pregnancy-induced biological changes. Predicted pharmacokinetic parameters in pregnancy were validated with published clinical datasets for once daily (OD) rifampicin 600 mg and clinical data for ATV/r (300/100 mg) in pregnancy (NCT03923231). Predicted atazanavir Ctrough was compared against its protein-adjusted IC90 (14 ng/ml) when simulating the coadministration of ATV/r 300/100 mg OD and rifampicin 600 mg OD in pregnancy. Alternative dosing regimens were also explored.
The pregnancy model was considered validated when the absolute average fold error (AAFE) for Ctrough and AUC0–24 of ATV/r 300/100 mg OD and for Cmax and AUC0–24 for rifampicin 600 mg OD were <2, when comparing predicted vs observed data. Similarly, comparison of predicted and observed plasma concentrations of atazanavir and ritonavir in the sparse pregnancy data (NCT03923231) gave AAFE values <2. Pregnancy was predicted to increase the rifampicin DDI effect on atazanavir. For the dosing regimens of ATV/r 300/100 mg OD, ATV/r 300/200 mg OD and ATV/r 300/100 mg BD (all with rifampicin 600 mg OD), predicted atazanavir Ctrough was above 14 ng/ml in 29%, 71% and 100%; and 32%, 73% and 100% of the population in second and third trimesters, respectively.
PBPK modelling suggests ATV/r 300/100 mg BD could maintain antiviral efficacy when co-administered with rifampicin 600 mg OD in pregnancy. Clinical studies are warranted to confirm safety and efficacy in pregnancy.
Children with Sickle Cell Disease (SCD) have decreased spleen function which is responsible for increased susceptibility of SCD patients to malaria and other infections. There is evidence that hemoglobinopathies such as SCD may influence the activity of artemisinin derivatives by altering their accumulation and binding to target molecules within the parasitized erythrocyte. If hemoglobinopathies alter the efficacy of Artemisinin-based Combination Therapies (ACTs) through an attenuated effect of the artemisinin component, further research into dose optimization would be justified. Currently there is no data on the disposition of ACTs and malaria parasite kinetics in children with sickle cell disease in Kenya.
A proposed five-arm open-label, prospective, randomized, clinical trial will be conducted at the KEMRI Kondele Children Hospital in Kisumu, Kenya. Children less than 18 years with SCD and co-infected with P. falciparum will be enrolled based on the set inclusion and exclusion criteria with up to 20 participants in each of the of the five (5) arms. The aim is to evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) of artemether-lumefantrine (AL), artesunate-amodiaquine (ASAQ), Dihydroartemisinin-piperaquine(DHA-PPQ), artesunate-mefloquine and artesunate-pyronaridine (AP) fixed-dose combinations in children with uncomplicated falciparum malaria and sickle cell disease. Samples for PK/PD analysis and malaria will be taken at specified time points. Mathematical modelling based on the following set criteria will be conducted: phenotype- percentage of haemoglobin F, makers of splenic dysfunction, previous exposure to prophylactic antimalaria drug- chlorproguanil and malaria parasite kinetics.
The results of this proposed study will bridge the gap of knowledge on the disposition of ACTs in children with SCD as well as help in formulating new or review current treatment for malaria in children with SCD.
The burden of MiP remains high with adverse effects on the health of both women and their offspring. In endemic areas, pregnant women are generally asymptomatic with low parasitemia which can be missed by malaria RDTs, but affecting the pregnancy course. We postulate that proactive screening with highly-sensitive RDTs (HS-RDT) and treatment of those found infected using dihydroartemisinin piperaquine (DP), in addition to standard intermittent preventive treatment in pregnancy with sulfadoxine-pyrimethamine (IPTp-SP) could improve maternal and infant health.
Pregnant women with gestational age of 16 to 24 weeks were randomized to receive screening and treatment with DP and IPTp-SP or IPTp-SP alone until delivery. Biological samples were collected for participant management and study purposes. Primary and secondary end- points were the prevalence of placental malaria, maternal anemia, maternal peripheral infection, and low birth weight.
Malaria infection was detected in almost one on four (1/4) of the pregnant women at recruitment. No difference was found between study arms in terms of placental malaria infection (adjusted odds ratio, 1.54 [95% confidence interval, 0.95–2.53]; P = 0.082). At delivery, the prevalence of peripheral maternal infection was slightly lower in the intervention group compared to the one of the control group but the difference was not statistically significant. Increasing number of IPTp-SP doses was associated with a significantly lower risk of peripheral malaria infection and low birth weight.
Pregnant women should initiate antenatal care as soon as possible in order to fully benefit of malaria preventives measures. Strategies addressing late attendance to ANC with early start of IPTp-SP among eligible pregnant women should be developed and implemented.
Funding: This project is part of the EDCTP2 programme supported by the European Union (grant number TMA2018CDF-2397-ASSER MALARIA)
This present study aimed to test whether providing Bacillus Calmette-Guérin (BCG) vaccine to health care workers (HCW) could reduce non-planned absenteeism due to infectious disease, including COVID-19, by 20% and thereby decrease the potential impact of the COVID-19 pandemic in health care systems in Africa.
We conducted a single-blinded placebo-controlled multi-center randomized trial in Guinea-Bissau and Mozambique between December 2020 and June 2022. Participants were randomized 1:1 to an intradermal standard dose of BCG vaccine or placebo (saline) and followed by telephone interviews every 2 weeks for 6 months. Days of unplanned absenteeism was analysed using Bayesian negative binomial regression yielding relative risk ratios (RRs). The incidence of infectious diseases, COVID-19 infections and all-cause hospitalizations were analysed in Cox proportional hazards models proving hazard ratios (HRs).
A total of 668 (Guinea-Bissau, n=503; Mozambique, n=165) HCWs were enrolled in the trial; 95% (636/668) completed follow-up. The RR of unplanned absenteeism for BCG vs placebo was 1.21 (0.52–2.46) in Mozambique, 1.34 (0.75–2.20) in Guinea-Bissau. The HR in the combined analysis HRcombined was 1.29 (0.81–1.94). The incidence of infectious disease episodes yielded a HRcombined of1.18 (0.97–1.45). No protection against COVID-19 infections was observed (HRcombined=1.19 (0.80–1.75). There tended to be a protection from all-cause hospitalization (HRcombined=0.51 (0.13–2.03)).
This study did not find that BCG could reduce absenteeism, on the contrary there was a tendency towards a greater risk of self-reported absenteeism, infection episodes and COVID-19 infection. However, BCG tended to reduce the risk of severe of disease in terms of the risk of hospitalizations, aligning with other randomized trials showing protective effects against more severe outcomes.
TB preventive therapy (TPT) is recommended to household contacts (HHCs) exposed to active tuberculosis (TB). Among contacts of multidrug-resistant tuberculosis, 80% were deemed eligible for TPT using World Health Organisation (WHO) criteria: HIV-infected, aged <5 years or TB-infection (TBI). This finding questions the need for TBI testing prior to TPT initiation. We determined TPT eligibility among drug-sensitive TB (DS-TB) index households in Lesotho, South Africa, and Tanzania.
We enrolled DS-TB index cases and their HHCs. Index cases were enrolled if aged ≥18 years, microbiologically confirmed with TB within ≤6 weeks of diagnosis. Blood specimens were taken from HHCs aged ≥5 years, HIV-uninfected or unknown status and tested with QuantiFERON-TB-Gold-Plus (QFT-Plus) for TBI. HIV testing was offered to HIV-uninfected HHCs and those who didn’t have recent HIV test. Those HIV-infected, aged <5 years, and those with TBI were considered eligible for TPT.
We enrolled 340 TB index cases and 964 HHCs [321 Lesotho, 300 South Africa, and 343 Tanzania] from July 2021 to September 2022. HHCs aged <5 years were 14% overall (138/964): [16% (50/321) Lesotho, 3% (9/300) South Africa, and 23% (79/343) Tanzania]. In total, 10% (96/964) of HHCs were HIV-infected, of whom 94% (90/96) were self-reported and 6% (6/96) diagnosed at baseline: [12% (40/321) Lesotho, 13% (39/300) South Africa and 5% (17/343) Tanzania]. Of 624/733 (85%) who tested for TBI, 49% (304/624) were QFT-Plus positive overall: [53% (100/187) Lesotho, 56% (119/212) South Africa, and 38% (85/225) Tanzania]. Overall, the proportion of HHCs eligible for TPT using WHO criteria was 63% [535/855, 95% Confidence Interval 59–66%]: 69% (190/277) Lesotho, 64% (166/259) South Africa, and 56% (179/319) Tanzania.
Approximately two-thirds of TB-exposed HHCs were eligible for TPT. Further work on cost-effectiveness of TBI testing should be considered to explore the utility of testing in high burden settings.
Lymphatic filariasis (LF) is a parasitic disease caused by filarial nematodes. An estimated 40 million individuals infected with the filarial nematodes present with the symptomatic LF manifestations of lymphedema (LE) and hydrocele. These symptoms develop in only a subgroup of infected people, and host genetics have been attributed to the disease heterogeneity. Studies that have sought associations between LF and host genetics have focused mainly on candidate genes. The current study aimed to conduct the first genome-wide association study (GWAS) to determine LF susceptibility.
Single nucleotide polymorphism (SNP) data from 3189 participants comprising 1508 LF cases and 1681 asymptomatic controls were analysed in the study. Cases were selected based on the presence of either LE and/or hydrocele while controls consisted of participants who had lived in the endemic community for at least 10 years and had no LE and/or hydrocele. These unrelated participants were genotyped using the Infinium Global screening array with multi-disease drop by Illumina®.
Independent signals, rs2245413 and rs2245710 were observed at genome-wide significance (p<5x10–8) to be associated with LF. At the HLA locus, SNP rs7742085 located near the HLA-DQB2 gene was identified at genome-wide significance to be associated with LF susceptibility (P = 3.93 x 10–8, odds ratio [OR] = 1.43 [confidence interval {CI} 1.26–1.63]. Other studies have associated these SNPs with renal abnormalities, LE and hydrocele. Additionally, at three non-HLA loci, close to the genes OR5V1 (rs1419637), RNU6ATAC11P (rs2243492), and PAK1 (rs2852388), suggestive evidence of LF associations (P 1.0 x 10–6) were also observed.
This first stage GWAS in Ghanaian population identified novel SNPs associated with LF risk, highlighting the potential of GWAS to provide gene candidates for functional analyses as therapeutic targets toward the World Health Organization’s 2030 elimination goal.
Tuberculosis infection (TBI) testing and treatment are fundamental to achieve TB elimination ambitions. Among household contacts (HHCs) of TB patients, the uptake of TBI testing is limited, in part due to a lack of gold standard test and challenges associated with implementation, which vary by available tests. Our study evaluated the prevalence of TBI among HHCs and determined concordance of QuantiFERON-TB-Gold-Plus (QFT-Plus) to QIAreach QuantiFERON-TB (QIAreach), a new field-friendly lateral-flow-nanoparticle-fluorescence assay.
In a cross-sectional study in Lesotho, South Africa and Tanzania, blood samples were collected from HHCs at an initial household visit using a single lithium heparin tube for paired QFT-Plus and QIAreach processing, testing and interpretation following manufacturer’s guidelines. TBI prevalence was determined using QFT-Plus result. We assessed percentage agreement between QFT-Plus and QIAreach using Cohen’s Kappa.
We enrolled 964 HHCs [321 in Lesotho, 300 in South Africa, and 343 in Tanzania]. Of this, 465 HHCs had paired results, of whom 65% (302/465) were females with a median age of 27 years (interquartile range: 13, 45). TBI prevalence was 51% (236/465). Among HHCs with paired results, 42% (197/465) were positive and 34% (156/465) negative on both assays, while 24% (112/465) had discordant results. Total agreement was 78% [353/451, 95% Confidence Interval (CI): 74 – 82, kappa = 0.5627, p<0.001] with a positive agreement of 77% (197/255, 95% CI: 71 – 82) and a negative agreement of 80% (157/195, 95% CI: 74 – 85).
Among HHCs in three high-burden countries, we identified a high TBI prevalence. QIAreach demonstrated a moderate concordance against QFT-Plus. However, in the absence of a gold standard test, it is difficult to interpret the implication of this finding. Further research is needed to understand its usability in this population, specifically if it addresses field implementation challenges associated with similar TBI tests.
Covid-19 emerged as global pandemic during the past three years, with an unprecedented impact on public health. SARS-CoV-2 epidemiology was poorly understood, especially in the African context. A particular gap in knowledge was the effect of HIV and tuberculosis (TB) on the outcomes of Covid-19 disease. We implemented a research study that addressed critical questions concerning Covid-19 disease epidemiology in the context of low resource countries with high burden of poverty, and high rates of TB and HIV. This study was highly collaborative, with investigators from Namibia and Botswana working with colleagues in Europe, and with an NGO in Namibia which supported rapid implementation. Here we are reporting on preliminary data since recruitment is ongoing, focusing on the co-infection rates of HIV, TB and Covid-19.
Recruitment commenced in July 2022; we followed a two-pronged approach: first, all primary healthcare facility (PHC) attendees were approached for TB infection, TB disease, Covid-19 and HIV screening. Second, we followed-up Covid-19 patients as diagnosed by the Ministries of Health, and tested these index cases and their households for TB infection, TB disease, Covid-19 and HIV.
Preliminary results for the primary healthcare facility component: we enrolled 1523 participants. 840/1523 (55%) were male, 55/1523 (4%) were younger than 20 years, 923/1523 (61%) between 20–40 years old, and 545/1523 (36%) older than 40 years. 246/1523 (16%) were HIV infected. 33/1157 (2.8%) had active TB and 624/1415 (44%) had latent TB infection. 470/1523 (31%) were not vaccinated against Covid-19, and 110/1523 (7%) partially vaccinated.
To note is the high active TB prevalence. Future analyses will include investigating risk factors associated with these differential rates. We believe our findings will contribute to the growing literature on Covid-19 in high burden TB/HIV settings, and to the rationale behind universal active TB screening at primary healthcare facilities.
Sexually transmitted infections (STIs) and bacterial vaginosis (BV) are often asymptomatic in women but cause genital inflammation, which increases HIV risk. The Genital InFlammation Test (GIFT) point-of-care device for detecting genital inflammation is being developed and evaluated. We aimed to explore the main purpose of GIFT and potential integration points within World Health Organization (WHO) STI guideline pathways.
An adapted Delphi method was employed to gather input from experts in the field of STI/BV management. Health service providers, programmers, researchers and policy makers were recruited as respondents. The survey was designed with input from the project’s International Advisory Board. Round-one had open-ended questions, including on the purpose of GIFT. Themes from round-one informed the round-two survey, which included integration points for the device into guidelines for the management of STIs/BV (WHO, 2021). Responses were measured on a 5-point Likert scale (strongly agree to strongly disagree) to build consensus. Consensus was reached if ≥70% of participants selected strongly agree or agree.
A total of 79 experts responded across both rounds. Most participants were aged 25–54 years, and 58% of respondents were female. Feedback from round-one suggested the GIFT device would be best used to screen for inflammation prior to etiological diagnosis. Round-two survey results showed that WHO-recommended syndromic management pathways 3 and 4 (where molecular assays and point-of-care tests are not available) are ideal integration points for the GIFT device in STI management.
The GIFT device promises to be a valuable point-of-care screening tool for detecting genital inflammation in asymptomatic women and may be useful to inform the management of women with symptoms. The device would be of greatest value in resource-constrained settings where molecular assays and other rapid diagnostics are lacking. Stakeholder consultations will facilitate its roll-out and use within healthcare systems.
Early detection of pathogens is of outmost importance for managing epidemic outbreaks. Primary healthcare laboratories in low-and middle-income countries often lack comprehensive diagnostic and surveillance capacities due to limited resources and infrastructures. The Gates Foundation supported the International Centre for Genetic Engineering and Biotechnology (ICGEB) in establishing a platform for the sustainable transfer of diagnostic and surveillance technologies to community laboratories in Africa. The technology transfer is facilitated through an initial testing at ICGEB followed by a multicentric clinical trial in recipient countries, while support for regulatory approval is also provided. This workflow was successfully applied to an isothermal amplification colorimetric molecular assay (RT-LAMP) for RNA viral detection.
The testing of RT-LAMP for SARS-CoV-2 developed by New England Biolabs was based on a multicentric observational and cross-sectional clinical study on 1657 prospective swabs collected in four African countries and Italy. The sample size included 25% negative, 50% positive and 25% weakly positive samples, while extracted RNA was tested in parallel with the diagnostic standard RT PCR. The test was rolled out to six additional African countries and a further optimized version allowing to skip RNA extraction was tested in four countries, such that the current field trial tested 2419 swabs and 589 saliva samples.
RT-LAMP from swabs resulted highly specific (98%), with positive predictive value 99%, and 87% sensitive with negative predictive value 70% compared to standard RT PCR. Stratification of RT-PCR data showed superior sensitivity achieved with a cycle threshold (Ct) below 35 (97%), which decreased to 60% above 35. Similar values were obtained with saliva direct testing. The test was approved in Kenya and Nigeria.
RT-LAMP performance is comparable to RT-PCR, particularly with medium-high viral loads, hence it can be deployed in resource-limited settings for timely management and prevention of COVID-19 and other diseases.
Gender is a social determinant of health. Gender power dynamics can impact women’s and children’s health outcomes. The Demographic and Health Survey (2015) showed that 68% of women participated in decisions about their own healthcare in Malawi, but there is a lack of information on the socio-determinants and gender attitudes associated with primary health decision-making. This study aims to examine these factors during the male clinic days (health education activities) in four healthcare facilities in Southern Malawi.
We included men who participated in the male clinic days between August and November 2022. The main outcome of interest was the extent of women’s participation in their own healthcare. We designed a questionnaire that included the Gender-equitable Men Scale (GEM), which measures attitudes toward gender equality on a scale of 0 to 1. In addition, we collected socio-demographic, relationship, and family-related variables. Univariable and multivariable analyses revealed the association between the main and the other variables.
422 men were included in this study. The average GEM score was 0.53 (0.37–0.67; 95% CI: 0.004). Among the participants, 64.2% (271/422) reported that their female partners did not have the final say in healthcare decisions. When female partners assumed primary decision-making roles (35.8%, 151/422), men reported higher levels of gender-equitable attitudes compared to cases where men were the primary decision-makers (0.57 vs 0.47, p=0.004). Factors such as higher education level, location, formal employment, and male village chiefs emerged as the main socio-determinants associated with women’s decision-making role in health.
This study emphasizes the significance of socio-economic factors and gender-equitable attitudes in healthcare decision-making. This suggests the need for targeted interventions involving both men and women in discussions about healthcare decisions.
Children under the age of five are generally more susceptible to respiratory viral infections, but during the pandemic there have been many reports that children have a low risk of severe SARS-CoV-2 infection. It has been questioned to what extend children have been infected with SARS-CoV-2. We therefore conducted a survey to determine the prevalence among children under 5 years of age in Guinea-Bissau and investigate potential risk factor related to COVID-19 infection.
This is a cross-sectional study, carried out in children under 5 years of age in the study area of the Bandim Health Project, a health and demographic surveillance system located in Guinea-Bissau, between April and July 2022. SARS-Cov-2 antibodies were investigated using rapid diagnostic tests (OnSite Rapid Test, CTK Biotech, USA) to determine the prevalence. Risk ratios (RR) were calculated with 95% confidence intervals using binomial regression.
The study included 831 children. The overall prevalence of SARS-Cov-2 antibodies was 51% (423/831). The prevalence was lowest among the youngest children aged 6–11 months. Older children had significant higher RRs, ranging from 1.47 (12 -23 months) to 1.80 (48–59 months). Other risk factors included whether the child had attended school/kindergarten: RR=1.33 (1.15–1.54); whether child had been ill during the pandemic: RR=1.22 (1.03–1.44); whether someone had died in the house, RR=1.40 (1.15–1.70) and children whose guardian (usually the mother) had attended school for more than five years, RR=1.49 (1.26–1.75).
Confirmed cases of SARS-CoV-2 in Guinea-Bissau only represent about 0.5% of the population. However, this study indicates extensive circulation of SARS-CoV-2 since more than half of children under five year of age tested positive for SARS-CoV-2. Age of the child, deaths occurred in the house and education level of the guardian were all associated with previous SARS-CoV-2 infection.
Stool-based TB diagnostics (SbTBD) are reported to contribute to increased rates of bacteriological confirmation in children and people living with HIV. However, there is a lack of evidence on perceived feasibility and acceptability of SbTD in TB high burden countries. Within the Stool4TB project, funded by EDCTP, this study aimed to assess healthcare providers’ (HPs) perspective on the feasibility and acceptability of SbTD.
A qualitative study was conducted across five health facilities and four communities within the Manhica District (Mozambique). Twenty-one semi-structured interviews were conducted with HPs, from February 2022 to March 2023. The interviews were transcribed, coded, entered in a matrix and analyzed using the Diffusion of Innovation and symbolic power theories.
According to HPs, the SbTD can be suitable for diagnosis of TB in people who have difficulty in producing sputum, especially children; the approach is considered simple, non-traumatic, and feasible supporting sample capture across all age groups. However, according to respondents, the acceptability of this technique might vary among the patients. Refusals might be due to delays in receiving assistance; lack of awareness about the technique; fear and disgust of touching stool; the association of stool with witchcraft and local beliefs about TB transmission. On the other hand, acceptability could depend on: feeling obliged to comply with government recommendations; the good experience with health services, and the expectation of being cured.
HPs view Stool-based TB diagnostics as a more advantageous approach in terms of feasibility compared to other diagnostic strategies, such as sputum-based approaches. However, patient acceptability may be compromised due to existing health services challenges and perceptions about stool and TB. Acceptability could be promoted by the dissemination of information about the SbTD, enforcement of awareness raising about TB and SbTD, and increasing experience and trust in the health services.
Antimalarial drug resistance is a major drawback to malaria elimination agenda. In response to widespread chloroquine (CQ) failure, Nigeria’s Health Ministry outlawed the drug for uncomplicated malaria treatment in 2005. Several studies have consistently reported a reversal to CQ susceptibility by Plasmodium falciparum years after hiatus. However, non-adherence to treatment guidelines and anecdotal repurposing of CQ potentially encourage the persistence of drug pressure favoring the fitness of the mutant allele. In this study, we investigated the existing prevalence of a point mutation at position 76 associated with P. falciparum chloroquine resistance.
Sixty-three P. falciparum isolates were collected from Oriokuta Health Centre, Ikorodu, Lagos, during the drug therapeutic efficacy assessments conducted in 2021. Deoxyribonucleic acid (DNA) was extracted and malaria positivity was confirmed by Pf 18S rRNA. Subsequently, the DNA samples were assayed by polymerase chain reaction (PCR) and restriction fragment length polymorphisms (RFLP) to determine the prevalence of Pfcrt-K76T mutation.
RFLP analysis identified 39/63 (62%) wild-type K76 and 24/63 (38%) mutant 76T genotype.
Our finding points to an evolving epidemiology of Pfcrt K76T alleles. There appears to be an indication of a potential decline in the frequency of 76T mutation. However, this requires further substantiation using advanced variant validation tools in a larger parasite population.
The development and validation of novel vaccines requires specific expertise in many subjects. Scientists often require specialized training when they enter vaccinology from an adjacent field or advance a vaccine candidate to the next stage of the pipeline. The limited availability of this training represents a key gap in the field. This issue affects academic labs and small biotech companies which lack in-house knowledge regarding specific areas. We have found that access to training opportunities is particularly needed by groups in sub-Saharan Africa, and is critical to strengthening local capacities.
From May 2017 through April 2023, the Horizon 2020 program TRANSVAC2 worked to address these gaps by offering free training courses in addition to scientific services.
14 modules were developed pertaining to various vaccinology subjects, and 31 separate trainings sessions were attended by over 400 trainees from 44 countries—including 19 different low- and middle-income countries (LMICs). Selected applicants were offered seats in the courses with no registration fees and free accommodation.
5 years of hosting the TRANSVAC courses has provided several lessons on the needs of professionals in both the academic and industrial vaccine fields. The course organizers are now transitioning from the European Commission-supported framework to a new operational model. Through this model, we will continue offering established, highly demanded courses to the vaccine community and introduce new trainings, including the development of accessible eLearning modules. This process aims to build upon the experiences and reputation of the program to form a new, sustainable platform for vaccine courses.
Vector control, identification of at-risk populations, and the encapsulation of community perceptions remains a prerequisite to planning and designing as well as the implementation of control measures. MDA is the gold stand technique in the control of schistosomiasis in Africa. Hence the objectives of this study were to investigate community perceptions of the disease and determine the prevalence and Risk factors of urogenital schistosomiasis in Northern Malawi.
A total of 1841 in-depth interviews (IDIs) were conducted between April 2022 and May 2023. The study also enrolled 251 participants that responded to the in-depth interview and submitted urine for microscopy. The study also conducted a seasonal snail survey in Karonga, Rumphi, Nkhatabay, and Nkhotakota districts for species distribution and infection status.
In general, out of the 1841 study participants involved in the IDIs, less than 20% had a fairly good level of knowledge about the disease, its spread, and prevention techniques. Out of 251 children that were enrolled 87 (34.7%) were found to have S. haematobium eggs. Chi-square analysis established that having a parent in rice farming (p=0.029) occupation is a key risk factors for urogenital schistosomiasis. It was also surprising to note that those schoolchildren who received Praziquantel during MDA had significantly higher prevalence (p=0.010). Furthermore, this study revealed that they are no association between a child involved in MDA advocacy campaigns and a level of knowledge on schistosomiasis transmission. Bulinus and Biomphalaria were found to be the abundant species and Bulinus was found to be the key vector.
At the local level, malaria transmission persists through hotspots. Besides other known factors, the distribution of malaria hotspots may be shaped by environmental variables. However, research focusing on this aspect has been relatively scarce in Gabon. This underscores the need for further investigations to elucidate the specific environmental factors together with a specific intervention, that may contribute to the distribution of malaria hotspots, taking into account the spatio-temporal effect in Gabon.
These data were part of the Demographic Health Survey program from 2000 to 2015. Hotspots of malaria prevalence for cluster of households were identified using the local Getis-Ord Gi* statistic. The effect of covariates on the outcome was assessed using a Bayesian space-time framework with a Binomial model, implemented in the Integrated Nested Laplace Approximation (INLA), using the Stochastic Partial Differential Equations approach (SPDE).
A total of 316 clusters were initially considered, out of which 257 clusters with known hotspot status were included in the analysis. Among these clusters, approximately thirty percent were persistent hotspot over time and concentrated in rural areas. Using a spatio-temporal model, association between malaria prevalence hotspot variation and two key factors was found: years and rainfall. Each additional year or amount of rainfall was associated with an increase in the odds of hotspot occurrence (adjusted posterior odds ratio [AOR]: 1.32, 95% confidence interval [CI]: 1.03–1.69 and AOR: 1.15, 95% CI: 1.02–1.30, respectively). Furthermore, the analysis found that clusters of households with high insecticide-treated net (ITN) coverage were less likely to be hotspots (0.19 (95% CI: 0.06–0.61)).
These findings highlight the spatio-temporal dynamics of hotspots and the role of the rainfall, in influencing their occurrence. Moreover, the protective effect of high ITN coverage suggests the importance of targeted interventions in mitigating hotspot formation and malaria transmission.
There exists a remarkable knowledge gap on the effectiveness of schistosomiasis control interventions for pregnant women and children below 5 years of age, resulting in a lack of public health policies and initiatives targeted to these vulnerable groups. We address this gap with the freeBILy trial in Madagascar, which evaluates a test-and-treat strategy (POC-CCA testing and PZQ treatment) in pregnant women and their young children against the status quo.
We model the cost-effectiveness of the strategy in comparison to three alternatives: PZQ treatment after a Kato-Katz positive result, presumptive treatment if symptomatic, and preventive chemotherapy. We develop separate models for pregnant women and their young children, which include deterministic and probabilistic sensitivity analyses. Notably, in the model for pregnant women, we employ health-related quality of life (HRQoL) as a metric to represent the health outcomes of the compared strategies. HRQoL was derived from the administration of EQ-5D-3L questionnaire to 500 pregnant women enrolled in two trial training sites at four time points, twice before and twice after giving birth. While this data will not be considered for the estimate of intervention effectiveness, it provides invaluable information for the economic evaluation. HRQoL was also estimated alongside Gabon freeBILy trial among 630 pregnant women and used in the sensitivity analysis.
Preliminary results point to a potential increase in HRQoL in the intervention group (POC-CCA testing and PZQ treatment) in comparison to the control group in Madagascar. However, these results will have to be validated against trial effectiveness measures. In addition, the final cost estimates of the compared strategies will determine the cost-effectiveness of the evaluated strategy.
The results will inform policy about which strategy to prioritize given resource constraints in Madagascar and similar settings.
Funding: EDCTP, RIA2016MC1626
During malaria in pregnancy (MiP), Plasmodium falciparum-infected erythrocytes sequester in the placenta, causing placental malaria (PM) and poor pregnancy outcomes, including low birthweight, preterm birth, and stillbirth. Mouse data indicate that innate immune response to PM on the placenta’s maternal side adversely affects the foetus and in response, the placenta’s foetal side mounts an innate counterresponse that improves foetal outcomes. However, this has not been observed in human PM.
We used histological and molecular analyses to characterize the PM status of bio banked placentas and corresponding maternal sera. Molecular tools were used to characterize innate immune responses to human PM in the foetal and maternal sides of the placenta.
Histology and molecular assays showed that 50% of women who had no history of MiP and had received malaria chemoprophylaxis, had PM. Among women with MiP history, the PM rate was 70%. RT-qPCR revealed that foetal sides of PM-negative samples had lower levels of Toll-like receptor (TLR)- 4 and 9 when compared with maternal sides of the same placentas. However, in PM-positive placentas, their levels were higher in foetal sides than maternal sides of the same placentas. Moreover, TLR4 was significantly upregulated in maternal sides of PM-positive placentas versus maternal sides of PM-negative placentas. Intriguingly, TLR4 was significantly upregulated in foetal sides of PM-positive placentas versus foetal sides of PM-free placentas. Immunohistochemical analysis revealed that when compared with PM-negative tissue, PM-positive samples expressed markedly higher levels of 8-hydroxy-2’-deoxyguanosine, a marker of oxidative DNA damage. RT-qPCR showed that this was accompanied by the upregulation of p21, a marker of DNA damage repair.
Our data indicate that human PM drives differential innate immune response in foetal vs maternal sides of the placenta, and triggers placental oxidative DNA damage. These observations may have implications for the diagnosis and management of PM.
In Zambia, from March 2019, strict adherence to public health guidelines during implementation of essential or COVID-19 related research studies inadvertently impacted the conduct of community engagement (CE). We share our experience of establishing and navigating CE in a TB research study pivoted to include COVID-19 in Zambia.
Different approaches were adapted to solicit CE for different study phases. Phone-based individual conversations (n=6) with community representatives and district health officials, and phone-based group discussions (n=4) with community members were held to obtain initial COVID-19 community experiences and informed protocol development. In addition, low-risk face-to-face meetings (n=8) were held with community members, following COVID-19 guidelines, to deepen understanding of the community experiences. Prior to study commencement, meetings (n=4) with community representatives were held, leading to formation of a COVID-19 Community Team (CCT) to guide study implementation. Meetings with the CCT (n=5), health facility staff (n=3), and sensitization activities (n=20) were held during implementation, and these CE activities were evaluated using observations (n=8), individual interviews (n=8) and focus group discussion (FGD: n=5).
Community engagement helped researchers to identify information and knowledge gaps and dynamics, local experience, and supported interaction between community and the health facility. Further, establishing the CCT generated community agency for COVID-19. However, phone-based conversations and discussions, though useful, were limited in quality by poor network, limited number of participants on a single call, and limited ownership of a working phone. Face-to-face CE activities were also undermined by strict adherence to COVID-19 public health and institutional guidelines that prevented social etiquette (e.g. handshakes) and more extended community interactions.
Although establishing and navigating CE during the COVID-19 pandemic was feasible, the reach and quality of community engagement was compromised by COVID-19 restrictions. Therefore, a combination of the remote and face-to-face research approaches is required going forward.
Health Care Workers (HCW) faced a high risk of exposure to SARS-CoV-2.
In the present study, we described the presence and duration of anti-S and anti-N IgG antibodies against SARS-CoV-2 among HCW to evaluate the immunity response induced by either SARS-CoV-2 infection or COVID-19 vaccination.
Case-cohort study of 465 HCW from hospitals from the islands of Santiago and São Vicente, conducted in 2021, of which 217 were cases (SARS-CoV-2 infection) and 248 controls (no SARS-CoV-2 infection). Study participants were followed-up until 6 months after recruitment for longitudinal analysis of antibody dynamics, independently of SARS-CoV-2 vaccination status. ELISA test for anti-N and anti-S1 SARS-CoV-2 IgG antibodies were performed on serum samples using collected at baseline (T0) and at 6 months (T6). Among vaccinated participants, these two time points corresponded to a mean time from vaccination of 115 (SD: 60 days) and 350 days (SD: 74 days) respectively.
Of the 396/465 (85%) tested for anti-SARS-CoV-2 antibodies at T0, 36% (n=66/185) of cases and 12% of controls (n=26/211) were positive for anti-N.
Among the vaccinated at T0 165/166 (96%) cases and 200/205 (97%) controls were positive for anti-S1.
The anti-S1 among the case and control group remained high at T6, with 177/179 (99%) cases and 197/198 (99%) controls of HCW tested at 6 months being positive.
Among 250 (67%) vaccinated, who were anti-N negative at T0-,115(32%) remain negative at T6.
These findings showed that only 31% of cases had anti-N. The results also showed positive results for IgG anti-N in HCW without previous SARS-CoV-2 infection, which could be considered asymptomatic cases. Most vaccinated participants had Anti-S after vaccination and they remained high during the 6 months of follow-up. Nonetheless, at least (65/354) had a new infection (32 cases, 33 controls).
Funding: EDCTP (RIA2020EF-3049)
Disparities in the use of maternal health services are, among other things, a consequence of socio-economic inequalities within and between countries. The insufficient use of antenatal care (ANC) deprives pregnant women of preventive and curative measures to reduce maternal morbidity and mortality. This study aimed to assess the socioeconomic inequalities in the uptake of ≥4 ANC visits in Mali and Burkina Faso (BF).
Data used were from the EDCTP-funded INTEGRATION project (2021–2024), a multicenter cluster-randomized implementation trial of intermittent preventive treatment with sulfadoxine-pyrimethamine delivered through the seasonal malaria chemoprevention channel. At baseline, a 3-stage sampling household survey was conducted among 780 and 810 women in Kangaba (Mali) and Boussé district (BF) respectively. ANC uptake during the last pregnancy and socioeconomic indicators were collected. The wealth index (WI) was calculated using household’s ownership of a selected set of assets, dwelling characteristics, type of drinking water source, and toilet and sanitation facilities. Concentration curves were drawn using WI to assess the socioeconomic inequalities in the uptake of ≥4 ANC visits. Finally, Erreyger’s corrected concentration indices were calculated to understand the magnitude of these inequalities.
Based on the concentration curves, the uptake of ≥4 ANC visits in Mali was concentrated among wealthy households, while in BF there was no difference considering WI. In Mali, inequalities in the uptake of ≥4 ANC visits (concentration index (CI)=0.0627, standard error (SE)=0.019; p<0.01) were in favor of the wealthier households. In BF, we did not see any statistically significant inequalities in the uptake of ≥4 ANC visits (CI=0.0012, SE=0.0102; p=0.90).
Socio-economic inequalities in the uptake of ≥4 ANCs was more evident in Mali than in BF where, unlike Mali, ANC visits are free of charge for the women. These findings highlight the ways to increase equity in access to ANC services.
TB treatment is prescribed to millions of individuals yearly, and after cure these individuals often develop recurrent post-TB complications. There is little information exists at the intersection of TB and AMR (i.e., resistance in microbes other than M. tuberculosis complex).The ESKAPE group (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp.) are considered key taxa in AMR acquisition. K. pneumoniae is a common isolate from blood stream infections in our setting, South Africa.
We used the Next-Gen Antimicrobial Resistance Detection (N-GARD) assay, a novel, multiplex, sequencing technique to profile AMR associated strains and genes present in stool of drug-susceptible and drug-resistant TB cases longitudinally.
In both cohorts, no significant changes were seen in the proportion of ESKAPE or AMR associated strains during treatment, but trends were noted. The drug-susceptible cohort showed trends of longitudinal increases in AMR-related strains; Enterobacter cloacae, Klebsiella pnemoniae, Klebsiella varicola. Significant longitudinal decreases in AMR-related gyrA (Escherichia coli), fluctuations in tetD, strB and trends of increased FosA, qnrD, qnrA, Sul3 and SaM2 were seen in the drug susceptible cohort. The drug-resistant cohort showed significant increase in npmA and trends of longitudinal increases of ermA and sul1. We also noticed trends of single nucleotide polymorphisms.
Overall, the drug-resistant cohort had more significant changes in AMR-associated genes compared to drug susceptible cohort. These changes in the resistome during TB treatment require future investigation and future studies will involve more targeted analysis of identified trends.
Funding: This project is part of the EDCTP2 programme supported by the European Union (grant number TMA2019CDF-2738-ESKAPE-TB) and is partly funded by the National Research Foundation.
Knowledge Translation (KT) is "the synthesis, exchange, and application of knowledge by relevant stakeholders to accelerate the benefits of global and local innovation in strengthening health systems and improving people’s health". For over 7 years now, the Data to Policy (D2P) program is one of the approaches Zambia has taken to build capacity for knowledge translation. The initiative is a year-long mentorship program that equips health professionals with skills to develop evidence-based policy briefs on public health priority issues. The D2P utilizes epidemiology with economic analysis and modelling to develop informative policy briefs. The D2P program is supported by the Bloomberg Philanthropies through CDC Foundation, and it is implemented by the National Health Research Authority (NHRA) whose functions among other this is research capacity building and KT.
Through a call for applications, eligible health professionals express their interest to participate in the program stating a public health issue they will work on during the mentorship. The NHRA reviews and admits eligible participants to the program. A curriculum of 21 modules and is delivered by trained mentors who are experts in various and appropriate fields. Four to five trainings, close mentor-mentee check-ins, stakeholder engagements, a policy forum and final presentation of policy briefs to policy makers in the Ministry of Health.
The policy briefs quantify the public health issue, bring out the cost and quality implications of interventions and policy options, and recommends the most feasible options. A total of 83 people have been trained under D2P and 43 policy briefs have been developed, disseminated and recommendations from some have been considered for policy for different programs.
The partnership plays an important role in strengthening the KT capacity and contributes to informed decision making in Zambia.
Vitamin D3 (vit.D3) plays an important role in immune responses, and deficiency has been linked to inflammation and higher susceptibility to infections. In vitro studies using pure cell cultures demonstrated vit.D3’s contribution to microbial killing capacity of macrophages. However, the effect on neutrophils is poorly described. We assessed the effect of high dose vit.D3 in vitro on activation and microbial killing capacities of neutrophils and monocytes under near-physiological conditions using fresh whole blood from adult healthy donors.
Whole blood was exposed to Mycobacterium bovis Bacille Calmette-Guérin (BCG) and Lipopolysaccharide (LPS) post treatment with 100 nM vit.D3 for 2hr, 6hr, and 24hr. Cellular phenotyping by flow cytometry was performed to quantify expression of neutrophil (CD16bri14low) and monocyte (CD14bri16low) activation markers (CD11b, CD62L), bacterial phagocytic capacity, and reactive oxygen species (ROS) production. Interleukin 8 (IL-8) and myeloperoxidase serum levels were quantified using ELISA, and correlated with intracellular killing capacities by performing colony forming unit (CFU) analysis.
Vit. D3 had no significant direct effect on CD11b/62L expression, phagocytic capacity, ROS production, inflammatory marker expression (IL-8, MPO) and killing efficacy independent of the pre-treatment durations. This may reflect differences in vit.D3 concentrations used and kinetics of vit.D3 mediated response patterns in the cells studied when compared to previous reports. Although these results cannot be extrapolated onto in vivo conditions as vit.D3 effects under physiological conditions can be more complex, the whole blood assay proves a valuable tool to analyse host responses ex vivo in patient cohorts. This assay is employed in our ongoing EDCTP funded 96-week randomized placebo-controlled clinical trial (VITALITY) involving high-dose vit.D3 supplementation (20,000 IU/week) in HIV positive adolescents to assess effects on neutrophil and monocyte antimicrobial responses.
An interplay of background effects of HIV and other comorbidities need to be considered as they may influence overall benefits of vit.D3 in this population.
The National Health Research Authority (NHRA) is implementing a program under the name institutionalization of research and knowledge translation (KT) in Zambia as a means to enhance evidence-based decision-making and ultimately improve health outcomes. The institutionalization of research and KT involves the integration of systematic research processes and the effective translation of research findings into policies and practices within the national health system. NHRA recognizes the critical role that research plays in informing health policies, programs, and interventions.
In order to actualize this program, the NHRA utilized a multi-faceted methodology. This involved carrying out a needs assessment of the ten (10) provinces in Zambia to identify the research and knowledge translation gaps for key personnel. Consequently, the NHRA conducted a research priority setting for each of the ten (10) provinces, through stakeholder engagements, to identify and prioritize research topics/areas aligned with Zambia’s health needs and policy priorities. NHRA also developed a robust frameworks to assess the impact of research and knowledge translation activities in the provinces.
The NHRA has since created Terms of References (TORs) and facilitated the appointment of Research and Knowledge Translation Focal Point Persons (R&KT FPPs) in all the ten (10) provinces to spearhead research and knowledge translation activities within respective provinces. Consequently, with support from CDC foundation, NHRA has engaged the R&KT FPPs in its research and knowledge translation training and KT mentorship programs. The R&KT FPPs have been trained in Research Methods and Scientific Writing, as well as a KT mentorship course dubbed as Data to Policy.
With greater funding and partnership, it is hoped that the program will cascade to the lower levels (district, facility and community) within the Ministry of Health for better health outcomes. Undoubtedly, this initiative represents a crucial and timely step towards evidence-based decision-making and improved health outcomes.
There is an urgent need for biomarkers that predict TB treatment response in clinical practice and research. Despite its poor specificity and sensitivity, sputum microscopy and culture conversion 8 weeks following treatment initiation remains the recommended surrogate for TB treatment response. A blood-based biomarker with the ability to predict TB treatment response will significantly improve research into TB treatment-shortening trials, trials testing new anti-TB therapy and clinical practice where it can potentially aid in early identification of patients at risk of poor treatment outcomes.
We conducted a pilot, nested case-control study to identify potential biomarkers to predict TB treatment response. All participants completed the PredictTB treatment-shortening clinical trial. All available confirmed relapses at the time of this pilot study (17) and one treatment failure participant were included and 54 controls were randomly selected. Multiplex immunoassays were used to measure serum expression of 50 cytokines at baseline, weeks 04, 08 and 16 and 24. In addition, demographic and symptom data, clinical examination parameters and laboratory results were collected.
Using baseline and week 8 parameters, we derived a model that discriminated between relapses and controls with an AUC of 0.81, sensitivity of 0.78 and a specificity of 0.85. Parameters that were most useful in discriminating between relapses and controls were changes from baseline to week 8 in TNF-alpha, sIL2R-alpha, IL 12p70, sVEFFR3, sVEGFR1, E-selectin, and MIP-1. In addition to chest pain and diastolic blood pressure; baseline Apo A1, IL-1beta, and Apo C3 also contributed to the model. Our data also validated a previously published treatment response signature.
Our results indicate that a multivariable model may be better at predicting TB treatment response compared to current measures. This work is preliminary and will be combined with a larger cohort.
Funders: Predict TB clinical trial- EDCTP2 programme
The devastating impacts of the sub-regional Ebola Virus Disease (EVD) outbreak clearly demonstrated a significant need to foster collaboration, build human capacity, strengthen laboratory infrastructure, promote community participation in outbreak response, and formulate strategies to harmonize ethical and regulatory pathways to successfully implement clinical trials on vaccines, therapeutics and diagnostics. This sub-regional concept led to a gathering of scientific leaders from the highly impacted EVD countries in the Republic of Guinea to identify a regional approach as the most ideal model to promote complex multi-site cross-border clinical trials, share information on case management during outbreak response, conduct capacity building workshops on regulatory and ethical challenges during public health emergencies (PHEs), identify and strengthen core laboratory systems, share biological samples, and create suitable platforms to share research findings for the mutual benefits of the vulnerable citizens of the sub-region. Accordingly, the West African Consortium (WAC) for Clinical Research on Epidemic Pathogens (WAC-CREP) was borne out of this shared interest by researchers from Liberia, Guinea, Sierra Leone and later Mali and Cote D’Ivoire to advance regional preparedness for global health security by sharing regional research, best practices, and evidence to inform infectious disease policies.
To-date, the consortium has supported the launch of a sub-regional multi-country clinical trial for EVD vaccines, conducted five successful sub-regional scientific conferences and sub-regional training workshops, developed strategic plan to strengthen sub-regional health systems, conducted sub-regional technical and policy expert meeting on EVD survivors, recruited Ministers of Health (MoHs) to serve as Ambassadors, and collaborated on grants, among others. The success of this sub-regional collaborative model clearly demonstrate the benefits of regional collaboration to mitigate emerging infectious diseases (EIDs) of poverty, especially in low and middle-income countries (LMICs).
]]>One of the key obstacles to malaria elimination is largely attributed to Plasmodium vivax’s ability to form resilient hypnozoites in the host liver that cause relapsing infections. As a result, interruption of P. vivax transmission is difficult. P. vivax transmission occurs in Duffy-positive individuals and have been mainly thought to be absent in Africa. However, increasing studies using molecular tools detected P. vivax among Duffy-negative individuals in various African countries. Studies on the African P. vivax has been severely limited because most of malaria control program focus mainly on falciparum malaria. In addition, there is a scarcity of laboratory infrastructures to overcome the biological obstacles posed by P. vivax.
Herein, we established field transmission of Ethiopian P. vivax for routine sporozoite supply followed by liver stage infection in Mali leveraging the EDCTP funded HypnoBio - TMA2017CDF-1892 outcome.
Furthermore, we evaluated local P. vivax hypnozoites and schizonts susceptibilities to reference antimalarial drugs. The study enabled the assessment of local African P. vivax hypnozoite production dynamics.
Our data displayed the ability of the African P. vivax to produce hypnozoite forms ex-vivo at different rates per field isolate. We report that while tafenoquine (1μM) potently inhibited both hypnozoites and schizont forms; atovaquone (0.25μM) and the phosphatidylinositol-4-OH kinase (PI4K)-specific inhibitor KDU691 (0.5μM) showed no activity against hypnozoites forms. Unlike hypnozoites forms, P. vivax schizont stages were fully susceptible to both atovaquone (0.25μM) and the (PI4K)-specific inhibitor KDU691 (0.5μM).
Together, the data revealed the importance of the local platform for further biological investigation and implementation of drug discovery program on the African P. vivax clinical isolates.
Acute febrile illness (AFI) management represents a challenge in sub-Saharan Africa where appropriate tools for the screening are often lacking. The aim of this study was to determine the prevalence of single and co-infection of malaria and arbovirus in children with AFI in a malaria sentinel site, Gabon.
From July to December 2022, patients with AFI and presenting at the malaria sentinel were screened for malaria and dengue (DENV), Chikungunya (CHIKV) and Zika (ZIKV). Malaria was diagnosed using microscopy, while arbovirus infections were investigated with RDT detecting specific IgM (CHIKV and DENV); NS1 antigen and IgM for ZIKA by. Haematological parameters were analysed.
A total of 524 acute febrile cases were included, their median age was 60 [24.0–132.0] months. The prevalence of malaria was 38.9% (n=199/524), P.falciparum was the only plasmodial species detected. Arbovirus RDT positivity rate was 39.1% (n=205/524). Overall, 184 (35.1%) participants were tested positive for ZIKV, 86 for NS1 antigen; 72 for ZIKV specific IgM and 26 for both NS1 antigen and IgM. DENV specific IgM was detected in 42 (8.0%) patients while CHIKV IgM rate was 0.6% (n=3). Considering the number of detected infections, 187 (35.7%) patients were infected by one pathogen, 92 (17.6%) by two and 19 (3.6%) by three pathogens. Co-infections were frequent, Malaria-Zika virus infection predominated (17.3%, n=92). The median Hb level was different according to the type of infection, it was the lowest in case of co-infection (p=0.03). The median platelet count was significantly lower in case of coinfection, patients were at 8-fold higher risk of having thrombocytopenia (OR: 8.7; IC95% [5.3- 14.2], p<0.01).
Arbovirus circulation is important in Gabon. There is a need for an adequate biological diagnosis of non-malaria AFI.
This paragraph highlights the progress made by Rwanda in enhancing nutrition and early childhood development (ECD). It acknowledges the importance of global health research innovation in further advancing these areas. To address this, a scoping review has been conducted to explore existing literature on the impact of global health research innovation on nutrition and ECD in Rwanda. The review aims to identify current knowledge gaps and suggest potential areas for future research.
A comprehensive search of electronic databases was conducted to identify relevant studies published between 2010 and 2021. The search strategy included keywords related to global health research innovation, nutrition, and early childhood development in Rwanda. Inclusion criteria encompassed studies reporting on interventions, programs, policies, or practices that utilized innovative approaches to improve nutrition and ECD outcomes. Data were extracted and analyzed thematically to identify key findings.
A search of 500 articles identified 25 studies that met the inclusion criteria. These studies highlight the significant influence of global health research innovation on nutrition and early childhood development (ECD) in Rwanda. Innovative approaches, such as community-based nutrition programs, mobile health technologies, and interdisciplinary collaborations, have played a crucial role in improving access to nutritious food, enhancing maternal and child health services, and promoting optimal ECD practices. The outcomes of these initiatives include a reduction in malnutrition rates, improvements in child growth and development, and increased awareness and adoption of positive parenting practices.
The review highlights the need for innovative approaches to tackling the complex challenges faced by vulnerable populations, such as limited access to nutritious food, healthcare services, and psychosocial support. The paragraph suggests that future research should concentrate on assessing the scalability, sustainability, and cost-effectiveness of these innovative interventions.
Previous studies have demonstrated secondary microbial infection of Buruli ulcer (BU) lesions before, during and after treatment. However, there is limited data on the resistance profile of these organisms and their influence on the development of paradoxical reactions. The present study aimed to investigate the microbiome and resistance profile in BU lesions during therapy and at the onset of a paradoxical reaction (PR).
We investigated the bacteria diversity in patients with PCR confirmed BU from 5 endemic districts within central Ghana. Samples were collected longitudinally from lesions and compared to normal skin flora in literature. Microbiological analyses including isolation of bacteria, species identification and antibiotic susceptibility testing (AST) were performed using the VITEK 2 system.
Of the 38 participants, 66 bacteria (Actinobacteria – 2.5%, Firmicutes – 48.1%, Proteobacteria – 49.4%) were isolated from BU lesions relative to healthy skin. Staphylococcus spp was dominant at baseline. There was a marked reduction in the number of isolates after treatment with Pseudomonas spp and Staphylococcus spp being the dominant bacterial isolates. Baseline AST profile revealed organisms in BU lesions were highly resistant to tetracycline (55%), benzylpenicillin (52%), and trimethoprim-sulfamethoxazole (26%). Organisms isolated after treatment completion showed high level of resistance to tetracycline (79%), benzylpenicillin (65%) and rifampicin (59%). Of note, 4/8isolates were Methicillin Resistant Staphylococcus aureus (MRSA). Opportunistic pathogens including Staphylococcus spp, Enterococcus spp and Klebsiella pneumoniae were isolated from 6/38 patients that developed PR.
Infection with BU alters the skin microbiome of patients. Most BU lesions are colonized by polymicrobial organisms resistant to commonly used antibiotics in Ghana. Our study demonstrated the presence of opportunistic pathogens in BU lesions that developed paradoxical reaction, suggesting a possible relationship.
Funding: Presenter is supported from the Senior Fellowship Grant under EDCTP2 Program supported by the European Union awarded to Richard Phillips
Assessments of global investments for COVID-19 research have revealed significant inefficiencies in the research funding process. These include duplicated and uncoordinated research efforts. We present an assessment of the funding for COVID-19 research in Africa during the COVID-19 pandemic response. In this work, which forms part of a DPhil project, we undertake "research-on-research", which involves understanding the research process itself.
Two reviews of the UKCDR and GloPID-R COVID-19 Research Project Tracker were undertaken in 2020 and 2022.
Our assessment of funding for COVID-19 research in Africa showed the few research projects being undertaken in Africa were mostly supported by funders in Europe. There was limited focus of research projects on the COVID-19 priorities defined by African researchers. We found a delayed research response in Africa compared to Europe and the United States. Further, we are undertaking qualitative assessments to explore the experiences of researchers and grant managers in African research institutions with obtaining and managing funding for COVID-19 research.
Tracking funding for infectious diseases research is essential for identifying opportunities for coordination among research system stakeholders. It also facilitates the identification of research gaps for action to avoid unmet research needs. Striving for resilient health systems through health policies and systems research is crucial for preparedness for future epidemics and pandemics in Africa, a continent with a high burden of infectious diseases and chronic local underinvestment in health.
The prevalence and impact of baseline archived HIV-1 drug resistance mutations (HDRMs) in people with HIV (PWH) switching to new regimen is not well understood. The aim of this study was to evaluate HDRMs among virologically suppressed individuals on NNRTI based ART in Botswana before they were switched to new dolutegravir (DTG) based ART.
We included a total of 4524 virologically suppressed PWH (aged >18 years) on ART with viral loads <400 copies/ml who were recruited into an HIV cohort, the Botswana Combination Prevention Project, in Botswana between 2013 and 2018. The near full-length HIV-1 proviral DNA pol sequences were analysed for the presence of NRTI and NNRTI DRMs. The Stanford HIV drug resistance database was used for identification of HDRMs.
Among the 4524 virologically suppressed individuals, the majority (72%, 3267/4524) were female, with median age of 40 years [interquartile range (IQR): 34–48]. The overall prevalence of DRMs was 16.4% (742/4524, 95% CI: 15.3% - 17.5%). Females had a higher proportion of DRMs than males (12.1% vs. 4.3%, respectively). The prevalence of NRTI resistance was 2.9% (129/4524, 95% CI 2.4% - 3.3%), while the majority of DRMs were associated with NNRTI resistance at 15.1% (685/4524, 95% CI: 14.1% - 16.2%). The NNRTI mutation E138A which confers resistance to etravirine and rilpivirine was the most common (9.3%, 419/4524), followed by K103N (1.6%, 74/4524) which is associated with efavirenz and nevirapine resistance. The most common NRTI associated mutation was M184V (1.1%, 48/4524) followed by M184I (0.8%, 37/4524) which confer resistance to 3TC and emtricitabine.
We report a prevalence of archived HDRMs in this cohort of 16.4%. Further research is warranted to understand the impact of the observed archived HDRMs on the efficacy of DTG based regimen.
To evaluate for potential alternative antiretroviral therapy (ART) among people living with HIV(PLWH) who have multi-drug resistance (MDR) variants, we determined resistance to second-generation non-nucleoside reverse transcriptase inhibitors (NNRTIs): Doravirine (DOR), Etravirine (ETR) and Rilpivirine (RPV), and entry inhibitors: Maraviroc (MVC), Enfuvirtide (T20) and Fostemsavir (FTR).
A total of 7473 HIV sequences were analysed, MDR was defined as resistance to ≥2 drug classes. The Stanford HIV drug resistance database was used for determining DOR-, ETR- and RPV-resistance. MVC-resistance was determined by evaluating for CXCR4 coreceptor usage using geno2pheno and WebPSSM. FTR-resistance was evaluated using previously reported FTR-resistance mutations. T20-resistance was determined according to the 2022 IAS resistance mutations update. Predictors of MDR were determined using the univariate and multivariate logistic regression hazard models.
The prevalence of PLWH with MDR was 682/7473 (9.1%: 95% CI; 8.3–9.6). Within the MDR group, resistance to the four drug classes was as follows: NNRTIs (84.6%), NRTIs (83.9%), PIs (55.3%) and INSTIs (6%). High prevalence of resistance to second generation NNRTIs was observed within MDR group: RPV (79.3%), ETR (63.6%) and DOR (67.1%). Within entry inhibitors, 7.9% (31/391) CXCR4 coreceptor usage was observed, indicating low prevalence of MVC-resistance. A total of 113/626 (18.1%) MDR individuals presented FTR-resistance. T20-resistance was observed in 313/623 (50.2%) of MDR individuals. ART experience, virologic failure at VL> 400 copies/mL and being male were significantly associated with developing MDR.
The study reports high prevalence of resistance to second generation NNRTIs and T20 in individuals with MDR HIV variants which reduces their potential use as alternative therapy for this group of PLWH. In contrast, low prevalence of FTR-and MVC-resistance allows for their potential use although we suggest genotypic testing prior to use of these drugs to avoid selection of ineffective ARV regimens.
The West the African Network of clinical trial of anti-malarial drug (WANECAM-II) is building a new clinical study team in Niger. There are no country-specific normal ranges for haematology and biochemistry parameters which are required for biological safety assessments in local trial participants. In preparation for upcoming Phase III trials of antimalarial drugs the aim this study was to determine the references values of biological parameters in Niger population and establish ranges of normal reference values for basic biochemical parameters and haematological parameters in the different seasons of the year.
A first cross sectional studies was conducted from September to October 2021 (rainy season) and a second from March to May 2022 (dry season). Venous blood was drawn from consenting participants in appropriate tubes for haematology and biochemistry parameters assessment. Parameters were analysed in three ages groups (3months- to 5 years, 6–14 years and 15–50 years) to refine the laboratory ranges by age-groups and by gender. Data were entered through Redcap, extracted, and analysed by RStudio. A Protocol specific training provided to the investigators before running the study. New calibrated Cobas c311 analyser for biochemistry and SYSMEX for haematology were provided to the team.
We enrolled 533 and 519 volunteers with 65.3% and 33.9% male for the first and second cross-sectional respectively. The age group of 15–50 years was most represented with 48.9% in both seasons while the two other groups were at 25% each. The median values of each parameter, the Lower and Upper normal Limit were determined, and a references document for haematology and biochemistry parameters for clinical study purpose was generated. Detailed results will be presented at the Forum.
Through these two cross-sectional studies, we established the first biological parameters for safety evaluation ready to be used for the EDCTP-WANECAM-II KALUMA study in Niger.
Shigella is one of the top five causative agents of childhood diarrhoea, particularly in lower-middle-income countries, and is one of the vaccine-preventable diseases prioritised for vaccine development by the WHO. The emergence of antibiotic-resistant strains of Shigella is a major public health concern as it reduces the effectiveness of available diarrhoeal treatment and management options. We performed drug susceptibility testing using the BD Phoenix 100 automated microbiology system on shigella isolates from Zambian children under five years presenting with diarrhoea at selected health facilities.
We tested 86 shigella isolates from children U5 from outpatient and hospitalised children during a Shigella surveillance study in Lusaka and Ndola collected between 2020–2021.
A high proportion of the Shigella isolates showed resistance to trimethoprim/sulfamethoxazole (79.1.4%), Ampicillin (56.9%), amoxicillin-clavulanate (49.4), Cefuroxime (55.8.1%), and gentamicin (49.4%). Resistance to Ciprofloxacin was observed in only two isolates. Overall, 83.7% (n=72) of the isolates exhibited resistance to at least one class of antibiotics. This included 59.3% (n=51) resistance to Cephalosporins, 79.1% (n=68) to Sulfonamides, 57% (n=49) to Penicillin, 48.8% (n=42) to Aminoglycosides and 25.6% (n=22) to beta-lactams. Multi-drug resistance (resistance to 3 or more drug classes) was observed in 62.8% (n=54) of the isolates. More MDR was observed in in-patient isolates, 71.4%( n=10/14), compared to 61.1% (n=44/72) in outpatient isolates. At the species level, multi-drug resistance was observed in 25/29 isolates identified as S. sonnei and 24/33 S. flexneri isolates.
Our research indicates a high proportion of antibiotic resistance among the Shigella isolates from young children, which has significant implications for managing Shigella infections. The results support the urgent need for action on effective strategies for Stewardship (i.e. revision of guidelines) and interventions such as vaccines to mitigate the evolution and spread of AMR.
Patient and Public Involvement (PPI) significantly contribute to clinical and implementation science research to make it relevant, acceptable, and beneficial to the public concerned. Research poses challenges to the lay public contributors to understand Medical Jargon, procedures, processes, and practice. Yet the need for their contribution towards research that is context specific remain critical. We formed a combined professional committee including medical professionals and lay members of the Public to contribute to the conduct of LACTATE and Active Prevention and Treatment of Maternal Sepsis (APT Sepsis) studies.
The research team contacted health care providers, staff, and fellow PPI members to help identify and nominate sepsis survivors, carers, and spouses to survivors to contribute to LACTATE and APT SEPSIS studies. Health care providers experienced in Maternal and Fetal health were contacted to be part of the committee. The committee reviews Study document, receive implementation updates and discuss progress of studies in a combo approach. Health care providers provide a learning platform to lay public contributors to understand medical jargon and contribute effectively to clinical research while the public contributors provide personal, community and public perspectives about research and care services. Together they shape the research conduct.
Twelve members, both lay public contributors and health care professionals formed a strong committee in Maternal and Fetal health research group. No negative power imbalances have been observed within the members. The committee successfully informed the development of participant information sheet for LACTATE Study, provided guidance on dissemination of the APT sepsis study during the intervention phase. More protocols use the committee to guide the development and implementation of the research studies.
Combining health care professional and lay public contributors is feasible and effective in contributing to research. Combination approach provides instant learning.
Burkina Faso has a high burden of malaria in pregnancy despite mass deployment of insecticide-treated nets (ITN) and use of intermittent preventive treatment in pregnancy (IPTp). Understanding how pregnant women contribute to the infectious reservoir will enable development of tools to effectively address malaria transmission.
A community-based longitudinal cohort with mosquito infection assays was carried out in pregnant women in Saponé Health District, central Burkina Faso. Pregnant women who were parasite positive were followed monthly after their antenatal care visits (ANC). Venous blood samples were collected for direct membrane feeding assays (DMFA) prior Sulfadoxine-Pyrimethamine (SP) dosing and on day 7 or 14 post DMFA to assess infectiousness to mosquito.
A total of 63 pregnant women were enrolled in the survey. 153 mosquitoes feeding experiments were conducted and 7,736 mosquitoes were dissected. 3.9% of feeds were infectious to mosquitoes with 18,3% of mosquito infection rate and 3.6% oocyst prevalence per infected midgut.
Key findings related to parasite and gametocyte density, duration of infection and mosquito exposure will be presented during the conference to address the hypothesis that pregnant women under IPTp may still constitute a significant source of mosquito infection.
Past years have seen an increase in clinical trials being conducted in Zambia and other countries, which demand for the need to enhance the capacities of ethics committees and regulators to provide ethical oversight. In Zambia, there are multiple institutions tasked with the mandates to provide regulatory oversight over clinical trials, with each having specific legal mandates that include the National Health Research Authority, Zambia Medicines and Regulatory Authority and National Biosafety Authority. As such, clinical trial oversight has been highly segmented causing duplications of efforts, increased turnaround time, worsened by linear approach to submission of applications.
NHRA proposed harmonization of key processes amongst the key regulators within Zambia in the Zambia Health Research Systems Strengthening Project: Working Towards a Harmonized Regulatory Framework Project (ZAHRSSP) implemented by NHRA and supported by EDCTP.
Desk review of existing Acts, guidelines and mandates was done during the implementation of the ZAHRSSP project.
a) Capacity building was conducted through provisions of training in research ethics, GCP, and protocol reviews. b) Transition from linear to parallel submission. In the implementation of ZAHRSSP project, the approach was changed into parallel submissions. c) Development of new clinical trial guidelines and regulations. The guidelines describe applications procedures for approvals, reviews, and approval of clinical trials. Key aspects of the harmonization process was realigning the submission forms amongst the key regulators. d) Memorandum of Understandings aimed at harmonizing key processes between NHRA and ZAMRA including conducting of joint clinical trial reviews and inspections.
Steps have been taken for intra-collaboration towards a harmonized working environment for clinical trials oversight in Zambia with key regulators working together. However, need for sustaining the key collaborations aspects after the ZAHSSP project and ensure actualization of the key aspects of the guidelines, MOUs and regulations.
The development of vaccines for SARS-CoV-2 had a major impact on the COVID-19 pandemic, protecting and vulnerable and dramatically reducing mortality and severe morbidity due to SARS-CoV-2 infection in countries where vaccine coverage was high. African countries faced various challenges in rolling out SARS-CoV-2 vaccination campaigns, with poorer access to vaccines, vaccine hesitancy and the logistical challenges of reaching communities in rural areas. Rural communities might have differential access to information that results in different levels of vaccine hesitancy compared with urban populations. The aim of this study was to compare the knowledge, attitudes and practices of urban and rural communities regarding immunisation.
We used a mixed-methods design combining individual surveys with focus group discussions. The 240 participants included healthcare workers and lay members of the community (patient carers & relatives), recruited through participating health centres in both rural and urban locations in each country.
Preliminary findings suggest that in urban areas, participants were overwhelmed by the multiplicity and contradiction of information sources. In rural areas, there was less access to information, and participants questioned the rationale for vaccination, less so because of anti-vaxx hysteria, but more because of a rational perception that they were at lower risk of COVID-19 due to to the lower population density. The majority of diagnoses were confirmed in urban settings, but this is deceptive, because that is where the greatest diagnostic capacity is.
There are disparities in knowledge, attitudes and perceptions between communities living in urban areas compared to those in villages. An in-depth analysis across all 4 participating countries will be presented. We will demonstrate how EDCTP networks of excellence can be used to implement impactful student-led multi-site research studies at low cost.
In the early months of 2020 as the COVID-19 pandemic took hold in Europe, there was much concern about how the pandemic would impact populations in Africa, both in terms of how the infection would interact with endemic diseases, and also with respect to the capacity for public health response. Initial case finding activities centred on urban travel hubs where the infection and transmission risk were highest. Rural communities were considered lower risk but were also given less access to diagnostics and other IPC measures. The aim of this study was to compare the knowledge, attitudes and practices of urban and rural communities regarding the government response to the pandemic.
We used a mixed-methods design combining individual surveys with focus group discussions. The 240 participants included healthcare workers and lay members of the community (patient carers & relatives), recruited through participating health centres in both rural and urban locations in each country.
Preliminary analysis suggested that rural dwellers were less satisfied with the government response than those in urban settings. Proactive government management and logistical organisation prevented the spread of the COVID-19 pandemic but there were challenges with respect to communication crisis and financial management. Results from both the individual interviews and focus group discussions across 4 countries will be presented.
There were clear gaps identified between the response to COVID-19 between rural and urban communities. The lessons learned should be incorporated into epidemic risk management plan in readiness for response to new and emerging threats. We will demonstrate how EDCTP networks of excellence can be used to implement impactful student-led multi-site research studies at low cost.
Our study aimed to determine the neutralizing capacity of anti-SARS-CoV-2 antibodies found in the plasma of pregnant women collected during the pre-pandemic period to COVID-19 in three settlements in Cameroon.
A total of 1,590 archival plasma from pregnant women during pregnancy (574) and at delivery (657) were tested for COVID-19 using the Abbott Panbio TM COVID-19 IgG/IgM rapid diagnostic test. Samples from 120 (9.75%) women were collected from the rural area, 663 (53.86%) in the peri-urban area, and 448 (36.40%) in an urban area at different antenatal visits. To ascertain our findings, randomly selected IgG & IgG/M positive samples (70) were further tested by the Luminex technology specific for viral N and S proteins. The neutralizing capacity of 21 samples with the highest titers against the S protein were assessed against the founder SAR CoV-2. Data was summarized in proportions.
During pregnancy with the Luminex technology, 12.50% (4/32) and 3.13% (1/32) of pregnant women were seropositive to the S-protein and N/S proteins respectively. At delivery, 50% (10/20) of women were seropositive for anti-coronaviruses IgG directed against the S-protein only and 15% (3/20) while had antibodies against the N&S protein. A transplacental transfer of protective S proteins from the mother to the child was found in 60% (3/5) of the tested dyads. During the neutralization assay, 0% of these antibodies found in these pregnant women before the pre-pandemic period at COVID-19 were neutralizing to the ancestral strain.
This study provides evidence of existing of cross-reactive anti-SARS-CoV-2 antibodies among pregnant Cameroonian women in the Pre-COVID-19 eras but are not neutralizing against the ancestral virus.
Funding source: ANRS