Schistosomiasis elimination in Madagascar: challenges and opportunities for implementing the new WHO guidelines

Introduction

Schistosomiasis has the third highest global burden attributable to a neglected tropical disease (NTD) behind Soil Transmitted Helmintiasis (STH) infections and dengue.1 The main control strategy for the disease is chemoprophylactic treatment with praziquantel through mass drug administration (MDA) campaigns.2 As per all NTDs, accurate estimates on burden and MDA coverage are an issue3 even though the worldwide effort established through ESPEN in 20164 is trying to address this gap supporting better planning for control and elimination.

Madagascar has the fifth largest burden of schistosomiasis2 worldwide, with 106 out of 113 districts considered endemic for the disease.5 According to the 2015 estimates, in 40.7% of the districts (46/113) schistosomiasis prevalence is >50%, in 37.2% (42/113) between 10% and 50%, and less than 10% in 16.8% (19/113), while only 5.3% of them (6/113) are not endemic (figure 1). Schistosoma haematobium, responsible for urogenital schistosomiasis, is present in the western and northern regions of the island, while intestinal schistosomiasis due to S. mansoni is present in the eastern and southern parts so as in the central highlands of the country.6 Efforts have been made in the last years to control the disease, but programme coverage is jeopardised by limited financial resources required for the implementation and distribution, poor coordination of donors and local implementation challenges, with some districts in need for MDA still uncovered (figure 1).5.

Request permission

Since 2001 World Health Resolution calling for widespread treatment for schistosomiasis and soil-transmitted diseases,7 schistosomiasis is receiving unprecedent attention from the global health community both in terms of research, guidelines and policies. The recently released WHO 2021–2030 road map for NTDs orients public health policies towards disease elimination as a public health problem (EPHP)3 by 2030.

In 2022, the WHO released additionally ad hoc guidelines for schistosomiasis with the purpose of boosting EPHP goal on the basis of six recommendations based on prevalence, target groups and type of interventions and ranked by strength and extent of scientific evidence8 (figure 2).

Request permission

In 2021, over 58 million children have been treated globally, corresponding to 43% of the worldwide target.9 Praziquantel (PZQ), the drug of choice for treatment of schistosomiasis, is available as a donation through the WHO.3 To boost the achievement of the target, tailored strategies based both on local disease burden, territorial and infrastructural challenges are required.

In Madagascar, geographical, climatic and socioeconomic peculiarities represent a barrier for the achievement of the ambitious goal of EPHP by 2030. Moreover, political attention needs to be raised for a disease that affects more than half of the population.

The aim of this paper is to critically discuss the national factors to consider for the implementation of new guidelines for the elimination of schistosomiasis in the country, proposing a national implementation plan to align with the WHO roadmap. Additionally, we aim at rising attention of policy makers and local stakeholders for the achievement of EPHP.

MDA in Madagascar: progress and shortfalls

The National Programme for Schistosomiasis Control (NPSC) in Madagascar was established in 1998 and activities started in 1999.5 However, the systematic implementation of MDA in all health districts was slow in the following years, due to distribution and logistics limitations, the political crisis in 2009 and the turnover of different stakeholders with limited coordination between each other.5 PZQ-based-MDA geographical coverage remained overall stable between 2010 and 2014 (34 districts in 2020, 30 districts in 2014), and then unsteadily increased, moving from 41 in 2015 to 59 in 2019 (maximum reached in 2017 with 87 districts).5 The raise of the COVID-19 pandemic generated a new scenario. Since 2020, new MDA strategies are being implemented to reduce the risk of virus transmission: PZQ is administered door-to-door, in churches and community sites instead of schools, resulting in increased financial and human resource demands. Overall coverage has improved, with 63 districts reached in 2020, and 94 and 31 in the two interventions performed in November 2021 and April–May 2022 for the 2021 MDA campaign.10 11 Remarkably, in 2021–2022, coverage rate reached 80% with the exception of three districts (Fianarantsoa I and Moramanga-Andilamena) and in two hyperendemic districts (Kandreho, Betsiboka Region and Ikalamavony, Matsiatra Ambony) MDA was also extended to adults.11

Despite the overall national success, several barriers were identified halting the implementation of MDAs in Madagascar.

National campaigns were interrupted in November 2021 after a serious adverse event (SAE) with fatal outcome occurred in the district of Betafo. A 10-year-old child died for ‘unspecified encephalopathy’ 2 days after the administration of PZQ and mebendazole. MDA was interrupted and an investigation opened by the national committee for SAEs. Given the high prevalence of taeniasis in Betafo district and being PZQ known as potential trigger for reactivation of latent neurocysticercosis, the investigation assumed the correlation, although severe consequences have rarely been reported.12 13 The SAE committee issued several recommendations, including investigation for medical history and signs of cysticercosis check before treatment, as also suggested by the WHO MDA surveillance mechanism.8 13

Finally, in 2018 the Malagasy Ministries of Instruction and of Health issued a mandatory recommendation to administer PZQ together with food, since at the time, feeding programmes were implemented in school in parallel with MDAs.14 Although, once the programme was discontinued, there was a consequent halt of PZQ administration in schools for a contingent incompatibility of procedures. Administration of PZQ with a small supplement of food is suggested by WHO to increase acceptability and to reduce side effects.8 However, frequently the provision of food can be unaffordable; hence, it is not considered to be mandatorily adopted for the treatment and consequently in the large majority of countries where high coverage of distribution of PZQ is achieved, food supplements are not routinely provided.

Due to COVID-19, PZQ administration in the country currently takes place in community settings or door-to-door, where the recommendation does not apply, as linked to the school-based joint programme (Rasoamanamihaja CF, personal communication).

Country biodiversity, climate and geographical distribution of Schistosoma sp

In Madagascar, schistosomiasis is endemic all over the country.5 The two major human species, S. mansoni and S. haematobium, exist on the island with a precise geographical distribution: S. haematobium predominates in the north-western regions, while S. mansoni is mainly found in the central highlands, south and east coast.5 The distribution of the intermediate hosts, Biomphalaria and Bulinus, can be the explanation, even though a fine mapping of the genera in the country has yet to be done.

WHO recommends environmental intervention with molluscicides in areas of focal transmission combined with ecological surveys to monitor the impact on biodiversity in areas where the local fish and amphibian species have not been fully described.15 16 Niclosamide, the molluscicide recommended for schistosomiasis control, is considered to carry a minimal risk for humans and environment if properly handled, but it is known to be toxic to fish and amphibia.16 Madagascar is a country with an extraordinary biodiversity, which is characterised by high levels of endemism (90% overall) still to be fully characterised, with an estimated 500 native amphibians of which only 369 described until June 2021, and freshwater fish already threatened.17 18

Bulinus and Biomphalaria species are overall considered resistant to temperature variations and adaptable to different ecosystem.19 20 However, a recent study conducted in South Africa showed a negative relationship between the population density of the genus Bulinus and rainfall, but not for the genus Biomphalaria, whose number of snails indeed decreased for low temperatures.21 Climate in Madagascar is diverse, generating five distinct ecosystems17: the distribution of snails over these ecosystems in the country still remains to be defined. Additionally, over the last decades, several natural hazards have been registered, including droughts, floods, cyclones and extreme temperatures having consequences on the environment and health,22 but the seasonal behaviour of local Bulinus and Biomphalaria of Madagascar yet remains unclear. The scarcity of knowledge about the environmental components of schistosomiasis limits the development of comprehensive plans based on the local context.

Health system and sociodemographic characteristics

Schistosomiasis is a chronic disease with a long-term asymptomatic phase, mostly neglected when other acute, contagious or more ‘clinically visible’ health issues coexist. This is particularly evident in Madagascar, burdened by infectious diseases (plague, malaria, tuberculosis), chronic conditions (malnutrition) and existing complexities in the healthcare system.23

Madagascar suffers, as many other Sub Saharan Africa (SSA) countries, for two major health system fragilities: health service providers and accessibility.24–26 On average, in 2018, 5.19 doctors, midwives, nurses and other health professionals per 10 000 people were registered in the urban areas of the country, while more than 60% of the population lives in rural areas.27 28 Overall, the Malagasy population is young, being 50% under the age of 18, 43% under 15 and 15% under 5.29 30 School attendance is still low: one in five children aged 6–10 years and one in three aged 11–14 years do not attend school.29

Madagascar is also the only country in the world facing the highest level of food insecurity without a conflict with high levels of malnutrition among children29 with scarce access to water and sanitation services if compared with other SSA countries. In Madagascar, still 42% of the population practices open defecation compared with the 22.55% of SSA overall.31 32

The country has significantly increased investments in health in recent years and initiated in 2015 a national policy for Universal Health Coverage.33 Nevertheless, despite the burden, schistosomiasis does not seem to represent a health priority for the country.

Challenges and opportunities for the implementation of the new WHO guidelines in Madagascar

In view of what described so far, we summarised in table 1 an analysis of strengths, weaknesses, opportunities and threats (SWOT) in Madagascar for the implementation of the novel guidelines.

A more detailed and updated national prevalence survey in Madagascar is currently ongoing, providing the estimates needed for the microplanning aimed by the novel guidelines.

Nevertheless, financial, distribution and logistics challenges will arise as a consequence of the new WHO guidelines, since an increased population should become eligible in Madagascar. Specifically, with the new 10% prevalence threshold set for the implementation of annual MDAs, 77.9% of health districts will be involved, instead of the previous 40.7%, and an increased population should be included given the broader age. This will consequently increase the demand of human resources and the number of boxes of PZQ required for each campaign. Notably, in 2021, it was reported a waste of about 5 000 000 PZQ tablets at the end of the MDA campaign in Madagascar mainly due to logistics constrains linked to drug packaging that do not allow to use open drug boxes in different locations.11

The NPSC identified possible solutions for the issues listed above. First, it earmarked two ministerial programmes as possible mitigators for the increased need of human resources. The first one is the Comité Communale de Développement Sanitaire (CCDS, community committee for health development), a system involving village chiefs and traditional leaders, which could support at municipality level the delivery of MDAs.34 The second one, which is currently under implementation by the minister for internal affairs and decentralisation, is the Plan National pour la Decentralisation Émergente (PNDE, National Plan for Emerging Decentralisation), established to involve peripheral health system and other local technical services to collaborate for local issues, including health. The possible introduction of schistosomiasis in the PNDE priorities could increase both the possibility of funding and staff for MDA at municipality level.

Additionally, the NPSC developed a system of redistribution in close health districts in order to administer unused packages.

The ‘Programme appui à la Décentralisation et à la Résilience Communautaire’ is currently contributing to end the practice of open defecation in the region of Menabe through the ‘Dinan'i Menabe’,35 a local community pact promoting the utilisation of family lavatories, often unused by the population even if present. If extended also to other regions, it could integrate recommendation 5 for schistosomiasis with other interventions for the community.

Recommendation 4 introduces for the first time the concept of test-and-treat for the general population, to control schistosomiasis morbidity in healthcare facilities. The first challenge for this recommendation is the availability of tests at PHC, for which currently a donation plan is not in place, nor accurate rapid tests for clinical diagnosis are commercially available. Testing will then rely on parasitological and clinical evaluation, which will need diagnostic tools (microscopies and consumables) and technical competencies. Indeed, the second major challenge for morbidity control, although not clearly stated in the new guidelines, is the development of medical competencies to handle the chronic manifestations of the infection, which is indeed advocated in the NTD roadmap.3 Once the infection has developed into chronic sequelae, morbidity is almost irreversible, although some treatment could be proposed to slow down the progression. Thanks to the sharp geographical distribution of species in Madagascar, a targeted training plan could be conceptualised in order to optimise by region the type of competencies required in specific areas on the basis of the endemicity. Due to complexity of their implementation, these types of interventions are not seen as a priority yet leaving morbidity management behind schedule. In this view, implementation and operational research studies represent an opportunity for evaluating their feasibility and sustainability, contributing in parallel to the establishment of proof of concepts for morbidity management in the country. Similar considerations can be applied to the adoption of one-health approaches for schistosomiasis control, which are still delayed at policy levels and can benefit from operational opportunities given by the Malagasy territory.

Three pillars to eliminate schistosomiasis as a public health problem in Madagascar: recommendations for national policies

Our SWOT analysis shows the complex interaction of sociopolitical and natural elements in Madagascar, calling for extraordinary efforts for the implementation of the novel WHO guidelines, especially for funding mobilisation and coordination, both within national stakeholders and international partners. Awareness on the urgency for action seems to exist in the country, where in October 2022, a first conference on the control and management of schistosomiasis was organised.36 A first achievement following the conference was the establishment of a working group putting together the WHO, the NPSP and the national and international academic stakeholders active in the country. This working group, which does not have yet an official status, was engaged in establishing a long-term intersectoral cooperation to strengthen the Malagasy capacity to implement schistosomiasis programmes.

In the following months, first action points were put into practices: the initiation of the updated national mapping of the epidemiology of schistosomiasis, the joint participation in grant applications for schistosomiasis and the organisation of the first national event on the occasion of the World NTD day.37 These three actions showed the importance of the multisectoral engagement of partners to boost actions and support implementation strategies for the fight against schistosomiasis in the country. This paper is a first concrete result of this working group, which hereby presents a three-pillar-based strategy to implement the new WHO guidelines in Madagascar (figure 3).

Request permission

1. Integrated, multisectoral implementation strategies: fostering dialogue among partners and stakeholders in the country from multiple disciplines to plan and implement national strategies.

2. Political stakeholders’ engagement and coordination: creating national awareness of the schistosomiasis needs in the country in order to stimulate political commitment for structured programmes.

3. Strengthening of laboratory, medical and research capacity: promoting and organising ad hoc training, adapting curricula for higher education and continuous postgraduate training, reinforcement of infrastructures.

By adopting an integrated approach which combines the multisectoral implementation strategies recommended for schistosomiasis with other public health interventions and balancing their coexistence, we believe that Madagascar could build a sustainable plan to meet the WHO targets set for schistosomiasis, ensuring continuity and wider engagement.

Reinforcing the workforce and the health system in terms of diagnostic and clinical management of chronic diseases is an undeniable effort to be made to effectively align with the WHO recommendations. Research, and specifically implementation and operational research, offers a unique opportunity to combine multisectoral and interdisciplinary interventions requiring adapted infrastructures and dedicated trainings. The implementation of this type of research projects can represent a starting point for rethinking of the educational offer available in the country aiming to create adapted programmes at both under and postgraduate level to build the work class of the future planning and leading schistosomiasis interventions.

These two pillars cannot exist without a strong coordination within all the involved stakeholders and political engagement. Country commitment and leadership is crucial to set the Malagasy timeline for the achievement of schistosomiasis EPHP and to develop a long-term plan of interventions and national guidelines, which will allow to advocate for the necessary continuous domestic and international economic support.

Conclusions

The establishment of an informal schistosomiasis working group in the country represents a promising starting point to foster the issuing of new policy documents to domesticate the implementation of the new WHO guidelines. A critical dimension that might arise will be the availability of sufficient funds for the implementation of new strategies. A combination of actors from different disciplines and sectors will mitigate this risk channelling resources from yet unexplored assets.