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Abstract
Introduction Although universal drug susceptibility testing (DST) is a component of the End-TB Strategy, over 70% of drug-resistant tuberculosis (DR-TB) cases globally remain undetected. This detection gap reflects difficulties in DST scale-up and substantial heterogeneity in policies and implemented practices. We conducted a systematic review and meta-analysis to assess whether implementation of universal DST yields increased DR-TB detection compared with only selectively testing high-risk groups.
Methods PubMed, Embase, Global Health, Cochrane Library and Web of Science Core Collection were searched for publications reporting on the differential yield of universal versus selective DST implementation on the proportion of DR-TB, from January 2007 to June 2019. Random-effects meta-analyses were used to calculate respective pooled proportions of DR-TB cases detected; Higgins test and prediction intervals were used to assess between-study heterogeneity. We adapted an existing risk-of-bias assessment tool for prevalence studies.
Results Of 18 736 unique citations, 101 studies were included in the qualitative synthesis. All studies used WHO-endorsed DST methods, and most (87.1%) involved both high-risk groups and the general population. We found only cross-sectional, observational, non-randomised studies that compared universal with selective DST strategies. Only four studies directly compared the testing approaches in the same study population, with the proportion of DR-TB cases detected ranging from 2.2% (95% CI: 1.4% to 3.2%) to 12.8% (95% CI: 11.4% to 14.3%) with selective testing, versus 4.4% (95% CI: 3.3% to 5.8%) to 9.8% (95% CI: 8.9% to 10.7%) with universal testing. Broad population studies were very heterogeneous. The vast majority (88/101; 87.1%) reported on the results of universal testing. However, while 37 (36.6%)/101 included all presumptive TB cases, an equal number of studies applied sputum-smear as a preselection criterion. A meaningful meta-analysis was not possible.
Conclusion Given the absence of randomised studies and the paucity of studies comparing strategies head to head, and selection bias in many studies that applied universal testing, our findings have limited generalisability. The lack of evidence reinforces the need for better data to inform policies.
- tuberculosis
- epidemiology
- systematic review
- diagnostics and tools
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Footnotes
Handling editor Seye Abimbola
Twitter @svadzianita, @giorgiasulis, @genski_g, @paimadhu, @cdenki
AS and GS contributed equally.
Contributors AS, GS, MP and CMD conceived the study and developed the review protocol. GG built the search strategies in collaboration with AS and GS. AS and GS conducted the study screening, data extraction, quality assessment and analyses under CMD’s supervision. AS and GS wrote the initial draft and contributed equally to all aspects of the paper. All authors revised and approved the final version.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests MP is on the editorial boards of BMJ Global Health. Dr Denkinger reports working for FIND until April 2019. FIND is a not-for-profit foundation, whose mission is to find diagnostic solutions to overcome diseases of poverty in LMICs. It works closely with the private and public sectors and receives funding from some of its industry partners. It has organisational firewalls to protect it against any undue influences in its work or the publication of its findings (incl. Cepheid). All industry partnerships are subject to review by an independent Scientific Advisory Committee or another independent review body, based on due diligence, TTPs and public sector requirements. FIND catalyses product development, leads evaluations, takes positions and accelerates access to tools identified as serving its mission. It provides indirect support to industry (eg, access to open specimen banks, a clinical trial platform, technical support, expertise, laboratory capacity strengthening in LMICs, etc) to facilitate the development and use of products in these areas. FIND also supports the evaluation of prioritised assays and the early stages of implementation of WHO-approved (guidance & PQ) assays using donor grants. In order to carry out test validations and evaluations, has product evaluation agreements with several private sector companies for the diseases FIND works in which strictly define its independence and neutrality vis-a-vis the companies whose products get evaluated, and describes roles and responsibilities. Since leaving FIND, Dr Denkinger continues to hold a collaborative agreement with FIND. All other authors declare that they have no conflicts of interest.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting or dissemination plans of this research.
Patient consent for publication Not required.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information. The information used for analysis was obtained from original publications.