The lymphatic filariasis treatment study landscape: A systematic review of study characteristics and the case for an individual participant data platform

Abstract

Background: Lymphatic filariasis (LF) is a neglected tropical disease (NTD) targeted by the World Health Organization for elimination as a public health problem (EPHP). Since 2000, more than 9 billion treatments of antifilarial medicines have been distributed through mass drug administration (MDA) programmes in 72 endemic countries and 17 countries have reached EPHP. Yet in 2021, nearly 900 million people still required MDA with combinations of albendazole, diethylcarbamazine and/or ivermectin. Despite the reliance on these drugs, there remain gaps in understanding of variation in responses to treatment. As demonstrated for other infectious diseases, some urgent questions could be addressed by conducting individual participant data (IPD) meta-analyses. Here, we present the results of a systematic literature review to estimate the abundance of IPD on pre- and post-intervention indicators of infection and/or morbidity and assess the feasibility of building a global data repository.

Methodology: We searched literature published between 1st January 2000 and 5th May 2023 in 15 databases to identify prospective studies assessing LF treatment and/or morbidity management and disease prevention (MMDP) approaches. We considered only studies where individual participants were diagnosed with LF infection or disease and were followed up on at least one occasion after receiving an intervention/treatment.

Principal findings: We identified 138 eligible studies from 23 countries, having followed up an estimated 29,842 participants after intervention. We estimate 14,800 (49.6%) IPD on pre- and post-intervention infection indicators including microfilaraemia, circulating filarial antigen and/or ultrasound indicators measured before and after intervention using 8 drugs administered in various combinations. We identified 33 studies on MMDP, estimating 6,102 (20.4%) IPD on pre- and post-intervention clinical morbidity indicators only. A further 8,940 IPD cover a mixture of infection and morbidity outcomes measured with other diagnostics, from participants followed for adverse event outcomes only or recruited after initial intervention.

Conclusions: The LF treatment study landscape is heterogeneous, but the abundance of studies and related IPD suggest that establishing a global data repository to facilitate IPD meta-analyses would be feasible and useful to address unresolved questions on variation in treatment outcomes across geographies, demographics and in underrepresented groups. New studies using more standardized approaches should be initiated to address the scarcity and inconsistency of data on morbidity management.

Fig 1. PRISMA flow diagram of the systematic search and screening.

Fig 2. Geographical coverage of studies collecting individual participant data (IPD) on lymphatic filariasis (LF) infection or morbidity indicators measured pre- and post-intervention.

The 23 countries are shaded from red to yellow in accordance with the estimated abundance of IPD. The 39 countries shaded in blue are endemic for LF but had no studies identified. China is shaded green because of language barriers in assessing the abundance of IPD potentially available. The map was created using World (naturalearthdata.com) and the tmap package [38] for R (v. 4.2.2) [39].

Fig 3. Frequency distribution (A) and estimated individual participant data (IPD) (B) of 138 eligible studies generating IPD on infection and morbidity indicators measured pre- and post-intervention, grouped by year of study publication.

Fig 4. Frequency distribution of 138 eligible studies generating individual participant data (IPD) on lymphatic filariasis infection and morbidity indicators measured pre- and post-intervention, grouped by months of longest follow-up.