Comparing antigenaemia- and microfilaraemia as criteria for stopping decisions in lymphatic filariasis elimination programmes in Africa

Background: Mass drug administration (MDA) is the main strategy towards lymphatic filariasis (LF) elimination. Progress is monitored by assessing microfilaraemia (Mf) or circulating filarial antigenaemia (CFA) prevalence, the latter being more practical for field surveys. The current criterion for stopping MDA requires <2% CFA prevalence in 6- to 7-year olds, but this criterion is not evidence-based. We used mathematical modelling to investigate the validity of different thresholds regarding testing method and age group for African MDA programmes using ivermectin plus albendazole.

Methodolgy/Principal findings: We verified that our model captures observed patterns in Mf and CFA prevalence during annual MDA, assuming that CFA tests are positive if at least one adult worm is present. We then assessed how well elimination can be predicted from CFA prevalence in 6-7-year-old children or from Mf or CFA prevalence in the 5+ or 15+ population, and determined safe (>95% positive predictive value) thresholds for stopping MDA. The model captured trends in Mf and CFA prevalences reasonably well. Elimination cannot be predicted with sufficient certainty from CFA prevalence in 6-7-year olds. Resurgence may still occur if all children are antigen-negative, irrespective of the number tested. Mf-based criteria also show unfavourable results (PPV <95% or unpractically low threshold). CFA prevalences in the 5+ or 15+ population are the best predictors, and post-MDA threshold values for stopping MDA can be as high as 10% for 15+. These thresholds are robust for various alternative assumptions regarding baseline endemicity, biological parameters and sampling strategies.

Conclusions/Significance: For African areas with moderate to high pre-treatment Mf prevalence that have had 6 or more rounds of annual ivermectin/albendazole MDA with adequate coverage, we recommend to adopt a CFA threshold prevalence of 10% in adults (15+) for stopping MDA. This could be combined with Mf testing of CFA positives to ensure absence of a significant Mf reservoir for transmission.

Author summary: Mass drug administration (MDA) of antifilarial drugs is the main strategy towards the elimination of lymphatic filariasis (LF), but defining when MDA can safely be stopped is challenging. Current stopping guidelines require that the prevalence of microfilaraemia (Mf) in the population falls below 1% or the prevalence of circulating filarial antigenaemia (CFA) in 6-and-7-year-old children falls below 2%. The evidence base underlying this threshold is limited. The accuracy of this threshold is hard to assess in field studies due to the long timespan between stopping MDA and the occurrence of either elimination or resurgence. We used mathematical modelling to assess how well elimination can be predicted at community-level from the Mf or CFA prevalence observed 1-year after the last MDA round and we determined safe stopping thresholds (>95% certainty that elimination is achieved). We found that the currently used CFA prevalence in 6–7 year-old children is a poor indicator for stopping decisions in LF elimination programmes implementing MDA with ivermectin plus albendazole, and that CFA prevalence among people aged 5 or 15 years and older is a much more reliable and practical indicator of elimination outcomes. Lymphatic filariasis elimination programmes should reconsider guidelines for stopping MDA.