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

PLoS Negl Trop Dis. 2022 Dec 12;16(12):e0010953. doi: 10.1371/journal.pntd.0010953. eCollection 2022 Dec.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Africa / epidemiology
  • Albendazole / therapeutic use
  • Animals
  • Elephantiasis, Filarial* / drug therapy
  • Elephantiasis, Filarial* / epidemiology
  • Elephantiasis, Filarial* / prevention & control
  • Filaricides* / therapeutic use
  • Ivermectin / therapeutic use
  • Prevalence
  • Wuchereria bancrofti

Substances

  • Albendazole
  • Ivermectin
  • Filaricides

Grants and funding

The authors WAS, LEC, TDH, EM, JMP, RMCR, SS, PT and SJdV gratefully acknowledge funding of the NTD Modelling Consortium by the Bill & Melinda Gates Foundation [OPP1184344, https://www.gatesfoundation.org]. WAS, FKB, OAE, PUF, BGK, AM, GJW and SJdV, acknowledge funding from Bill & Melinda Gates Foundation [OPPGH5342, https://www.gatesfoundation.org]. LEC further acknowledges funding from the Dutch Research Council NOW [grant 016.Veni.178.023, https://www.nwo.nl/]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.