On the Bijagós Archipelago off West Africa, a cluster-randomised trial will test whether adding ivermectin—a drug that kills mosquitoes feeding on treated people—to standard antimalarial mass drug administration can drive malaria transmission lower than antimalarials alone. Malaria elimination has stalled in many seasonal low-transmission settings because antimalarials clear the parasite from humans but do not stop mosquitoes from biting and re-introducing infection. Ivermectin targets the vector directly, reducing mosquito survival and potentially breaking the cycle. This is the first trial to combine both approaches in a controlled community study. If ivermectin proves effective, national malaria programmes could adopt a dual-action strategy: drugs that clear human infection plus a drug that shortens the mosquito lifespan. On islands like the Bijagós, where vector populations are confined, this approach could push transmission toward zero. The trial also includes cost-effectiveness analysis, so funders and policymakers will know whether the added expense is justified. Even if ivermectin shows only a modest effect, the detailed entomological and serological data will clarify how transmission persists and how best to interrupt it.
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This trial will be the first to investigate the impact of adding ivermectin (IVM) to mass drug administration (MDA) with an efficacious antimalarial (eg dihydroartemisinin-piperaquine (DP)) to reduce malaria transmission in a seasonal low-transmission setting. Additive IVM MDA will be compared to DP-only MDA (with treatment daily for three days during the three months of peak malaria transmission (July-September)) in combination with standard programmatic interventions for malaria control (long-lasting insecticidal nets (LLIN) and intermittent preventative treatment in pregnancy (IPTp)) in a cluster-randomized community-based trial. Primary outcome measures will be population-based Plasmodium falciparum (malaria infection) prevalence (estimated using ultra-sensitive PCR tests) and Anopheles gambiae (malaria vector) survival (measured using parity estimated by dissection of Anopheles ovaries). Data on MDA coverage, acceptability and feasibility of the intervention and a cost-effectiveness analysis will be included. We have established field infrastructure on the Bijagós Archipelago (including trained field entomologists and field laboratory technicians) and have detailed recent baseline data on the burden of disease caused by malaria and other neglected tropical diseases (NTDs) and vector populations on the islands. This 'natural laboratory' island setting provides an unparalleled opportunity to understand transmission and its interruption using a combined MDA strategy through investigating the impact of imported infections (through an expanded community-based CDSAT (case detection screen and treat) intervention which we will include in both arms), using serological (immune) markers in the blood to define transmission dynamics and estimate entomological inoculation rate (EIR) and monitoring the effect of IVM MDA on confined vector populations over time.
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