In several countries where malaria is nearing elimination, Plasmodium falciparum (Pf) and Plasmodium vivax (Pv) are co-endemic. Plasmodium vivax infections pose unique challenges for malaria elimination, including that Pv cases are more easily missed through standard diagnostics and that Pv has the ability to remain latent in liver-stage (hypnozoites), which can cause relapses for weeks to years.~Active case detection (ACD) is an effective tool used by many malaria elimination programs, however, asymptomatic infections can still be missed due to limited sensitivity of ACD diagnostic tools. Mass drug administration (MDA) has been recommended for Pf elimination as an alternative approach to ACD in regions where there is sufficient access to treatment. Recommendations for use of MDA do not yet extend to Pv as a result of limited evidence and difficulty in administering existing anti-malarial drugs daily for one to two weeks.~This study aims to assess the effectiveness of MDA in the Loreto Department in Peru by implementing a more targeted approach: focal MDA. This approach targets drug administration to households at the highest risk of infection to minimize the potential adverse effects of MDA and promote uptake. Further, preliminary data from the study site region suggests that recurrences of malaria infections in index cases and clustering of infections around these index cases drive continued transmission of Pv. Thus, fMDA is an appropriate approach to study in this region.~The primary research objectives are:~To determine the effectiveness of three rounds of fMDA to reduce Pv transmission in the Loreto Department, Peru compared to standard interventions.~To evaluate the safety and tolerability of fMDA by measuring incidence of severe adverse events or severe malaria in the treatment arm.~To measure the cost-effectiveness and acceptability of fMDA by calculating the cost per malaria case averted for intervention and control arms.
FLAME is an open-label cluster-randomized controlled trial that aims to determine the effectiveness of focal mass drug administration (fMDA) to reduce the incidence of Plasmodium vivax malaria in the Loreto Department in Peru. Standard interventions, including symptomatic and asymptomatic screening for malaria infections, provision of insecticide-treated bednets, and environmental transmission monitoring, will be compared to clusters of villages randomized to receive anti-malarial drugs.