Background and rationale {6a}
malaria, deaths, insectary-based
MALARIA, ONCHOCERCIASIS, LYMPHATIC FILARIASIS, MALARIA
This protocol was submitted to Malaria is preventable and treatable, and yet it remains a significant public health problem around the world. In 2020, there were 241 million cases and 627,000 malaria deaths globally. Around 93% of the cases and 94% of the deaths occurred in the WHO Africa Region [Based on substantive progress in the 2000–2015 period, the World Health Organization (WHO), through the Global Technical Strategy (GTS) [However, the global fight against malaria is at a crossroads [One critical challenge to achieving the 2030 goals is residual transmission, which is defined as “persistence of malaria transmission following the implementation in time and space of a widely effective malaria programme” [Endectocides are drugs that kill endo- and ectoparasites. Ivermectin is an endectocide licensed for human use in the 1980s. It has been a key drug in the treatment and control of onchocerciasis and lymphatic filariasis (LF) [The capability of ivermectin to kill mosquitoes has been evaluated in dozens of insectary-based experiments of colony or wild mosquito survival after feeding on ivermectin-containing blood [Ivermectin increases the mortality of Mosquito mortality is directly related to the ivermectin-blood concentration (i.e., dose-response relationship).The lethal effect is driven by the time the drug is present in the blood and the concentration reached (area under the curve, AUC); the time-in-blood above a certain threshold is the most important factor.The drug causes a series of sublethal effects that can contribute beyond the killing effect to reduce transmission (mosquito knock-down, reduced fertility, reduce motility).It appears that different mosquito species have different degrees of susceptibility to the drug, some species such as Additional evidence has emerged from mosquito collections conducted in onchocerciasis-endemic areas before and after ivermectin MDA was administered at the onchocerciasis dose of 150–200 mcg/kg [A reduction of 33% in the 3-day mosquito survival lasting for about 1 week after MDA,A shifting of the mosquito age population structure towards younger, less infectious, ages lasting for about 3 weeks, andA reduction of 77% in the proportion of mosquitoes carrying malaria parasites in their salivary glands (the sporozoite rate) lasting for about 2 weeks after MDA.There are two published cluster-randomized trials of ivermectin MDA for malaria to date. One conducted in Burkina Faso concluded that six doses of ivermectin (150–200 mcg/kg) given three weeks apart reduced malaria incidence by 20% in children under five years of age who did not receive ivermectin, reflecting decreased transmission [Several modeling exercises have also assessed the potential impact of ivermectin MDA on malaria transmission [The duration of the drug in the blood of treated subjects, reflecting both the dose and the regimen used,The coverage achieved in both human and livestock blood, andThe timing of the intervention in relation to the transmission season.Importantly, modeling suggests that adding ivermectin to other drug-based interventions, such as seasonal malaria chemoprevention (SMC) or MDA with antimalarials, could significantly enhance the effect and potentially reduce the number of rounds or coverage needed to achieve impact with the strategy.BOHEMIA will conduct two cluster-randomized, individually powered trials in parallel in different eco-epidemiological settings [The BOHEMIA trial will be carried out in Mopeia, Mozambique [
