Ivermectin against malaria: a One-Health Approach to Treating Humans and Peridomestic Animals (ANIVERMATE)
In this project, the concept of using ivermectin mass drug administration (MDA) to humans for vector control is expanded. The research team believes that only a strategy that will combine ivermectin MDAs targeted at humans and their peridomestic animals will be successful at controlling residual transmission.
This project proposes to establish the proof of concept that the major malaria vector species can be controlled using this “One Health” approach. Injectable slow-release formulations of ivermectin based upon a combination of biodegradable polymers that will release the molecule over 6 months will be used, encompassing a whole rainy season.
The success of current control tools like Insecticide Residual Spraying and Long Lasting Mosquitocidal Nets is frequently undermined by peculiar behaviours of vectors allowing them to escape the exposure to insecticides. Exophagy and zoophagy minimize contact between mosquito and insecticides, and contribute to the build-up of reservoirs of residual vectors populations. Addressing these behaviours, mass drug administration (MDA) to humans of the endectocide ivermectin (IVM) for vector control is receiving increasing attention. By this, the treated human directly delivers the insecticide to any blood-feeding mosquito, thus targeting any human-feeding vector. However, vectors feeding outdoors upon animals escape from this promising approach.
This approach stands as a preliminary study to test for the feasibility of integrated community-wide ivermectin administration to humans and livestock in the “One-Health” concept for a sustainable control of malaria disease. This approach could be generalized to virtually any vector species of human diseases in any environmental settings. By this approach, the research team will also target virtually all disease vectors that bite humans and animals in a “One-health” concept for community-wide protection, in areas where humans are at risk of zoonotic diseases like in rural zones of Africa.
In the lab, the research team will measure detrimental effects of the formulations when injected to cattle on life-history traits of Anopheles coluzzii as well as the potential appearance of ivermectin resistance on mosquitoes artificially fed with blood including sub-lethal doses of ivermectin for few successive generations. They will assess potential toxicity of the treatments for non-target fauna by monitoring ecotoxicological endpoints with terrestrial invertebrates.
Ivermectin dosage will be optimized considering calves’ plasma, feces, and blood-fed mosquitoes. These results will allow understanding potential variations in the formulations’ effects and to optimize the concentration of the formulation in order to induce toxicity for the vectors. For the first time, concentrations directly imbibed by the vectors will be known, allowing a better knowledge of ivermectin dose-response relationship and the concentrations lethal to the mosquitoes.
Lastly, they will adapt available models predicting transmission that they will feed with empirical data on survival probability, fecundity and potential induced repellency. The team will be able to predict effects of long-lasting IVM formulations for malaria vectors by simulating their zoophagy proclivities and the number of cattle relative to humans.
Using entomological and social science data collected in the field, the model will allow producing georeferenced maps of efficacy that will be available for use by stakeholders and human and animal health workers involved in malaria vector control.