Ivermectin against Malaria (ANIVERMATE)

FR: Ivermectine et lutte contre le paludisme: approche One-Health intégrant le traitement des hommes et des animaux d’élevage tout en limitant la toxicité pour l’environnement

Project: Ivermectin against malaria: a One-Health approach to treat humans and peridomestic animals with regard to minimal ecological side-effects

Principal investigator: Prof. Dr. Rolf-Alexander Düring

Period: 2018-2020

Summary:

The success of current control tools like Insecticide Residual Spraying and Long Lasting Mosquitocidal Nets is frequently undermined by peculiar behaviors 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 behaviors, 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.
In this project, we expand the concept of using IVM MDA to humans for vector control but we believe that only a strategy that will combine IVM MDAs targeted at humans and their peridomestic animals will be successful at controlling residual transmission. We propose to establish the proof of concept that the major malaria vector species can be controlled using this “One Health” approach. We will use injectable slow-release formulations of IVM based upon combination of biodegradable polymers that will release the molecule over 6 months, encompassing a whole rainy season. In the lab, we will measure detrimental effects of the formulations when injected to cattle on life history traits of Anopheles coluzzii as well as potential appearance of ivermectin resistance on mosquitoes artificially fed with blood including sub-lethal doses of ivermectin for few successive generations. We 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, we will adapt available models predicting transmission that we will feed with our empirical data on survival probability, fecundity and potential induced repellency. We 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, our 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. Our approach stands as a preliminary study to test for the feasibility of integrated community-wide IVM 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, we 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.

Funding: Deutsche Forschungsgemeinschaft (DU 1021/5-1)

Further information (FR): ANIVERMATE