Controlled Human Malaria Infection by Mosquito Bites Using a Local Strain of Plasmodium Falciparum

The project aims to reproduce the malaria infection cycle using African mosquitoes, namely Anopheles gambiae and a local strain of Plasmodium parasites. The study will be conducted in two steps: (i) the production of infected mosquitoes and (ii) human infection with malaria parasites, known as Controlled Human Malaria Infection (CHMI). During the first step, Anopheles gambiae mosquitoes raised in the Centre de Recherches Médicales de Lambaréné (CERMEL) entomology laboratory in Lambaréné, Gabon, will be fed with blood collected from a person living in Lambaréné or the surrounding area who is positive for Plasmodium falciparum parasites, with the presence of asexual and sexual stages (responsible for malaria transmission) of the parasites in his/her blood. The Plasmodium-infected mosquitoes will be used two weeks later to infect healthy adult volunteers by mosquito bites under the supervision of the research team. After exposure, we will follow all exposed participants daily, starting on the fifth day after exposure. During the daily visits, we will perform malaria tests to detect the presence of malaria parasites in the blood of the participant. If participants test positive, they will receive usual antimalarial treatment if they simultaneously present malaria symptoms or if their parasitaemia is equal to or greater than 1,000 parasites per microlitre of blood. To ensure participants are effectively treated, we will perform two malaria tests after treatment, which should be negative. Otherwise, a different treatment will be administered. We will consider the process successful if we manage to infect (presence of malaria parasites in the blood) at least 50% of exposed participants. We also want the process to be safe, assuming that no unexpected clinical or biological events occur. Such an approach could contribute to a better assessment of the efficacy of antimalarial drugs and vaccine candidates, taking into account the specific characteristics of each endemic area.