Partial clearance of pre-established Plasmodium falciparum infection in mosquitoes by feeding on patients treated with Artemether+Lumefantrine + Atovaquone-Proguanil
Résumé
Background : Effective treatment of malaria involves targeting both the disease-causing stages and the transmissible sexual stages to impede further transmission and prevent drug resistance. The present study relies on a clinical trial testing the benefits of combining Atovaquone Proguanil (AP) with Artemetherlumefantrine (AL) in the treatment of uncomplicated malaria. AP treatment has been shown to block Plasmodium falciparum transmission by affecting gametocyte carriage and transmission to mosquitoes. Additionally, exposure to atovaquone has been found to impact pre-established P. falciparum infection in mosquitoes. Here, we aimed to assess the impact of meal intake on blood from patients treated with AL versus AL+AP for pre-infected mosquitoes on the further development of parasites until sporozoites. Methods : We collected infectious blood meals from naturally infected donors in Burkina Faso and fed them to laboratory-reared female Anopheles gambiae. Four days later, these mosquitoes were exposed to a second blood meal containing plasma from patients treated with either AL+placebo or AL+AP, collected at eight time points from Day 0 to Day 28. Results : A total of 9,259 mosquitoes were dissected, with 4,850 at 7 days and 4,409 at 14 days post-infection (dpi). Our preliminary analysis shows that in P. falciparum-infected mosquitoes, a blood meal with plasma from AL+AP treated patients significantly inhibits parasite development. This inhibition includes a decrease in infection prevalence, reduced infection intensity, and slower sporogonic development. Plasma from patients treated with AL alone had no effect. The impact of AL+AP was significant for plasma samples collected between 5 hours and 5 days post-treatment. Further analysis, including correlation with drug dosage and sporozoite quantification in salivary glands, is underway. Conclusion : These findings underscore the benefits of triple ACT containing AP, as treated patients may help reduce the vector competence of the local mosquito population and contribute to partial community protection against malaria transmission.