GHES LMIC Fellow 2018-2019
FELLOWSHIP SITE: IRSS, Burkina Faso
U.S. INSTITUTION: Yale University
Project Title: Drug resistance surveillance in mosquitoes and humans at multiple sites in Burkina Faso
Emergence and spread of antimalarial resistance has occurred with every antimalarial that has been deployed to date. Artemisinin-based combination therapies, now the mainstay of treatment in all malaria-endemic regions, are threatened by the independent emergence and spread of artemisinin resistance, as well as resistance to the partner drug, piperaquine, in multiple regions throughout Southeast Asia.
Typical approaches for monitoring the emergence and spread of antimalarial resistance rely on blood sample collection from human studies conducted in endemic regions. Methods include in vivo clinical drug efficacy studies, in vitro/ex vivo drug efficacy studies, and assessing the prevalence of molecular markers of antimalarial drug resistance from human samples. While these approaches are important, they have several important limitations. Among the most important limitations is the prohibitive cost of performing human studies, as well as the time, personnel, and regulatory oversight required for each study. In addition, due to delays in the availability of resistance data, treatment and policy decisions are often based on prevalence estimates that are outdated by up to several years. Finally, because of infrastructure needs for human studies, resistance data tends to be acquired in a very limited geographic area, providing only a snapshot of resistance profiles for a given district or region. In Burkina Faso, Artemether-Lumefantrine (AL) or Artesunate-Amodiaquine (AS-AQ) have been recommended since 2005 first line drugs for the treatment of uncomplicated malaria whereas quinine is being used for severe cases. Recently, the country has adopted the large-scale implementation of seasonal malaria chemoprevention with Amodiaquine-Sulfadoxine-Pyrimethamine (AQ-SP) in children under five. Although ACTs and AQ-SP have demonstrated high efficacies respectively for the treatment and prevention of malaria it remains important to closely monitor their efficacy through evaluation of mutations in K13, pfcrt, pfmdr1, pfdhfr, pfdhps genes.
The use of "mosquito"-based sampling approaches affords the potential to significantly improve our surveillance efforts. We argue that assessing the prevalence of molecular markers of drug-resistance in field-captured mosquitoes may offer a simpler and less expensive to track the prevalence of drug resistant malaria, as well as offer an easier way to scale-up surveillance to remote areas where human studies are more challenging. In addition, the collection of large numbers of mosquitoes in multiple different sites allows for the additional benefit of monitoring for insecticide resistance and changes in vector species composition.
We propose to assess for the prevalence of known molecular markers of antimalarial drug resistance in parasite populations obtained from household-captured mosquitoes and compare them to the prevalence of same molecular markers of antimalarial drug resistance in parasites isolated from contemporaneously collected human samples in health facilities. We will conduct cluster-randomized cross-sectional studies in five different regions in Burkina Faso including regions in the border of neighboring countries during the malaria transmission season, and that span a range of malaria transmission intensities, and drug pressures. Parasites will be genotyped from household-captured mosquito blood meals and contemporaneously collected human samples from malaria patients visiting health center.