The emergence and spread of antimalarial resistance has occurred with every antimalarial deployed to date. The newer artemisinin-based combination therapies (ACTs) are again threatened by the independent emergence and spread of artemisinin resistance, as well as resistance to partner drugs. Typical approaches for tracking the emergence and spread of antimalarial resistance rely on sample collection from human studies. While informative, these approaches have several important limitations. Among the most important are the prohibitive costs 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 In addition, due to delays in the availability of resistance data, treatment and policy decisions are often based on outdated prevalence estimates. Finally, due to infrastructure needs for human studies, resistance data tends to be acquired in limited, typically urban, geographic settings, providing only a snapshot of resistance profiles for a given district or region. We argue that the characterization of drug resistance mutations in mosquito blood meals will provide a comparable estimate of drug resistance prevalence based on human studies. Such an approach would be less expensive, require less infrastructure, and allow for the scale- up of drug resistance surveillance to remote areas where human studies are more challenging to conduct. Importantly, exclusive use of human-based studies of drug resistance also ignores the role of mosquito stages in generating and transmitting drug resistance. Importantly, mutations in parasite transporters and other target genes have been well described, and impact the 1st line antimalarials used in Burkina Faso for both treatment and prevention. As an initial study, we propose the following aims: 1) To assess the potential for mosquito blood meals to be used as a surveillance tool for antimalarial resistance, and 2) To characterize the prevalence of molecular markers of drug resistance throughout the parasites' developmental stages within the mosquito. We will assess and compare the prevalence of known molecular markers of antimalarial drug resistance in parasite populations obtained from mosquito blood meals, dissected oocysts, and salivary glands, as well as from humans dwelling in those houses. Cross-sectional surveys in two distinct geographic sites Burkina Faso before, during, and after the malaria transmission season will be conducted, drug resistant mutations will be genotyped, and the prevalence of mutations will be compared between samples at select time points. In summary, we propose mosquito surveillance as a novel, cost-effective, and more rapid method for assessing the emergence and spread of antimalarial resistance in Plasmodium parasites, while also affording the possibility of further understanding the impact of drug resistance on parasite fitness.
Current approaches for the surveillance of antimalarial resistance rely on sample collection from human studies conducted in endemic regions which are limited by high costs, infrastructure and regulatory oversight requirements, delays in the availability of resistance data, and limited geographic coverage. We propose to assess the utility of using mosquito blood meals as sentinels for the emergence and spread of drug resistance. Our approach promises to shed light on the impact of drug resistance on parasite fitness and transmission, and provide samples that can be used for other applications such as tracking vector species composition and insecticide resistance.
