Antimalarial drugs are a critical tool in both the treatment and prevention malaria worldwide, yet their success has been hampered by the continual emergence and spread of antimalarial resistance (AMR). In the current climate of multidrug resistance, including resistance to the global front-line drug artemisinin, there is a need to scale up timely and widespread surveillance of AMR. The development of artemisinin resistance in sub- Saharan Africa would have a devastating impact on malaria-related morbidity and mortality. Molecular surveillance, which involves the screening of blood samples to determine the prevalence of molecular markers associated with drug resistance, can be a valuable tool for detecting emergent resistance genotypes before they become widespread. This proposal will first characterize the state of molecular monitoring efforts across sub-Saharan Africa. With the hypothesis that studies remain temporally and geographically clustered, we will use model-based geostatistics to interpolate the prevalence of AMR markers and suggest optimal strategies for future sampling sites. Next, in Burkina Faso, we will assess the utility of an alternative surveillance tool: the use of bloodmeals collected by arthropods, a technique known as xenosurveillance, to monitor molecular markers in humans that have been recently fed upon. We believe xenosurveillance may act as a complementary, rapidly deployable, and acceptable tool for the molecular surveillance of AMR. Finally, because molecular surveillance relies primarily on human-based interventional or cross-sectional trials, the role of the mosquito in transmitting drug resistant parasites remains unexplored. We will leverage our xenosurveillance samples to investigate the impact of vector behavior on the differential transmission of AMR parasites. This project will investigate the prevalence and dynamics of antimalarial resistance at multiple spatial scales. The goal of the proposed research is to help guide policymakers in their efforts to control the spread of AMR in sub-Saharan Africa, where drug pressure stems from both treatment and prevention regimens, and this pharmacological landscape changes regularly alongside the vector control landscape. After the completion of this two-year research and training fellowship, the applicant will have an advanced skillset in geostatistical modeling, molecular epidemiology, scientific communication and extensive field experience. Ultimately, the candidate seeks expertise in spatial analysis and applied epidemiology in order to advance surveillance efforts and improve our understanding of the geographic factors that influence vector-borne disease transmission. A multidisciplinary mentoring team will prepare the applicant for research independence in a career as a global health researcher and vector-borne disease epidemiologist at the nexus of environmental and human health.

Public Health Relevance

Antimalarial resistance has developed against every drug deployed to date and remains a major global health concern, particularly in sub-Saharan Africa. The need for improved understanding of the spatial distribution and inter-host transmission dynamics of antimalarial resistance is timely and necessary. Through the proposed aims, we will identify gaps in current human-based AMR surveillance strategies, and elucidate the role of a novel xenosurveillance tool to monitor AMR prevalence at different geographic scales.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31AI150168-02
Application #
10107663
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Costero-Saint Denis, Adriana
Project Start
2020-01-16
Project End
2023-01-15
Budget Start
2021-01-16
Budget End
2022-01-15
Support Year
2
Fiscal Year
2021
Total Cost
Indirect Cost
Name
Yale University
Department
Public Health & Prev Medicine
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520