Genetic Variation and Evolution of Artemisinin Resistance Malaria is one of the biggest killers in the world. The 2010 World Malaria Report estimates that almost 225 million people each year become acutely ill from the disease-and approximately one million will die from malaria. In the absence of an effective malaria vaccine, chemotherapy remains the mainstay for treatment and prevention of the disease. Genetic variability of the most dangerous type of malaria, Plasmodium falciparum, underlies its transmission success and impedes efforts to control disease. Drug resistance to antimalarial drugs such as antifolates and chloroquine has spread from Asia throughout Africa and resistance to second and third line drugs is now commonplace. Using the tools of population genetics and genomics, the """"""""Genetic Variation and Evolution of Artemisinin Resistance"""""""" project will expand our fundamental understanding of both the genetic variation of malaria and microbial drug resistance among malaria parasites by confirming artemisinin resistance phenotypes, identify the gene (or genes) involved in artemisinin drug resistance, and validate the candidate gene (or genes) involved in artemisinin resistance. Because the emergence of drug resistance threatens to outpace the development of effective new antimalarial drugs, the development of an early warning system for emerging resistance is an essential component to defeating malaria.

Public Health Relevance

Genetic Variation and Evolution of Artemisinin Resistance Chemotherapy remains the mainstay for treatment and prevention of malaria, with current efforts focused on the use of artemisinin-based antimalarial drugs in combination with other partner compounds. New reports of emerging drug resistance signal a threat to the effectiveness of these artemisinin-based drugs. Leveraging genetic variation and evolution, we will identify genetic variants associated with changing artemisinin responses and detect the early stages of drug resistance before catastrophic loss of these still effective anti- malarial compounds takes hold.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
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Genetic Variation and Evolution Study Section (GVE)
Program Officer
Joy, Deirdre A
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Harvard University
Schools of Public Health
United States
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Rice, Benjamin L; Golden, Christopher D; Anjaranirina, Evelin Jean Gasta et al. (2016) Genetic evidence that the Makira region in northeastern Madagascar is a hotspot of malaria transmission. Malar J 15:596
Molina-Cruz, Alvaro; Zilversmit, Martine M; Neafsey, Daniel E et al. (2016) Mosquito Vectors and the Globalization of Plasmodium falciparum Malaria. Annu Rev Genet 50:447-465
Magistrado, Pamela A; Corey, Victoria C; Lukens, Amanda K et al. (2016) Plasmodium falciparum Cyclic Amine Resistance Locus (PfCARL), a Resistance Mechanism for Two Distinct Compound Classes. ACS Infect Dis 2:816-826
Sackton, Timothy B; Hartl, Daniel L (2016) Genotypic Context and Epistasis in Individuals and Populations. Cell 166:279-287
Galinsky, Kevin; Valim, Clarissa; Salmier, Arielle et al. (2015) COIL: a methodology for evaluating malarial complexity of infection using likelihood from single nucleotide polymorphism data. Malar J 14:4
Bei, Amy K; Diouf, Ababacar; Miura, Kazutoyo et al. (2015) Immune characterization of Plasmodium falciparum parasites with a shared genetic signature in a region of decreasing transmission. Infect Immun 83:276-85
Daniels, Rachel F; Rice, Benjamin L; Daniels, Noah M et al. (2015) The utility of genomic data for Plasmodium vivax population surveillance. Pathog Glob Health 109:153-61
Corbett-Detig, Russell B; Hartl, Daniel L; Sackton, Timothy B (2015) Natural selection constrains neutral diversity across a wide range of species. PLoS Biol 13:e1002112
Daniels, Rachel F; Schaffner, Stephen F; Wenger, Edward A et al. (2015) Modeling malaria genomics reveals transmission decline and rebound in Senegal. Proc Natl Acad Sci U S A 112:7067-72
Daniels, Rachel; Hamilton, Elizabeth J; Durfee, Katelyn et al. (2015) Methods to Increase the Sensitivity of High Resolution Melting Single Nucleotide Polymorphism Genotyping in Malaria. J Vis Exp :e52839

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