Our research program focuses on five subject areas: (1) the nature of protection against malaria that is conferred to individuals carrying red blood cell (RBC) polymorphisms including hemoglobin C, hemoglobin S, hemoglobin E, alpha-thalassemia and G6PD deficiency;(2) the nature of naturally-acquired immunity to malaria and how it is influenced by RBC polymorphisms;(3) the molecular mechanisms by which RBC polymorphisms reduce the expression of PfEMP1, the main virulence factor of Plasmodium falciparum, on the surface of parasitized RBCs;(4) the contributions of parasite genetic and host immune factors to the clearance of P. falciparum-infected RBCs in patients treated with the antimalarial drug artesunate;and (5) the nature of the selective invasion of reticulocytes by Plasmodium vivax. In each of these areas we seek research advances that can improve the knowledge of disease processes and antimalarial drug resistance mechanisms in patients with malaria and thereby support the development of new antimalarial therapeutics and vaccines that aim to prevent illness and death. The research activities in our program are multidisciplinary and include four field studies in malarious regions of Africa and Southeast Asia as well as programs of basic laboratory investigation at NIH-sponsored laboratories in Mali and Cambodia.

Project Start
Project End
Budget Start
Budget End
Support Year
7
Fiscal Year
2013
Total Cost
$992,443
Indirect Cost
City
State
Country
Zip Code
Amaratunga, Chanaki; Witkowski, Benoit; Dek, Dalin et al. (2014) Plasmodium falciparum Founder Populations in Western Cambodia Have Reduced Artemisinin Sensitivity In Vitro. Antimicrob Agents Chemother 58:4935-7
Amaratunga, Chanaki; Neal, Aaron T; Fairhurst, Rick M (2014) Flow Cytometry-Based Analysis of Artemisinin-Resistant Plasmodium falciparum in the Ring-Stage Survival Assay. Antimicrob Agents Chemother 58:4938-40
Preston, Mark D; Assefa, Samuel A; Ocholla, Harold et al. (2014) PlasmoView: a web-based resource to visualise global Plasmodium falciparum genomic variation. J Infect Dis 209:1808-15
Sangaré, Modibo; Hendrickson, Brant; Sango, Hammadoun Ali et al. (2014) Genetics of low spinal muscular atrophy carrier frequency in sub-Saharan Africa. Ann Neurol 75:525-32
Ocholla, Harold; Preston, Mark D; Mipando, Mwapatsa et al. (2014) Whole-genome scans provide evidence of adaptive evolution in Malawian Plasmodium falciparum isolates. J Infect Dis 210:1991-2000
Ariey, Frederic; Witkowski, Benoit; Amaratunga, Chanaki et al. (2014) A molecular marker of artemisinin-resistant Plasmodium falciparum malaria. Nature 505:50-5
Glushakova, Svetlana; Balaban, Amanda; McQueen, Philip G et al. (2014) Hemoglobinopathic Erythrocytes Affect the Intraerythrocytic Multiplication of Plasmodium falciparum in Vitro. J Infect Dis :
Aird, William C; Mosnier, Laurent O; Fairhurst, Rick M (2014) Plasmodium falciparum picks (on) EPCR. Blood 123:163-7
Beaudry, Jeanette T; Krause, Michael A; Diakite, Seidina A S et al. (2014) Ex-vivo cytoadherence phenotypes of Plasmodium falciparum strains from Malian children with hemoglobins A, S, and C. PLoS One 9:e92185
Ashley, Elizabeth A; Dhorda, Mehul; Fairhurst, Rick M et al. (2014) Spread of artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med 371:411-23

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