Our research program focuses on six subject areas: (1) the nature of protection against malaria that is conferred to individuals carrying hemoglobin mutations and red blood cell polymorphisms including but not limited to hemoglobin C, hemoglobin S, hemoglobin E, alpha- and beta-thalassemia, and G6PD deficiency; (2) the nature of infant protection against malaria in the first few months of life, involving cooperative interactions between fetal hemoglobin and maternal-derived immune antibodies; (3) the molecular mechanisms by which malaria-protective polymorphisms reduce the expression of PfEMP-1, the main virulence factor of Plasmodium falciparum, on the surface of parasitized red blood cells; (4) the nature of microvessel inflammation and other pathogenic processes caused by the adherence of parasitized red blood cells to human microvascular endothelial cells and blood monocytes. In each of these areas we seek research advances that can improve the knowledge of fatal disease processes in individuals with malaria and thereby support the development of new antimalarial therapeutics and vaccines that aim to prevent death. 5) the genotypic nature of malaria parasites in Cambodia 6) the biology of the Anopheline mosquito vectors of malaria in Cambodia in areas where NIAID sponsored studies are ongoing. These studies will examine the ecology of the various vector species and their relative importance in the epidemiology of transmission.

Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2009
Total Cost
$509,672
Indirect Cost
City
State
Country
Zip Code
Ataide, Ricardo; Ashley, Elizabeth A; Powell, Rosanna et al. (2017) Host immunity to Plasmodium falciparum and the assessment of emerging artemisinin resistance in a multinational cohort. Proc Natl Acad Sci U S A 114:3515-3520
Amato, Roberto; Lim, Pharath; Miotto, Olivo et al. (2017) Genetic markers associated with dihydroartemisinin-piperaquine failure in Plasmodium falciparum malaria in Cambodia: a genotype-phenotype association study. Lancet Infect Dis 17:164-173
Mukherjee, Angana; Bopp, Selina; Magistrado, Pamela et al. (2017) Artemisinin resistance without pfkelch13 mutations in Plasmodium falciparum isolates from Cambodia. Malar J 16:195
Fairhurst, Rick M; Dondorp, Arjen M (2016) Artemisinin-Resistant Plasmodium falciparum Malaria. Microbiol Spectr 4:
Pearson, Richard D; Amato, Roberto; Auburn, Sarah et al. (2016) Genomic analysis of local variation and recent evolution in Plasmodium vivax. Nat Genet 48:959-64
Amaratunga, Chanaki; Lim, Pharath; Suon, Seila et al. (2016) Dihydroartemisinin-piperaquine resistance in Plasmodium falciparum malaria in Cambodia: a multisite prospective cohort study. Lancet Infect Dis 16:357-65
St Laurent, Brandyce; Miller, Becky; Burton, Timothy A et al. (2016) Corrigendum: Artemisinin-resistant Plasmodium falciparum clinical isolates can infect diverse mosquito vectors of Southeast Asia and Africa. Nat Commun 7:10345
Rasmussen, Charlotte; Ariey, Frédéric; Fairhurst, Rick M et al. (2016) Role of K13 Mutations in Artemisinin-Based Combination Therapy. Clin Infect Dis 63:1680-1681
Hostetler, Jessica B; Lo, Eugenia; Kanjee, Usheer et al. (2016) Independent Origin and Global Distribution of Distinct Plasmodium vivax Duffy Binding Protein Gene Duplications. PLoS Negl Trop Dis 10:e0005091
Srimuang, Krongkan; Miotto, Olivo; Lim, Pharath et al. (2016) Analysis of anti-malarial resistance markers in pfmdr1 and pfcrt across Southeast Asia in the Tracking Resistance to Artemisinin Collaboration. Malar J 15:541

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