(1) Completed a third and final year of follow-up on our cohort study in Thmar Da on the Cambodia-Thailand border. Due to significant loss to follow up (several hundred individuals have moved permanently away from the area) and declining incidence of both falciparum and vivax malaria, we decided to terminate this study in May 2011. We are presently preparing a final spreadsheet, which includes 3 years of follow-up for episodes of falciparum and vivax malaria and five cross-sectional surveys for asymptomatic P. falciparum and P. vivax parasitemia. With this spreadsheet, we will investigate whether hemoglobin E and other RBC polymorphisms influence the incidence of malaria. (2) Performed a final analysis of our case-control study of severe malaria, conducted 2005-2008 in Pursat, Cambodia. (3) Completed a 2-year study of parasite clearance rates in Pursat, Cambodia. (4) Completed a 1-year study of parasite clearance rates in Ratanakiri, Cambodia. (5) Initiated three parasite clearance studies in Pursat, Preah Vihear (new site), and Ratanakiri. We are conducting these studies in collaboration with TRAC the Tracking Artemisinin Resistance Collaboration. This consortium, which Dr. Fairhurst presently co-chairs with Dr. Arjen Dondorp (Mahidol-Oxford Research unit), involves our three sites in Cambodia, as well as additional sites in Cambodia, Thailand, Burma, Laos, Vietnam, India, Bangladesh, Nigeria and Kenya. The purpose of TRAC and our own studies is to (i) map the artemisinin resistance phenotype across Southeast Asia and (ii) to improve our understanding of parasite clearance in response to artesunate. Specifically, we are interested in how hemoglobin E (HbE), naturally-acquired immunity and intrinsic parasite susceptibility to artemisinins influence the parasite clearance curve. Our three sites were chosen for study because while they each have high prevalence of HbE, they differ in levels of acquired immunity and in parasite IC50s to artemisinins and other antimalarial drugs.

Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
2011
Total Cost
$159,531
Indirect Cost
City
State
Country
Zip Code
Amato, Roberto; Pearson, Richard D; Almagro-Garcia, Jacob et al. (2018) Origins of the current outbreak of multidrug-resistant malaria in southeast Asia: a retrospective genetic study. Lancet Infect Dis 18:337-345
Bopp, Selina; Magistrado, Pamela; Wong, Wesley et al. (2018) Plasmepsin II-III copy number accounts for bimodal piperaquine resistance among Cambodian Plasmodium falciparum. Nat Commun 9:1769
Mukherjee, Angana; Bopp, Selina; Magistrado, Pamela et al. (2017) Artemisinin resistance without pfkelch13 mutations in Plasmodium falciparum isolates from Cambodia. Malar J 16:195
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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
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
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
St Laurent, Brandyce; Oy, Kolthida; Miller, Becky et al. (2016) Cow-baited tents are highly effective in sampling diverse Anopheles malaria vectors in Cambodia. Malar J 15:440
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

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