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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Comparative impacts over 5 years of artemisinin-based combination therapies on Plasmodium falciparum polymorphisms that modulate drug sensitivity in Ugandan children
Journal of Infectious Diseases, Volume 210, No. 3, Year 2014
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Description
Background. Artemisinin-based combination therapies, including artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP), are recommended to treat uncomplicated falciparum malaria. Sensitivities to components of AL and DP are impacted by polymorphisms in pfmdr1 and pfcrt. We monitored changes in prevalences of polymorphisms in Tororo, Uganda, from 2008 to 2012. Methods. Polymorphic loci in pfmdr1 and pfcrt were characterized in samples from 312 children randomized to AL or DP for each episode of uncomplicated malaria (50 samples per arm for each 3-month interval) utilizing a fluorescent microsphere assay. Treatment outcomes and impacts of prior therapies were also characterized. Results. Prevalence increased significantly over time for pfmdr1 N86 (AL: odds ratio [OR], 2.08 [95% confidence interval {CI}, 1.83-2.38]; DP: 1.41 [95% CI, 1.25-1.57]), pfmdr1 D1246 (AL: 1.46 [95% CI, 1.29-1.64]; DP: 1.36 [95% CI, 1.23-1.50]), and pfcrt K76 (AL: 3.37 [95% CI, 1.85-6.16]; DP: 5.84 [95% CI, 1.94-17.53], and decreased for pfmdr1 Y184 (AL: 0.78 [95% CI, .70-.86]; DP: 0.84 [95% CI, .76-1.50]); changes were consistently greater in the AL arm. Recent AL treatment selected for pfmdr1 N86, D1246, and 184F in subsequent episodes; DP selected for the opposite alleles. Conclusions. Genotypes with decreased sensitivity to AL components increased over time. This increase was greater in children receiving AL, suggesting that the choice of treatment regimen can profoundly influence parasite genetics and drug sensitivity. © The Author 2014.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC4110461/bin/supp_210_3_344__index.html
Authors & Co-Authors
Conrad, Melissa D.
United States, San Francisco
Ucsf School of Medicine
LeClair, Norbert P.
United States, San Francisco
Ucsf School of Medicine
Arinaitwe, Emmanuel S.
Uganda, Kampala
Makerere University College of Health Sciences
Wanzira, Humphrey
Uganda, Kampala
Makerere University College of Health Sciences
Kakuru, Abel
Uganda, Kampala
Makerere University College of Health Sciences
Bigira, Victor
Uganda, Kampala
Makerere University College of Health Sciences
Muhindo, Mary Kakuru
Uganda, Kampala
Makerere University College of Health Sciences
Kamya, Moses Robert K.
Uganda, Kampala
Makerere University College of Health Sciences
Tappero, Jordan W.
United States, Atlanta
Centers for Disease Control and Prevention
Greenhouse, Bryan R.
United States, San Francisco
Ucsf School of Medicine
Dorsey, Grant M.
United States, San Francisco
Ucsf School of Medicine
Rosenthal, Philip Jon
United States, San Francisco
Ucsf School of Medicine
Statistics
Citations: 97
Authors: 12
Affiliations: 3
Identifiers
Doi:
10.1093/infdis/jiu141
ISSN:
00221899
e-ISSN:
15376613
Research Areas
Genetics And Genomics
Infectious Diseases
Maternal And Child Health
Study Design
Cross Sectional Study
Case-Control Study
Study Locations
Uganda