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Temporal Changes in Prevalence of Molecular Markers Mediating Antimalarial Drug Resistance in a High Malaria Transmission Setting in Uganda

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  • Infectious Diseases Research Collaboration, Kampala, Uganda; Le Tourneau University, Longview, Texas; Global AIDS Program, Centers for Disease Control and Prevention, Atlanta, Georgia; London School of Hygiene and Tropical Medicine, United Kingdom; University of California, San Francisco, California

Standard therapy for malaria in Uganda changed from chloroquine to chloroquine + sulfadoxine-pyrimethamine in 2000, and artemether-lumefantrine in 2004, although implementation of each change was slow. Plasmodium falciparum genetic polymorphisms are associated with alterations in drug sensitivity. We followed the prevalence of drug resistance-mediating P. falciparum polymorphisms in 982 samples from Tororo, a region of high transmission intensity, collected from three successive treatment trials conducted during 2003–2012, excluding samples with known recent prior treatment. Considering transporter mutations, prevalence of the mutant pfcrt 76T, pfmdr1 86Y, and pfmdr1 1246Y alleles decreased over time. Considering antifolate mutations, the prevalence of pfdhfr 51I, 59R, and 108N, and pfdhps 437G and 540E were consistently high; pfdhfr 164L and pfdhps 581G were uncommon, but most prevalent during 2008–2010. Our data suggest sequential selective pressures as different treatments were implemented, and they highlight the importance of genetic surveillance as treatment policies change over time.

Author Notes

* Address correspondence to Philip J. Rosenthal, Box 0811, University of California, San Francisco, CA 94143. E-mail: prosenthal@medsfgh.ucsf.edu

Financial support: This study was funded by an International Center of Excellence in Malaria Research grant (AI089674) and a Fogarty International Center training grant (TW007375), both from the National Institutes of Health. Some study samples were from a trial supported by the Doris Duke Charitable Foundation; the U.S. President's Emergency Plan for AIDS Relief; and Cooperative Agreement U62P024421 from the Centers for Disease Control and Prevention (CDC); the National Center for HIV, Viral Hepatitis, STD, and TB Prevention; and the Global AIDS Program. The funders were not involved with study design, data analysis, or manuscript preparation.

Authors' addresses: George W. Mbogo, Sheila Nankoberanyi, Stephen Tukwasibwe, Samuel L. Nsobya, Emmanuel Arinaitwe, and Moses Kamya, Infectious Diseases Research Collaboration, Kampala, Uganda, E-mails: mbggeorge@yahoo.co.uk, nankshila@yahoo.com, stephentukwasibwe@yahoo.com, samnsobya@yahoo.co.uk, earinaitwe@idrc-uganda.org, and mkamya@infocom.co.ug. Frederick N. Baliraine, Le Tourneau University, Longview, TX, E-mail: FredBaliraine@letu.edu. Melissa D. Conrad, Grant Dorsey, Bryan Greenhouse, and Philip J. Rosenthal, Department of Medicine, University of California, San Francisco, CA, E-mails: ConradM@medsfgh.ucsf.edu, gdorsey@medsfgh.ucsf.edu, bgreenhouse@medsfgh.ucsf.edu, and prosenthal@medsfgh.ucsf.edu. Jordan Tappero, Global AIDS Program, Centers for Disease Control and Prevention, Atlanta, GA, E-mail: jtappero@cdc.gov. Sarah G. Staedke, London School of Hygiene and Tropical Medicine, UK, E-mail: sarah.staedke@lshtm.ac.uk.

Reprints requests: Philip J. Rosenthal, Department of Medicine, Box 0811, University of California, San Francisco, CA 94143-0811. E-mail: prosenthal@medsfgh.ucsf.edu.

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