Prevalence of Molecular Markers of Antimalarial Drug Resistance across Altitudinal Transmission Zones in Highland Western Uganda

Ross M. Boyce Division of Infectious Diseases, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina;
Department of Community Health, Mbarara University of Science and Technology, Mbarara, Uganda;

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Nicholas Brazeau Division of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina;

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Travis Fulton Division of Infectious Diseases, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina;

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Nick Hathaway Program in Bioinformatics and Integrative Biology, University of Massachusetts, Worcester, Massachusetts;

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Michael Matte Department of Community Health, Mbarara University of Science and Technology, Mbarara, Uganda;

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Moses Ntaro Department of Community Health, Mbarara University of Science and Technology, Mbarara, Uganda;

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Edgar Mulogo Department of Community Health, Mbarara University of Science and Technology, Mbarara, Uganda;

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Jonathan J. Juliano Division of Infectious Diseases, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina;
Division of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina;
Curriculum in Genetics and Microbiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina

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We explored spatial variation in the prevalence of established molecular markers of antimalarial resistance across a geographically diverse, highland region of western Uganda. We identified Plasmodium falciparum CQ resistance transporter 76T mutations in all pools, but there was no evidence of spatial differences across village-based strata defined by either altitude or river valley. In contrast, we identified a significant inverse association between altitude and the prevalence of Plasmodium falciparum multidrug resistance 1 mutations with the largest proportion of Y184F mutations observed in the low-elevation, high-transmission villages. These results demonstrate the substantial heterogeneity in resistance markers observed across geographic settings, even at relatively small scales, but highlight the complex nature of these ecological relationships.

Author Notes

Address correspondence to Ross Boyce, Division of Infectious Diseases, University of North Carolina at Chapel Hill, 130 Mason Farm Rd., Chapel Hill, NC 27599. E-mail: roboyce@med.unc.edu

Financial support: R. M. B. (T32 AI007151) and J. J. J. (K24AI134990, R01AI121558, and R21AI121465) received support from the National Institutes of Health. Funding for the prospective cohort study was provided by a Thrasher Research Foundation Early Career Award to RMB.

Authors’ addresses: Ross Boyce and Travis Fulton, Division of Infectious Diseases, University of North Carolina at Chapel Hill, Chapel Hill, NC, E-mails: roboyce@med.unc.edu and travismfulton@gmail.com. Nicholas Brazeau, Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, E-mail: nbrazeau1@gmail.com. Nick Hathaway, University of Massachusetts Medical School, School of Medicine, Worcester, MA, E-mail: nickjhathaway@gmail.com. Michael Matte, Moses Ntaro, and Edgar Mulogo, Department of Community Health, Mbarara University of Science and Technology, Mbarara, Uganda, E-mails: mattemichael18@gmail.com, ntaro2001@gmail.com, and emulogo2000@gmail.com. Jonathan J. Juliano, Division of Infectious Diseases, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, E-mail: jonathan_juliano@med.unc.edu.

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