Talisuna AO et al. 2012. Mitigating the threat of artemisinin resistance in Africa: improvement of drug-resistance surveillance and response systems. Lancet Infect Dis 12: 888–896.
Packard RM, 2014. The origins of antimalarial-drug resistance. N Engl J Med 371: 397–399.
WHO, 2011. Global Plan for Artemisinin Resistance Containment (GPARC). Geneva, Switzerland: World Health Organization.
Plowe CV, 2009. The evolution of drug-resistant malaria. Trans R Soc Trop Med Hyg 103 (Suppl 1): S11–S14.
Kamya MR, Bakyaita NN, Talisuna AO, Were WM, Staedke SG, 2002. Increasing antimalarial drug resistance in Uganda and revision of the national drug policy. Trop Med Int Health 7: 1031–1041.
Nanyunja M, Nabyonga Orem J, Kato F, Kaggwa M, Katureebe C, Saweka J, 2011. Malaria treatment policy change and implementation: the case of Uganda. Malar Res Treat 2011: 683167.
Kublin JG, Cortese JF, Njunju EM, Mukadam RA, Wirima JJ, Kazembe PN, Djimde AA, Kouriba B, Taylor TE, Plowe CV, 2003. Reemergence of chloroquine-sensitive Plasmodium falciparum malaria after cessation of chloroquine use in Malawi. J Infect Dis 187: 1870–1875.
Mbogo GW et al. 2014. Temporal changes in prevalence of molecular markers mediating antimalarial drug resistance in a high malaria transmission setting in Uganda. Am J Trop Med Hyg 91: 54–61.
Talisuna AO, Erhart A, Samarasinghe S, Van Overmeir C, Speybroeck N, D’Alessandro U, 2006. Malaria transmission intensity and the rate of spread of chloroquine resistant Plasmodium falciparum: why have theoretical models generated conflicting results? Infect Genet Evol 6: 241–248.
Boyce RM et al. 2018. Reuse of malaria rapid diagnostic tests for amplicon deep sequencing to estimate Plasmodium falciparum transmission intensity in western Uganda. Scientific Rep 8: 10159.
Boyce R, Reyes R, Matte M, Ntaro M, Mulogo E, Siedner MJ, 2017. Use of a dual-antigen rapid diagnostic test to screen children for severe Plasmodium falciparum malaria in a high-transmission, resource-limited setting. Clin Infect Dis 65: 1509–1515.
Hathaway NJ, Parobek CM, Juliano JJ, Bailey JA, 2018. SeekDeep: single-base resolution de novo clustering for amplicon deep sequencing. Nucleic Acids Res 46: e21.
Pongtavornpinyo W, Yeung S, Hastings IM, Dondorp AM, Day NP, White NJ, 2008. Spread of anti-malarial drug resistance: mathematical model with implications for ACT drug policies. Malar J 7: 229.
Wang LT, Bwambale R, Keeler C, Reyes R, Muhindo R, Matte M, Ntaro M, Mulogo E, Sundararajan R, Boyce RM, 2018. Private sector drug shops frequently dispense parenteral anti-malarials in a rural region of western Uganda. Malar J 17: 305.
Tumwebaze P et al. 2017. Changing antimalarial drug resistance patterns identified by surveillance at three sites in Uganda. J Infect Dis 215: 631–635.
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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.
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.
Talisuna AO et al. 2012. Mitigating the threat of artemisinin resistance in Africa: improvement of drug-resistance surveillance and response systems. Lancet Infect Dis 12: 888–896.
Packard RM, 2014. The origins of antimalarial-drug resistance. N Engl J Med 371: 397–399.
WHO, 2011. Global Plan for Artemisinin Resistance Containment (GPARC). Geneva, Switzerland: World Health Organization.
Plowe CV, 2009. The evolution of drug-resistant malaria. Trans R Soc Trop Med Hyg 103 (Suppl 1): S11–S14.
Kamya MR, Bakyaita NN, Talisuna AO, Were WM, Staedke SG, 2002. Increasing antimalarial drug resistance in Uganda and revision of the national drug policy. Trop Med Int Health 7: 1031–1041.
Nanyunja M, Nabyonga Orem J, Kato F, Kaggwa M, Katureebe C, Saweka J, 2011. Malaria treatment policy change and implementation: the case of Uganda. Malar Res Treat 2011: 683167.
Kublin JG, Cortese JF, Njunju EM, Mukadam RA, Wirima JJ, Kazembe PN, Djimde AA, Kouriba B, Taylor TE, Plowe CV, 2003. Reemergence of chloroquine-sensitive Plasmodium falciparum malaria after cessation of chloroquine use in Malawi. J Infect Dis 187: 1870–1875.
Mbogo GW et al. 2014. Temporal changes in prevalence of molecular markers mediating antimalarial drug resistance in a high malaria transmission setting in Uganda. Am J Trop Med Hyg 91: 54–61.
Talisuna AO, Erhart A, Samarasinghe S, Van Overmeir C, Speybroeck N, D’Alessandro U, 2006. Malaria transmission intensity and the rate of spread of chloroquine resistant Plasmodium falciparum: why have theoretical models generated conflicting results? Infect Genet Evol 6: 241–248.
Boyce RM et al. 2018. Reuse of malaria rapid diagnostic tests for amplicon deep sequencing to estimate Plasmodium falciparum transmission intensity in western Uganda. Scientific Rep 8: 10159.
Boyce R, Reyes R, Matte M, Ntaro M, Mulogo E, Siedner MJ, 2017. Use of a dual-antigen rapid diagnostic test to screen children for severe Plasmodium falciparum malaria in a high-transmission, resource-limited setting. Clin Infect Dis 65: 1509–1515.
Hathaway NJ, Parobek CM, Juliano JJ, Bailey JA, 2018. SeekDeep: single-base resolution de novo clustering for amplicon deep sequencing. Nucleic Acids Res 46: e21.
Pongtavornpinyo W, Yeung S, Hastings IM, Dondorp AM, Day NP, White NJ, 2008. Spread of anti-malarial drug resistance: mathematical model with implications for ACT drug policies. Malar J 7: 229.
Wang LT, Bwambale R, Keeler C, Reyes R, Muhindo R, Matte M, Ntaro M, Mulogo E, Sundararajan R, Boyce RM, 2018. Private sector drug shops frequently dispense parenteral anti-malarials in a rural region of western Uganda. Malar J 17: 305.
Tumwebaze P et al. 2017. Changing antimalarial drug resistance patterns identified by surveillance at three sites in Uganda. J Infect Dis 215: 631–635.
Past two years | Past Year | Past 30 Days | |
---|---|---|---|
Abstract Views | 962 | 871 | 39 |
Full Text Views | 805 | 8 | 0 |
PDF Downloads | 217 | 13 | 0 |