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      Molecular markers for failure of sulfadoxine-pyrimethamine and chlorproguanil-dapsone treatment of Plasmodium falciparum malaria.

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          Abstract

          Molecular assays for monitoring sulfadoxine-pyrimethamine-resistant Plasmodium falciparum have not been implemented because of the genetic and statistical complexity of the parasite mutations that confer resistance and their relation to treatment outcomes. This study analyzed pretreatment dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS) genotypes and treatment outcomes in a double-blind, placebo-controlled trial of sulfadoxine-pyrimethamine and chlorproguanil-dapsone treatment for uncomplicated P. falciparum malaria. Multiple logistic regression was used to identify mutations that were predictive of treatment failure and to identify interactions and confounding factors. Infections caused by parasites with 3 DHFR mutations and 2 DHPS mutations (the "quintuple mutant") were associated with sulfadoxine-pyrimethamine treatment failure but not with chlorproguanil-dapsone treatment failure. The presence of a single DHFR mutation (Arg-59) with a single DHPS mutation (Glu-540) accurately predicted the presence of the quintuple mutant. If this model is validated in other populations, it will finally be possible to use molecular markers for surveillance of antifolate-resistant P. falciparum malaria in Africa.

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          Author and article information

          Journal
          J Infect Dis
          The Journal of infectious diseases
          University of Chicago Press
          0022-1899
          0022-1899
          Feb 01 2002
          : 185
          : 3
          Affiliations
          [1 ] Malaria Section, Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, MD, USA. jkublin@medicine.umaryland.edu
          Article
          JID010620
          10.1086/338566
          11807721
          379d0004-481b-439f-86b1-62bd4730826c
          History

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