Persistence of Sulfadoxine-Pyrimethamine Resistance Despite Reduction of Drug Pressure in Malawi
| Autor: | Miriam K. Laufer, James G. Kublin, Elena Artimovich, Shannon Takala-Harrison, Kristan A. Schneider, Ananias A. Escalante, Christopher V. Plowe, Fraction K. Dzinjalamala, Terrie E. Taylor |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Malawi
Combination therapy Genotype Plasmodium falciparum Drug Resistance Mutation Missense Protozoan Proteins DHPS Major Articles and Brief Reports Antimalarials Gene Frequency Chloroquine parasitic diseases Sulfadoxine medicine Immunology and Allergy Humans Artemisinin Malaria Falciparum Selection Genetic Dihydropteroate Synthase biology Haplotype DNA Protozoan medicine.disease biology.organism_classification Virology Sulfadoxine/pyrimethamine Drug Combinations Tetrahydrofolate Dehydrogenase Infectious Diseases Pyrimethamine Haplotypes Malaria medicine.drug |
| Popis: | Background. In 2007, Malawi replaced sulfadoxine-pyrimethamine (SP) with an artemisinin-based combination therapy as the first-line treatment for uncomplicated Plasmodium falciparum malaria in response to failing SP efficacy. Here we estimate the effect of reduced SP pressure on the prevalence of SP-resistant parasites and the characteristics of the associated selective sweeps flanking the resistance loci. Methods. Samples obtained from individuals with clinical malaria during a period of high SP use (1999–2001), a transitional period (2007–2008), and a period of low SP use (2012) were genotyped for resistance markers at pfdhfr-ts codons 51, 59, and 108 and pfdhps codons 437, 540, and 581. Expected heterozygosity was estimated to evaluate the genetic diversity flanking pfdhfr-ts and pfdhps. Results. An increase in the prevalence of the resistance haplotypes DHFR 51I/59R/108N and DHPS 437G/540E occurred under sustained drug pressure, with no change in haplotype prevalence 5 years after reduction in SP pressure. The DHPS 437G/540E/581G haplotype was observed in 2007 and increased in prevalence during a period of reduced SP pressure. Changes to the sweep characteristics flanking pfdhfr-ts and pfdhps were minimal. Conclusions. In contrast to the rapid and complete return of chloroquine-susceptible falciparum malaria after chloroquine was withdrawn from Malawi, a reemergence of SP efficacy is unlikely in the near future. |
| Databáze: | OpenAIRE |
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