Persistence of Sulfadoxine-Pyrimethamine Resistance Despite Reduction of Drug Pressure in Malawi.
J Infect Dis
; 212(5): 694-701, 2015 Sep 01.
Article
em En
| MEDLINE
| ID: mdl-25672905
ABSTRACT
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In contrast to the rapid and complete return of chloroquine-susceptible falciparum malaria after chloroquine was withdrawn from Malawi, a reemergence of SP efficacy is unlikely in the near future.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Plasmodium falciparum
/
Pirimetamina
/
Sulfadoxina
/
Resistência a Medicamentos
/
Antimaláricos
Tipo de estudo:
Risk_factors_studies
Limite:
Humans
País como assunto:
Africa
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article