TY - JOUR
T1 - Persistence of sulfadoxine-pyrimethamine resistance despite reduction of drug pressure in Malawi
AU - Artimovich, Elena
AU - Schneider, Kristan
AU - Taylor, Terrie E.
AU - Kublin, James G.
AU - Dzinjalamala, Fraction K.
AU - Escalante, Ananias A.
AU - Plowe, Christopher V.
AU - Laufer, Miriam K.
AU - Takala-Harrison, Shannon
N1 - Publisher Copyright:
© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.
PY - 2015/9/1
Y1 - 2015/9/1
N2 - 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In contrast to the rapid and complete return of chloroquine-susceptible falciparum malaria after chloroquine was withdrawn from Malawi, a reemergence of SP efficacy is unlikely in the near future.
AB - 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.
KW - DHFR
KW - DHPS
KW - Malaria
KW - Pyrosequencing
KW - Resistance
KW - Selective sweeps
KW - Sulfadoxine-pyrimethamine
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U2 - 10.1093/infdis/jiv078
DO - 10.1093/infdis/jiv078
M3 - Article
AN - SCOPUS:84927790743
SN - 0022-1899
VL - 212
SP - 694
EP - 701
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 5
ER -