Persistence of Sulfadoxine-Pyrimethamine Resistance Despite Reduction of Drug Pressure in Malawi

摘要: 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 effect of reduced pressure on prevalence SP-resistant parasites and characteristics associated selective sweeps flanking resistance loci. Methods. Samples obtained from individuals clinical during a period high use (1999–2001), transitional (2007–2008), low (2012) were genotyped markers at pfdhfr-ts codons 51, 59, 108 pfdhps 437, 540, 581. Expected heterozygosity was estimated evaluate genetic diversity pfdhps. Results. An increase haplotypes DHFR 51I/59R/108N DHPS 437G/540E occurred under sustained drug pressure, no change haplotype 5 years after reduction pressure. The 437G/540E/581G observed 2007 increased Changes sweep minimal. Conclusions. contrast rapid complete return chloroquine-susceptible chloroquine withdrawn Malawi, reemergence efficacy is unlikely near future.