Related Articles Evidence of Selective Sweeps in Genes Conferring Resistance to Chloroquine and Pyrimethamine in Plasmodium falciparum within India.

Antimicrob Agents Chemother. 2009 Dec 28;

Authors: Mixson-Hayden T, Jain V, McCollum AM, Poe A, Nagpal AC, Dash AP, Stiles JK, Udhayakumar V, Singh N

Treatment of Plasmodium falciparum is complicated by the emergence and spread of parasite resistance to many of the first line drugs used to treat malaria. Anti-malarial drug resistance has been associated with specific point mutations in several genes, suggesting that these single nucleotide polymorphisms can be useful in tracking the emergence of drug resistance. In India, P. falciparum can manifest itself as asymptomatic, mild, or severe malaria, with or without cerebral involvement. We tested whether chloroquine and antifolate drug resistant genotypes would be more commonly associated with cases of cerebral malaria than with cases of mild malaria in the province of Jabalpur, India by genotyping the genes dhps, dhfr, pfmdr-1, and pfcrt using pyrosequencing, direct sequencing, and real time PCR. Further, we used microsatellites surrounding the genes to determine the origins and spread of the drug resistant genotypes in this area. Resistance to chloroquine was essentially fixed with 95% of the isolates harboring the pfcrt K76T mutation. Resistant genotypes of dhfr, dhps, and pfmdr-1 were found in 94%, 17%, and 77% of the isolates, respectively. Drug resistant genotypes were equally likely to be associated with cerebral malaria as they were with cases of mild malaria. We found evidence of a selective sweep in pfcrt and, to a lesser degree, dhfr, indicating high levels of resistance to chloroquine and evolving resistance to pyrimethamine. Microsatellites surrounding pfcrt indicate that the resistant genotypes (SVMNT) were most similar to those found in Papua New Guinea.

PMID: 20038626 [PubMed - as supplied by publisher]