Prevalence of Plasmodium falciparum Resistance Markers to Sulfadoxine-Pyrimethamine among Pregnant Women Receiving Intermittent Preventive Treatment for Malaria in Uganda

Abstract

ABSTRACTThe aim of this study was to assess the prevalence of mutations inPlasmodium falciparumdihydrofolate reductase (Pfdhfr) and dihydropteroate synthase (Pfdhps) genes among pregnant women using sulfadoxine-pyrimethamine (SP) as an intermittent preventive treatment (IPTp). A molecular epidemiological study ofP. falciparumparasite resistance markers to SP was conducted from August 2010 to February 2012 in Mukono district in central Uganda. DNA was extracted from 413P. falciparum-positive samples. Real-time PCR, followed by melting curve analysis, was used to characterize point mutations in thePfdhfrandPfdhpsgenes that are associated with SP resistance. The prevalence of the single-nucleotide mutations inPfdhfrat codons 51I, 59R, and 108N and inPfdhpsat codons 437G and 540E was high (>98%), reaching 100% fixation after one dose of SP, while the prevalence of 581G was 3.3% at baseline, reaching 12.5% after one dose of SP. At baseline, the prevalence ofPfdhfrandPfdhpsquintuple mutations was 89%, whereas the sextuple mutations (including 581G) were not prevalent (3.9%), reaching 16.7% after one dose of SP. However, the numbers of infections at follow-up visits were small, and hence there was insufficient statistical power to test whether there was a true rise in the prevalence of this allele. The overall high frequency ofPfdhfrandPfdhpsquintuple mutations throughout pregnancy excluded further analyses of possible associations between certain haplotypes and the risk of lower birth weight and anemia. However, women infected withP. falciparumhad 1.3-g/dl-lower hemoglobin levels (P= 0.001) and delivered babies with a 400-g-lower birth weight (P= 0.001) compared to nonparasitemic women. Despite this, 44 women who wereP. falciparumpositive at baseline became negative after one or two doses of SP (i.e., 50.5%), implying that SP-IPTp still has some efficacy.P. falciparumresistance markers to SP are high in this population, whereasP. falciparuminfection was associated with poor birth outcomes.