Evaluation of dihydrofolate reductase and dihydropteroate synthetase genotypes that confer resistance to sulphadoxine-pyrimethamine in <it>Plasmodium falciparum</it> in Haiti

<p>Abstract</p> <p>Background</p> <p>Malaria caused by <it>Plasmodium falciparum</it> infects roughly 30,000 individuals in Haiti each year. Haiti has used chloroquine (CQ) as a first-line treatment for malaria for many years and as a result there are concerns that malaria parasites may develop resistance to CQ over time. Therefore it is important to prepare for alternative malaria treatment options should CQ resistance develop. In many other malaria-endemic regions, antifolates, particularly pyrimethamine (PYR) and sulphadoxine (SDX) treatment combination (SP), have been used as an alternative when CQ resistance has developed. This study evaluated mutations in the dihydrofolate reductase (<it>dhfr</it>) and dihydropteroate synthetase (<it>dhps</it>) genes that confer PYR and SDX resistance, respectively, in <it>P. falciparum</it> to provide baseline data in Haiti. This study is the first comprehensive study to examine PYR and SDX resistance genotypes in <it>P. falciparum</it> in Haiti.</p> <p>Methods</p> <p>DNA was extracted from dried blood spots and genotyped for PYR and SDX resistance mutations in <it>P. falciparum</it> using PCR and DNA sequencing methods. Sixty-one samples were genotyped for PYR resistance in codons 51, 59, 108 and 164 of the <it>dhfr</it> gene and 58 samples were genotyped for SDX resistance codons 436, 437, 540 of the <it>dhps</it> gene in <it>P. falciparum</it>.</p> <p>Results</p> <p>Thirty-three percent (20/61) of the samples carried a mutation at codon 108 (S108N) of the <it>dhfr</it> gene. No mutations in <it>dhfr</it> at codons 51, 59, 164 were observed in any of the samples. In addition, no mutations were observed in <it>dhps</it> at the three codons (436, 437, 540) examined. No significant difference was observed between samples collected in urban <it>vs</it> rural sites (Welch’s T-test p-value = 0.53 and permutations p-value = 0.59).</p> <p>Conclusion</p> <p>This study has shown the presence of the S108N mutation in <it>P. falciparum</it> that confers low-level PYR resistance in Haiti. However, the absence of SDX resistance mutations suggests that SP resistance may not be present in Haiti. These results have important implications for ongoing discussions on alternative malaria treatment options in Haiti.</p