Molecular characterization of antifolates resistance-associated genes, <it>(dhfr </it>and <it>dhps) </it>in <it>Plasmodium vivax </it>isolates from the Middle East

<p>Abstract</p> <p>Background</p> <p>In Iran, co-infections of <it>Plasmodium vivax </it>and <it>Plasmodium falciparum </it>are common and <it>P. vivax </it>infections are often exposed to sulphadoxine-pyrimethamine (SP). In the present study, the frequency distribution of mutations associated to SP resistance was investigated in <it>pvdhfr </it>and <it>pvdhps </it>genes from field isolates.</p> <p>Methods</p> <p>Clinical isolates of <it>P. vivax </it>were collected in two different malaria endemic regions in northern and south-eastern Iran, between 2001 and 2006. All 189 collected isolates were analysed for SNP/haplotypes at positions 13, 33, 57, 58, 61, 117 and 173 of the <it>pvdhfr </it>and 383 and 553 of <it>pvdhps </it>genes using nested PCR-RFLP methods</p> <p>Results</p> <p>All 189 examined isolates were found to carry wild-type amino acids at positions 13, 33, 61 and 173, while 57L and 58R and 117N mutations in pure form was detected among 1.1%, 17.5% and 26% examined samples, respectively, with no polymorphisms in different loci of <it>dhps </it>genes. Based on size polymorphism of <it>pvdhfr </it>genes at repeat region, among northern isolates, the frequency distribution for type A and B were 2.2% and 97.8% respectively. However, in southern samples the prevalence of type A, B and C were 7%, 89.5% and 7.7%, respectively. Mixed genotype infections (type B and C) were detected in only 4.2% (6/143) of southern, but in none of the northern isolates. The combination of <it>pvdhfr and pvdhps </it>haplotypes among all 189 samples demonstrated six distinct haplotypes. The two most prevalent haplotypes among all examined samples were I₁₃P₃₃F₅₇S₅₈T₆₁S₁₁₇I₁₇₃/A₃₈₃A₅₅₃(65.6%) and I₁₃P₃₃F₅₇S₅₈T₆₁<b>N</b>₁₁₇I₁₇₃(16.4%). Two other alleles with one point mutation I₁₃P₃₃F₅₇<b>R</b>₅₈T₆₁S₁₁₇I₁₇₃/A₃₈₃A₅₅₃and two mutations I₁₃P₃₃F₅₇<b>R</b>₅₈T₆₁<b>N</b>₁₁₇I₁₇₃/A₃₈₃A₅₅₃accounted for 7.4% and 9.5% of the total isolates.</p> <p>Conclusion</p> <p>The present molecular data provide important information for making decisions on population based drug use in Iran. In addition, since October 2005, with more availability of SP as first-line treatment, <it>P. vivax </it>isolates are more exposed to SP and the selection or spread of resistant <it>pvdhfr </it>and <it>pvdhps </it>alleles might increase in the near future in this region.</p>

Abstract licence: CC BY-NC-ND

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