Abstract
BackgroundIn Iran, co-infections of Plasmodium vivax and Plasmodium falciparum are common and P. vivax infections are often exposed to sulphadoxine-pyrimethamine (SP). In the present study, the frequency distribution of mutations associated to SP resistance was investigated in pvdhfr and pvdhps genes from field isolates.MethodsClinical isolates of P. vivax 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 pvdhfr and 383 and 553 of pvdhps genes using nested PCR-RFLP methodsResultsAll 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 dhps genes. Based on size polymorphism of pvdhfr 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 pvdhfr and pvdhps haplotypes among all 189 samples demonstrated six distinct haplotypes. The two most prevalent haplotypes among all examined samples were I13P33F57S58T61S117I173/A383A553 (65.6%) and I13P33F57S58T61N117I173 (16.4%). Two other alleles with one point mutation I13P33F57R58T61S117I173/A383A553 and two mutations I13P33F57R58T61N117I173/A383A553 accounted for 7.4% and 9.5% of the total isolates.ConclusionThe 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, P. vivax isolates are more exposed to SP and the selection or spread of resistant pvdhfr and pvdhps alleles might increase in the near future in this region.
Highlights
In Iran, co-infections of Plasmodium vivax and Plasmodium falciparum are common and P. vivax infections are often exposed to sulphadoxine-pyrimethamine (SP)
Chloroquine-resistant P. vivax parasites have been reported in several locations, with high level resistance confirmed in parts of Thailand, Indonesia and New Guinea and in Central America [2,3,4,5,6,7]
Molecular and epidemiological studies of both Plasmodium falciparum and P. vivax have revealed that the dihyrofolate reductase (DHFR) and dihydropteroate synthase (DHFR) enzymes are the therapeutic targets of SP [10,11,12,13,14,15,16,17]
Summary
In Iran, co-infections of Plasmodium vivax and Plasmodium falciparum are common and P. vivax infections are often exposed to sulphadoxine-pyrimethamine (SP). Chloroquine-resistant P. vivax parasites have been reported in several locations, with high level resistance confirmed in parts of Thailand, Indonesia and New Guinea and in Central America [2,3,4,5,6,7] In those countries, where sulfadoxine/ pyrimethamine (SP) has been used extensively, high grade antifolate resistance has emerged in P. vivax populations [8,9,10,11,12,13]. Resistance to SP is determined by specific point mutations in the parasite dhfr and dhps genes These mutations cause alterations of key amino acid residues in the active sites of these enzymes, which reduce the affinity of the enzyme for the drug [15,18,19,20,21,22,23,24,25]. Detection of these mutations in wild isolates has proved valuable in the mapping and monitoring of resistance for guiding malaria control measures
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