Plasmodium vivax dihydrofolate reductase point mutations from the Indian subcontinent

Different Allele Prevalence in the Dihydrofolate Reductase and Dihydropteroate Synthase Genes in Plasmodium vivax Populations from China

“…The remaining samples can be divided into three types on the basis of the mutation at residue 99. We identified a deletion mutation, a previously reported H99S mutation, 28 and a novel H99D mutation, which accounted for 23.0%, 49.2%, and 5.7% of the parasite samples, respectively.…”

“…17,28,36 Size polymorphism in this region is resulted from variation in number of copies of the 18-basepair repeat, which is not essential for substrate binding. 21 Most (77.0%) of the isolates sequenced contain three copies of the repeat, and 23.0% contained two 18-basepair repeats.…”

“…18 In comparison, in southern Asia areas such as India, Pakistan, and Sri Lanka, parasites harboring multiple mutations in pvdhfr and pvdhps are relatively rare. 28,30,40 In such regions where P. falciparum and P. vivax coexist, mutations in pvdhfr and pvdhps have been attributed to selective pressure of antifolate drugs specific for controlling P. falciparum . Accordingly, pvdhfr and pvdhps mutation rates are expected to be much lower in temperate zone regions where P. vivax is the only or predominant malaria parasite.…”

“…vivax -endemic areas have detected different geographic distributions and prevalences of pvdhfr and pvdhps mutations; some regions showed near fixation of some mutant alleles, which is correlated with regional difference in the use of SP. [27][28][29][30] The extensive use of SP in malaria treatment in many malarious regions may be responsible to the multiple origins of resistance-conferring mutations in pvdhfr and pvdhps . 31,32 Most of the studies on antifolate resistance in P. vivax were performed in regions where P. vivax and P. falciparum coexist.…”

Current Status of Malaria and Anti-Malarial Drug Resistance in Sri Lanka

“…This frequency of mutant haplotypes was significantly higher in the Northern region and this may be indirectly caused by the armed conflict in the region. Furthermore, a certain Pvdhfr haplotype was only observed in the northern districts and it was speculated that the frequent visits of people to south India from the northern parts of Sri Lanka may been have introduced this particular haplotype from Chennai where it was highly prevalent (Kaur et al, 2006). Thus, In vivo drug resistance on Sri Lanka is relatively restricted to P. falciparum and absent in P. vivax, but the prevalence of resistance alleles seems to be high (Hapuarachchi et al, 2006;Schousboe et al, 2007) and may be an early warning of evolving resistance in the parasite populations.…”