Presence of novel triple mutations in the pvdhfr from Plasmodium vivax in Mangaluru city area in the southwestern coastal region of India

Abstract

BackgroundGenes encoding dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) are the targets of sulfadoxine–pyrimethamine (SP) present in artemisinin based combination therapy (ACT; artesunate + sulfadoxine pyrimethamine) for Plasmodium falciparum. Although SP is generally not used to treat vivax infection, mutations in dhfr and dhps that confer antifolate resistance in Plasmodium vivax are common; which may be attributed to its sympatric existence with P. falciparum. Current study was aimed to determine the pattern of mutations in dhfr and dhps in P. vivax isolates from Mangaluru region.MethodsA total of 140 blood samples were collected from P. vivax-infected people attending Wenlock Hospital Mangaluru during July 2014 to January 2016. Out of 140 isolates, 25 (18%) and 50 (36%) isolates were selected randomly for sequence analysis of pvdhfr and pvdhps genes respectively. Fragment of pvdhps and full length pvdhfr were amplified, sequenced and analysed for single nucleotide polymorphisms. dhps was analysed by PCR–RFLP also, to detect the two specific mutations (A383G and A553G).ResultsAnalysis of pvdhps sequences from 50 isolates revealed single and double mutants at 38 and 46% respectively. Three non-synonymous mutations (K55R, S58R and S117N) were identified for pvdhfr. Among these, K55R was detected for the first time.ConclusionsThe current study indicates that P. vivax dhps and dhfr mutant alleles are prevalent in this area, suggesting significant SP pressure.Electronic supplementary materialThe online version of this article (10.1186/s12936-018-2316-3) contains supplementary material, which is available to authorized users.

Polymorphisms in Plasmodium vivax antifolate resistance markers in Afghanistan between 2007 and 2017

“…These findings agree with previously published reports showing low prevalence (less than 5%) of triple and quadruple mutant pvdhfr and pvdhps haplotypes in P. vivax parasite populations from Iran, Pakistan and India (Table 2) [21,22,[26][27][28][29][30][31][36][37][38][39]. In the wider study region, it was observed that the pyrimethamine resistance marker at position 117 in pvdhfr arose first and was followed by the subsequent mutation in positions 117 and 58, conferring increasing levels of resistance as report earlier [23,[26][27][28][29][30][31].…”

“…The frequencies of SP resistance related pvdhfr and pvdhps mutations have been extensively reported from various malaria-endemic areas, including Thailand [8,[11][12][13][14], Cambodia [15], Myanmar [16], Vietnam [17], Indonesia [18], Papua New Guinea [19], Madagascar [20] and India [21][22][23][24]. However, reports from Afghanistan and Middle East countries are scarce.…”

Nationwide spatiotemporal drug resistance genetic profiling from over three decades in Indian Plasmodium falciparum and Plasmodium vivax isolates

“…In this study, double and single mutants were found at overall proportion of 11.9% and 17%, respectively. Double mutants R 58 N 117 were predominant in this study, especially in Delhi, as also previously reported from southern and western parts of India (i.e., Tamil Nadu, Karnataka, and West Bengal) [ 77 – 79 ]. This finding is also consistent with other P. vivax endemic countries such as China–Myanmar border, Ethiopia, and Sudan [ 75 , 80 , 81 ].…”

Surveillance of molecular markers of antimalarial drug resistance in Plasmodium falciparum and Plasmodium vivax in Federally Administered Tribal Area (FATA), Pakistan

“…Quadruple 57L/58R/61M/117T, triple 57L/58R/117 and double pvdhfr (57L/117N) mutant haplotypes have been associated with in vitro drug resistance 16 . This study found pvdhfr double mutant S58R + S117N in 25% of clinical isolates reported from neighboring countries like India, Afghanistan and Iran [27][28][29] .…”