K13 Kelch Propeller Domain and mdr1 Sequence Polymorphism in Field Isolates From Northeast Region, India

Abstract

Emergence of artemisinin-resistant Plasmodium falciparum in Southeast Asia has made an intense warning to global malaria control programme since Southeast Asia is playing a key role in the evolution of drug resistant malaria parasites. Several polymorphisms in K13 gene have been designated with developing resistance either in vitro or in vivo. In this study, polymorphisms within K13 kelch propeller domain and Pf mdr1 gene were investigated in a total of 134 P. falciparum field isolates circulating in 3 states of Northeast region of India, namely, Assam, Arunachal Pradesh, and Tripura because information regarding this is limited from this region. Six polymorphisms were detected, out of which 2 were new. A481V mutation was found in 4.5% of the total field isolates. A675V and D702N new mutations were present in 3.7% and 1.5% isolates, respectively. Synonymous polymorphism at codon 703 was highly observed (6.7%) than other polymorphisms. N86Y allele in Pf mdr1 gene was also noticed in isolates that contained mutation in K13 propeller domain, but N86 wild-type allele was found comparatively higher in frequency within overall isolates. Moreover, both nucleotide and haplotype diversities in K13 gene were high in Arunachal Pradesh isolates than other 2 states. This is the first report from Northeast region of India with evidence of A675V candidate mutation along with 2 other new mutations which pays attention for further molecular surveillance in this region to document detailed scenario of K13 polymorphism pattern corresponding to artemisinin resistance.

Emergence and Spread of kelch13 Mutations Associated with Artemisinin Resistance in Plasmodium falciparum Parasites in 12 Thai Provinces from 2007 to 2016

“…In northwestern Thailand, A675V was unique to Mae Hong Son in 2011 to 2012, while R561H was unique to both Mae Hong Son and Tak (90 km south of Mae Sot) during the period from 2011 to 2014. The A675V mutation has been reported in neighboring Myanmar, China, India, and more recently in Rwanda (26)(27)(28)(29). The R561H mutation appears to be unique to Myanmar, China, and northwestern Thailand, suggesting that the introduction of these mutant lineages occurred with cross-border movements of people (28).…”

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

“…This is in line with previous studies, even though four ART-resistance validated mutations (i.e., 446I, 539T, 561H, 625R) have been reported at very marginal proportions in two areas of India (Arunanchal Pradesh, West Bengal) [ 63 – 65 ]. Other pfk13 polymorphisms (189T, 481V, 533A, 549Y, 578S, 579T, 657H, 672S, 675V, and 702N) have been also reported in these two regions and elsewhere (Mizoram, Tripura, Madhya Pradesh, and Assam) [ 63 , 64 , 66 – 68 ]. This implies that ART-resistance has not yet emerged, but molecular surveillance should be continuously carried out in malarious regions in India.…”