Spatio-temporal distribution of PfMDR1 polymorphism among uncomplicated Plasmodium falciparum malaria cases along international border of north east India

Abstract

PfMDR1 single nucleotide polymorphisms (SNP) are good correlate markers for antimalarial drug resistance worldwide. Present study is a comprehensive view of screening of PfMDR1 polymorphism to antimalarials practiced with geography and time. Study sites Mizoram, Tripura, Meghalaya chosen are at multivariate drug pressure due to cross border migration and transmission. Mizoram is gateway to south east Asia through Myanmar whereas Tripura, Meghalaya share porous border with Bangladesh. Baseline finger pricked blood stained filter paper for confirmed uncomplicated Plasmodium falciparum infected patients (year 2015) were obtained from National Institute of Malaria Research, New Delhi, India. PfMDR1 polymorphism for codon N86Y, Y184F, D1246Y was determined by PCR-RFLP, further confirmed by sequencing. There observed marked predominance of Plasmodium isolates with PfMDR1 wild type alleles for all codons under study i.e. 86, 184, 1246. Spatially, Plasmodium isolates from Mizoram were most diverse with co-existence of PfMDR1 genotype with NYD, YYD, NFD haplotypes, followed by Tripura. Isolates from Meghalaya were of all NYD haplotype. Reports, referring to screening of PfMDR1 SNPs to CQ/SP/AS-SP across India, were archived. Temporal study show distinct rise in proportion of PfMDR1 wild type N86 allele since introduction of Artemether-Lumefantrine as first line antimalarial. Hence spatio-temporal screening of Plasmodium population with PfMDR1 single nucleotide polymorphism accounts for its association with antimalarial susceptibility and validate PfMDR1 SNPs as antimalarial drug resistant marker.

Keywords: Artemisinin combined therapy (ACT); Multi drug resistance; Plasmodium falciparum; Single nucleotide polymorphism (SNP).