A Comprehensive Analysis of Pfmsp1, Pfmsp2 and Pfcrt Genotypes in India and Global Perspectives for Evolving Epidemiological Patterns in Plasmodium falciparum.

Abstract

Understanding genetic variability of Plasmodium falciparum (Pf) is essential for addressing malaria transmission patterns and formulating effective treatment strategies. This study aims to examine the genetic structure of Indian Pf population over the past three decades by analysing the evolving patterns of Pfmsp1 and Pfmsp2 genes and the prevalence of Pfcrt-resistant genotypes, while exploring their correlation with infection clonality. A total of 304 malaria-positive samples from 14 Indian states between 1993 and 2023 were analysed. Allelic polymorphism of Pfmsp1 and Pfmsp2 was assessed using PCR, while Pfcrt genetic polymorphism was analysed via amplicon sequencing. Period-wise, multiplicity of infection (MOI) for both Pfmsp1 and Pfmsp2 peaked in 1990s, declining over time, with the lowest MOI observed during 2020-2023. K1 allele of Pfmsp1 and FC27 allele of Pfmsp2 were the most prevalent. Clonality varied significantly across six Indian regions and four time periods. The K76T mutation in Pfcrt, a marker for chloroquine resistance, was predominant in 83.54% of samples. The K1 allele was significantly associated with CVMNK (P = 0.026), FC27 with SVMNT (P = 0.005), and IC/3D7 with both CVMNK and CVIET haplotypes (P < 0.001). The study also included analysis of Indian and global distribution of Pfcrt genotypes. The decline in MOI and polyclonality of Pf populations highlights the success of ongoing malaria control strategies. However, chloroquine-sensitive Pf parasites have yet to re-emerge, as resistant strains continue to persist. To monitor the sensitivity towards chloroquine, molecular surveillance needs to be carried out regularly along with in-vivo studies.

Supplementary information: The online version contains supplementary material available at 10.1007/s12088-025-01519-3.