Associations betweenPlasmodium falciparummerozoite surface variants and drug-resistant haplotypes inPlasmodium falciparumfield isolates

Abstract

Objective: To investigate the associations between Plasmodium falciparum merozoite surface protein allelic families (Pfmsp1, Pfmsp2), infection clonality and drug-resistant haplotypes (Pfcrt, Pfdhfr, Pfdhps, Pfmdrl and Pfkelch13) in malaria samples collected over 30 years in India.

Methods: Infection clonality was assessed using Pfmsp1 (K1, MAD20, RO33) and Pfmsp2 (IC/3D7, FC27) allelic families. Five key drug resistance genes were analysed by PCR and Sanger sequencing. Statistical analyses were performed to evaluate associations between specific Pfmsp allelic families, infection clonality and drug-resistant haplotypes.

Results: Significant associations were observed between Pfmsp allelic families, infection clonality and resistant haplotypes across four genes (Pfcrt, Pfdhfr, Pfdhps and Pfmdrl). For Pfcrt, K1 (P=0.026) and IC/3D7 (P<0.001) alleles were significantly associated with wild-type CVMNK haplotype, while FC27 allele was linked to SVMNT haplotype (P=0.005). Similarly, Pfmdr1 FC27 allele was significantly associated with NFSND haplotype (P=0.034) and IC/3D7 allele with NYSND haplotype (P<0.001). Analyses revealed that both K1 and RO33 alleles were associated with resistant Pfdhfr and Pfdhps haplotypes, whereas MAD20 was exclusively associated with resistant Pfdhps (P<0.001) haplotypes. Additionally, Pfdhfr and Pfdhps haplotypes exhibited distinct associations with both Pfmsp2 allelic families.

Conclusions: The findings suggest potential associations between antigenic diversity markers and drug-resistant haplotypes, and some patterns may reflect shared ancestral origins, though the basis of certain associations remains unclear. Further studies with larger datasets are needed to validate these observations and elucidate the genetic and ecological factors underlying these relationships.

Keywords

Drug resistance / India

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