P-1273. Molecular Epidemiology of Antimalarial Drug Resistance in Vivax Malaria Clinical Samples from the Southwestern Region of India

TL;DR

This study examines drug resistance in Plasmodium vivax malaria in southwestern India, identifying genetic mutations that may affect treatment efficacy.

Contribution

The study provides new insights into the molecular epidemiology of antimalarial drug resistance in P. vivax from southwestern India.

Findings

The K10 'AAG' insertion in Pvcrt-o was detected in 26% of samples, with one case showing persistent fever after chloroquine treatment.

High prevalence of S58R and S117N mutations in Pvdhfr is likely due to selective pressure from ACT AS+SP use for P. falciparum.

The Y976F mutation in Pvmdr1, associated with chloroquine resistance in vitro, was detected in one sample, indicating a need for continued monitoring.

Abstract

Plasmodium vivax is a major cause of malaria in India, especially in the southwest. Chloroquine (CQ) followed by 14-day Primaquine is the recommended treatment for vivax malaria in India. However, antimalarial drug resistance poses a significant threat to effective treatments. Therefore, this study investigates the molecular epidemiology of drug resistance in vivax malaria clinical samples from southwestern India.Fig 1.Prevalence of Pvcrt-o, Pvmdr1, Pvdhfr, and Pvdhps haplotypes among 93 P. vivax samplesWT – wild type; SM – Single mutant; DM – Double mutant, TM – Triple mutant, QM – Quadruple mutant

Prevalence of Pvcrt-o, Pvmdr1, Pvdhfr, and Pvdhps haplotypes among 93 P. vivax samples

WT – wild type; SM – Single mutant; DM – Double mutant, TM – Triple mutant, QM – Quadruple mutant

A total of 93 P. vivax malaria samples were collected from symptomatic adult patients hailing from two districts (i.e., Udupi and Mangalore) of the southwestern region of India between June 2021 and 2023. All samples were amplified and sequenced for antimalarial drug resistance markers, including Pvcrt-o, Pvmdr1, Pvdhfr, and Pvdhps genes using Sanger sequencing. Genetic polymorphisms and haplotypes were identified and analyzed to assess the prevalence of resistance-associated mutations.

In Pvcrt-o, the K10 “AAG” insertion was detected in 26% of clinical samples, with only one case among those harboring this mutation showing persistent fever after treatment with CQ. For Pvmdr1, mutations M908L, T958M, Y976F, and F1076L were detected in 100%, 86.02%, 2.15%, and 84.94% of samples, respectively. In Pvdhps, mutations A383G and A553G occurred in 26.88% and 13.97% of samples, respectively. Meanwhile, Pvdhfr exhibited the S58R and S117N mutations in 59.13% and 56.98% of samples, with the double mutant (S58R+S117N) emerging as the most prevalent haplotype (Fig. 1).

While mutations in P. vivax clinical samples do not indicate complete CQ resistance, they raise concerns about reduced drug efficacy. Detection of the Y976F mutation, known for chloroquine resistance in vitro, in one sample warrants continued monitoring. Furthermore, the high prevalence of S58R and S117N mutations in Pvdhfr (56.98%) likely results from selective pressure due to widespread ACT AS+SP use for P. falciparum malaria. Although CQ treatment showed minimal clinical failure in P. vivax with follow-up data, these genetic markers highlight the need for ongoing molecular surveillance and targeted antimalarial strategies to maintain efficacy.

All Authors: No reported disclosures

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