Genetic surveillance shows spread of ACT resistance during period of malaria decline in Vietnam (2018-2020).

INTRODUCTION

Vietnam's goal to eliminate malaria by 2030 is challenged by the further spread of drug-resistant malaria to key antimalarials, particularly dihydroartemisinin-piperaquine (DHA-PPQ).

METHODS

The custom targeted NGS amplicon sequencing assay, AmpliSeq Pf Vietnam v2, targeting drug resistance, population genetic- and other markers, was applied to detect genetic diversity and resistance profiles in samples from 8 provinces in Vietnam (n = 354), in a period of steep decline of incidence (2018-2020). Variants in 14 putative resistance genes, including and , were analyzed and within-country parasite diversity was evaluated. Other targets included KEL1-lineage markers and diagnostic markers of .

RESULTS

A concerning level of DHA-PPQ resistance was detected. The C580Y mutation in was found in nearly 80% of recent samples, a significant rise from previous data. Vietnam has experienced a significant challenge with the spread of DHA-PPQ resistant malaria parasites, particularly in the provinces of Binh Phuoc and Gia Lai. Resistance spread to high levels in Binh Thuan prior to the country-wide treatment policy change from DHA-PPQ to pyronadine-artesunate (PA). A complex picture of PPQ-resistance dynamics was observed, with an increase of PPQ-resistance associated mutations, indicating an evolutionary response to antimalarial pressure. Additionally, the compensatory mutation C258W in , which increases chloroquine (CQ) resistance while reversing PPQ resistance, is emerging in Gia Lai following the adoption of PA as the first-line treatment. This study found high levels of multidrug resistance, with over 70% of parasites in 6 out of 8 provinces showing significant sulfadoxine-pyrimethamine (SP) resistance and widespread chloroquine-resistant haplotypes. We also report an absence of gene deletions, ensuring the continued reliability of HRP2/3-based rapid diagnostic tests. populations in Vietnam are becoming more isolated, with clonal populations showing high geographical clustering by province. The central highlands, particularly Gia Lai province, have the highest residual malaria burden but exhibit low diversity and clonal populations, likely due to the pressures from the antimalarial drugs and targeted national malaria control program (NMCP) efforts.

DISCUSSION

In conclusion, examining a broad panel of full-length resistance genes and SNPs provided high-resolution insights into genetic diversity and resistance evolution in Vietnam, offering valuable information to inform local treatment and intervention strategies.