Reporting the impact of artemisinin resistance: Molecular surveillance of PFK13 and PFEXO mutations in plasmodium falciparum in southern provinces of Vietnam

Abstract

Malaria, mainly caused by Plasmodium falciparum(P. falciparum), is a major global health concern. In Vietnam, resistance to artemisinin-based combination therapies (ACTs) is rising, jeopardizing malaria control efforts. This study focuses on mutations in the pfK13and pfEXOgenes, particularly the E415G mutationin the pfEXO gene, in southernVietnam.The study encompassed 421 patientsdistributedacross two cohorts. The firstcohort, comprising63 patients from Binh Phuoc and Dak Nong, had uncomplicated P. falciparum malaria and constituted a segment of the Therapeutic Efficacy Studies (TES). These individuals received treatment in accordance with the 2009 World Health Organization (WHO) guidelines. The second cohort, comprising 358 patients from the Central Highlands, was established to evaluate the frequency of mutations in genes associated with artemisinin resistance.Molecular marker analysis, including Sanger sequencing for pfK13and ARMS-PCR for E415G in pfEXO, was conducted. The study also examined the association of these mutations with Day 3 parasitemia and treatment outcomes using Dihydroartemisinin-Piperaquine (DHA-PPQ).Most cases showed mutations in pfK13,linked to delayed parasite clearance and higher treatment failure, indicating pfK13as a key marker for artemisinin resistance. The E415G mutation in pfEXO was common but not significantly associated with resistance or treatment outcomes, though there was a tendency towards increased treatment failure among these patients.Our study impliedthe critical role of the C580Y mutation in the pfK13gene in artemisinin resistance and its impact on the efficacy of ACTs in Vietnam. The findings highlight the necessity ofmonitoring these mutations as molecular markers for drug resistance and call for the exploration of alternative treatment strategies in the face of evolving antimalarial drug resistance. This study contributes valuable insights to the molecular epidemiology of malaria in the southern provinces of Vietnam and emphasizes the urgency of addressing artemisinin resistance in the global fight against malaria.