Front. Genet.

Sec. Applied Genetic Epidemiology

Volume 15 - 2024 | doi: 10.3389/fgene.2024.1478706

This article is part of the Research Topic Advanced Genetic and Genomic Methods and Applications for Malaria Surveillance View all 4 articles

Provisionally accepted

Johanna Helena Kattenberg 1* Mathijs Mutsaers 1 Hong Van Nguyen 2 Ngoc Thi Hong Nguyen 3 Arlette Umugwaneza 1 Maria Lara-Escandell 1 Nguyen Xuan Xa 4 Binh Thi Huong Nguyen 3 Anna Rosanas Urgell 1* 1 Institute of Tropical Medicine Antwerp, Antwerp, Belgium 2 Department of Clinical Research, National Institute of Malariology, Parasitology and Entomology, Hanoi, Vietnam, Hanoi, Vietnam 3 Department of molecular Biology, National Institute of Malariology, Parasitology and Entomology, Hanoi, Vietnam, Hanoi, Vietnam 4 RAI project, National Institute of Malariology, Parasitology and Entomology, Hanoi, Vietnam, Hanoi, Vietnam

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Vietnam's goal to eliminate malaria by 2030 is challenged by the further spread of drug-resistant Plasmodium falciparum malaria. The AmpliSeq Pf Vietnam v2 assay was applied to detect genetic diversity and resistance profiles in samples from 8 provinces in Vietnam (n= 354), revealing a concerning level of resistance to artemisinin and piperaquine. The C580Y mutation in the P. falciparum Kelch 13 (pfK13) gene was found in nearly 80% of recent samples, a significant rise from previous data. Vietnam has experienced a significant challenge with the spread of dihydroartemisininpiperaquine (DHA-PPA) resistant malaria parasites, particularly in the provinces of Binh Phuoc and Gia Lai, and now it has also spread to high levels in Binh Thuan. This resistance in the parasite population has led to a policy shift around the same time, where DHA-PPQ was replaced with pyronadine-artesunate (PA) as the primary treatment for P. falciparum malaria. A complex picture of piperaquine resistance dynamics was observed, with an increase of piperaquine-resistant associated P. falciparum chloroquine resistance transporter (Pfcrt) mutations, indicating an evolutionary response to antimalarial pressure. Additionally, the compensatory mutation C258W in Pfcrt, 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 Pfcrt haplotypes. We also report an absence of P. falciparum histidine rich protein 2 and 3 (Pfhrp2/3) gene deletions, ensuring the continued reliability of HRP2/3-based rapid diagnostic tests. P. falciparum populations in Vietnam are becoming more isolated, with clonal populations showing high geographical clustering by province. The central highlands, particularly Gai 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. In conclusion, examining a broad panel of fulllength 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.

Keywords: Plasmodium falciparum, malaria molecular surveillance, Drug Resistance, Vietnam, Artemisinin resistance, Piperaquine resistance, next generation sequencing

Received: 10 Aug 2024; Accepted: 13 Nov 2024.

Copyright: © 2024 Kattenberg, Mutsaers, Nguyen, Nguyen, Umugwaneza, Lara-Escandell, Xuan Xa, Nguyen and Rosanas Urgell. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Johanna Helena Kattenberg, Institute of Tropical Medicine Antwerp, Antwerp, Belgium
Anna Rosanas Urgell, Institute of Tropical Medicine Antwerp, Antwerp, Belgium

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