Genetic surveillance shows spread of ACT resistance during period of malaria decline in Vietnam (2018-2020)
IntroductionVietnam’s goal to eliminate malaria by 2030 is challenged by the further spread of drug-resistant Plasmodium falciparum malaria to key antimalarials, particularly dihydroartemisinin-piperaquine (DHA-PPQ).MethodsThe custom targeted NGS amplicon sequencing assay, AmpliSeq Pf Vietnam v2, ta...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2024-12-01
|
| Series: | Frontiers in Genetics |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2024.1478706/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850108347608465408 |
|---|---|
| author | Johanna Helena Kattenberg Mathijs Mutsaers Van Hong Nguyen Thi Hong Ngoc Nguyen Arlette Umugwaneza Maria Lara-Escandell Xuan Xa Nguyen Thi Huong Binh Nguyen Anna Rosanas-Urgell |
| author_facet | Johanna Helena Kattenberg Mathijs Mutsaers Van Hong Nguyen Thi Hong Ngoc Nguyen Arlette Umugwaneza Maria Lara-Escandell Xuan Xa Nguyen Thi Huong Binh Nguyen Anna Rosanas-Urgell |
| author_sort | Johanna Helena Kattenberg |
| collection | DOAJ |
| description | IntroductionVietnam’s goal to eliminate malaria by 2030 is challenged by the further spread of drug-resistant Plasmodium falciparum malaria to key antimalarials, particularly dihydroartemisinin-piperaquine (DHA-PPQ).MethodsThe 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 P. falciparum Kelch 13 (PfK13) and P. falciparum chloroquine resistance transporter (Pfcrt), were analyzed and within-country parasite diversity was evaluated. Other targets included KEL1-lineage markers and diagnostic markers of Pfhrp2/3.ResultsA concerning level of DHA-PPQ resistance was detected. The C580Y mutation in PfK13 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 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 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.DiscussionIn 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. |
| format | Article |
| id | doaj-art-dfa7a0669a9941eaa813980f4747cfee |
| institution | OA Journals |
| issn | 1664-8021 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj-art-dfa7a0669a9941eaa813980f4747cfee2025-08-20T02:38:23ZengFrontiers Media S.A.Frontiers in Genetics1664-80212024-12-011510.3389/fgene.2024.14787061478706Genetic surveillance shows spread of ACT resistance during period of malaria decline in Vietnam (2018-2020)Johanna Helena Kattenberg0Mathijs Mutsaers1Van Hong Nguyen2Thi Hong Ngoc Nguyen3Arlette Umugwaneza4Maria Lara-Escandell5Xuan Xa Nguyen6Thi Huong Binh Nguyen7Anna Rosanas-Urgell8Biomedical Sciences Department, Institute of Tropical Medicine, Antwerp, BelgiumBiomedical Sciences Department, Institute of Tropical Medicine, Antwerp, BelgiumDepartment of Clinical Research, National Institute of Malariology, Parasitology and Entomology, Hanoi, VietnamDepartment of Molecular Biology, National Institute of Malariology, Parasitology and Entomology, Hanoi, VietnamBiomedical Sciences Department, Institute of Tropical Medicine, Antwerp, BelgiumBiomedical Sciences Department, Institute of Tropical Medicine, Antwerp, BelgiumRegional Artemisinin Initiative, RAI project, National Institute of Malariology, Parasitology and Entomology, Hanoi, VietnamDepartment of Clinical Research, National Institute of Malariology, Parasitology and Entomology, Hanoi, VietnamBiomedical Sciences Department, Institute of Tropical Medicine, Antwerp, BelgiumIntroductionVietnam’s goal to eliminate malaria by 2030 is challenged by the further spread of drug-resistant Plasmodium falciparum malaria to key antimalarials, particularly dihydroartemisinin-piperaquine (DHA-PPQ).MethodsThe 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 P. falciparum Kelch 13 (PfK13) and P. falciparum chloroquine resistance transporter (Pfcrt), were analyzed and within-country parasite diversity was evaluated. Other targets included KEL1-lineage markers and diagnostic markers of Pfhrp2/3.ResultsA concerning level of DHA-PPQ resistance was detected. The C580Y mutation in PfK13 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 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 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.DiscussionIn 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.https://www.frontiersin.org/articles/10.3389/fgene.2024.1478706/fullPlasmodium falciparummalaria molecular surveillancedrug resistanceVietnamartemisinin resistancepiperaquine resistance |
| spellingShingle | Johanna Helena Kattenberg Mathijs Mutsaers Van Hong Nguyen Thi Hong Ngoc Nguyen Arlette Umugwaneza Maria Lara-Escandell Xuan Xa Nguyen Thi Huong Binh Nguyen Anna Rosanas-Urgell Genetic surveillance shows spread of ACT resistance during period of malaria decline in Vietnam (2018-2020) Frontiers in Genetics Plasmodium falciparum malaria molecular surveillance drug resistance Vietnam artemisinin resistance piperaquine resistance |
| title | Genetic surveillance shows spread of ACT resistance during period of malaria decline in Vietnam (2018-2020) |
| title_full | Genetic surveillance shows spread of ACT resistance during period of malaria decline in Vietnam (2018-2020) |
| title_fullStr | Genetic surveillance shows spread of ACT resistance during period of malaria decline in Vietnam (2018-2020) |
| title_full_unstemmed | Genetic surveillance shows spread of ACT resistance during period of malaria decline in Vietnam (2018-2020) |
| title_short | Genetic surveillance shows spread of ACT resistance during period of malaria decline in Vietnam (2018-2020) |
| title_sort | genetic surveillance shows spread of act resistance during period of malaria decline in vietnam 2018 2020 |
| topic | Plasmodium falciparum malaria molecular surveillance drug resistance Vietnam artemisinin resistance piperaquine resistance |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2024.1478706/full |
| work_keys_str_mv | AT johannahelenakattenberg geneticsurveillanceshowsspreadofactresistanceduringperiodofmalariadeclineinvietnam20182020 AT mathijsmutsaers geneticsurveillanceshowsspreadofactresistanceduringperiodofmalariadeclineinvietnam20182020 AT vanhongnguyen geneticsurveillanceshowsspreadofactresistanceduringperiodofmalariadeclineinvietnam20182020 AT thihongngocnguyen geneticsurveillanceshowsspreadofactresistanceduringperiodofmalariadeclineinvietnam20182020 AT arletteumugwaneza geneticsurveillanceshowsspreadofactresistanceduringperiodofmalariadeclineinvietnam20182020 AT marialaraescandell geneticsurveillanceshowsspreadofactresistanceduringperiodofmalariadeclineinvietnam20182020 AT xuanxanguyen geneticsurveillanceshowsspreadofactresistanceduringperiodofmalariadeclineinvietnam20182020 AT thihuongbinhnguyen geneticsurveillanceshowsspreadofactresistanceduringperiodofmalariadeclineinvietnam20182020 AT annarosanasurgell geneticsurveillanceshowsspreadofactresistanceduringperiodofmalariadeclineinvietnam20182020 |