Genomic analysis of global Plasmodium vivax populations reveals insights into the evolution of drug resistance
Increasing reports of chloroquine resistance (CQR) in Plasmodium vivax endemic regions have led to several countries, including Indonesia, to adopt dihydroarteminsin-piperaquine instead. However, the molecular drivers of CQR remain unclear. Using a genome-wide approach, we perform a genomic analysis of 1534 P. vivax isolates across 29 endemic countries, detailing population structure, patterns of relatedness, selection, and resistance profiling, providing insights into potential drivers of CQR. Selective sweeps in a locus proximal to pvmdr1, a putative marker for CQR, along with transcriptional regulation genes, distinguish isolates from Indonesia from those in regions where chloroquine remains highly effective. In 106 isolates from Indonesian Papua, the epicentre of CQR, we observe an increasing prevalence of novel SNPs in the candidate resistance gene pvmrp1 since the introduction of dihydroartemisinin-piperaquine. Overall, we provide novel markers for resistance surveillance, supported by evidence of regions under recent directional selection and temporal analysis in this continually evolving parasite.
Authors
- Cláudio Romero Farias Marinho (ORCID: https://orcid.org/0000-0002-1227-3845)
- Debbie Nolder (ORCID: https://orcid.org/0000-0002-5637-7785)
- Susana Campino (ORCID: https://orcid.org/0000-0003-1403-6138)
- Martha Cecília Suárez-Mútis (ORCID: https://orcid.org/0000-0003-2809-6799)
- Alberto Tobón-Castaño (ORCID: https://orcid.org/0000-0002-1671-2649)
- Colin J. Sutherland (ORCID: https://orcid.org/0000-0003-1592-6407)
- Jamille Gregório Dombrowski (ORCID: https://orcid.org/0000-0002-1863-1914)
- Taane Gregory Clark (ORCID: https://orcid.org/0000-0001-8985-9265)
- Jody Phelan (ORCID: https://orcid.org/0000-0001-8323-7019)
- Emilia Mańko (ORCID: https://orcid.org/0000-0001-7405-6523)
- Simone da Silva Santos (ORCID: https://orcid.org/0000-0003-1093-8919)
- Ricardo Luiz Dantas Machado (ORCID: https://orcid.org/0000-0002-8955-3204)
- Gabrielle C. Ngwana-Joseph
- Gabriel Jaime Vélez Tobón (ORCID: https://orcid.org/0000-0002-4859-1124)
- François Henry Nosten (ORCID: https://orcid.org/0000-0002-7951-0745)
Institutions
- Universidade Federal Fluminense (BR)
- Universidade de São Paulo (BR)
- Mahidol University (TH)
- Universidad de Antioquia (CO)
- University of Oxford (GB)
- London School of Hygiene & Tropical Medicine (GB)
- Shoklo Malaria Research Unit (TH)
- Mahidol Oxford Tropical Medicine Research Unit (TH)
- Fundação Oswaldo Cruz (BR)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-12-30
- DOI
- https://doi.org/10.1038/s41467-024-54964-x
- Citations
- 4
- Primary Topic
- Malaria Research and Control
- Type
- article
- Field-Weighted Citation Impact
- 2.17
Funders
- Wellcome Trust
- UK Research and Innovation
- Fundação de Amparo à Pesquisa do Estado de São Paulo
- Conselho Nacional de Desenvolvimento Científico e Tecnológico
- Medical Research Council
- Engineering and Physical Sciences Research Council
- Biotechnology and Biological Sciences Research Council