Genomic analysis of global Plasmodium vivax populations reveals insights into the evolution of drug resistance
Abstract 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...
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Nature Portfolio
2024-12-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-54964-x |
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| author | Gabrielle C. Ngwana-Joseph Jody E. Phelan Emilia Manko Jamille G. Dombrowski Simone da Silva Santos Martha Suarez-Mutis Gabriel Vélez-Tobón Alberto Tobón Castaño Ricardo Luiz Dantas Machado Claudio R. F. Marinho Debbie Nolder François Nosten Colin J. Sutherland Susana Campino Taane G. Clark |
| author_facet | Gabrielle C. Ngwana-Joseph Jody E. Phelan Emilia Manko Jamille G. Dombrowski Simone da Silva Santos Martha Suarez-Mutis Gabriel Vélez-Tobón Alberto Tobón Castaño Ricardo Luiz Dantas Machado Claudio R. F. Marinho Debbie Nolder François Nosten Colin J. Sutherland Susana Campino Taane G. Clark |
| author_sort | Gabrielle C. Ngwana-Joseph |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-b06abdab48c54fe39ef6faf7dd30b554 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-b06abdab48c54fe39ef6faf7dd30b5542025-01-05T12:34:47ZengNature PortfolioNature Communications2041-17232024-12-0115111310.1038/s41467-024-54964-xGenomic analysis of global Plasmodium vivax populations reveals insights into the evolution of drug resistanceGabrielle C. Ngwana-Joseph0Jody E. Phelan1Emilia Manko2Jamille G. Dombrowski3Simone da Silva Santos4Martha Suarez-Mutis5Gabriel Vélez-Tobón6Alberto Tobón Castaño7Ricardo Luiz Dantas Machado8Claudio R. F. Marinho9Debbie Nolder10François Nosten11Colin J. Sutherland12Susana Campino13Taane G. Clark14Department of Infection Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical MedicineDepartment of Infection Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical MedicineDepartment of Infection Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical MedicineDepartment of Infection Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical MedicineOswaldo Cruz Foundation – FiocruzOswaldo Cruz Foundation – FiocruzGrupo Malaria, Facultad de Medicina, Universidad de AntioquiaGrupo Malaria, Facultad de Medicina, Universidad de AntioquiaCentro de Investigação de Microrganismos – CIM, Departamento de Microbiologia e Parasitologia, Universidade Federal FluminenseDepartment of Parasitology, Institute of Biomedical Sciences, University of São PauloUK Health Security Agency, Malaria Reference Laboratory, London School of Hygiene and Tropical MedicineCentre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of OxfordDepartment of Infection Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical MedicineDepartment of Infection Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical MedicineDepartment of Infection Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical MedicineAbstract 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.https://doi.org/10.1038/s41467-024-54964-x |
| spellingShingle | Gabrielle C. Ngwana-Joseph Jody E. Phelan Emilia Manko Jamille G. Dombrowski Simone da Silva Santos Martha Suarez-Mutis Gabriel Vélez-Tobón Alberto Tobón Castaño Ricardo Luiz Dantas Machado Claudio R. F. Marinho Debbie Nolder François Nosten Colin J. Sutherland Susana Campino Taane G. Clark Genomic analysis of global Plasmodium vivax populations reveals insights into the evolution of drug resistance Nature Communications |
| title | Genomic analysis of global Plasmodium vivax populations reveals insights into the evolution of drug resistance |
| title_full | Genomic analysis of global Plasmodium vivax populations reveals insights into the evolution of drug resistance |
| title_fullStr | Genomic analysis of global Plasmodium vivax populations reveals insights into the evolution of drug resistance |
| title_full_unstemmed | Genomic analysis of global Plasmodium vivax populations reveals insights into the evolution of drug resistance |
| title_short | Genomic analysis of global Plasmodium vivax populations reveals insights into the evolution of drug resistance |
| title_sort | genomic analysis of global plasmodium vivax populations reveals insights into the evolution of drug resistance |
| url | https://doi.org/10.1038/s41467-024-54964-x |
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