Plasmodium falciparum multidrug resistance 1 gene polymorphisms associated with outcomes after anti-malarial treatment
Abstract Background Plasmodium falciparum multidrug resistance transporter 1 (Pfmdr1) gene mutations are associated with altered response to artemisinin-based combination therapy (ACT), particularly the combinations containing the partner drugs lumefantrine and amodiaquine (i.e., artemether-lumefant...
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2025-06-01
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| author | Veronika R. Laird Mateusz M. Plucinski Meera Venkatesan Kelsey A. Rondini Milijaona Randrianarivelojosia Mauricette N. Andriamananjara Hawela Moonga Deus S. Ishengoma Arlindo Chidimatembue Pedro Rafael Dimbu Adicatou-Laï Adeothy Abdoul Habib Beavogui Simon Kariuki Sam L. Nsobya Aline Uwimana Gauthier Mesia Kahunu Ashenafi Assefa Ousmane A. Koita Naomi W. Lucchi Samaly S. Svigel Souza Zhiyong Zhou Leah F. Moriarty Eric S. Halsey |
| author_facet | Veronika R. Laird Mateusz M. Plucinski Meera Venkatesan Kelsey A. Rondini Milijaona Randrianarivelojosia Mauricette N. Andriamananjara Hawela Moonga Deus S. Ishengoma Arlindo Chidimatembue Pedro Rafael Dimbu Adicatou-Laï Adeothy Abdoul Habib Beavogui Simon Kariuki Sam L. Nsobya Aline Uwimana Gauthier Mesia Kahunu Ashenafi Assefa Ousmane A. Koita Naomi W. Lucchi Samaly S. Svigel Souza Zhiyong Zhou Leah F. Moriarty Eric S. Halsey |
| author_sort | Veronika R. Laird |
| collection | DOAJ |
| description | Abstract Background Plasmodium falciparum multidrug resistance transporter 1 (Pfmdr1) gene mutations are associated with altered response to artemisinin-based combination therapy (ACT), particularly the combinations containing the partner drugs lumefantrine and amodiaquine (i.e., artemether-lumefantrine [AL] and artesunate-amodiaquine [ASAQ]). Past studies of Pfmdr1 single nucleotide polymorphisms (SNPs) at codons 86, 184, and 1246 have shown different responses to AL and ASAQ. Methods To determine whether infection with parasites carrying specific Pfmdr1 SNPs leads to increased risk of recurrent parasitaemia (recrudescent or new infection), data from 3,915 samples from 16 therapeutic efficacy studies from 13 African countries between 2013 and 2019 were analysed. Results Patients treated with AL and infected with parasites carrying Pfmdr1 N86 were at greater risk of recurrent infection than those whose parasites carried 86Y. After treatment with ASAQ, individuals infected with parasites that carried Pfmdr1 86Y were more likely to experience a recurrent infection. Conclusions These results support prior studies that suggested: (1) patients given AL and infected with parasites carrying N86 were more likely to experience a recurrent infection; (2) patients given ASAQ and infected with parasites carrying 86Y were more likely to experience a recurrent infection. These findings suggest that ACT and Pfmdr1 genotype may influence outcome after Plasmodium falciparum infection. |
| format | Article |
| id | doaj-art-6aa7ec9f6efb403fbcdab7f5d1c469f7 |
| institution | DOAJ |
| issn | 1475-2875 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | BMC |
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| series | Malaria Journal |
| spelling | doaj-art-6aa7ec9f6efb403fbcdab7f5d1c469f72025-08-20T03:20:59ZengBMCMalaria Journal1475-28752025-06-0124111310.1186/s12936-025-05248-2Plasmodium falciparum multidrug resistance 1 gene polymorphisms associated with outcomes after anti-malarial treatmentVeronika R. Laird0Mateusz M. Plucinski1Meera Venkatesan2Kelsey A. Rondini3Milijaona Randrianarivelojosia4Mauricette N. Andriamananjara5Hawela Moonga6Deus S. Ishengoma7Arlindo Chidimatembue8Pedro Rafael Dimbu9Adicatou-Laï Adeothy10Abdoul Habib Beavogui11Simon Kariuki12Sam L. Nsobya13Aline Uwimana14Gauthier Mesia Kahunu15Ashenafi Assefa16Ousmane A. Koita17Naomi W. Lucchi18Samaly S. Svigel Souza19Zhiyong Zhou20Leah F. Moriarty21Eric S. Halsey22Department of Epidemiology, Emory UniversityMalaria Branch, Division of Parasitic Diseases and Malaria, Centers for Disease Control and Prevention, US President’s Malaria InitiativeUS President’s Malaria Initiative, United States Agency for International DevelopmentDepartment of Epidemiology, Emory UniversityInstitut Pasteur de MadagascarDirection de La Démographie et des Statistiques Sociales, Institut National de La StatistiqueNational Malaria Elimination Centre, Zambia Ministry of HealthNational Institute for Medical ResearchCentro de Investigação em Saúde de Manhiça (CISM)National Malaria Control Program, Ministry of HealthNational Malaria Control Program, Ministry of HealthCentre National de Formation et de Recherche en Santé Rurale de MaferinyahKenya Medical Research Institute (KEMRI)-Centre for Global Health ResearchInfectious Diseases Research Collaboration (IDRC)Malaria and Other Parasitic Diseases Division, Rwanda Biomedical Centre (RBC)Unit of Clinical Pharmacology and Pharmacovigilance University of KinshasaEthiopian Public Health InstituteLaboratoire de Biologie Moléculaire Appliquée, Université des Sciences, des Techniques et des Technologies de BamakoU.S. President’s Malaria Initiative, US Centers for Disease Control and PreventionLaboratory Science and Diagnostic Branch, Malaria Branch, U.S. Centers for Disease Control and PreventionLaboratory Science and Diagnostic Branch, Malaria Branch, U.S. Centers for Disease Control and PreventionMalaria Branch, Division of Parasitic Diseases and Malaria, Centers for Disease Control and Prevention, US President’s Malaria InitiativeMalaria Branch, Division of Parasitic Diseases and Malaria, Centers for Disease Control and Prevention, US President’s Malaria InitiativeAbstract Background Plasmodium falciparum multidrug resistance transporter 1 (Pfmdr1) gene mutations are associated with altered response to artemisinin-based combination therapy (ACT), particularly the combinations containing the partner drugs lumefantrine and amodiaquine (i.e., artemether-lumefantrine [AL] and artesunate-amodiaquine [ASAQ]). Past studies of Pfmdr1 single nucleotide polymorphisms (SNPs) at codons 86, 184, and 1246 have shown different responses to AL and ASAQ. Methods To determine whether infection with parasites carrying specific Pfmdr1 SNPs leads to increased risk of recurrent parasitaemia (recrudescent or new infection), data from 3,915 samples from 16 therapeutic efficacy studies from 13 African countries between 2013 and 2019 were analysed. Results Patients treated with AL and infected with parasites carrying Pfmdr1 N86 were at greater risk of recurrent infection than those whose parasites carried 86Y. After treatment with ASAQ, individuals infected with parasites that carried Pfmdr1 86Y were more likely to experience a recurrent infection. Conclusions These results support prior studies that suggested: (1) patients given AL and infected with parasites carrying N86 were more likely to experience a recurrent infection; (2) patients given ASAQ and infected with parasites carrying 86Y were more likely to experience a recurrent infection. These findings suggest that ACT and Pfmdr1 genotype may influence outcome after Plasmodium falciparum infection.https://doi.org/10.1186/s12936-025-05248-2MalariaPlasmodium falciparumAfricaAntimalarialsDrug resistance |
| spellingShingle | Veronika R. Laird Mateusz M. Plucinski Meera Venkatesan Kelsey A. Rondini Milijaona Randrianarivelojosia Mauricette N. Andriamananjara Hawela Moonga Deus S. Ishengoma Arlindo Chidimatembue Pedro Rafael Dimbu Adicatou-Laï Adeothy Abdoul Habib Beavogui Simon Kariuki Sam L. Nsobya Aline Uwimana Gauthier Mesia Kahunu Ashenafi Assefa Ousmane A. Koita Naomi W. Lucchi Samaly S. Svigel Souza Zhiyong Zhou Leah F. Moriarty Eric S. Halsey Plasmodium falciparum multidrug resistance 1 gene polymorphisms associated with outcomes after anti-malarial treatment Malaria Journal Malaria Plasmodium falciparum Africa Antimalarials Drug resistance |
| title | Plasmodium falciparum multidrug resistance 1 gene polymorphisms associated with outcomes after anti-malarial treatment |
| title_full | Plasmodium falciparum multidrug resistance 1 gene polymorphisms associated with outcomes after anti-malarial treatment |
| title_fullStr | Plasmodium falciparum multidrug resistance 1 gene polymorphisms associated with outcomes after anti-malarial treatment |
| title_full_unstemmed | Plasmodium falciparum multidrug resistance 1 gene polymorphisms associated with outcomes after anti-malarial treatment |
| title_short | Plasmodium falciparum multidrug resistance 1 gene polymorphisms associated with outcomes after anti-malarial treatment |
| title_sort | plasmodium falciparum multidrug resistance 1 gene polymorphisms associated with outcomes after anti malarial treatment |
| topic | Malaria Plasmodium falciparum Africa Antimalarials Drug resistance |
| url | https://doi.org/10.1186/s12936-025-05248-2 |
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