Decreased dihydroartemisinin-piperaquine protection against recurrent malaria associated with Plasmodium falciparum plasmepsin 3 copy number variation in Africa
Abstract Dihydroartemisinin-piperaquine (DHA-PPQ) is being recommended in Africa for the management of uncomplicated Plasmodium falciparum malaria and for chemoprevention strategies, based on the ability of piperaquine to delay re-infections. Although therapeutic resistance to piperaquine has been l...
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Nature Portfolio
2025-03-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-57726-5 |
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| author | Leyre Pernaute-Lau Mario Recker Mamadou Tékété Tais Nóbrega de Sousa Aliou Traore Bakary Fofana Kassim Sanogo Ulrika Morris Juliana Inoue Pedro E. Ferreira Nouhoum Diallo Jürgen Burhenne Issaka Sagara Alassane Dicko Maria I. Veiga Walter Haefeli Anders Björkman Abdoulaye A. Djimde Steffen Borrmann José Pedro Gil |
| author_facet | Leyre Pernaute-Lau Mario Recker Mamadou Tékété Tais Nóbrega de Sousa Aliou Traore Bakary Fofana Kassim Sanogo Ulrika Morris Juliana Inoue Pedro E. Ferreira Nouhoum Diallo Jürgen Burhenne Issaka Sagara Alassane Dicko Maria I. Veiga Walter Haefeli Anders Björkman Abdoulaye A. Djimde Steffen Borrmann José Pedro Gil |
| author_sort | Leyre Pernaute-Lau |
| collection | DOAJ |
| description | Abstract Dihydroartemisinin-piperaquine (DHA-PPQ) is being recommended in Africa for the management of uncomplicated Plasmodium falciparum malaria and for chemoprevention strategies, based on the ability of piperaquine to delay re-infections. Although therapeutic resistance to piperaquine has been linked to increased copy number in plasmepsin-coding parasite genes (pfpm), their effect on the duration of the post-treatment prophylactic period remains unclear. Here, we retrospectively analyzed data from a randomized clinical trial, where patients received either DHA-PPQ or artesunate-amodiaquine for recurrent malaria episodes over two years. We observed an increase in the relative risk of re-infection among patients receiving DHA-PPQ compared to artesunate-amodiaquine after the first malaria season. This was driven by shorter average times to reinfection and coincided with an increased frequency of infections comprising pfpm3 multi-copy parasites. The decline in post-treatment protection of DHA-PPQ upon repeated use in a high transmission setting raises concerns for its wider use for chemopreventive strategies in Africa. |
| format | Article |
| id | doaj-art-dfae4ea607de44f998b4732ff7683514 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-dfae4ea607de44f998b4732ff76835142025-08-20T03:41:49ZengNature PortfolioNature Communications2041-17232025-03-011611710.1038/s41467-025-57726-5Decreased dihydroartemisinin-piperaquine protection against recurrent malaria associated with Plasmodium falciparum plasmepsin 3 copy number variation in AfricaLeyre Pernaute-Lau0Mario Recker1Mamadou Tékété2Tais Nóbrega de Sousa3Aliou Traore4Bakary Fofana5Kassim Sanogo6Ulrika Morris7Juliana Inoue8Pedro E. Ferreira9Nouhoum Diallo10Jürgen Burhenne11Issaka Sagara12Alassane Dicko13Maria I. Veiga14Walter Haefeli15Anders Björkman16Abdoulaye A. Djimde17Steffen Borrmann18José Pedro Gil19Department of Microbiology and Tumour Cell Biology, Karolinska InstitutetCentre for Ecology and Conservation, University of Exeter, Penryn CampusMalaria Research and Training Center, Faculty of Pharmacy, University of Science, Techniques and Technologies of BamakoDepartment of Microbiology and Tumour Cell Biology, Karolinska InstitutetMalaria Research and Training Center, Faculty of Pharmacy, University of Science, Techniques and Technologies of BamakoMalaria Research and Training Center, Faculty of Pharmacy, University of Science, Techniques and Technologies of BamakoMalaria Research and Training Center, Faculty of Pharmacy, University of Science, Techniques and Technologies of BamakoDepartment of Microbiology and Tumour Cell Biology, Karolinska InstitutetInstitute for Tropical Medicine, University of TübingenLife and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus de GualtarMalaria Research and Training Center, Faculty of Pharmacy, University of Science, Techniques and Technologies of BamakoGerman Center for Infection Research (DZIF)Malaria Research and Training Center, Faculty of Pharmacy, University of Science, Techniques and Technologies of BamakoMalaria Research and Training Center, Faculty of Pharmacy, University of Science, Techniques and Technologies of BamakoLife and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus de GualtarGerman Center for Infection Research (DZIF)Department of Microbiology and Tumour Cell Biology, Karolinska InstitutetMalaria Research and Training Center, Faculty of Pharmacy, University of Science, Techniques and Technologies of BamakoInstitute for Tropical Medicine, University of TübingenDepartment of Microbiology and Tumour Cell Biology, Karolinska InstitutetAbstract Dihydroartemisinin-piperaquine (DHA-PPQ) is being recommended in Africa for the management of uncomplicated Plasmodium falciparum malaria and for chemoprevention strategies, based on the ability of piperaquine to delay re-infections. Although therapeutic resistance to piperaquine has been linked to increased copy number in plasmepsin-coding parasite genes (pfpm), their effect on the duration of the post-treatment prophylactic period remains unclear. Here, we retrospectively analyzed data from a randomized clinical trial, where patients received either DHA-PPQ or artesunate-amodiaquine for recurrent malaria episodes over two years. We observed an increase in the relative risk of re-infection among patients receiving DHA-PPQ compared to artesunate-amodiaquine after the first malaria season. This was driven by shorter average times to reinfection and coincided with an increased frequency of infections comprising pfpm3 multi-copy parasites. The decline in post-treatment protection of DHA-PPQ upon repeated use in a high transmission setting raises concerns for its wider use for chemopreventive strategies in Africa.https://doi.org/10.1038/s41467-025-57726-5 |
| spellingShingle | Leyre Pernaute-Lau Mario Recker Mamadou Tékété Tais Nóbrega de Sousa Aliou Traore Bakary Fofana Kassim Sanogo Ulrika Morris Juliana Inoue Pedro E. Ferreira Nouhoum Diallo Jürgen Burhenne Issaka Sagara Alassane Dicko Maria I. Veiga Walter Haefeli Anders Björkman Abdoulaye A. Djimde Steffen Borrmann José Pedro Gil Decreased dihydroartemisinin-piperaquine protection against recurrent malaria associated with Plasmodium falciparum plasmepsin 3 copy number variation in Africa Nature Communications |
| title | Decreased dihydroartemisinin-piperaquine protection against recurrent malaria associated with Plasmodium falciparum plasmepsin 3 copy number variation in Africa |
| title_full | Decreased dihydroartemisinin-piperaquine protection against recurrent malaria associated with Plasmodium falciparum plasmepsin 3 copy number variation in Africa |
| title_fullStr | Decreased dihydroartemisinin-piperaquine protection against recurrent malaria associated with Plasmodium falciparum plasmepsin 3 copy number variation in Africa |
| title_full_unstemmed | Decreased dihydroartemisinin-piperaquine protection against recurrent malaria associated with Plasmodium falciparum plasmepsin 3 copy number variation in Africa |
| title_short | Decreased dihydroartemisinin-piperaquine protection against recurrent malaria associated with Plasmodium falciparum plasmepsin 3 copy number variation in Africa |
| title_sort | decreased dihydroartemisinin piperaquine protection against recurrent malaria associated with plasmodium falciparum plasmepsin 3 copy number variation in africa |
| url | https://doi.org/10.1038/s41467-025-57726-5 |
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