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Decreased dihydroartemisinin-piperaquine protection against recurrent malaria associated with Plasmodium falciparum plasmepsin 3 copy number variation in Africa
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Resumo(s)
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.
Descrição
Funding Information: This work was supported by a Swedish Research Council Grant (no. 2021-05666, ref. 2021-06048 and ref. 2021-03105) (J.P.G.). The WANECAM study was funded by the European and Developing Countries Clinical Trial Partnership and by the Medicines for Malaria Venture (Geneva, Switzerland) and is co-funded by the United Kingdom Medical Research Councils, the Swedish International Development Cooperation Agency, the German Ministry for Education and Research, the University Claude Bernard (Lyon, France), the University of Science, Techniques, and Technologies of Bamako (Bamako, Mali), the Center National de Recherche et de Formation sur le Paludisme (Burkina Faso), the Institut de Recherche en Sciences de la Sante (Bobo-Dioulasso, Burkina Faso), and the Center National de Formation et de Recherche en Sante Rurale (Guinea) (all authors). This work has been funded by Portuguese funds: Foundation for Science and Technology (FCT) - project UIDB/50026/2020, UIDP/50026/2020 and contract 2020.03113.CEECIND (M.I.V.). Projects NORTE-01-0145-FEDER-000039, supported by Norte Portugal Regional Operational Program (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF) (J.P.G.). Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq), Brazil, Grant ref. 200075/2022-5 (T.N.S). In addition, funded by the European and Developing Countries Clinical Trial Partnership (EDCTP), Medicines for Malaria Venture (MMV, Geneva, Switzerland), Federal Ministry of Education and Research (BMBF, Germany), and German Research Foundation (DFG), German Academic Exchange Service (DAAD) (all authors). A fellowship from BioSys PhD program PD65-2012 (Ref SFRH/BD/142860/2018) from Fundac & atilde;o para a Ciencia e Tecnologia (Portugal) (L.P.L.). Funding Information: Open access funding provided by Karolinska Institute. Publisher Copyright: © The Author(s) 2025.
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General Chemistry General Biochemistry,Genetics and Molecular Biology General Physics and Astronomy SDG 3 - Good Health and Well-being