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DECREASED DIHYDROARTEMISININ-PIPERAQUINE PROTECTION AGAINST RECURRENT MALARIA ASSOCIATED WITH PLASMODIUM FALCIPARUM PLASMEPSIN 3 COPY NUMBER VARIATION IN AFRICA.
Pernaute-Lau, Leyre et al. | Date Issued: 2025
Author
Pernaute-Lau, Leyre
Recker, Mario
Tékété, Mamadou
Sousa, Tais Nóbrega de
Traore, Aliou
Fofana, Bakary
Sanogo, Kassim
Morris, Ulrika
Inoue, Juliana
Ferreira, Pedro E.
Diallo, Nouhoum
Burhenne, Jürgen
Sagara, Issaka
Dicko, Alassane
Veiga, Maria I.
Haefeli, Walter
Björkman, Anders
Djimde, Abdoulaye A.
Borrmann, Steffen
Gil, José Pedro
Affilliation
Department of Microbiology and Tumour Cell Biology. Karolinska Institutet. Stckholm, Sweden. / Biosystems & Integrative Sciences Institute. Faculty of Sciences. University of Lisbon. Lisbon, Portugal. / The Art of Discovery. Derio, Basque Country, Spain.
Centre for Ecology and Conservation. University of Exeter. Penryn, UK. / Institute for Tropical Medicine. University of Tübingen. Tübingen, Germany.
Malaria Research and Training Center. Faculty of Pharmacy, University of Science, Techniques and Technologies of Bamako, Bamako, Mali. / Dept. of Clinical Pharmacology. University of Heidelberg. Heidelberg, Germany.
Department ofMicrobiology and Tumour Cell Biology. Karolinska Institutet. Stckholm, Sweden. / Fundação Oswaldo Cruz. Instituto René Rachou. Grupo de Pesquisa em Biologia Molecular e Imunologia da Malária. Belo Horizonte, MG, Brasil.
Malaria Research and Training Center. Faculty of Pharmacy, University of Science, Techniques and Technologies of Bamako, Bamako, Mali.
Malaria Research and Training Center. Faculty of Pharmacy, University of Science, Techniques and Technologies of Bamako, Bamako, Mali.
Malaria Research and Training Center. Faculty of Pharmacy, University of Science, Techniques and Technologies of Bamako, Bamako, Mali.
Department ofMicrobiology and Tumour Cell Biology. Karolinska Institutet. Stckholm, Sweden.
Institute for Tropical Medicine. University of Tübingen. Tübingen, Germany. / German Center for Infection Research. Tübingen, Germany.
Life and Health Sciences Research Institute. School of Medicine. University of Minho, Braga, Portugal. / ICVS/3B’s─PT Government Associate Laboratory. Braga, Portugal.
Malaria Research and Training Center. Faculty of Pharmacy, University of Science, Techniques and Technologies of Bamako, Bamako, Mali.
German Center for Infection Research. Tübingen, Germany.
Malaria Research and Training Center. Faculty of Pharmacy, University of Science, Techniques and Technologies of Bamako, Bamako, Mali.
Malaria Research and Training Center. Faculty of Pharmacy, University of Science, Techniques and Technologies of Bamako, Bamako, Mali.
Life and Health Sciences Research Institute. School of Medicine. University of Minho, Braga, Portugal. / ICVS/3B’s─PT Government Associate Laboratory. Braga, Portugal.
German Center for Infection Research. Tübingen, Germany.
Department ofMicrobiology and Tumour Cell Biology. Karolinska Institutet. Stckholm, Sweden. / Department of Global Public Health. Karolinska Institutet. Stockholm, Sweden.
Malaria Research and Training Center. Faculty of Pharmacy, University of Science, Techniques and Technologies of Bamako, Bamako, Mali.
Institute for Tropical Medicine. University of Tübingen. Tübingen, Germany. / German Center for Infection Research. Tübingen, Germany. / Centre de Recherches Médicales de Lambaréné. Lambaréné, Gabon.
Department ofMicrobiology and Tumour Cell Biology. Karolinska Institutet. Stckholm, Sweden. / Clinical Tropical Medicine. Global Health and Tropical Medicine. Institute of Hygiene and Tropical Medicine. Nova University of Lisbon. Lisbon, Portugal.
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 reinfections. 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.
Publisher
Nature
Citation
PERNAUTE-LAU, Leyre et al. Decreased dihydroartemisinin-piperaquine protection against recurrent malaria associated with Plasmodium falciparum plasmepsin 3 copy number variation in Africa. Nature Communications, v. 16, n. 1, 2680, 2025.
DOI
1038/s41467-025-57726-5
ISSN
2041-1723