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Decreased dihydroartemisinin-piperaquine protection against recurrent malaria associated with Plasmodium falciparum plasmepsin 3 copy number variation in Africa

Author

Listed:
  • Leyre Pernaute-Lau

    (Karolinska Institutet
    Faculty of Sciences, University of Lisbon
    The Art of Discovery)

  • Mario Recker

    (University of Exeter, Penryn Campus
    University of Tübingen)

  • Mamadou Tékété

    (University of Science, Techniques and Technologies of Bamako
    University of Heidelberg)

  • Tais Nóbrega Sousa

    (Karolinska Institutet
    Fundação Oswaldo Cruz (FIOCRUZ); Belo)

  • Aliou Traore

    (University of Science, Techniques and Technologies of Bamako)

  • Bakary Fofana

    (University of Science, Techniques and Technologies of Bamako)

  • Kassim Sanogo

    (University of Science, Techniques and Technologies of Bamako)

  • Ulrika Morris

    (Karolinska Institutet)

  • Juliana Inoue

    (University of Tübingen)

  • Pedro E. Ferreira

    (University of Minho, Campus de Gualtar
    ICVS/3B’s─PT Government Associate Laboratory; 4806-909 Guimarães)

  • Nouhoum Diallo

    (University of Science, Techniques and Technologies of Bamako)

  • Jürgen Burhenne

    (German Center for Infection Research (DZIF))

  • Issaka Sagara

    (University of Science, Techniques and Technologies of Bamako)

  • Alassane Dicko

    (University of Science, Techniques and Technologies of Bamako)

  • Maria I. Veiga

    (University of Minho, Campus de Gualtar
    ICVS/3B’s─PT Government Associate Laboratory; 4806-909 Guimarães)

  • Walter Haefeli

    (German Center for Infection Research (DZIF))

  • Anders Björkman

    (Karolinska Institutet
    Karolinska Institutet)

  • Abdoulaye A. Djimde

    (University of Science, Techniques and Technologies of Bamako)

  • Steffen Borrmann

    (University of Tübingen
    German Center for Infection Research (DZIF)
    Centre de Recherches Médicales de Lambaréné (CERMEL))

  • José Pedro Gil

    (Karolinska Institutet
    Nova University of Lisbon)

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.

Suggested Citation

  • Leyre Pernaute-Lau & Mario Recker & Mamadou Tékété & Tais Nóbrega Sousa & Aliou Traore & Bakary Fofana & Kassim Sanogo & Ulrika Morris & Juliana Inoue & Pedro E. Ferreira & Nouhoum Diallo & Jürgen Bur, 2025. "Decreased dihydroartemisinin-piperaquine protection against recurrent malaria associated with Plasmodium falciparum plasmepsin 3 copy number variation in Africa," Nature Communications, Nature, vol. 16(1), pages 1-7, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-57726-5
    DOI: 10.1038/s41467-025-57726-5
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    References listed on IDEAS

    as
    1. Selina Bopp & Pamela Magistrado & Wesley Wong & Stephen F. Schaffner & Angana Mukherjee & Pharath Lim & Mehul Dhorda & Chanaki Amaratunga & Charles J. Woodrow & Elizabeth A. Ashley & Nicholas J. White, 2018. "Plasmepsin II–III copy number accounts for bimodal piperaquine resistance among Cambodian Plasmodium falciparum," Nature Communications, Nature, vol. 9(1), pages 1-10, December.
    2. Palang Chotsiri & Issaka Zongo & Paul Milligan & Yves Daniel Compaore & Anyirékun Fabrice Somé & Daniel Chandramohan & Warunee Hanpithakpong & François Nosten & Brian Greenwood & Philip J. Rosenthal &, 2019. "Optimal dosing of dihydroartemisinin-piperaquine for seasonal malaria chemoprevention in young children," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
    3. repec:plo:pone00:0007871 is not listed on IDEAS
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