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<p>Dihydroartemisinin-piperaquine (DHA-PPQ) is being recommended in Africa for the management of uncomplicated <i>Plasmodium falciparum</i> 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 (<i>pfpm</i>), 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 <i>pfpm3</i> 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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年3月18日

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  • 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

摘要

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.