Pernaute-Lau Leyre, Recker Mario, Tékété Mamadou, de Sousa Tais Nóbrega, 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
Department of Microbiology and Tumour Cell Biology, Karolinska Institutet, Stockholm, Sweden.
BioISI - Biosystems & Integrative Sciences Institute, Faculty of Sciences, University of Lisbon, Lisbon, Portugal.
Nat Commun. 2025 Mar 18;16(1):2680. doi: 10.1038/s41467-025-57726-5.
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.
双氢青蒿素哌喹（DHA-PPQ）因哌喹具有延缓再次感染的能力，在非洲被推荐用于治疗非复杂性恶性疟原虫疟疾及化学预防策略。尽管对哌喹的治疗耐药性与疟原虫天冬氨酸蛋白酶编码基因（pfpm）拷贝数增加有关，但其对治疗后预防期时长的影响仍不明确。在此，我们回顾性分析了一项随机临床试验的数据，该试验中患者在两年内接受DHA-PPQ或青蒿琥酯阿莫地喹治疗复发性疟疾发作。我们观察到，在第一个疟疾季节后，与接受青蒿琥酯阿莫地喹治疗的患者相比，接受DHA-PPQ治疗的患者再次感染的相对风险增加。这是由再次感染的平均时间缩短所导致的，并且与包含pfpm3多拷贝寄生虫的感染频率增加相吻合。在高传播环境中重复使用DHA-PPQ后治疗后保护作用的下降，引发了人们对其在非洲更广泛用于化学预防策略的担忧。
