Conan Pierre-Louis, Thellier Marc, Kendjo Eric, Houzé Sandrine, Seng Rémonie, Jauréguiberry Stéphane
Service des Maladies Infectieuses et Tropicales, Hôpital d'Instruction des Armées Bégin, Saint-Mandé, France.
Sorbonne Université, Institut Pierre Louis d'Epidémiologie et de Santé publique, Inserm, Paris, France; Centre National de Référence du Paludisme, Paris, France; Sorbonne Université, Service de Parasitologie, Hôpital Pitié-Salpétrière, APHP, Paris, France.
Travel Med Infect Dis. 2025 Mar-Apr;64:102801. doi: 10.1016/j.tmaid.2025.102801. Epub 2025 Jan 23.
Post-Artesunate delayed hemolysis (PADH) occurs in approximately 15 % of treated patients 2-3 weeks after artesunate administration. Identifying risk markers for PADH would help predict which patients are at higher risk.
In this prospective national cohort study conducted in a non-malaria endemic area from 2011 to 2016, a Cox proportional hazards model was used to assess the association between clinical and biological data available at Day 0 and the occurrence of PADH within 30 days of artesunate administration.
In the analyzed population (n = 327), 49 PADH events occurred after a median time of 14 days (IQR, 13-17) after artesunate initiation. Higher initial parasitemia was associated with an increased risk of PADH, with a significant interaction found with patient origin. The cumulative probability of PADH event at Day 30 post-artesunate was 65 % (95 % confidence interval [CI], 44-79) for European patients vs. 14 % (95 % CI, 0-26) for those with recent African ancestry [RAA] when the initial parasitemia was >10 %. After adjustment for weight, history of malaria, initial hemoglobin, very severe malaria and residence in an endemic area, compared to recent African ancestry with initial parasitemia <4 %, the adjusted hazard ratio for PADH occurrence was 18.8 (95 % CI, 4-89) for Europeans and 4.77 (95 % CI, 0.8-29.2) for recent African ancestry with initial parasitemia >10 %.
This study showed that initial parasitemia and patient origin were the main predictors of developing PADH, with the highest risk observed in Europeans with an initial parasitemia >10 %.
青蒿琥酯治疗后延迟性溶血（PADH）发生于约15%接受治疗的患者，在青蒿琥酯给药后2至3周出现。识别PADH的风险标志物将有助于预测哪些患者风险更高。
在2011年至2016年于非疟疾流行地区开展的这项前瞻性全国队列研究中，采用Cox比例风险模型评估第0天的临床和生物学数据与青蒿琥酯给药后30天内PADH发生之间的关联。
在分析的人群（n = 327）中，49例PADH事件发生于青蒿琥酯开始应用后中位时间14天（四分位间距，13 - 17天）。初始寄生虫血症水平较高与PADH风险增加相关，且发现与患者来源存在显著交互作用。当初始寄生虫血症>10%时，青蒿琥酯给药后第30天PADH事件的累积概率在欧洲患者中为65%（95%置信区间[CI]，44 - 79），而在近期有非洲血统[RAA]的患者中为14%（95%CI，0 - 26）。在对体重、疟疾病史、初始血红蛋白、极重度疟疾及在流行地区居住情况进行校正后，与初始寄生虫血症<4%的近期非洲血统相比，初始寄生虫血症>10%的欧洲人发生PADH的校正风险比为18.8（95%CI，4 - 89），初始寄生虫血症>10%的近期非洲血统者为4.77（95%CI，0.8 - 29.2）。
本研究表明，初始寄生虫血症水平和患者来源是发生PADH的主要预测因素，初始寄生虫血症>10%的欧洲人风险最高。
