To egress from its erythrocyte host, the malaria parasite, Plasmodium falciparum, must destabilize the erythrocyte membrane by activating an erythrocyte tyrosine kinase. Because imatinib inhibits erythrocyte tyrosine kinases and because imatinib has a good safety profile, we elected to determine whether coadministration of imatinib with standard of care (SOC) might be both well tolerated and therapeutically efficacious in malaria patients. Patients with uncomplicated P. falciparum malaria from a region in Vietnam where one third of patients experience delayed parasite clearance (DPC; continued parasitemia after 3 d of therapy) were treated for 3 d with either the region’s SOC (40 mg dihydroartemisinin + 320 mg piperaquine/d) or imatinib (400 mg/d) + SOC. Imatinib + SOC–treated participants exhibited no increase in number or severity of adverse events, a significantly accelerated decline in parasite density and pyrexia, and no DPC. Surprisingly, these improvements were most pronounced in patients with the highest parasite density, where serious complications and death are most frequent. Imatinib therefore appears to improve SOC therapy, with no obvious drug-related toxicities.

中文翻译：

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伊马替尼增强标准疟疾联合治疗，但不增加毒性

为了从其红细胞宿主中排出，疟原虫恶性疟原虫必须通过激活红细胞酪氨酸激酶来破坏红细胞膜的稳定性。因为伊马替尼抑制红细胞酪氨酸激酶并且伊马替尼具有良好的安全性，我们选择确定伊马替尼与护理标准 (SOC) 的共同给药在疟疾患者中是否具有良好的耐受性和治疗效果。单纯性恶性疟患者来自越南一个地区的疟疾，其中三分之一的患者经历寄生虫清除延迟（DPC；治疗 3 天后持续寄生虫血症）用该地区的 SOC（40 毫克双氢青蒿素 + 320 毫克哌喹/天）或伊马替尼治疗 3 天（ 400 毫克/天）+ SOC。伊马替尼 + SOC 治疗的参与者没有表现出不良事件的数量或严重程度增加，寄生虫密度和发热显着加速下降，并且没有 DPC。令人惊讶的是，这些改善在寄生虫密度最高的患者中最为明显，其中严重并发症和死亡最常见。因此，伊马替尼似乎可以改善 SOC 治疗，没有明显的药物相关毒性。