The relapsing nature of Plasmodium vivax infection is a major barrier to its control and elimination. Factors such as adequate dosing, adherence, drug quality, and pharmacogenetics can impact the effectiveness of radical cure of P. vivax and need to be adequately evaluated. CYP2D6 pathway mediates the activation of primaquine (primaquine) into an active metabolite(s) in hepatocytes, and impaired activity has been linked to a higher risk of relapse. Three patients diagnosed with P. vivax malaria presented repeated relapses after being initially treated with chloroquine (25 mg/kg) and primaquine (3.5 mg/kg in 14 days) at a non-endemic travel clinic. Recurring episodes were subsequently treated with a higher dose of primaquine (7 mg/kg in 14 days), which prevented further relapses in two patients. However, one patient still presented two episodes after a higher primaquine dose and was prescribed 300 mg of chloroquine weekly to prevent further episodes. Impaired CYP2D6 function was observed in all of them. Lack of response to primaquine was associated with impaired CYP2D6 activity in three patients presenting multiple relapses followed in a non-endemic setting. Higher primaquine dosage was safe and effectively prevented relapses in two patients and should be further investigated as an option in Latin America. It is crucial to investigate the factors associated with unsuccessful radical cures and alternative therapeutic options.

中文翻译：

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增加伯氨喹总剂量可防止 CYP2D6 活性受损患者间日疟原虫复发：三例报告

间日疟原虫感染的复发性质是其控制和消除的主要障碍。适当的剂量、依从性、药物质量和药物遗传学等因素会影响间日疟原虫根治的有效性，需要进行充分评估。CYP2D6 通路介导伯氨喹 (primaquine) 在肝细胞中活化为活性代谢物，活性受损与较高的复发风险有关。三名被诊断患有间日疟原虫疟疾的患者在一家非地方性旅行诊所接受氯喹（25 毫克/千克）和伯氨喹（14 天内 3.5 毫克/千克）初始治疗后反复复发。随后用更高剂量的伯氨喹（14 天 7 毫克/千克）治疗反复发作，这防止了两名患者的进一步复发。然而，一名患者在使用较高的伯氨喹剂量后仍出现两次发作，并每周服用 300 毫克氯喹以防止进一步发作。在所有这些患者中都观察到 CYP2D6 功能受损。在非地方性环境中出现多次复发的三名患者中，对伯氨喹缺乏反应与 CYP2D6 活性受损有关。较高的伯氨喹剂量是安全的，并有效地防止了两名患者的复发，应作为拉丁美洲的一种选择进行进一步研究。调查与不成功的根治性治疗和替代治疗选择相关的因素至关重要。在非地方性环境中出现多次复发的三名患者中，对伯氨喹缺乏反应与 CYP2D6 活性受损有关。较高的伯氨喹剂量是安全的，并有效地防止了两名患者的复发，应作为拉丁美洲的一种选择进行进一步研究。调查与不成功的根治性治疗和替代治疗选择相关的因素至关重要。在非地方性环境中出现多次复发的三名患者中，对伯氨喹缺乏反应与 CYP2D6 活性受损有关。较高的伯氨喹剂量是安全的，并有效地防止了两名患者的复发，应作为拉丁美洲的一种选择进行进一步研究。调查与不成功的根治性治疗和替代治疗选择相关的因素至关重要。