Safety of single low-dose primaquine in glucose-6-phosphate dehydrogenase deficient falciparum-infected African males: two open-label, randomized, safety trials

Background: Primaquine (PQ) actively clears mature Plasmodium falciparum gametocytes but in glucose-6-phosphate dehydrogenase deficient (G6PDd) individuals can cause hemolysis. We assessed the safety of low-dose PQ in combination with artemether-lumefantrine (AL) or dihydroartemisinin-piperaquine (DP) in G6PDd African males with asymptomatic P. falciparum malaria. Methods and findings: In Burkina Faso, G6PDd adult males were randomized to treatment with AL alone (n = 10) or with PQ at 0.25 (n = 20) or 0.40 mg/kg (n = 20) dosage; G6PD-normal males received AL plus 0.25 (n = 10) or 0.40 mg/kg (n = 10) PQ. In The Gambia, G6PDd adult males and boys received DP alone (n = 10) or with 0.25 mg/kg PQ (n = 20); G6PD-normal males received DP plus 0.25 (n = 10) or 0.40 mg/kg (n = 10) PQ. The primary study endpoint was change in hemoglobin concentration during the 28-day follow-up. Cytochrome P-450 isoenzyme 2D6 (CYP2D6) metabolizer status, gametocyte carriage, haptoglobin, lactate dehydrogenase l...

背景：伯氨喹（Primaquine, PQ）可主动清除成熟恶性疟原虫（Plasmodium falciparum）配子体，但在葡萄糖-6-磷酸脱氢酶缺乏症（glucose-6-phosphate dehydrogenase deficient, G6PDd）个体中可引发溶血。本研究评估了低剂量伯氨喹联合蒿甲醚-苯芴醇（artemether-lumefantrine, AL）或双氢青蒿素-哌喹（dihydroartemisinin-piperaquine, DP）用于葡萄糖-6-磷酸脱氢酶缺乏症非洲男性无症状恶性疟原虫感染的安全性。
方法与结果：在布基纳法索，葡萄糖-6-磷酸脱氢酶缺乏症成年男性被随机分配至单纯蒿甲醚-苯芴醇治疗组（n=10），或联合0.25 mg/kg（n=20）或0.40 mg/kg（n=20）伯氨喹治疗组；葡萄糖-6-磷酸脱氢酶正常男性则接受蒿甲醚-苯芴醇联合0.25 mg/kg（n=10）或0.40 mg/kg（n=10）伯氨喹治疗。在冈比亚，葡萄糖-6-磷酸脱氢酶缺乏症成年男性及男童被随机分配至单纯双氢青蒿素-哌喹治疗组（n=10），或联合0.25 mg/kg伯氨喹治疗组（n=20）；葡萄糖-6-磷酸脱氢酶正常男性接受双氢青蒿素-哌喹联合0.25 mg/kg（n=10）或0.40 mg/kg（n=10）伯氨喹治疗。本研究的主要终点为28天随访期间的血红蛋白浓度变化。检测指标包括细胞色素P450同工酶2D6（CYP2D6）代谢型、配子体携带率、结合珠蛋白、乳酸脱氢酶……