In areas co-endemic for and there is an increased risk of parasitaemia following malaria. Radical cure is currently only recommended for patients presenting with malaria. Expanding the indication for radical cure to patients presenting with malaria could reduce their risk of subsequent parasitaemia. We did a multicentre, open-label, superiority randomised controlled trial in five health clinics in Bangladesh, Indonesia, and Ethiopia. In Bangladesh and Indonesia, patients were excluded if they were younger than 1 year, whereas in Ethiopia patients were excluded if they were younger than 18 years. Patients with uncomplicated monoinfection who had fever or a history of fever in the 48 h preceding clinic visit were eligible for enrolment and were required to have a glucose-6-dehydrogenase (G6PD) activity of 70% or greater. Patients received blood schizontocidal treatment (artemether–lumefantrine in Ethiopia and Bangladesh and dihydroartemisinin–piperaquine in Indonesia) and were randomly assigned (1:1) to receive either high-dose short-course oral primaquine (intervention arm; total dose 7 mg/kg over 7 days) or standard care (standard care arm; single dose oral primaquine of 0·25 mg/kg). Random assignment was done by an independent statistician in blocks of eight by use of sealed envelopes. All randomly assigned and eligible patients were included in the primary and safety analyses. The per-protocol analysis excluded those who did not complete treatment or had substantial protocol violations. The primary endpoint was the incidence risk of parasitaemia on day 63. This trial is registered at , . Between Aug 18, 2019, and March 14, 2022, a total of 500 patients were enrolled and randomly assigned, and 495 eligible patients were included in the intention-to-treat analysis (246 intervention and 249 control). The incidence risk of parasitaemia at day 63 was 11·0% (95% CI 7·5–15·9) in the standard care arm compared with 2·5% (1·0–5·9) in the intervention arm (hazard ratio 0·20, 95% CI 0·08–0·51; p=0·0009). The effect size differed with blood schizontocidal treatment and site. Routine symptom reporting on day 2 and day 7 were similar between groups. In the first 42 days, there were a total of four primaquine-related adverse events reported in the standard care arm and 26 in the intervention arm; 132 (92%) of all 143 adverse events were mild. There were two serious adverse events in the intervention arm, which were considered unrelated to the study drug. None of the patients developed severe anaemia (defined as haemoglobin <5 g/dL). In patients with a G6PD activity of 70% or greater, high-dose short-course primaquine was safe and relatively well tolerated and reduced the risk of subsequent parasitaemia within 63 days by five fold. Universal radical cure therefore potentially offers substantial clinical, public health, and operational benefits, but these benefits will vary with endemic setting. Australian Academy of Science Regional Collaborations Program, Bill & Melinda Gates Foundation, and National Health and Medical Research Council.

中文翻译：

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伯氨喹对恶性疟和间日疟共流行地区的恶性疟患者进行根治（PRIMA）：一项多中心、开放标签、优效性随机对照试验

在疟疾共同流行的地区，疟疾后寄生虫血症的风险增加。目前仅建议对患有疟疾的患者进行根治。扩大疟疾患者根治的适应症可以降低他们随后发生寄生虫血症的风险。我们在孟加拉国、印度尼西亚和埃塞俄比亚的五个卫生诊所进行了一项多中心、开放标签、优效性随机对照试验。在孟加拉国和印度尼西亚，年龄小于 1 岁的患者被排除在外，而在埃塞俄比亚，年龄小于 18 岁的患者被排除在外。患有单纯性单一感染且在就诊前 48 小时内有发热或发热史的患者有资格入选，并且葡萄糖 6 脱氢酶 (G6PD) 活性必须达到 70% 或更高。患者接受血液裂殖治疗（埃塞俄比亚和孟加拉国的蒿甲醚-本芴醇，印度尼西亚的双氢青蒿素-哌喹），并被随机分配（1:1）接受大剂量短程口服伯氨喹（干预组；总剂量 7 mg/kg） 7 天以上）或标准护理（标准护理组；单剂量口服伯氨喹 0·25 mg/kg）。随机分配是由独立统计学家使用密封信封以八个为一组进行的。所有随机分配且符合条件的患者均纳入主要分析和安全性分析。按方案分析排除了那些未完成治疗或严重违反方案的患者。主要终点是第 63 天的寄生虫血症发生风险。该试验注册于 , 。2019年8月18日至2022年3月14日期间，共有500名患者入组并随机分配，495名符合条件的患者纳入意向治疗分析（246名干预组和249名对照组）。第 63 天时，标准护理组的寄生虫血症发生风险为 11·0% (95% CI 7·5–15·9)，而干预组的发生风险为 2·5% (1·0–5·9)。风险比 0·20，95% CI 0·08–0·51；p=0·0009)。效果大小因血液裂殖杀伤治疗和部位而异。第 2 天和第 7 天的常规症状报告在各组之间相似。在最初的 42 天内，标准护理组报告了 4 起与伯氨喹相关的不良事件，干预组报告了 26 起；所有 143 项不良事件中有 132 项 (92%) 为轻微不良事件。干预组中有两起严重不良事件，被认为与研究药物无关。没有患者出现严重贫血（定义为血红蛋白<5 g/dL）。对于 G6PD 活性为 70% 或更高的患者，高剂量短程伯氨喹是安全的，耐受性相对良好，并且可将 63 天内发生寄生虫血症的风险降低五倍。因此，普遍根治可能会带来巨大的临床、公共卫生和操作效益，但这些效益会因流行情况而异。澳大利亚科学院区域合作计划，