Prevention of malaria recurrence is essential for malaria elimination in Brazil. We evaluated the real-world effectiveness of an updated treatment algorithm for radical cure in the Brazilian Amazon. In this non-interventional observational study, we used retrospective data from the implementation of a treatment algorithm at 43 health facilities in Manaus and Porto Velho, Brazil. The treatment algorithm consisted of chloroquine (25 mg/kg over 3 days) and point-of-care quantitative glucose-6-phosphate dehydrogenase (G6PD) testing followed by single-dose tafenoquine 300 mg (G6PD normal, aged ≥16 years, not pregnant and not breastfeeding), 7-day primaquine 0·5 mg/kg per day (G6PD intermediate or normal, aged ≥6 months, not pregnant, and not breastfeeding or breastfeeding for >1 month), or primaquine 0·75 mg/kg per week for 8 weeks (G6PD deficient, aged ≥6 months, not pregnant, and not breastfeeding or breastfeeding for >1 month). recurrences were identified from probabilistic linkage of routine patient records from the Brazilian malaria epidemiological surveillance system. Recurrence-free effectiveness at day 90 and day 180 was estimated using Kaplan–Meier analysis and hazard ratios (HRs) by multivariate analysis. This clinical trial is registered with , , and is completed. Records from Sept 9, 2021, to Aug 31, 2022, included 5554 patients with malaria. In all treated patients of any age and any G6PD status, recurrence-free effectiveness at day 180 was 75·8% (95% CI 74·0–77·6) with tafenoquine, 73·4% (71·9–75·0) with 7-day primaquine, and 82·1% (77·7–86·8) with weekly primaquine. In patients aged at least 16 years who were G6PD normal, recurrence-free effectiveness until day 90 was 88·6% (95% CI 87·2–89·9) in those who were treated with tafenoquine (n=2134) and 83·5% (79·8–87·4) in those treated with 7-day primaquine (n=370); after adjustment for confounding factors, the HR for recurrence following tafenoquine versus 7-day primaquine was 0·65 (95% CI 0·49–0·86; p=0·0031), with similar outcomes between the two treatments at day 180 (log-rank p=0·82). Over 180 days, median time to recurrence in patients aged at least 16 years who were G6PD normal was 92 days (IQR 76–120) in those treated with tafenoquine and 68 days (52–94) in those treated with 7-day primaquine. In this real-world setting, single-dose tafenoquine was more effective at preventing recurrence in patients aged at least 16 years who were G6PD normal compared with 7-day primaquine at day 90, while overall efficacy at 180 days was similar. The public health benefits of the radical cure treatment algorithm incorporating G6PD quantitative testing and tafenoquine support its implementation in Brazil and potentially across South America. Brazilian Ministry of Health, Municipal and State Health Secretariats; Fiocruz; Medicines for Malaria Venture; Bill & Melinda Gates Foundation; Newcrest Mining; and the UK Government. For the Portuguese translation of the abstract see Supplementary Materials section.

中文翻译：

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他非诺喹和伯氨喹在巴西预防间日疟原虫复发的操作有效性：一项回顾性观察研究


预防疟疾复发对于巴西消除疟疾至关重要。我们评估了巴西亚马逊地区根治性更新治疗算法的现实有效性。在这项非干预性观察研究中，我们使用了巴西马瑙斯和韦柳港 43 家医疗机构实施治疗算法的回顾性数据。治疗方案包括氯喹（25 mg/kg，持续 3 天）和护理点定量葡萄糖-6-磷酸脱氢酶 (G6PD) 检测，然后单剂量他非诺喹 300 mg（G6PD 正常，年龄≥16 岁，未怀孕且未哺乳），每天 7 天伯氨喹 0·5 mg/kg（G6PD 中间或正常，年龄≥6 个月，未怀孕，未哺乳或哺乳时间 >1 个月），或伯氨喹 0·75 mg/kg每周公斤，持续 8 周（G6PD 缺乏、年龄≥6 个月、未怀孕、未母乳喂养或母乳喂养超过 1 个月）。复发情况是通过巴西疟疾流行病学监测系统的常规患者记录的概率关联来确定的。使用 Kaplan-Meier 分析和多变量分析的风险比 (HR) 估计第 90 天和第 180 天的无复发有效性。该临床试验已于 、 、 注册并已完成。 2021年9月9日至2022年8月31日的记录包括5554名疟疾患者。在所有年龄和任何 G6PD 状态的接受治疗的患者中，第 180 天时的无复发疗效为 75·8% (95% CI 74·0–77·6)，而他非诺喹则为 73·4% (71·9–75· 0) 使用 7 天伯氨喹，82·1% (77·7–86·8) 使用每周伯氨喹。 在年龄至少 16 岁且 G6PD 正常的患者中，接受他非诺喹治疗的患者 (n=2134) 和接受他非诺喹治疗的患者直至第 90 天的无复发有效性为 88·6% (95% CI 87·2–89·9) 和 83 ·5% (79·8–87·4) 在接受 7 天伯氨喹治疗的患者中 (n=370)；调整混杂因素后，他非诺喹与 7 天伯氨喹治疗后复发的 HR 为 0·65（95% CI 0·49–0·86；p=0·0031），两种治疗在第 180 天的结果相似（对数秩 p=0·82）。在 180 天以上，年龄至少 16 岁且 G6PD 正常的患者中，接受他非诺喹治疗的患者的中位复发时间为 92 天 (IQR 76-120)，而接受 7 天伯氨喹治疗的患者则为 68 天 (52-94)。在这一现实环境中，在第 90 天时，单剂量他非诺喹在预防 G6PD 正常的至少 16 岁患者的复发方面比第 7 天的伯氨喹更有效，而第 180 天的总体疗效相似。结合 G6PD 定量检测和他非诺喹的根治治疗算法对公共健康的益处支持其在巴西乃至整个南美洲的实施。巴西卫生部、市和州卫生秘书处；菲奥克鲁兹；疟疾药物风险投资；比尔及梅琳达·盖茨基金会；纽克雷斯特矿业公司；和英国政府。有关摘要的葡萄牙语翻译，请参阅补充材料部分。