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Abstract：
BACKGROUND: Prevention of Plasmodium vivax malaria recurrence is essential for malaria elimination in Brazil. We evaluated the real-world effectiveness of an updated treatment algorithm for P vivax radical cure in the Brazilian Amazon.
METHODS: In this non-interventional observational study, we used retrospective data from the implementation of a P vivax 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). P vivax 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 ClinicalTrials.gov, NCT05096702, and is completed.
RESULTS: Records from Sept 9, 2021, to Aug 31, 2022, included 5554 patients with P vivax 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.
CONCLUSIONS: In this real-world setting, single-dose tafenoquine was more effective at preventing P vivax 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 P vivax radical cure treatment algorithm incorporating G6PD quantitative testing and tafenoquine support its implementation in Brazil and potentially across South America.
BACKGROUND: Brazilian Ministry of Health, Municipal and State Health Secretariats; Fiocruz; Medicines for Malaria Venture; Bill & Melinda Gates Foundation; Newcrest Mining; and the UK Government.
UNASSIGNED: For the Portuguese translation of the abstract see Supplementary Materials section.
METHODS: In this non-interventional observational study, we used retrospective data from the implementation of a P vivax 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). P vivax 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 ClinicalTrials.gov, NCT05096702, and is completed.
RESULTS: Records from Sept 9, 2021, to Aug 31, 2022, included 5554 patients with P vivax 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.
CONCLUSIONS: In this real-world setting, single-dose tafenoquine was more effective at preventing P vivax 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 P vivax radical cure treatment algorithm incorporating G6PD quantitative testing and tafenoquine support its implementation in Brazil and potentially across South America.
BACKGROUND: Brazilian Ministry of Health, Municipal and State Health Secretariats; Fiocruz; Medicines for Malaria Venture; Bill & Melinda Gates Foundation; Newcrest Mining; and the UK Government.
UNASSIGNED: For the Portuguese translation of the abstract see Supplementary Materials section.
摘要：
背景：预防间日疟原虫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对间日疟原虫根治的更新治疗算法的实际有效性。
方法：在这项非干预性观察研究中，我们使用了来自马瑙斯和波尔图韦略的43个医疗机构实施间日疟原虫治疗算法的回顾性数据，巴西。治疗算法包括氯喹（25mg/kg，3天）和即时定量葡萄糖-6-磷酸脱氢酶（G6PD）测试，然后单剂量他非诺喹300mg（G6PD正常，年龄≥16岁，不怀孕也不母乳喂养)，7天伯氨喹每天0·5毫克/千克(G6PD中度或正常，年龄≥6个月，没有怀孕,而不是母乳喂养或母乳喂养>1个月)，或伯氨喹每周0·75毫克/千克，持续8周(G6PD缺乏，年龄≥6个月，没有怀孕,而不是母乳喂养或母乳喂养>1个月）。从巴西疟疾流行病学监测系统的常规患者记录的概率联系中确定了间日疟原虫的复发。使用Kaplan-Meier分析和通过多变量分析的风险比(HRs)估计第90天和第180天的无复发有效性。这项临床试验在ClinicalTrials.gov注册，NCT05096702，并完成。
结果：2021年9月9日至2022年8月31日的记录包括5554例间日疟疾患者。在所有接受治疗的患者中，任何年龄和任何G6PD状态，他非诺喹在第180天的无复发有效率为75·8%（95%CI74·0-77·6），73·4%(71·9-75·0)服用7天伯氨喹，每周服用伯氨喹的比例为82·1%（77·7-86·8）。在G6PD正常的年龄至少16岁的患者中，在使用他非诺喹治疗的患者(n=2134)中,90天前无复发有效率为88·6%(95%CI87·2-89·9),在使用7天伯氨喹治疗的患者(n=370)中,无复发有效率为83·5%(79·8-87·4);在校正混杂因素后,他非诺喹与7天伯氨喹后复发的HR为0·65（95％CI0·49-0·86；p=0·0031），在第180天，两种治疗之间的结果相似（log-rankp=0·82）。超过180天,在接受他非诺喹治疗的患者中,G6PD正常的年龄≥16岁患者的中位复发时间为92天(IQR76~120),在接受7天伯氨喹治疗的患者中为68天(52~94).
结论：在现实世界中，对于年龄在16岁以上且G6PD正常的患者,单剂量他非诺喹在预防间日疟原虫复发方面更有效,而在180日时的总体疗效相似.结合G6PD定量测试和他非诺喹的间日疟原虫根治治疗算法的公共卫生益处支持其在巴西乃至整个南美的实施。
背景：巴西卫生部，市政和州卫生秘书处；Fiocruz；疟疾风险药物；比尔和梅林达·盖茨基金会；纽克雷斯特矿业；和英国政府。
■有关摘要的葡萄牙语翻译，请参见补充材料部分。
方法：在这项非干预性观察研究中，我们使用了来自马瑙斯和波尔图韦略的43个医疗机构实施间日疟原虫治疗算法的回顾性数据，巴西。治疗算法包括氯喹（25mg/kg，3天）和即时定量葡萄糖-6-磷酸脱氢酶（G6PD）测试，然后单剂量他非诺喹300mg（G6PD正常，年龄≥16岁，不怀孕也不母乳喂养)，7天伯氨喹每天0·5毫克/千克(G6PD中度或正常，年龄≥6个月，没有怀孕,而不是母乳喂养或母乳喂养>1个月)，或伯氨喹每周0·75毫克/千克，持续8周(G6PD缺乏，年龄≥6个月，没有怀孕,而不是母乳喂养或母乳喂养>1个月）。从巴西疟疾流行病学监测系统的常规患者记录的概率联系中确定了间日疟原虫的复发。使用Kaplan-Meier分析和通过多变量分析的风险比(HRs)估计第90天和第180天的无复发有效性。这项临床试验在ClinicalTrials.gov注册，NCT05096702，并完成。
结果：2021年9月9日至2022年8月31日的记录包括5554例间日疟疾患者。在所有接受治疗的患者中，任何年龄和任何G6PD状态，他非诺喹在第180天的无复发有效率为75·8%（95%CI74·0-77·6），73·4%(71·9-75·0)服用7天伯氨喹，每周服用伯氨喹的比例为82·1%（77·7-86·8）。在G6PD正常的年龄至少16岁的患者中，在使用他非诺喹治疗的患者(n=2134)中,90天前无复发有效率为88·6%(95%CI87·2-89·9),在使用7天伯氨喹治疗的患者(n=370)中,无复发有效率为83·5%(79·8-87·4);在校正混杂因素后,他非诺喹与7天伯氨喹后复发的HR为0·65（95％CI0·49-0·86；p=0·0031），在第180天，两种治疗之间的结果相似（log-rankp=0·82）。超过180天,在接受他非诺喹治疗的患者中,G6PD正常的年龄≥16岁患者的中位复发时间为92天(IQR76~120),在接受7天伯氨喹治疗的患者中为68天(52~94).
结论：在现实世界中，对于年龄在16岁以上且G6PD正常的患者,单剂量他非诺喹在预防间日疟原虫复发方面更有效,而在180日时的总体疗效相似.结合G6PD定量测试和他非诺喹的间日疟原虫根治治疗算法的公共卫生益处支持其在巴西乃至整个南美的实施。
背景：巴西卫生部，市政和州卫生秘书处；Fiocruz；疟疾风险药物；比尔和梅林达·盖茨基金会；纽克雷斯特矿业；和英国政府。
■有关摘要的葡萄牙语翻译，请参见补充材料部分。
