Abstract：
BACKGROUND: Post-exposure prophylaxis (PEP) using single-dose rifampicin reduces progression from infection with Mycobacterium leprae to leprosy disease. We compared effectiveness of different administration modalities, using a higher (20 mg/kg) dose of rifampicin-single double-dose rifampicin (SDDR)-PEP.
METHODS: We did a cluster randomised study in 16 villages in Madagascar and 48 villages in Comoros. Villages were randomly assigned to four study arms and inhabitants were screened once a year for leprosy, for 4 consecutive years. All permanent residents (no age restriction) were eligible to participate and all identified patients with leprosy were treated with multidrug therapy (SDDR-PEP was provided to asymptomatic contacts aged ≥2 years). Arm 1 was the comparator arm, in which no PEP was provided. In arm 2, SDDR-PEP was provided to household contacts of patients with leprosy, whereas arm 3 extended SDDR-PEP to anyone living within 100 m. In arm 4, SDDR-PEP was offered to household contacts and to anyone living within 100 m and testing positive to anti-phenolic glycolipid-I. The main outcome was the incidence rate ratio (IRR) of leprosy between the comparator arm and each of the intervention arms. We also assessed the individual protective effect of SDDR-PEP and explored spatial associations. This trial is registered with ClinicalTrials.gov, NCT03662022, and is completed.
RESULTS: Between Jan 11, 2019, and Jan 16, 2023, we enrolled 109 436 individuals, of whom 95 762 had evaluable follow-up data. Our primary analysis showed a non-significant reduction in leprosy incidence in arm 2 (IRR 0·95), arm 3 (IRR 0·80), and arm 4 (IRR 0·58). After controlling for baseline prevalence, the reduction in arm 3 became stronger and significant (IRR 0·56, p=0·0030). At an individual level SDDR-PEP was also protective with an IRR of 0·55 (p=0·0050). Risk of leprosy was two to four times higher for those living within 75 m of an index patient at baseline.
CONCLUSIONS: SDDR-PEP appears to protect against leprosy but less than anticipated. Strong spatial associations were observed within 75 m of index patients. Targeted door-to-door screening around index patients complemented by a blanket SDDR-PEP approach will probably have a substantial effect on transmission.
BACKGROUND: European and Developing Countries Clinical Trials Partnership.
UNASSIGNED: For the French translation of the abstract see Supplementary Materials section.
METHODS: We did a cluster randomised study in 16 villages in Madagascar and 48 villages in Comoros. Villages were randomly assigned to four study arms and inhabitants were screened once a year for leprosy, for 4 consecutive years. All permanent residents (no age restriction) were eligible to participate and all identified patients with leprosy were treated with multidrug therapy (SDDR-PEP was provided to asymptomatic contacts aged ≥2 years). Arm 1 was the comparator arm, in which no PEP was provided. In arm 2, SDDR-PEP was provided to household contacts of patients with leprosy, whereas arm 3 extended SDDR-PEP to anyone living within 100 m. In arm 4, SDDR-PEP was offered to household contacts and to anyone living within 100 m and testing positive to anti-phenolic glycolipid-I. The main outcome was the incidence rate ratio (IRR) of leprosy between the comparator arm and each of the intervention arms. We also assessed the individual protective effect of SDDR-PEP and explored spatial associations. This trial is registered with ClinicalTrials.gov, NCT03662022, and is completed.
RESULTS: Between Jan 11, 2019, and Jan 16, 2023, we enrolled 109 436 individuals, of whom 95 762 had evaluable follow-up data. Our primary analysis showed a non-significant reduction in leprosy incidence in arm 2 (IRR 0·95), arm 3 (IRR 0·80), and arm 4 (IRR 0·58). After controlling for baseline prevalence, the reduction in arm 3 became stronger and significant (IRR 0·56, p=0·0030). At an individual level SDDR-PEP was also protective with an IRR of 0·55 (p=0·0050). Risk of leprosy was two to four times higher for those living within 75 m of an index patient at baseline.
CONCLUSIONS: SDDR-PEP appears to protect against leprosy but less than anticipated. Strong spatial associations were observed within 75 m of index patients. Targeted door-to-door screening around index patients complemented by a blanket SDDR-PEP approach will probably have a substantial effect on transmission.
BACKGROUND: European and Developing Countries Clinical Trials Partnership.
UNASSIGNED: For the French translation of the abstract see Supplementary Materials section.
摘要：
背景：使用单剂量利福平的暴露后预防（PEP）减少了从麻风分枝杆菌感染到麻风病的进展。我们比较了不同给药方式的有效性，使用较高（20mg/kg）剂量的利福平-单双剂量利福平（SDDR）-PEP。
方法：我们在马达加斯加的16个村庄和科摩罗的48个村庄进行了一项集群随机研究。村庄被随机分配到四个研究小组，居民每年接受一次麻风病筛查，连续4年。所有永久居民（无年龄限制）均有资格参加，所有已确定的麻风病患者均接受多药治疗（SDDR-PEP提供给年龄≥2岁的无症状接触者）。1臂是比较臂，其中没有提供PEP。在第2组中，向麻风病人的家庭接触者提供了SDDR-PEP，而第3臂将SDDR-PEP扩展到居住在100米以内的任何人。在第4臂中，SDDR-PEP被提供给家庭联系人和居住在100米以内的任何人，并且对抗酚糖脂-I测试呈阳性。主要结果是比较组和每个干预组之间麻风病的发生率比（IRR）。我们还评估了SDDR-PEP的个体保护作用并探索了空间关联。该试验已在ClinicalTrials.gov注册，NCT03662022，并已完成。
结果：在2019年1月11日至2023年1月16日之间，我们招募了109436名个人，其中95762人具有可评估的随访数据.我们的主要分析显示，第2臂的麻风病发病率没有显着降低（IRR0·95），臂3（IRR0·80），和第4臂(IRR0·58)。在控制基线患病率后，第3组的减少变得更强和显著(IRR0·56，p=0·0030)。在个体水平上，SDDR-PEP也具有保护作用，IRR为0·55（p=0·0050）。在基线时，生活在索引患者75m以内的人的麻风病风险高出2至4倍。
结论：SDDR-PEP似乎对麻风病有保护作用，但低于预期。在75m的索引患者中观察到了很强的空间关联。在索引患者周围进行有针对性的门到门筛查，辅以一揽子SDDR-PEP方法可能对传播产生重大影响。
背景：欧洲和发展中国家临床试验伙伴关系。
■有关摘要的法语翻译，请参见补充材料部分。
方法：我们在马达加斯加的16个村庄和科摩罗的48个村庄进行了一项集群随机研究。村庄被随机分配到四个研究小组，居民每年接受一次麻风病筛查，连续4年。所有永久居民（无年龄限制）均有资格参加，所有已确定的麻风病患者均接受多药治疗（SDDR-PEP提供给年龄≥2岁的无症状接触者）。1臂是比较臂，其中没有提供PEP。在第2组中，向麻风病人的家庭接触者提供了SDDR-PEP，而第3臂将SDDR-PEP扩展到居住在100米以内的任何人。在第4臂中，SDDR-PEP被提供给家庭联系人和居住在100米以内的任何人，并且对抗酚糖脂-I测试呈阳性。主要结果是比较组和每个干预组之间麻风病的发生率比（IRR）。我们还评估了SDDR-PEP的个体保护作用并探索了空间关联。该试验已在ClinicalTrials.gov注册，NCT03662022，并已完成。
结果：在2019年1月11日至2023年1月16日之间，我们招募了109436名个人，其中95762人具有可评估的随访数据.我们的主要分析显示，第2臂的麻风病发病率没有显着降低（IRR0·95），臂3（IRR0·80），和第4臂(IRR0·58)。在控制基线患病率后，第3组的减少变得更强和显著(IRR0·56，p=0·0030)。在个体水平上，SDDR-PEP也具有保护作用，IRR为0·55（p=0·0050）。在基线时，生活在索引患者75m以内的人的麻风病风险高出2至4倍。
结论：SDDR-PEP似乎对麻风病有保护作用，但低于预期。在75m的索引患者中观察到了很强的空间关联。在索引患者周围进行有针对性的门到门筛查，辅以一揽子SDDR-PEP方法可能对传播产生重大影响。
背景：欧洲和发展中国家临床试验伙伴关系。
■有关摘要的法语翻译，请参见补充材料部分。
