Institute of Tropical Medicine, Antwerp, Belgium.
National Tuberculosis and Leprosy Control Program, Moroni, Comoros.
Lancet Glob Health. 2024 Jun;12(6):e1017-e1026. doi: 10.1016/S2214-109X(24)00062-7.
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.
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.
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.
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.
European and Developing Countries Clinical Trials Partnership.
For the French translation of the abstract see Supplementary Materials section.
使用单剂量利福平的暴露后预防（PEP）可降低从感染麻风分枝杆菌到麻风病的进展。我们比较了使用较高（20mg/kg）剂量利福平的单双倍剂量利福平（SDDR）-PEP 的不同给药方式的效果。
我们在马达加斯加的 16 个村庄和科摩罗的 48 个村庄进行了一项群组随机研究。村庄被随机分配到四个研究臂，居民每年筛查一次麻风病，连续 4 年。所有常住居民（无年龄限制）都有资格参加，所有确诊的麻风病患者均接受多药治疗（无症状接触者≥2 岁者提供 SDDR-PEP）。第 1 臂为对照组，未提供 PEP。第 2 臂中，SDDR-PEP 提供给麻风病患者的家庭接触者，第 3 臂将 SDDR-PEP 扩大到居住在 100 米以内的任何人。第 4 臂将 SDDR-PEP 提供给家庭接触者和居住在 100 米以内且对苯丙氨酸糖脂 I 呈阳性的任何人。主要结局是与对照组相比，每个干预组的麻风病发病率比值比（IRR）。我们还评估了 SDDR-PEP 的个体保护作用，并探讨了空间关联。该试验在 ClinicalTrials.gov 注册，NCT03662022，现已完成。
2019 年 1 月 11 日至 2023 年 1 月 16 日期间，我们共招募了 109436 人，其中 95762 人有可评估的随访数据。我们的主要分析显示，第 2 臂（IRR0.95）、第 3 臂（IRR0.80）和第 4 臂（IRR0.58）的麻风病发病率无显著降低。在控制基线患病率后，第 3 臂的降幅更强且具有统计学意义（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）。基线时距索引患者 75 米以内的人，麻风病的风险是两倍到四倍。
SDDR-PEP 似乎可以预防麻风病，但效果低于预期。在距索引患者 75 米以内观察到强烈的空间关联。在索引患者周围进行有针对性的逐户筛查，并辅以全面的 SDDR-PEP 方法，可能会对传播产生重大影响。
欧洲和发展中国家临床试验伙伴关系。
