Characteristics of the study sample.

Background/Introduction Leprosy control remains a challenge in Nepal. Single-dose rifampicin post-exposure prophylaxis (SDR-PEP) shows promise in reducing leprosy incidence among contacts of index cases, contributing to reducing the transmission of Mycobacterium (M.) leprae. This study evaluates the effectiveness of routine SDR-PEP implementation in Nepal in addition to contact screening, focusing on its impact on reducing leprosy risk among contacts and potential population-level effects. Methodology We conducted a retrospective cohort study to compare leprosy case notification rates and leprosy risk among close contacts. We compared two districts implementing SDR-PEP (the intervention group) and two without (the comparator group). Data from 2015 onwards included demographics, index case types, and contact relationships. Statistical analyses, including Cox regression and Kaplan-Meier survival curves, assessed the impact of SDR-PEP implementation. Findings All four districts showed a decrease in case notification rates since 2015, with the steepest decline in the intervention districts. The risk of developing leprosy among contacts was significantly lower in the intervention districts (HR 0.28, 95% CI 0.18–0.44). SDR-PEP offered 72% protection, consistent over time, as shown in Kaplan-Meier plots. The protective effect was equally strong in blood-related contacts (HR 0.29 versus 0.27 in others, p = 0.32), and the proportion of MB cases among incident cases was not significantly different post-PEP (51.4% vs. 53.6%, p = 0.82). Conclusions This study demonstrates the substantial protective effect of integrating SDR-PEP in routine leprosy control programs with contact screening, significantly lowering leprosy risk among contacts. SDR-PEP is equally effective for blood-related contacts and does not preferentially prevent PB cases. While suggesting potential population-level impact, the study design does not allow for firm conclusions at this level. Further research is needed to fully assess SDR-PEP’s effectiveness in diverse contexts and optimize its implementation. Integrating SDR-PEP within well-organized contact screening programs is effective and is expected to reduce leprosy transmission when applied as a rolling intervention.背景/引言 麻风病防控在尼泊尔仍是一项艰巨挑战。单剂量利福平暴露后预防（single-dose rifampicin post-exposure prophylaxis, SDR-PEP）在降低麻风病指示病例（index case）密切接触者的麻风发病风险方面展现出应用前景，有助于减少麻风分枝杆菌（Mycobacterium leprae，简称M. leprae）的传播。本研究旨在评估尼泊尔在开展接触者筛查的基础上，常规实施SDR-PEP的防控效果，重点关注其对密切接触者麻风发病风险的降低作用，以及潜在的人群层面效应。 研究方法 本研究采用回顾性队列研究（retrospective cohort study）设计，对比分析密切接触者的麻风病例报告率与麻风发病风险。研究纳入两个实施SDR-PEP的县区作为干预组，以及两个未实施该措施的县区作为对照组。2015年及之后收集的数据包括人口统计学特征、指示病例类型以及接触关系等信息。采用Cox回归（Cox regression）、Kaplan-Meier生存曲线（Kaplan-Meier survival curves）等统计分析方法，评估SDR-PEP实施的防控效果。 研究结果 2015年以来，四个研究县区的麻风病例报告率均呈下降趋势，其中干预组县区的降幅最为显著。干预组县区中，密切接触者的麻风发病风险显著低于对照组（风险比HR=0.28，95%置信区间CI：0.18~0.44）。Kaplan-Meier曲线显示，SDR-PEP的保护效力达72%，且该保护作用随时间保持稳定。血缘接触者与非血缘接触者的保护效果相当（HR分别为0.29与0.27，P=0.32）；PEP实施后，新发多菌型（Multibacillary, MB）麻风病例占比与实施前无显著差异（51.4% vs 53.6%，P=0.82）。 结论 本研究证实，在常规麻风病防控方案中结合接触者筛查并整合SDR-PEP措施，可显著降低密切接触者的麻风发病风险，具有显著的保护效应。SDR-PEP对血缘接触者同样有效，且不会优先阻断少菌型（Paucibacillary, PB）麻风病例的发生。本研究结果提示SDR-PEP可能存在人群层面的防控效应，但受研究设计限制，目前尚无法在人群层面得出确定性结论。未来仍需开展进一步研究，以全面评估SDR-PEP在多样化场景中的防控效果，并优化其实施策略。将SDR-PEP整合入规范有序的接触者筛查项目中具有良好的防控效果，作为滚动式干预措施应用时，有望降低麻风病的传播水平。