Smith W Cairns S, Aerts Ann
Lepr Rev. 2014 Mar;85(1):2-17.
The global prevalence of leprosy has declined from 5.2 million in the 1980 s to 200,000 today. However, the new case detection rate remains high: over the last 8 years, around 220,000-250,000 people have been diagnosed with leprosy each year. In June 2013, an international meeting was organised by the Novartis Foundation for Sustainable Development in Geneva, Switzerland,2 with the objective of discussing the feasibility of interrupting the transmission of leprosy. The group of physicians, epidemiologists and public health professionals concluded that a successful programme would require early diagnosis and prompt multidrug therapy (MDT) for all patients, tracing and post-exposure prophylaxis (PEP) for contacts of patients newly diagnosed with leprosy, improvements in diagnostic tools, as well as strict epidemiological surveillance and response systems to monitor progress. As a follow-up, a second expert group meeting was convened by the Novartis Foundation in January 2014 in Zurich, Switzerland, with the objective of reviewing the evidence for chemoprophylaxis in contacts and high-risk communities. The meeting also considered the definitions of 'contacts' and 'contact tracing', discussed alternative prophylaxis regimens, preliminary findings of operational pilot projects on PEP in Indonesia, as well as the development of diagnostic tools, and identified the priority questions for operational research in leprosy transmission. The meeting outlined how contact tracing and chemoprophylaxis programmes can be implemented to interrupt leprosy transmission. The expert panel reached the following conclusions: Chemoprophylaxis with single-dose rifampicin (SDR) is efficacious in reducing the risk of developing leprosy, although the protective effect appears to be smaller in contacts closer to the index patient than in more distant contacts.3 SDR can be targeted to contacts or implemented as community mass prophylaxis in certain circumstances; the preferred approach depends on local factors, such as the case detection rate, the level of community stigma against leprosy, and the degree of access to healthcare for patients and contacts. Alternative prophylaxis regimens and the role of post-exposure immunoprophylaxis need to be further investigated. Contact tracing combined with PEP across very diverse settings offers protection rates similar to those reported in controlled trials. For high-incidence pockets ('hotspots') or remote or confined high-incidence populations ('hotpops'), blanket administration of PEP may be a better option. Implementation of contact-tracing programmes is feasible and cost-effective, particularly in high-risk groups, but it should be integrated into local healthcare services to ensure their long-term sustainability. Funding and support must be maintained after an initial pilot has finished. New programmes for contact tracing need effective surveillance systems to enable appropriate follow-up and outcome evaluation. The Novartis Foundation and Netherlands Leprosy Relief (NLR) are currently developing and implementing a large international programme to demonstrate the feasibility, acceptability, cost-effectiveness and real-world efficacy of PEP as a strategy to interrupt leprosy transmission, in six pilot projects in Asia, Africa and South America. These new pilot projects will be developed together with the local health authorities, healthcare workers, communities and patients, in order to create local ownership from the outset. The pilots should aim to be scalable and sustainable, and should therefore include an objective outcome assessment. Local ownership ensures that locally appropriate language and definitions of contacts are used in each of the pilots. A test to identify subclinical disease and distinguish M. leprae exposure from infection would facilitate early and appropriate therapy (with PEP or MDT). The identification and validation of new, sensitive biomarkers for M. leprae infection and exposure may allow better targeting of PEP to those contacts at highest risk of developing leprosy.
全球麻风病患病率已从20世纪80年代的520万下降至如今的20万。然而,新病例发现率仍然很高:在过去8年中,每年约有22万至25万人被诊断为麻风病。2013年6月,诺华可持续发展基金会在瑞士日内瓦组织了一次国际会议,目的是讨论阻断麻风病传播的可行性。医生、流行病学家和公共卫生专业人员小组得出结论,一个成功的项目需要对所有患者进行早期诊断和及时的多药联合治疗(MDT),对新诊断麻风病患者的接触者进行追踪和暴露后预防(PEP),改进诊断工具,以及建立严格的流行病学监测和应对系统以监测进展情况。作为后续行动,诺华基金会于2014年1月在瑞士苏黎世召开了第二次专家组会议,目的是审查接触者和高危社区化学预防的证据。会议还审议了“接触者”和“接触者追踪”的定义,讨论了替代预防方案、印度尼西亚PEP操作试点项目的初步结果,以及诊断工具的开发,并确定了麻风病传播操作研究的优先问题。会议概述了如何实施接触者追踪和化学预防项目以阻断麻风病传播。专家小组得出以下结论:单剂量利福平(SDR)化学预防在降低患麻风病风险方面是有效的,尽管在与索引患者关系较近的接触者中,其保护作用似乎比关系较远的接触者要小。SDR可针对接触者,或在某些情况下作为社区大规模预防措施实施;首选方法取决于当地因素,如病例发现率、社区对麻风病的污名化程度,以及患者和接触者获得医疗服务的程度。替代预防方案和暴露后免疫预防的作用需要进一步研究。在非常不同的环境中,接触者追踪与PEP相结合可提供与对照试验报告相似的保护率。对于高发病地区(“热点地区”)或偏远或封闭的高发病人群(“热点人群”),全面实施PEP可能是更好的选择。实施接触者追踪项目是可行且具有成本效益的,特别是在高危人群中,但应将其纳入当地医疗服务以确保其长期可持续性。在最初的试点完成后,必须维持资金和支持。新的接触者追踪项目需要有效的监测系统,以便进行适当的随访和结果评估。诺华基金会和荷兰麻风病救济组织(NLR)目前正在制定和实施一个大型国际项目,以在亚洲、非洲和南美洲的六个试点项目中展示PEP作为一种阻断麻风病传播策略的可行性、可接受性、成本效益和实际效果。这些新的试点项目将与当地卫生当局、医护人员、社区和患者共同开展,以便从一开始就形成当地的自主所有权。试点项目应旨在具有可扩展性和可持续性,因此应包括客观的结果评估。当地的自主所有权确保在每个试点项目中使用适合当地的接触者语言和定义。一种识别亚临床疾病并区分麻风分枝杆菌暴露与感染的检测方法将有助于早期和适当的治疗(采用PEP或MDT)。识别和验证新的、敏感的麻风分枝杆菌感染和暴露生物标志物,可能使PEP能更好地针对那些患麻风病风险最高的接触者。