目标:每年,超过20万人被诊断为麻风病,也被称为汉森病。在过去几年中,这一数字相对稳定。在预防麻风病的化学预防和免疫预防领域取得了进展,主要关注患者的密切接触者。在这个描述性荟萃分析中,我们总结了证据并确定了有关麻风病暴露后预防的知识差距.
方法:通过搜索医学科学数据库Cochrane,Embase,Pubmed/MEDLINE,研究门,1月的Scopus和WebofScience22,2020,使用四种语言的索引术语的同义词组合:“麻风病”和“人口”或“接触”和“预防”或“预防”。“随后,搜索了Infolep.org和GoogleScholar,并使用“雪球方法”检索了其他可能相关的文献。使用预定的纳入和排除标准对发现的文章进行资格筛选。
结果:重复数据删除后,筛选了1515篇文章,本描述性荟萃分析包括125篇文章。已知通过卡介苗(BCG)疫苗接种的免疫预防提供针对麻风病的保护。与普通人群相比,它在麻风病人的家庭接触中提供的保护更高,并且随着时间的推移会下降。接触随访筛查在卡介苗给药后的第一阶段是重要的,因为大量新的麻风病人在接种疫苗后三个月出现。重新接种疫苗的好处的证据是相互矛盾的。世界卫生组织(WHO)将BCG纳入其诊断指南,麻风病的治疗和预防,指出出生时的卡介苗应至少在所有麻风病高负担地区保持。文献表明,与BCG相比,使用其他免疫预防剂的几种疫苗接种干预措施在降低麻风病风险方面表现出相似或稍低的功效。然而,这些研究中的大多数并不完全集中于暴露后预防.两种疫苗被认为是预防麻风病的未来候选者:印度分枝杆菌(MiP)和LepVax。对于化学预防,试验用氨苯砜/阿司他酮进行,利福平,和ROM,利福平的组合,氧氟沙星,还有米诺环素.单剂量利福平作为暴露后预防是有利的,缩写为SDR-PEP。在对麻风患者的接触者给药后的头两年中,它表现出57%的保护作用。它很便宜,和不良事件是罕见的。SDR-PEP诱导利福平耐药的风险被认为可以忽略不计,但是应鼓励按照世卫组织政策进行持续监测。发现将接触筛查和SDR-PEP施用整合到不同的麻风病控制计划中是可行的并且被广泛接受。自2018年以来,SDR-PEP被纳入世卫组织诊断指南,麻风病的治疗和预防。
结论:在预防接触患者的麻风病的化学预防和免疫预防方面取得了进展。投资疫苗研究,比如LepVax和MiP,结核病(TB)和麻风病研究小组之间的协调非常重要。SDR-PEP有望作为化学预防剂,并应进一步促进实施。需要更多的化学预防研究:加强药物治疗方案;不同(流行病学)环境中的干预措施,包括局部药物管理(fMDA);每种接触类型的具体方法;结合筛选变化和现场友好的快速测试,如果将来可用;社区和卫生人员教育;持续的抗生素耐药性监测;并在BCG给药前使用SDR-PEP进行化学预防。此外,在全国范围内注册麻风病预防药物和在全球范围内以低成本或免费提供预防药物对于实施和进一步扩大麻风病预防措施很重要,如SDR-PEP和新疫苗。
OBJECTIVE: Annually, over 200,000 people are diagnosed with leprosy, also called Hansen\'s disease. This number has been relatively stable over the past years. Progress has been made in the fields of chemoprophylaxis and immunoprophylaxis to prevent leprosy, with a primary focus on close contacts of patients. In this descriptive meta-analysis, we summarize the evidence and identify knowledge gaps regarding post-exposure prophylaxis against leprosy.
METHODS: A systematic literature search according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology was conducted by searching the medical scientific databases Cochrane, Embase, Pubmed/MEDLINE, Research Gate, Scopus and Web of Science on Jan. 22, 2020, using a combination of synonyms for index terms in four languages: \"leprosy\" and \"population\" or \"contacts\" and \"prevention\" or \"prophylaxis.\" Subsequently, Infolep.org and Google Scholar were searched and the \"snowball method\" was used to retrieve other potentially relevant literature. The found articles were screened for eligibility using predetermined inclusion and exclusion criteria.
RESULTS: After deduplication, 1,515 articles were screened, and 125 articles were included in this descriptive meta-analysis. Immunoprophylaxis by bacillus Calmette-Guérin (BCG) vaccination is known to provide protection against leprosy. The protection it offers is higher in household contacts of leprosy patients compared with the general population and is seen to decline over time. Contact follow-up screening is important in the first period after BCG administration, as a substantial number of new leprosy patients presents three months post-vaccination. Evidence for the benefit of re-vaccination is conflicting. The World Health Organization (WHO) included BCG in its Guidelines for the Diagnosis, Treatment and Prevention of Leprosy by stating that BCG at birth should be maintained in at least all leprosy high-burden regions. Literature shows that several vaccination interventions with other immunoprophylactic agents demonstrate similar or slightly less efficacy in leprosy risk reduction compared with BCG. However, most of these studies do not exclusively focus on post-exposure prophylaxis. Two vaccines are considered future candidates for leprosy prophylaxis: Mycobacterium indicus pranii (MiP) and LepVax. For chemoprophylaxis, trials were performed with dapsone/acedapsone, rifampicin, and ROM, a combination of rifampicin, ofloxacin, and minocycline. Single-dose rifampicin is favored as post-exposure prophylaxis, abbreviated as SDR-PEP. It demonstrated a protective effect of 57% in the first two years after administration to contacts of leprosy patients. It is inexpensive, and adverse events are rare. The risk of SDR-PEP inducing rifampicin resistance is considered negligible, but continuous monitoring in accordance with WHO policies should be encouraged. The integration of contact screening and SDR-PEP administration into different leprosy control programs was found to be feasible and well accepted. Since 2018, SDR-PEP is included in the WHO Guidelines for the Diagnosis, Treatment and Prevention of Leprosy.
CONCLUSIONS: Progress has been made in the areas of chemoprophylaxis and immunoprophylaxis to prevent leprosy in contacts of patients. Investing in vaccine studies, like LepVax and MiP, and increasing harmonization between tuberculosis (TB) and leprosy research groups is important. SDR-PEP is promising as a chemoprophylactic agent, and further implementation should be promoted. More chemoprophylaxis research is needed on: enhanced medication regimens; interventions in varying (epidemiological) settings, including focal mass drug administration (fMDA); specific approaches per contact type; combinations with screening variations and field-friendly rapid tests, if available in the future; community and health staff education; ongoing antibiotic resistance surveillance; and administering chemoprophylaxis with SDR-PEP prior to BCG administration. Additionally, both leprosy prophylactic drug registration nationally and prophylactic drug availability globally at low or no cost are important for the implementation and further upscaling of preventive measures against leprosy, such as SDR-PEP and new vaccines.