Molecular Epidemiology of Leprosy

麻风病的分子流行病学

• 批准号: 7172577
• 负责人: VARALAKSHMI D VISSA
• 金额: $ 35.2万
• 依托单位: COLORADO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-05-15 至 2010-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7172577
• 关键词: Animal Model; Area; Basic Science; Biological Assay; Clinical; Clinical Research; Communicable Diseases; Communities; Country; DNA; Dapsone; Data; Data Set; Databases; Detection; Development; Disease; Drug resistance; Early Diagnosis; Elements; Environment; Epidemiology; Evolution; Expert Opinion; Field Workers; Gene Targeting; Genes; Healthcare; Histology; Human; Immune response; Immunity; In Vitro; Incidence; Indium; Infection; Institution; Integration Host Factors; Investments; Knowledge; Laboratories; Lead; Leprosy; Light; Link; Medical Surveillance; Messenger RNA; Methods; Molecular; Molecular Epidemiology; Multi-Drug Resistance; Mutation; Mycobacterium leprae; Numbers; Onset of illness; Organism; Pathogenicity; Patients; Persons; Pharmaceutical Preparations; Pharmacotherapy; Physicians; Polymerase Chain Reaction; Population; Prevalence; RNA; Range; Rate; Research; Research Personnel; Resources; Rifampin; Scientist; Serologic tests; Soil; Solutions; Source; Structure; Study of serum; Techniques; Therapeutic; Training; Treatment Protocols; Virulence; Water; World Health Organization; base; cytokine; disorder control; genome sequencing; indexing; method development; programs; stem; success; transmission process

DESCRIPTION (provided by applicant): 670,000 new cases of leprosy were detected during the year 2002. What are the factors that contributed to this high incidence even though effective multidrug therapy implemented by the World Health Organization has been used to treat leprosy patients over the last 10-20 years? For leprosy, the underlying mechanisms of transmission of Mycobacterium leprae, the causative organism, are still unclear with respect to the source, reservoir, mode of transmission and interaction with the host. Multiple hypotheses exist, but answers remain speculative owing to the inability to cultivate M. leprae in vitro, the slow onset of disease, and the broad spectrum of clinical manifestations. The recent availability of the genome sequence of an isolate of M. leprae is a valuable new resource applicable to the epidemiology of leprosy. This proposal presents a unique approach aimed at a concerted effort to study multiple factors in order to obtain a more comprehensive understanding of the most plausible causes for continued incidence of leprosy. The objectives are to advance the research endeavors at several independent laboratories through development and application of sensitive, specific and simple molecular methods. The specific aims are: 1.To evaluate the contribution of the extra-human environment in leprosy transmission by: a) PCR amplification of M. leprae specific DNA and mRNA in soil and water; and b) strain typing for comparison with clinical strains found in the endemic region; 2. To evaluate sub-clinical infections in contacts of leprosy patients by: a) PCR amplification of M. leprae specific DNA and mRNA; b) strain typing for comparison with clinical strains found in index cases; and c) demonstration of mRNA of cytokines involved in infection and immunity; and 3. To evaluate the contribution of incident leprosy cases by: a) PCR amplification of M. leprae specific DNA and mRNA; b) strain typing for comparison with epidemiologically linked cases and; c) identification of primary and acquired drug resistance conferred by mutations in folP and rpoB genes, targets of dapsone and rifampicin respectively. It is important to prove identity of M. leprae within the chain of transmission by strain typing methods. The application of nine newly discovered polymorphic loci for strain typing is a key component of this proposal. It is envisioned that the practical solutions and the knowledge database that will emerge from this research investment will have a tangible impact on leprosy surveillance and control of transmission in the most endemic areas and to studies regarding virulence, evolution and pathogenicity of M. leprae.

描述（由申请人提供）： 2002 年期间，发现了 670,000 例新麻风病病例。尽管世界卫生组织在过去 10-20 年中已采用有效的多种药物疗法来治疗麻风病患者，但造成这种高发病率的因素是什么？对于麻风病，致病微生物麻风分枝杆菌的传播机制在来源、储存库、传播方式以及与宿主的相互作用方面仍不清楚。存在多种假设，但由于无法在体外培养麻风分枝杆菌、疾病起病缓慢以及临床表现广泛，答案仍然是推测性的。最近获得的麻风分枝杆菌分离株的基因组序列是适用于麻风病流行病学的宝贵新资源。该提案提出了一种独特的方法，旨在共同努力研究多种因素，以便更全面地了解麻风病持续发病的最可能原因。其目标是通过开发和应用敏感、特异和简单的分子方法来推进几个独立实验室的研究工作。具体目标是： 1. 通过以下方式评估人类外环境在麻风传播中的作用： a) 对土壤和水中的麻风分枝杆菌特异性 DNA 和 mRNA 进行 PCR 扩增； b) 菌株分型，以便与流行地区发现的临床菌株进行比较； 2. 通过以下方法评估麻风患者接触者的亚临床感染情况： a) 麻风分枝杆菌特异性 DNA 和 mRNA 的 PCR 扩增； b) 菌株分型，用于与指标病例中发现的临床菌株进行比较； c) 证明与感染和免疫相关的细胞因子的 mRNA； 3. 通过以下方式评估麻风病例的贡献： a) 麻风分枝杆菌特异性 DNA 和 mRNA 的 PCR 扩增； b) 菌株分型，用于与流行病学相关病例进行比较； c) 鉴定由foP和rpoB基因（分别是氨苯砜和利福平的靶点）突变所赋予的原发性和获得性耐药性。通过菌株分型方法证明麻风分枝杆菌在传播链中的身份非常重要。应用九个新发现的多态性位点进行菌株分型是该提案的关键组成部分。预计这项研究投资产生的实用解决方案和知识数据库将对麻风病流行地区的监测和传播控制以及麻风分枝杆菌的毒力、进化和致病性的研究产生切实的影响。