Evaluating Trichophyton tonsurans Carriage and Infection

描述（由申请方提供）：头癣是儿科人群中的一种非常普遍的疾病，估计约1/20的儿童发生。此外，同样数量的、往往更多数量的儿童是无症状的病原体携带者。特别令人感兴趣的是，一种真菌，即断毛癣菌，是负责这两种临床表现。对于其他感染因子，独特的血清型已明确与致病性和毒力相关（例如，E.杆菌M. meningitides、H.流感）;然而，还没有尝试鉴定和链接T.有临床疾病状态的扁桃体炎患者。认识到变异的存在并将特定亚型与疾病表现联系起来是确定不同分子靶点的第一步，这些靶点可能会指导旨在减缓或阻止疾病传播和进展的治疗干预措施的开发。本研究将采用有针对性的分子分析，结合横断面抽样和纵向监测，在健康儿童人群中探索T. Tonsurans。调查将由一般假设驱动：儿童暴露的基因型变异类型解释了断尾毛癣菌感染中观察到的表现状态。该假设将通过一系列旨在解决以下具体目标的研究来检验：（1）确定T的基因型分布。从“高危”儿童的固定人群中获得的tonsurans分离物，并评估基因型的变化是否是疾病表现差异的原因，特别是感染与携带，人与人之间（2）表征个体内连续分离株的相关性程度，并确定疾病表现之间的转化是否发生在相同的遗传变异中，或者是由于获得了遗传上不同的真菌变种

DESCRIPTION (provided by the applicant): Tinea capitis is an overwhelmingly prevalent disease in the pediatric population being estimated to occur in approximately 1 in 20 children. Moreover, an equal and often larger number of children serve as asymptomatic carriers of the pathogen. Of particular interest is that a single species of fungus, namely Trichophyton tonsurans, is responsible for both clinical presentations. With other infectious agents, unique serotypes have been clearly associated with pathogenicity and virulence (e.g., E. coli. M. meningitides, H. influenzae); however, there has been no attempt to identify and link genotypic variants of T. tonsurans with clinical disease status. Recognizing that variants exist and linking specific subtypes to disease presentation is the first step toward identifying distinct molecular targets that may guide the development of therapeutic interventions designed to slow or halt disease transmission and progression. The proposed investigation will employ a targeted molecular analysis in tandem with cross sectional sampling and longitudinal surveillance in a population of normal healthy children to explore the carrier and infection states of T. tonsurans. The investigation will be driven by the general hypotheses: the type of genotypic variant to which a child is exposed accounts for the presentation status observed in Trichophyton tonsurans infection. The hypothesis will be tested by a series of studies designed to address the following specific aims: (1) determine the genotype distribution of T. tonsurans isolates acquired from a fixed population of "high-risk" children and evaluate whether variations in genotype are responsible for differences in disease presentation, specifically infection vs. carriage, between individuals and (2) characterize the degree of relatedness for sequential isolates within an individual and identify whether transformation between disease presentations occurs with the same genetic variant or as a result of acquiring a genetically distinct fungal variant.