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.

R21AR053234

2005-09-20

2007-08-31