: 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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AR053234-01
Application #
6955511
Study Section
Pathogenic Eukaryotes Study Section (PTHE)
Program Officer
Baker, Carl
Project Start
2005-09-20
Project End
2007-08-31
Budget Start
2005-09-20
Budget End
2006-08-31
Support Year
1
Fiscal Year
2005
Total Cost
$157,300
Indirect Cost
Name
Children's Mercy Hosp (Kansas City, MO)
Department
Type
DUNS #
073067480
City
Kansas City
State
MO
Country
United States
Zip Code
64108
Abdel-Rahman, Susan M; Preuett, Barry L (2012) Genetic predictors of susceptibility to cutaneous fungal infections: a pilot genome wide association study to refine a candidate gene search. J Dermatol Sci 67:147-52
Abdel-Rahman, Susan M; Sugita, Takashi; González, Gloria M et al. (2010) Divergence among an international population of Trichophyton tonsurans isolates. Mycopathologia 169:1-13
Shroba, Jodi; Olson-Burgess, Cindy; Preuett, Barry et al. (2009) A large outbreak of Trichophyton tonsurans among health care workers in a pediatric hospital. Am J Infect Control 37:43-8
Abdel-Rahman, Susan M; Talib, Nasreen; Solidar, Ada et al. (2008) Examining Trichophyton tonsurans genotype and biochemical phenotype as determinants of disease severity in tinea capitis. Med Mycol 46:217-23
Abdel-Rahman, Susan M; Preuett, Barry; Gaedigk, Andrea (2007) Multilocus genotyping identifies infections by multiple strains of Trichophyton tonsurans. J Clin Microbiol 45:1949-53
Abdel-Rahman, Susan M; Simon, Steve; Wright, Krista J et al. (2006) Tracking Trichophyton tonsurans through a large urban child care center: defining infection prevalence and transmission patterns by molecular strain typing. Pediatrics 118:2365-73