FUNGAL PROTEIN/GLYCOPROTEIN EXPRESSION IN TINEA CAPITIS
Principal Investigator: Susan M Abdel-Rahman
Abstract: Worldwide, tinea capitis remains a persistent and highly infection in children with as many as 1 in 10 children at any ne time demonstrating active infection or serving as carriers of the fungus. At the applicant institution we treated 4.5 children per day in 1999. Although tinea capitis is not life threatening, it is a major pediatric health concern for a number of reasons: 1) the causative organisms are communicable and non- opportunistic, 2) the infection does not adequately respond to topical therapy requiring systemic antifungal treatment for months to years, 3) concerns regarding appearance and spread of infection lead to the exclusion of children from participation in academic and social activities and 4) psychological concerns surround those children who develop permanent alopecia as a result of infection. Moreover, the cost of health care systems from clinic visits, drug failure, adverse events, drug interactions, non-compliance, drug acquisition and monitoring costs and associated morbidity present an overwhelming problem in pediatric medicine. Despite the fact that tinea capitis was described over a century ago, the rate of infection continues to grow and little remains known regarding the factors involved in the pathogenesis of this disease. For example, it is unclear why a single species of fungus is capable of resulting in vastly divergent clinical presentations including an asymptomatic carrier state, a chronic non-inflammatory disease state and an acute severely-inflammatory disease state. It is likely that both host and fungal factors are involved in a complex interaction that defines disease progression in the human host. We hypothesize that strain- specific variability in the balance between antigenic protease expression and immunoinhibitory glycoprotein production dictates the variability in the response seen between different children with tinea capitis. This study is designed to determine whether strain specific differences exist in (1) the type of fungal proteases liberated, (2) the extent of fungal proteases activity and (3) the type of fungal glycoproteins produced for fungal isolates collected from children with inflammatory and non-inflammatory disease. Identification of a correlation between fungal protein/glycoprotein expression and the severity of clinical disease will more clearly define the role of these factors in disease pathogenesis. Successful characterization of these fungal elements is the first step toward developing potential treatment that targets critical steps in fungal intermediary metabolism and is critical for the isolation of fungal epitopes sufficient to evoke an immune response that can subsequently serve as the basis for the development of a vaccine sufficient to prevent infection.
Funding Period: 2001-03-01 - 2005-02-28
more information: NIH RePORT
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Division of Pediatric Clinical Pharmacology and Medical Toxicology, The Children s Mercy Hospital and Clinics, Kansas City, MO, USA
Mycopathologia 160:265-72. 2005..tonsurans strains, but they also reveal the presence of a genetic variation with functional consequences at the transcript level that may play a role in regulating disease severity...
- Examining Trichophyton tonsurans genotype and biochemical phenotype as determinants of disease severity in tinea capitisSusan M Abdel-Rahman
Division of Pediatric Clinical Pharmacology, The Children s Mercy Hospitals and Clinics, and Department of Pediatrics, University of Missouri Kansas City, School of Medicine, Kansas City, MO 64108, USA
Med Mycol 46:217-23. 2008..tonsurans cause more severe disease. These observations are consistent with reports that recently diverge anthropophilies are associated with diminished inflammatory involvement...