Lateral flow immunoassay for rapid diagnosis of tinea capitis and onychomycosis

Tinea capitis (ringworm of the scalp) and onychomycosis (fungal nail infection) are infections that are most often caused by dermatophytes of the fungal genera Trichophyton and Microsporum. These two infections affect approximately 14 million people in the U.S. each year. Dermatophyte infections of the hair and nails are treated with oral antifungals for up to 12 weeks. Due to potential adverse effects, both the American Academy for Dermatology and the FDA recommend that treatment be based on laboratory confirmation. Laboratory diagnosis requires microscopy and culture which are expensive, may take days to weeks to a result, and require a high level of skill. As a consequence, oral antifungals are increasingly used without laboratory confirmation. Indeed, the majority of primary care physicians make a diagnosis on the basis of clinical signs alone, which is often incorrect. There is a need for a rapid, inexpensive diagnostic that can be used at the point-of-care (POC) within the time frame of a typical office visit and without the need for expensive instrumentation. The goal of this Phase II project is a rapid test that will use hair and nail specimens to diagnose dermatophyte infection. The target population will be individuals who seek care at the offices of dermatologists, podiatrists or primary care physicians for tinea capitis or onychomycosis. The approach will be an immunoassay for the presence of dermatophyte mannan, a cell wall carbohydrate produced by all dermatophyte fungi. The product will be a test in the lateral flow immunoassay (LFIA) format that is rapid, inexpensive, and easy to use. The project is supported by an extensive set of results produced during and prior to Phase I. First, a monoclonal antibody was produced that is highly reactive with cell wall mannans from all genera of the dermatophytes. Second, a method was developed for extraction of dermatophyte mannan from mycelia and infected tissue that is simple, rapid and usable at the POC. Third, a sensitive 2nd generation prototype LFIA was developed that readily detects extracted mannan. Finally, preliminary studies demonstrated that combined use of the specimen extraction procedure and the LFIA can identify dermatophyte infection in skin/hair and nails. The project will advance the dermatophyte LFIA to the point of clinical evaluation needed for regulatory approval and commercialization. Specific Aims are to 1) lay the foundation for regulatory approval by the FDA via a Presubmission, 2) develop an advanced LFIA prototype, 3) assess analytical performance, and 4) assess test performance in laboratory and clinical settings. If successful, the dermatophyte LFIA is a potential game changer that would end the debate over the cost effectiveness for confirmation of fungal infection prior to therapy. The results will be better patient care, improved antibiotic stewardship, and reduced cost to the health care system.Tinea capitis (ringworm of the scalp) and onychomycosis (fungal nail infection) are common fungal infections that affect approximately 14 million people in the U.S. each year. Laboratory confirmation of infection is not ordered by many health care providers because current methods are expensive, may take days to weeks to a result, and require a high level of skill. The project goal is a test, similar to the home pregnancy test, which is rapid, inexpensive and usable at the point of patient care.