. Coccidioidomycosis is an endemic mycosis caused by the fungi Coccidioides immitis and Coccidioides posadasii and has been increasing over the last decade in the Southwestern United States. The most common clinical manifestation is primary pneumonia, which causes 15-30% of all community acquired pneumonias in endemic areas. The morbidity is substantial: median duration of illness 120 days, time to resumption of normal activity 47 days, and lost work 14 days. 41% of patients were hospitalized with a calculated inpatient cost of $30,000 per patient, and $86 million total cost. A California study reported annual costs of hospitalization was $186 million. Detection of anti-Coccidioides antibodies provides the laboratory basis for diagnosis in most cases. However, the antibody tests may be negative in one quarter to one third of immunosuppressed patients and half of patients with primary pulmonary coccidioidomycosis. A more sensitive enzyme immunoassay has been developed at MiraVista Diagnostics, with an overall sensitivity of 88.3% and 83.3% in immunocompromised patients. An additional limitation of the current antibody assays is turnaround time of at least one day and up to one week. Diagnosis by antigen detection was commercialized at MiraVista Diagnostics in 2007. The sensitivity for diagnosis of moderately severe or severe cases, most of whom are immunocompromised, is good (71-87%). Currently the test is available only by sending specimens to MiraVista Diagnostics, resulting in turnaround times of at least 1 day and up to 5 days if the specimen must pass through an intermediary reference laboratory. Combined antigen and antibody testing provides the highest sensitivity for diagnosis in severe cases, in which rapid diagnosis may be lifesaving. Point-of-care (POC) testing for Coccidioides antigen and anti-Coccidioides antibodies at the hospital at which the patient is evaluated will speed diagnosis and treatment, improve outcome and reduce cost. The objective of this phase I application is to develop lateral flow immunoassays (LFI) for rapid diagnosis of coccidioidomycosis. To accomplish this objective, monoclonal antibodies recognizing the antigens found in patients will be produced and evaluated for development of Coccidioides antigen detection LFIs. Recombinant or purified antigens recognizing antibodies detected in patients with coccidioidomycosis will be produced and used in developing anti-Coccidioides antibody LFIs. MiraVista Diagnostics has 30 years of experience in development of fungal diagnostic assays and provision of CLIA certified fungal diagnostic services. MiraVista?s medical director is recognized as a leader in development of fungal diagnostic tests and use of these tests in care of patients. MiraVista scientists, production department, and quality section possesses the expertise, resources, and essential materials needed to accomplish these objectives, including production of Coccidioides antigens, production of anti-Coccidioides monoclonal antibodies, development and production of antigen and antibody detection LFIs and EIAs. Furthermore, MiraVista Diagnostics is an ISO 13485 certified facility experienced with design control, GMP practices, CLSI methods for assay validation, conduct of the clinical trials to develop in vitro diagnostic devices, and FDA 510 K submission.
. Coccidioidomycosis is a common cause (15%-29%) of community acquired pneumonia in healthy individuals and disseminated infection in immunocompromised subject from endemic areas of the US, and is associated with high morbidity, mortality and cost. Detection of anti-Coccidioides antibodies provides the basis for diagnosis in most cases but current tests suffer from inadequate sensitivity and slow turnaround time (2 days to more than 1 week). A more sensitive antibody test has been developed at MiraVista Diagnostics. Diagnosis by antigen detection in body fluids, commercialized at MiraVista Diagnostics in 2007, is positive in 71-87% of severe cases and in the spinal fluid of 93% of patients with meningitis, providing a diagnosis in 1-2 days. Combined antigen and antibody testing provides the highest sensitivity for diagnosis in severe cases, in which rapid diagnosis may be lifesaving. Point-of-care (POC) testing for Coccidioides antigen and anti- Coccidioides antibodies at local hospitals will speed diagnosis and treatment, improve outcomes and reduce cost. We propose to develop lateral flow immunoassays for detection of anti-Coccidioides antibodies and Coccidioides antigens.
