A Point-of-Care Test for Rapid Diagnosis of Valley Fever

A Point-Of-Care Test for Rapid Diagnosis of Valley Fever PROJECT SUMMARY Coccidioidomycosis (Valley Fever) is a respiratory disease caused by inhalation of spores from the desert soil- dwelling fungus, Coccidioides spp. In endemic areas, up to 30% of community acquired pneumonia (CAP) is caused by Coccidioides spp.1 Valley Fever mimics other viral and bacterial respiratory infections and is challenging to diagnose. Nearly three million tests for Valley Fever are done in clinical laboratories each year in humans. Typically, a tube of blood is sent to a clinical laboratory to test for antibodies against a Coccidioidal fungal antigen preparation using Enzyme ImmunoAssay (EIA), ImmunoDiffusion (ID) and/or complement fixation (CF) tests. The time from blood draw to assay result may be 48 hours to 2 weeks. This SBIR proposal focuses on a rapid antibody test that can be performed in 10 minutes while the patient is present. Based on clues in previous publications2,3, our preliminary data demonstrate that CTS1, a chitinase, is the primary sero-reactive immunodominant Coccidioidal antigen. Therefore, we developed a rapid test that employs recombinant CTS1 (rCTS1) to detect Coccidioidal-specific IgG or IgM, independent of species being tested (e.g. human or canine). Excluding the large veterinary market, the primary human market for this test is Urgent Care Clinics, Emergency Departments and many primary care practices. First Innovation: Although rapid antibody tests using lateral flow technology are not new, a 10-minute rapid test for VF that provides sufficient sensitivity and specificity and detects either IgM or IgG antibodies against the fungus would dramatically advance clinical care for human (and canine) patients. One example is in the urgent care clinic where a patient with a community acquired pneumonia caused by Coccidioides spp. could receive an accurate diagnosis using our rapid test during their visit with a simple finger-stick drop of blood. Without the availability of a rapid, sensitive and specific test, an urgent care physician is unlikely to order a VF test because the result comes back to the physician up to 4 days after the patient has been discharged. Instead, patients usually receive a prescription for an antibiotic for pneumonia–which is an inappropriate treatment for coccidioidomycosis–and leave urgent care with an incorrect/incomplete diagnosis, potentially lost to follow up. The innovation of our rapid 10-minute test is that it provides a clinically actionable answer in 10 minutes with a single drop of blood instead of 2-4 days using current testing methods. Second Innovation: Growth of Coccidioides spp. requires a certified BSL3 laboratory, highly trained personnel and special facilities which are expensive and time-consuming; this BSL3 effort cannot be overstated. Our innovative hypothesis is that rCTS1 can serve as the primary antigen target for antibodies in patients with coccidioidomycosis. We will test the performance of our rCTS-1-based rapid test using VF patient sera ranging in titers from 1:2 to 1:1024 while also comparing it with existing commercial tests to show equivalence as required by the FDA. Control sera include patients with other fungal, viral and bacterial infections. Compared to the only commercially available lateral flow test for Valley Fever (Immy’s Sona test), Cactus Bio’s rapid test is faster (10 minutes compared to 30 minutes), quantifiable, more accurate, can use whole blood, and is amenable to consistent, high-quality production.