CERSI Collaborators: Molly Jeffery, PhD (Mayo Clinic) (CERSI-PI); Joseph Ross, MD, MHS (Yale) (CERSI-PI); Thomas Grys, PhD (Mayo Clinic) (PI); Douglas Lake, PhD (ASU) (Co-PI); Janis Blair, MD (Co-I)

FDA Collaborators: Sara Brenner, MD, MPH; Pooja Jani, MD, MPH; Rebecca Ward, MPH; Jules Nchoutmboube, PhD; Sarah Sheikh, DO; Hiba Zwiya, PhD MPH

Project Start: March 1, 2023

Regulatory Science Challenge

Valley fever (VF), the common name for coccidioidomycosis,,is caused by a desert soil-dwelling fungus, Coccidioides, and accounts for up to one-third of community acquired pneumonia in endemic areas such as the southwestern USA (Phoenix, Tucson) and the central valley in California. Diagnosis of VF is clinically challenging because symptoms mimic viral and bacterial pneumonias. A diagnosis is often determined by interpreting different types of patient information, including symptoms, radiology, and serology. Unlike other diseases, antibodies against Coccidioides are not protective, and antibody levels (“titers”) decrease as patient symptoms improve, and usually revert to negative when disease is controlled. For patients already diagnosed with VF, healthcare providers often monitor patient antibody titers, but there are no FDA cleared methods to provide a titer. Titers are difficult to standardize due to different testing methods and the result is that research studies and clinical trials are difficult to compare with one another.

This project has two aims: One is to investigate laboratory and symptom information that is most informative for VF treatment decisions. The second is to understand the potential benefit of a rapid lateral flow test that could provide antibody titer results in less than 15 minutes.

The intended benefit to public health is that the project will help establish the most useful clinical data and data formats to further understand the disease at the population level, inform treatment recommendations, and enable multi-center treatment trials. Furthermore, a rapid and simple to use test could allow for more efficient studies and clinical trials with results that are more comparable.

Project Description and Goals

The Mayo Clinic healthcare center provides care for hundreds of VF patients per year, allowing the opportunity to study when patients are treated and not, and how their disease changes over time. Researchers developed a rapid (10 minute) antibody test in a lateral flow format that can provide a quantitative measure of antibodies against the Coccidioides fungus. The test can be performed with a fingerstick drop of blood or a similar amount of serum. Researchers aim to better understand the role of antibody titers in managing VF, and whether a rapid test for titers could potentially facilitate better studies and clinical trials.

Objective 1. To measure how closely a prototype rapid antibody test can approximate the traditional methods used to measure titers of antibodies against Coccidioides. Researchers will compare the newly developed prototype rapid test performance against the traditional clinical test results using leftover clinical specimens. They intend to collect 200 comparison samples from patients with potential for more. The information learned has the potential to allow scientists to provide a rapid test result that is familiar to healthcare providers but in a timeframe that allows for real-time care of the patient.

Objective 2. Researchers seek to understand how the information known at each time point contributes to decisions about treatment, and whether more could be learned about how the combinations of clinical information (e.g., certain symptoms and certain lab values) might predict improvement or worsening of valley fever disease. The electronic medical record of Mayo Clinic will be used to investigate the course of disease for patients with VF. For at least 100 patients with VF, researchers will closely review the clinical information at each timepoint a titer was measured, or doctor visit occurred. The data will be compiled and analyzed to understand the most important factors.