Valley fever, also known as coccidioidomycosis or “cocci,” is a serious illness that affects thousands of Californians each year, and researchers at UCSF Fresno, a referral center for Valley fever, are studying ways to improve disease diagnosis, treatment, and patient outcomes.
Geetha Sivasubramanian, MD, FIDSA, Associate Professor of Medicine and Division Chief of Infectious Diseases at UCSF Fresno, emphasized that the UCSF School of Medicine Regional Campus at Fresno is uniquely positioned to be a hub for Valley fever research. The San Joaquin Valley has the highest burden of the disease, and Fresno serves as a referral center for the diverse populations most affected. Given that Valley fever derives its name from the region, it is both historically and scientifically appropriate for Fresno to lead in advancing research and innovation.
Valley fever causes flu-like symptoms for many, but also serious lung infections, such as pneumonia, and in some cases, serious long-term symptoms that require lifelong treatment. Importantly, the disease is on the rise, with 12,500 cases reported in the state in 2024, the highest year on record in California. This year, the number of cases is expected to be at least as high as the previous year, if not higher. The disease is increasing in areas beyond the Valley, including the north Central Valley and the Central Coast.
As a referral center for Valley fever, UCSF Fresno has three affiliated clinics for patients. Inspire Health Specialty on Kashian Lane, Fresno; United Health Centers Ambulatory Care Center, Wayte Lane Fresno; and United Health Centers Specialty Clinic, Bullard Avenue, Fresno. Many of the patients have severe Valley fever illness with chronic health conditions, such as diabetes.
There is no question that Valley fever is a well-established disease in the state and region. There is much more to learn about it, said Dr. Sivasubramanian, an Inspire Health Medical Group infectious diseases specialist, who is a national expert on Valley fever, and who is a part of the clinical consortium advisory panel to the federal Centers for Disease Control and Prevention regarding Valley fever.
“We don’t yet understand why Valley fever can cause such severe illness in some otherwise healthy individuals. We often see young patients with no prior medical problems who present with an unexpectedly aggressive form of the disease, leaving them with lasting, life-altering complications”, she said.
“While medications are available to treat Valley fever, important questions remain. We don’t fully understand why therapies fail to work in some patients with the most severe disease. We also lack a highly sensitive and specific point-of-care diagnostic test. And here in the Central Valley, many of our patients face significant barriers that limit their ability to access and complete treatment.”
She added, “The bottom line is that there are still many unknowns about this disease, particularly as it affects the Central California population.”
And UCSF Fresno is involved in research to help answer some of those questions.
Research to understand how underlying medical conditions affect patients with Valley fever has already yielded important findings. Working with Mohamed Fayed, MD, a pulmonary and critical care physician and associate clinical professor at UCSF Fresno. Dr. Sivasubramanian has published on the severe forms of Valley fever seen in ICU patients. She has also collaborated with Seema Policepatil, MD, a primary care physician and associate clinical professor at UCSF Fresno, to examine the impact of comorbidities such as diabetes, noting that most patients in her study had very poorly controlled diseases.
“We found that many of these patients lacked access to primary care or endocrinology, and their average A1C, which measures glucose control, was significantly high,” she said. “As expected, they did not do well. They experienced more lung complications from Valley fever, had slower recovery, and many suffered relapsing infections when their blood sugar was not controlled. What we saw was a linear correlation: the higher the A1C, the worse the outcomes with cocci.”
Dr. Sivasubramanian is also collaborating with Dr. Marina Roytman, MD, FACP, professor and director of the UCSF Fresno Liver Program, on a study of Valley fever in patients with severe liver disease.
For patients with chronic diabetes and liver disease, “these are two distinct conditions that intersect, with each one influencing the course of the other,” she explained.
These findings highlight the importance of a multidisciplinary approach, Dr. Sivasubramanian emphasized. “We need to collaborate closely with endocrinologists, hepatologists, and primary care physicians, because managing this cannot be done in isolation.”
Patients from small towns across Kings, Kern, Tulare, and other nearby counties in Central California come to the UCSF Fresno Valley Fever Center for care. Many are diagnosed with the most serious form of the illness, Valley fever meningitis, a dangerous infection that affects the brain and spinal cord.
Valley fever meningitis, the rarest and most severe form, requires lifelong treatment. In a published study of 133 patients, UCSF Fresno found that more than 40% struggled to stay current with their medications. “They were either unable to adhere to treatment, experienced medication failure, or were lost to follow-up,” Dr. Sivasubramanian said. Many required multiple surgeries and repeated hospitalizations.
To build on these findings, an implementation research project is now underway in collaboration with Nancy Burke, PhD, professor of Public Health and Anthropology at UC Merced. Dr. Burke, who focuses on health challenges at the population level, is working with Dr. Sivasubramanian to study patient outcomes in Valley fever meningitis.
Results from the first phase of the pilot study, where researchers sat down and interviewed patients, will be presented in October during the annual meeting of the Infectious Disease Society of America, in Atlanta, Ga.
“What we found was a huge knowledge gap,” Dr. Sivasubramanian said. “Many patients did not realize how serious this infection can become or that it requires lifelong treatment. More patient education is clearly needed.”
The pilot study also revealed significant delays in diagnosis. “Patients were often told they had bronchitis or pneumonia, given antibiotics, and sent to urgent care after urgent care before finally being diagnosed with Valley fever,” she explained. “Even here in Central California, where the disease is well known, these delays are still happening.”
This pilot work dovetails with another project Dr. Sivasubramanian is leading at UCSF Fresno which aims to educate urgent care providers about Valley fever testing and to connect patients with UCSF Fresno clinics for timely care.
Additionally, UCSF Fresno is collaborating with researchers at UC Davis, UCLA, the University of Utah, the University of Arizona in Tucson, and the Mayo Clinic in Scottsdale, Arizona, on a range of Valley fever studies. While some projects are testing new medications for the illness and others are exploring therapies that work through the immune system, still others are focused on genetic studies aimed at better understanding the fungus itself.
“There are many different facets to this disease, and it’s exciting to see so many research efforts underway here in Fresno,” Dr. Sivasubramanian said. “Through collaborative work, each study adds a piece to the puzzle, and together they are helping us learn how to diagnose earlier, treat more effectively, and provide better long-term care for our patients.”
