Researchers are still a decade away from seeing a Valley Fever vaccine realized for humans, who are in recent years being infected at a greater degree with the fungal spores that cause the disease. The illness primarily affects people living in the Southwestern United States.
Federal officials plan to expediate the vaccine development process under the Finding Orphan-disease Remedies with Antifungal Research and Development (FORWARD) Act, including a priority review voucher program by the U.S. Food and Drug Administration which supports a vaccine through market incentives. The legislation, H.R. 6562, allocates $95 million for programs to combat Valley Fever and is supported by U.S. Reps. Kevin McCarthy (R-CA), David Schweikert (R-AZ), and other legislators.
Recent studies from the University of Arizona’s Valley Fever Center for Excellence show that the results of animal models, specifically of mice, advance a vaccine called delta-cps1 for potential use in humans. The next steps for researchers are to hold trials of the same vaccine in canines.
“Testing dogs will be a stepping stone for humans,” said John Galgiani, director of the Center. “We have a vaccine under development funded by a four-year grant from the National Institutes of Health.”
Dogs are also at risk of Valley Fever and are more likely than people to encounter the spores that transmit the fungi, Coccidioides, which is found in the desert soil. The trials in dogs should take three to five years to complete, Galgiani said.
Monitoring disease spread
When Galgiani arrived in Arizona, few scientists were working on Valley Fever research.
“Scientifically speaking, the fungal infection was under appreciated,” he said.
But in the 1970s, the disease—which causes everything from skin legions to swollen joints, and meningitis in the most severe cases—afflicted few people. However, last year about 7,000 cases were reported to the Arizona Department of Health Services, up by nearly 1,000 from 2016. Two-thirds of infections in this country are Arizona-based with 80 percent of those in Maricopa county. The other third of cases occurs in southern California.
Scientists are not sure why the illness is more prevalent now. One guess is that population centers have expanded in the region where the disease is most likely to strike. Scientists are also hesitant to attribute increased cases to fickle weather patterns. This is primarily because infection rates from year to year over the last three decades show no consistent increases, despite a significant rise in cases during the last two years.
Rainfall data might be one place to look, as one theory suggests that increased precipitation might provide ideal circumstances for fungi to grow. However, determining where the fungi originate in the first place is an arduous task, especially as wind carries the spores containing Coccidioides.
“Most of the endemic [native] desert doesn’t have the fungus in it,” Galgiani said. “The fungus is very patchy in the landscape.”
Scientists do not have a map of where exactly the fungus is more likely to grow, and Galgiani said that one person’s backyard might have it, while a neighbor’s does not.
“The ecology is complex,” he added.
A pathway to a drug
Beyond a vaccine, creating treatments for Valley Fever is also a decade in the making. However, there is promise that ongoing drug development approaches may tackle the disease from different angles.
One such tactic includes using Nikkomycin Z, an antifungal drug discovered in the 1970s that inhibits fungal cell wall development, and studies in mice show it might cure the disease. The University of Arizona acquired the drug’s development program in 2005, according to the Arizona Daily Star.
However, antifungal use is a treatment option that can be best enhanced if there is greater genetic understanding of why some people get gravely sick from Valley Fever and others barely break a fever. Although 200,000 people might be exposed to the fungal spores that cause Valley Fever during any given year, only 2 to 4 percent of those will develop the severest forms of the disease that may lead to death. As there are few people who experience extreme symptoms, past efforts to treat Valley Fever were hard to examine systematically, categorizing the illness as an “orphan disease.” Scientists are still not entirely certain why specific populations, such as Filipinos and people of African descent, are more likely to develop the most severe symptoms.
Steven Holland, director of the Division of Intramural Research at the National Institute of Allergy and Infectious Diseases at the National Institutes of Health, is trying to understand why. Holland oversees research into identifying what genes and gene pathways make people more susceptible to Valley Fever.
“For some of the patients we see now, it’s clear their discrete genetic differences are what makes it difficult to treat the illness,” he said.
To understand these differences, Holland and his team have sequenced the DNA of 65 people with severe coccidioidomycosis. The scientists must then sort through approximately 23,000 genes per individual to determine the handful of genes they suspect contribute to the progression of Valley Fever. Then, researchers must assemble that information.
“Finding the genes that have variants in them is like finding a clue,” Holland said. “It doesn’t mean you’ve solved the crime.”
Ultimately the goal is personalized medicine, treating people with Valley Fever based on their genetic blueprint to tailor therapy. This may mean a combination of immune stimulating and antifungal drugs to address individual needs.