Fellowship Story Showcase
Just One Breath: Valley fever treatments can do harm as they heal
Current treatments for valley fever can take so long to work that they allow the disease to spread, becoming more damaging and more deadly. What can be done? This story is part of the ReportingonHealth Collaborative's "Just One Breath" investigative series on valley fever.
Thousands of California and Arizona adults and children annually contract valley fever and find themselves battling the disease for months or years — missing work and school, spending weeks in the hospital — with frequent recurrences.
If they had a bacterial infection — food poisoning, strep throat or a boil on the skin — their doctor could reach for multiple, cost-effective antibiotics that usually are able to kill the bacteria, even though resistance to antibiotics is on the rise.
If those same patients acquire an internal fungal infection, though, their doctors have far fewer options.
Current treatments can take so long to work that they allow the disease to spread, becoming more damaging and more deadly. Many of the treatments are extremely expensive, costing thousands of dollars a month. While scientists are working to perfect new treatments, valley fever and other fungal infections have been so low on the national priority list that treatment research doesn’t receive much funding.
It’s “a clear, unmet clinical need,” said Dr. Joseph Heitman, chairman of Duke University’s Department of Molecular Genetics and Microbiology.
“In some patients, the treatment is as harsh as the disease itself,” said Dr. Arash Heidari, an assistant clinical professor at UCLA and an infectious disease specialist for Kern County and Kern Medical Center. Even when treatments do fight off valley fever, they can cause significant side effects. Pregnant women can’t take the most common and least expensive treatment, the antifungal pill fluconazole, because of extreme fetal side effects. Other treatments can cause fatal heart or kidney damage.
Hundreds of people throughout the United States in recent weeks discovered the difficulty of treating fungal infections during the outbreak of fungal meningitis caused by tainted steroidal drugs.
The U.S. Centers for Disease Control reported as of Dec. 3 that 36 people died and a total of 541 people in 19 states were infected with fungal meningitis linked to tainted medication manufactured by the New England Compounding Center in Massachusetts.
Although the fungus that causes that disease is different from the one that causes valley fever, many of the drugs used to treat it are the same.
TREATMENTS FALL SHORT
Valley fever is caused by a fungus that grows naturally in the dry, warm dirt of the U.S. Southwest. When the wind kicks up, everyone can inhale the spores. Most people don’t get sick, but in some, especially those with compromised immune systems, the spores begin a potentially deadly voyage.
"It can go anywhere in the body,” said Dr. Steven Larson, a Riverside infectious disease specialist and member of the California Medical Association’s executive committee.
Traveling through the bloodstream, the fungus can attack everything from lungs to the brain. It can destroy joints — causing people to lose strength and mobility — and it can rupture onto the skin, causing painful and unsightly abscesses.
Research shows that immunization against the disease could work in theory, but funding for vaccine research has been scarce.
“Unfortunately, there's not much the public can do to prevent this,” he said. "It's so ubiquitous; there's no way to eradicate it in nature."
That’s why doctors have to rely on antifungal treatments. Most often, doctors turn to a class of drugs called azoles that can be taken as pills.
Developed out of research from England in the 1930s, azoles were designed to fight, but generally not kill, a range of fungal infections. Almost all of the drugs, including the most popular one, fluconazole, are available as generic prescriptions, which helps reduce their cost.
Fluconazole, for example, costs about $100 a month and, for many patients, is “a lifesaving medication,” said Larson. But it can take several weeks or months for the medication to alter the course of the disease. This gives the fungus more time to spread from the lungs and harm other parts of the body. It also means patients can be forced to stay home from work or to endure long hospital stays.
For the most severely ill, doctors use intravenous drugs called amphotericins.
They generally work more quickly than the azoles and can kill valley fever. But they don’t work for everyone, especially in cases where the fungus has spread to the brain and caused meningitis. And relapses are common.
Amphotericin B, the most commonly used intravenous drug for valley fever, is very expensive, costing at least $3,000 a month. Because patients can be required to have infusions of the drug for more than a year, the costs can mount. And because the drugs aren’t proven to be effective in all patients, insurance companies may not cover the costs.
Patients in Tennessee who were diagnosed with fungal meningitis recently sued their insurance company for failure to pay for treatments.
Heidari, of Kern Medical Center, runs one of the nation’s few valley fever clinics and says he has one hand tied behind his back in the fight against the disease.
“We don’t have a good effective medication available for valley fever,” he said. “The ideal treatment would be a medication that can be taken by mouth and kill the fungus. And it’s cheap and approved by most of the insurance companies.”
SIDE EFFECTS CAN BE DEVASTATING
Doctors also have to worry about the damage that today’s treatments might do to patients.
Azoles can’t be taken by pregnant women or women who are considering having a child because they cause severe deformities in unborn children. They can cause nausea, diarrhea and other side effects.
If doctors have to put a patient on amphotericin B, the side effects can be even worse. They can damage the kidneys, cause severe anemia and lead to fatal illnesses.
A study in a 2004 Journal of Antimicrobial Chemotherapy said that up to 80 percent of patients treated with amphotericin B develop some degree of kidney impairment and can end up needing dialysis.
In spite of its proven track record in halting the fungus’ spread, amphotericin B’s well-known side effects and toxicity will sometimes prompt doctors to halt therapy even when a patient has a life-threatening fungal infection, a 2009 research article found.
That’s why amphotericin B is considered a drug of last resort, said Dr. Paul Goebel, chief of medical services at the Veterans Affairs Central California Health Care System in Fresno.
“That treatment led to convulsion-like seizures, and I had to take the Demerol to calm them down,” Magana wrote in an email to the Reporting on Health Collaborative. “Being so young, I don’t think I realized the gravity of my condition. All I knew was that I was very sick.”Anna Magana, who lives in Wasco, was treated with amphotericin B in 1991. She was 16 years old and four months pregnant. Immediately, she felt the side effects of the drug.
Her daughter, Brianna, was born three weeks early. They were both kept in the hospital to make sure Magana’s valley fever treatment hadn’t affected her infant. Brianna didn’t experience any side effects.
LACK OF RESEARCH FOR FUNGAL TREATMENTS
The limitations of valley fever treatments reflect the state of the science around fungal infections, said Michael Kurilla, director of the Office of Biodefense Research Affairs within the National Institutes of Health.
“We still have a long ways to go to know how to use the immune system to effectively attack the fungal infections in general,” Kurilla said.
The basic issue that has confounded researchers for decades is the core structure of a fungus.
Unlike bacteria, “fungi and our own cells share a lot of common features,” said Heitman, the expert at Duke University. “As weird as it sounds, fungi and humans are sort of kissing cousins.”
That means treatments that damage or destroy fungus infections can have serious side effects, potentially harming human kidneys or other organs.
The trick is to administer enough of a drug to control a fungus infection like valley fever, but not harm the patient.
Dr. William Schaffner, infectious disease specialist at the Vanderbilt University Medical Center in Nashville, Tenn., said fungal infections are much harder to treat because they have a more complicated metabolism. A clinical breakthrough would require financial support from the government and commercial interest by pharmaceutical companies, he said.
But pharmaceutical companies’ interest in developing new drugs to treat infections of any kind has waned over the past decade, he said.
“There’s very little antibiotic research going on overall,” said Schaffner. And the research funding that exists tends to focus on treatments for far more common bacterial and viral infections.
The Infectious Disease Society of America has lobbied Congress to create financial incentives for pharmaceutical companies to develop new antibiotics, including new antifungal drugs.
In the meantime, researchers like Dr. Joshua Fierer at the University of California, San Diego continue to scramble to bring in NIH research grants for valley fever studies.
"They have to establish priorities, and unfortunately we are a long ways from Washington," he said. "I think it's regrettable."
Heidari said hopefully the recent fungal meningitis outbreak was a wake-up call for those who make research funding possible to further develop treatments for fungal infections.
“This devastation itself might open the door for any other fungal infections, including valley fever,” he said.
— Kellie Schmitt contributed to this report.
Photo credit: Duke University
Photo Credit: Henry A. Barrios/The Bakersfield Californian