August 7, 2013
The fungal spores that cause valley fever are found in the soil in the southwestern United States and northern Mexico. So why should veterinarians and pet owners living outside of places such as Phoenix and San Diego familiarize themselves with valley fever’s symptoms and treatments?
"We have an enormous winter population that comes with their pets, and when Fluffy goes home and is coughing, limping or has seizures, then it is no longer a regional issue,” said Lisa Shubitz, DVM, who studies the disease in people at the University of Arizona’s Valley Fever Center for Excellence in Tucson.
The infection, also known as coccidioidomycosis, or "cocci” for short, usually starts off as a persistent cough in dogs or as a draining skin lesion in cats, Dr. Shubitz noted.
While everything from humans to alpacas are susceptible to the potentially fatal disease, dogs are most likely to contract it. Animal mortality rates have not been tracked.
"Dogs are far and away the most affected and economically important species we see clinical cocci in,” she said.
Shubitz has been a consulting veterinarian at the Veterinary Specialty Center of Tucson since 2004, when she was recruited by Michael Matz, DVM, Dipl. ACVIM. All great partnerships produce results, and the team of Shubitz and Dr. Matz is no exception.
While valley fever has no vaccine or cure, and all the medicines used to treat cocci in animals are formulated for people, Shubitz pointed to research at the Veterinary Specialty Center that has led to a promising breakthrough: the antifungal nikkomycin Z.
"Most pets are treated with oral fluconazole, itraconazole or ketoconazole, and treatment lasts months,” Shubitz said. "If an animal is very sick and in danger of dying, intravenous medication can be given … followed by oral medication after the pet improves.”
The crop of antifungals traditionally used to treat valley fever in animals has a downside, though: side effects such as a lack of appetite, vomiting, elevated liver enzymes and diarrhea.
Treatments may last anywhere from six to 12 months in uncomplicated canine pneumonia cases to years or a lifetime in complicated cases, Shubitz said.
"I call ‘uncomplicated’ [any] valley fever pneumonia that responds promptly to drugs,” she stated. "Skin lesions, bone lesions [and] brain lesions are by definition disseminated disease and are ‘complicated.’”
Shubitz focuses on cocci cases when she consults one day a week at the Veterinary Specialty Center.
Before she expanded her cocci research to dogs and cats, most of her work involved people.
"The manifestation and progression of the disease is similar in humans and dogs,” she said.
Outside of Shubitz, Matz and a few other investigators, cocci research in animals doesn’t get a lot of attention.
"It is being studied for humans in several labs, such as the University of California, Davis, the University of Texas Health Science Center at San Antonio and in San Diego, but there is no primary research being done on animals anywhere,” Shubitz said.
"Everything with a veterinary slant is probably going on here because I have an interest in animals,” she added.
While Shubitz’s expertise has proven invaluable, advances in cocci treatment would have been next to impossible without the Veterinary Specialty Center’s bringing its assets to bear in research involving dogs and cats.
The hospital opened its doors to valley fever research, offering veterinarians diagnostic options and some treatment choices not usually found in their practices, Matz pointed out.
The Veterinary Specialty Center treats about 250 cases of cocci in dogs and cats annually, according to Matz. About 100 miles north in Phoenix, Maricopa County Animal Care & Control reported 67 valley fever cases in 2012 and 14 this year through April.
Matz and Shubitz suggested that the number of documented cases is only a fraction of the actual count.
In 1997, well before the Veterinary Specialty Center of Tucson was on the map, Matz, Shubitz and Sharon Dial, DVM, Ph.D., Dipl. ACVP, conducted a study and estimated that 6 percent of the dog population in Arizona’s Pima, Pinal and Maricopa counties contracted cocci annually.
Cocci is a difficult organism to identify, Matz said. Symptoms in dogs include coughing, lethargy, weight loss, fever and lameness. Less common are seizures, back or neck pain, and draining skin lesions.
In cats, skin lesions that don’t heal with antibiotics are the most common sign, Shubitz added, but cats also may display difficulty breathing, a lack of appetite, lethargy, weight loss and fever.
Even with myriad symptoms, 70 percent of dogs and cats with cocci are asymptomatic, Shubitz noted.
"The diagnosis usually requires a combination of history, physical examination findings, laboratory findings, imaging, serology, cytology and histopathology,” Matz added.
Both veterinarians stressed that veterinarians anywhere in the United States need to know a pet’s travel history.
"Some of these [cases] are winter visitors, and when they leave Tucson or Phoenix it is no longer a regional problem,” Matz advised.
At the Veterinary Specialty Center, a team led by Matz and Shubitz treated nine dogs using the experimental antifungal nikkomycin Z from August 2011 through May 2012.
Dogs with radiographically apparent lung cocci, or pneumonia, were enrolled and received 60 days of medication, Shubitz said.
The study results were more than the researchers could have hoped for.
"Nine dogs were given the drug treatment and seven had good to excellent responses,” Shubitz reported.
And the best part: no side effects.
"It is a very nontoxic oral antifungal, which is good because everything we have now has side effects,” Shubitz remarked. "The dogs that didn’t get better still recorded weight gain and improvement in appetite, which I attribute to a lack of toxicity in the drug.”
Nik Z, discovered by Bayer and patented by the University of Arizona, has not been tested on humans, but "dogs are a pretty good model for humans because there is some overlap,” she added.
The Veterinary Specialty Center is working on an investigative new drug application and plans to file the document with the U.S. Food and Drug Administration. Nikkomycin Z may be available to veterinarians and pet owners in about five years, Shubitz said.
"We’re excited,” she added. "It works—not in every case, but nothing works in every case.”
Nik Z is not expected to cure valley fever, but it should be a leap forward in treating veterinary cocci patients, Shubitz said.
She is hopeful that a vaccine eventually will be discovered. In the meantime, commercially available antifungals will have to do. But much remains unknown about the disease.
"We do not currently understand why cocci has a predilection for certain dissemination sites, especially as they vary in different species,” Shubitz said.
Some animals overcome the disease on their own, but the researchers can’t predict which ones will self-cure.
"The current standard of care is to treat clinically ill dogs because we do not know how to identify dogs that might get over it on their own from dogs which will progress,” Shubitz said.
She and Matz are working to increase awareness of the disease through continuing education sessions and published papers. In the meantime, their work continues unabated at the Veterinary Specialty Center.
"We have a grant studying a brand-new drug for another company,” Shubitz reported, "and if it looks promising. They are interested in testing it in dogs in a few years.”
The hospital’s goal, Matz said, is to continually improve on the prevention, diagnosis and treatment of cocci.
And who better than him and Shubitz?
Valley fever is so named because it was first identified in California’s San Joaquin Valley. The funguses that cause the illness also are found in other parts of California as well as in Arizona, Nevada, Utah, New Mexico, Texas and northern Mexico.
In 2001, eight members of an archaeological dig and two National Park Service personnel contracted valley fever at Dinosaur National Monument in northwestern Colorado.
Cocci is caused by the inhalation of Coccidioides immitis, or C. posadasii, spores stirred up from the soil by wind or activities such recreation, construction and digging.
People, dogs, cats, llamas, alpacas, horses and zoo animals, especially monkeys and apes, are all susceptible.
Once inhaled, the spores may lead to pneumonia, spread to the bones, skin and brain, and in severe cases result in death.
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