Digging Up a Diagnosis

Valley fever can affect people, pets and livestock here in Southern Arizona, and can be hard to diagnose.

The University of Arizona’s Valley Fever Center for Excellence and Banner Health have created a tutorial to help local physicians speed up the process. Here’s what you need to know about this pervasive disease.

By Anne Kellogg | Photography by Kris Hanning

It can come on like the flu but may take weeks or months to run its course.  In rare cases, Valley fever can result in severe lung issues or meningitis.  Its symptoms mimic many other illnesses — such as rheumatism and even cancer — causing patients to undergo painful testing and unneeded treatment with antibiotics or steroids.  John Galgiani, M.D., director of the Valley Fever Center for Excellence, professor of medicine in the Divisions of Infectious Diseases at the UA Colleges of Medicine in Tucson and Phoenix, member of the UA BIO5 Institute and medical director of the Banner — University Medicine Valley Fever Program, has developed a way to assist physicians in the timely diagnosis of this challenging disease.

What is Valley Fever?

Have you experienced a fever, profuse sweating at night, chest pain and cough, muscle and joint aches — especially in the ankles and knees — loss of appetite, and a rash that resembles measles or hives?  You In Health may have thought you had the flu, but these symptoms also are those of Valley fever, which is caused by spores that live in the soil in Southern Arizona.  In addition to areas of our state, Valley fever can occur in semi-arid and arid soils of California, Nevada, Utah, New Mexico and Texas, as well as the states of Sonora and Chihuahua in Mexico, and Central and South America.

The corridor between Tucson and Phoenix is one of the most endemic regions for Valley fever, so the University of Arizona’s Valley Fever Center for Excellence (VFCE) was established by the Arizona Board of Regents in 1996 to promote education, research and care for this disease.  Dr. Galgiani explains that Valley fever is a difficult disease to detect and treat, frequently leading to misdiagnosis.

Its medical name, coccidioidomycosis, means fungal infection caused by the fungus Coccidioides . The name is often shortened to “Cocci” (pronounced “kok-see”).  This organism grows in the top six inches of soils in areas of low rainfall, high summer temperatures and Moderate winter temperatures.  In susceptible people or animals, infection occurs when a spore is inhaled.

Infection by the spores doesn’t always lead to detectable disease.  In nearly 60 percent of cases, the symptoms are so mild that individuals may not even realize they are infected.  In the remaining cases, symptoms may range from uncomfortable to miserable to even fatal.  It occasionally can develop into a severe, life-threatening form that may involve skin, bones, or other parts of the body, as well as the brain.  Overall statistics for Valley fever show about 150,000 infections per year, with only one-quarter of one percent contracting meningitis (i.e., roughly two cases per thousand), but increased numbers of cases cause a corresponding increase in serious disease.  Serious forms of the infection require anti fungal therapy.

The diagnosis of this disease is complicated because of the way the lungs respond to the inhaled spores.  Initially the infection causes a pneumonia, which sometimes can turn into a lung nodule or even a

The catheterization lab at Tucson Medical Center.

cavity.  Nodules are small, residual patches of infection that generally appear as single lesions (from one, to one and a half inches, in diameter).  If it is documented that the nodule is caused by Valley fever, no other treatment is required.  However, if the original Valley fever infection goes undiagnosed and the nodule is found on a chance X-ray, it looks no different fromfrom a lung cancer, and a physician may suggest biopsy or even removal.  Nodules caused by cocci can remain forever.  Those who had a mild case may have no symptoms or scarring.  Cavities occur in about 5 percent of patients, and may cause the patient to cough blood or have other chest symptoms.  For some patients, the best management is to have the cavity surgically removed.

In Arizona, infection is likely to occur from May to July and again following Monsoon season, from October to the end of December.  Those in occupations that involve disturbing the soil (such as construction, agriculture or archeology), as well as recreational gardeners, may be at greater risk of contracting the disease.

Two-thirds of all U.S. Valley fever infections occur in Arizona.  Roughly 75 percent occur in Maricopa county, with 20 percent or so occurring in Pima County.  According to Arizona Department of Health Statistics, those susceptible to the most serious consequences of Valley fever include people on chemotherapy, on immune suppression medications because of organ transplant, the elderly, or those with immunodeficiency, such as AIDS.

The Benefits of Early Diagnosis

A primary reason for diagnosing early is removing the patient’s fear of the unknown.  Patients suffering from these long-lasting Respiratory symptoms often undergo multiple diagnostic blood tests, chest X-rays, CT scans, PET scans, bronchoscopy, percutaneous fine-needle aspiration, and even thoracotomies.  They often are prescribed multiple courses of antibiotics from their primary care physicians.  In one study, 81 percent of patients with Valley fever pneumonia received at least one course, and 31 percent received multiple courses.  In addition to the cost, it can create antibiotic resistance.  Another issue is doctors prescribing corticosteroids for the rheumatologic complaints (a synonym for Valley fever is “desert rheumatism”).  The anti-inflammatory effects of corticosteroids may create adverse reactions in patients, as well as increasing the chances of Valley fever complications.

Developing the Tutorial

Out of the need to get Valley fever patients treated early and effectively, Dr. Galgiani and his cohorts at the VFCE teamed with Banner Health to help physicians.  “I am quite excited about this — it’s one of the most positive things to come out of the merger between Banner Health and the University of Arizona faculty medical group,” Dr. Galgiani enthuses.  “Banner Health has specific clinical practices that they share with all of their physicians, and the Valley Fever Center for Excellence developed this information for local and national dissemination.  This will help doctors in other states whose patients visited our area and now have respiratory symptoms associated with Valley fever.

“We spent last year in a planning process, where we designed and refined the ABCs of what a primary care physician should do to diagnose Valley fever early and manage it correctly.  This past September we held a webinar on the topic, and we’ll be training Banner physicians all year.  VFCE is a department of the University of Arizona, not part of Banner, so we’ve made all the tools we developed in this process publically available to any doctor who wants to do what we’re doing.”

The new approach for recognizing and treating a new Valley fever infection is centered around the acronym COCCI:

Consider the diagnosis
Order the right tests
Check for risk factors
Check for complications
Initiate management

Physicians are encouraged to consider Valley fever if any of the following indications are present:

  • Respiratory symptoms and at least one of the following:
    • more than one office visit
    • chest X-ray ordered
    • antibiotics prescribed
  • Two of the following have been present for a prolonged period: fever, fatigue and/or arthralgia (joint pain)
  • High numbers of eosinophils (a type of white blood cell) found in a blood sample
  • Skin rashes known as erythema nodosum or erythema multiforme

The tutorial and all the other resources created for the clinical practice training can be accessed online at https://vfce.arizona. edu/education/banner-valley-fever-clinical- practice-toolbox.

For more information on the new UA/ Banner clinical practice protocols, see the Valley Fever Clinical Practice Toolbox at the VFCE website, which includes the webinar mentioned earlier.

The protocols were developed with assistance from David Valenzuela, M.D., a Phoenix-area family practice physician, clinical assistant professor at the UA College of Medicine — Phoe

nix and the physician executive who heads Banner Medical Group Primary Care.

As part of the effort, Dr. Galgiani and Fariba Donovan, M.D., Ph.D., another VFCE researcher and faculty physician with the UA Division of Infectious Diseases, are providing small group training sessions for six to 12 clinicians each at 39 Banner Health clinical sites across the State.

They completed about a half dozen sessions by the end of January.

I Want a New Drug…

“There have been no recent breakthroughs or changes in the antifungals that are used in Valley fever,” Dr. Galgiani notes.  “There are a lot of divergent opinions on whether to start patients on fluconazole … it depends on the patient’s clinical presentation.  The antifungal treatments don’t cure it — they can help, but only by suppressing it.  If the patient’s immune system doesn’t ‘step up to the challenge’ when the antifungal drugs are stopped, those who really needed treatment will relapse.”

Researchers at UA have been working on a drug called nikkomycin Z as a new treatment for fungal infections, particularly Cocci.  “It works by blocking an enzyme that is important in making the cell wall,” Dr. Galgiani explains.  “An key part of the cell wall is ‘chitin.’ Chitin is made by an enzyme called chitin synthase, and nikkomycin Z blocks that enzyme.  In that regard it’s similar to penicillin, which acts by blocking formation of the cell wall of a bacterium.”

Because this drug’s most important use would be for Valley fever here in the Southwest, which isn’t a worldwide disease, drug companies haven’t had a strong incentive to develop it.

“We’re trying very hard to get it back into clinical trials, and have been making progress, but the bottom line is that it needs more financial support than we’ve been able to get.  The National Institutes of Health has been very supportive, but they’re not a pharmaceutical company.

They want this drug to go forward, but we haven’t yet gotten the support to do it.  It’s frustrating … we hope to find a pharmaceutical company that would be willing to partner with us.”

When a medication or a vaccine is created for human use, it must go through many clinical trials and intense scrutiny by the Federal Drug Administration (FDA).  Drugs for dogs and other veterinary purposes also require FDA approval.  However, veterinary vaccines are cleared by the United States Department of Agriculture (USDA).  “Work on an effective vaccine for the prevention of Valley fever has been ongoing for decades,” says Dr. Galgiani.  “Currently, we have a vaccine candidate that shows excellent protection in mice.  We are proceeding through the steps to bring this Vaccine through USDA approval for use in our canine patients.  That itself would be a wonderful accomplishment.  Just as exciting, if our vaccine candidate is found to protect dogs from Valley fever, that will add to the evidence that a similar vaccine might ultimately be used to protect ourselves.”

Work on the vaccine is being coordinated through the following VFCE research partners: Marc Orbach, Ph.D., Jeffrey Frelinger, Ph.D., and Lisa Shubitz, DVM, at the University of Arizona; Colorado State University’s Richard Bowen, DVM, Ph.D.; and Anivive Lifesciences Inc., a Californiabased biotechnology company that licensed the vaccine in 2017 from the UA through Tech Launch Arizona, the university unit that helps commercialize innovations developed at UA.

Getting the Word Out

In addition to helping physicians diagnose Valley fever earlier, the Valley Fever Center for Excellence (VFCE) at the University of Arizona and the Arizona Department of Health Services (AzDHS) also are trying to educate the public.

For example, a billboard will go up this month in Phoenix with the words ““Pneumonia or flu for weeks? It could be Valley fever. Ask your doctor for the test.”

The campaign is being funded by a grant from IMMY, a Norman, Oklahoma-based firm that specializes in high-quality diagnostic tools for diseases caused by fungi such as Aspergillus, Blastomyces, Candida, Coccidioides, Cryptococcus and Histoplasma.

It’s coordinated through the VFCE; Kenneth Komatsu, M.P.H., state epidemiologist and chief of the Office of Infectious Diseases with the AzDHS Division of Public Health Preparedness; and Rebecca Sunenshine, M.D., a captain in the U.S. Public Health Service, epidemiology field officer for the U.S. Center for Disease Control and Prevention and medical director of disease control for Maricopa County Public Health.

Look for the billboard along Interstate 10 or the 202 Loop in Phoenix starting March 4.

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