From soil to systemic disease

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Coccidioidomycosis, also known as valley fever, is caused by the dimorphic Coccidioides fungi (Coccidioides posadasii and Coccidioides immitis), which live in the soil in dry and hot environments. In the United States, Coccidioides fungi are most common in the Southwest, specifically in Arizona and Southern California, where it is considered endemic, but also as far north as Washington and as far east as Texas.¹ Internationally, it is also seen in Mexico and parts of Central and South America.¹

Arthroconidia are inhaled from the environment and phagocytosed by alveolar macrophages, where they first develop into a spherule. The spherule then develops hundreds of endospores inside it, which eventually rupture, releasing the endospores. Those endospores cause local pyogranulomatous inflammation and can disseminate via lymphatics to the tracheobronchial lymph nodes and/or hematogenously throughout the rest of the body.¹

Clinical manifestations

Clinical signs of Coccidioides can range from asymptomatic to life-threatening. Most commonly, dogs experience mild signs such as coughing, lethargy, hyporexia, fever, and weight loss, which all can present acutely or chronically.¹ If there is dissemination, clinical signs will vary based on the site, which commonly include the central nervous system (CNS), bones, eyes, skin, and pericardium. Neurologic signs may include seizures, which are the most common; central vestibular signs; head pressing; and back pain or paresis.² Coccidioides osteomyelitis in the appendicular bones often presents with lameness, pain, or a visible swelling.³ Cardiac/pericardial involvement often leads to right-sided heart failure with ascites and/or pleural effusion.⁴

Diagnosis

The diagnosis of coccidioidomycosis can be made using serology, cytology, histopathology, or fungal cultures. Most commonly, diagnosis is based on antibody serology, consisting of IgM and IgG titers via an agar gel immunodiffusion (AGID) assay.¹ IgM antibodies are generally detectable within 2 to 5 weeks and IgG antibodies in 8 to 12 weeks after initial infection.¹ There is no documented correlation of initial titers and disease severity; therefore, dogs with low titers can have significant disease, and on the other hand, dogs in endemic areas can have positive titers from exposure alone.^3,5,6 The author generally treats all dogs with positive results and consistent clinical signs, even with low titers, and will treat asymptomatic dogs with positive results if the titer is 1:8 or higher. False-negative results may occur in up to 13% of cases.⁷

Over the past few years, a point-of-care lateral flow assay (LFA), sōna Coccidioides (IMMY), has also become commercially available and subsequently tested in comparison with AGID in canine patients.^8,9 In comparison with AGID, findings from a study showed that the point-of-care LFA had a positive predictive value of 100% and a negative predictive value of 75%.⁹ This point-of-care test can be helpful in situations where teams may be looking to provide more information quickly, prior to either same-day additional procedures/testing or euthanasia. As this is a qualitative test and there can be false-negative results, it is still recommended to submit titers for confirmation and monitoring.

Cytology results from aspirates, fluid, or skin impressions may also show Coccidioides spherules and/or endospores, but this method has a generally low sensitivity and results can be easy to miss due to low numbers of organisms.¹ Fungal cultures can also be used, but due to potentially long incubation time and human health hazards to laboratory workers, this method is not commonly performed.¹

Treatment options

Azole antifungal therapy is the mainstay of treatment for valley fever, with fluconazole being most common due to its lower cost. In clinical practice, fluconazole is generally dosed close to 10 mg/kg twice daily.^2,3,10 Fluconazole comes in generic 50-mg, 100-mg, 150-mg, and 200-mg tablets, which can be easily halved to facilitate dosing close to 10 mg/kg, even in small patients. There is also a generic 40-mg/mL solution available.

Itraconazole is preferred over fluconazole in cases with bone or joint involvement due to increased bone penetration11 and is commonly used in cases with disease refractory to fluconazole. The recommended dosing for itraconazole is 5 mg/kg once daily. Itraconazole comes in 100-mg generic capsules as well as human-labeled and veterinary-labeled liquid solutions in a 10-mg/mL concentration. Newer generation azoles such as posaconazole and voriconazole can also be considered in refractory cases.^12,13 Hepatotoxicity can occur in up to 26% of patients on azole antifungal therapy.¹⁴

It is recommended to avoid compounding these medications. In findings from a 2018 study comparing compounded, generic, and brand-name itraconazole, 95% of animals in the compounded medication group had subtherapeutic itraconazole blood levels,¹⁵ and findings from a 2017 study on compounded fluconazole showed poor accuracy and precision in compounded fluconazole suspension.¹⁶

For dogs with ocular valley fever, enucleation may be required, and in dogs with valley fever pericarditis, subtotal pericardectomy and epicardial excision may be required.⁴ In patients with severe infection or refractory disease, amphotericin B can be considered.¹

Monitoring

Treatment duration can range from 6 months to many years, but in the author’s experience, the average treatment duration is 9 to 12 months. Antibody titers should decrease with successful treatment.^2,3,10 Treatment is commonly continued until the titer is 1:2 or lower and the initial lesions have resolved.¹ Titers are commonly checked every 3 to 6 months.

Many clinicians will treat for an additional 3 to 6 months after the first negative or low (1:1 or 1:2) titer, rechecking the titer again prior to discontinuing treatment. Osteomyelitis and CNS cases often require long-term to potentially lifelong treatment.^2,3

A valley fever vaccine?

A coccidioidomycosis vaccine, which is an attenuated live vaccine using an avirulent strain of Coccidioides, is currently in development by Anivive Lifesciences.¹⁷ Findings from a 2021 study where research dogs were vaccinated (initial and a booster at day 28) and then subsequently infected with Coccidioides showed that vaccinated dogs had significantly reduced fungal burden and disease scores, with approximately 90% of those dogs having minimal measures of disease.¹⁸ Keep an eye out for more information in the future about more studies on a vaccine, FDA approval, and commercial availability.

Valley fever in cats

Although less common than in dogs, likely due to their indoor lifestyle, valley fever can also be seen in cats. Similar to those in dogs, clinical signs are often related to disease localization, which can include respiratory signs, skin lesions, lameness, neurologic signs, and ocular lesions.¹⁹

Dissemination is common in cats, with findings from one study reporting dissemination in 60% of cats, with the skin being the most common site of dissemination.¹⁹ Diagnosis is generally made from antibody serology and/or cytology, similar to dogs.¹⁹ Treatment is with azole antifungal therapy, with fluconazole being the first choice of medication at 50 mg twice daily, with alternative azole therapy (itraconazole and posaconazole) or amphotericin B in refractory cases.¹⁹

REFERENCES

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17. Biologics. Anivive Lifesciences. Accessed June 3, 2025. https://www.anivive.com/treatments/biologics
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