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Infectious Disease and Microbiology – Coccidioidomycosis
Coccidioidomycosis is a pulmonary and/or extrapulmonary infection caused by the dimorphic fungus Coccidioides immitis. The disease is commonly referred to as “Valley fever” and may range from a mild respiratory illness to severe disseminated infection.
In the United States, the incidence is approximately 91 cases per 100,000 people. C. immitis is endemic to the southwestern United States, particularly California, Arizona, and Texas, as well as parts of Mexico and Central and South America. Increasingly, cases are recognized outside endemic areas, typically in travelers or due to reactivation of latent infection. Periodic outbreaks with sharp increases in case numbers occur.
Risk is increased in individuals with immunosuppressive conditions or therapies, including AIDS, solid-organ transplantation, lymphoma, and glucocorticoid or other immunosuppressive treatments. Among patients with AIDS, infection is especially likely when CD4 counts are below 250 cells/mm³. Even distant past exposure to endemic regions is important, as latent infection may reactivate during immunosuppression. Pregnancy, particularly in late stages, and diabetes mellitus are also associated with increased risk of severe disease.
The fungus resides in soil and grows optimally at approximately 30°C but also proliferates at body temperature (37°C). Infection occurs through inhalation of airborne arthroconidia. In most cases, acute pulmonary infection resolves spontaneously. However, some patients develop progressive pneumonia or chronic pulmonary infection. Approximately 5% of infected individuals develop asymptomatic residual lung nodules or thin-walled cavities. Disseminated disease occurs in roughly 1 in 200 infected individuals and most commonly involves the meninges, bones, joints, skin, and soft tissues. Extrapulmonary disease usually develops within one year of primary infection but may occur later if immunity declines.
Symptoms typically appear 1–3 weeks after exposure. The most common presentation is a lower respiratory tract infection accompanied by systemic symptoms such as fever, cough, sputum production, chest pain, weakness, anorexia, sweating, and arthralgias. Erythema nodosum or erythema multiforme may occur. Extrapulmonary disease presents with focal symptoms depending on the organ involved. Skin lesions often appear as wart-like nodules. Joint involvement is usually unilateral. Meningitis often affects the basilar meninges and may present with headache as the most prominent symptom.
Physical examination should include careful evaluation of the skin and neurologic system to identify extrapulmonary involvement. Coccidioidal lesions are typically focal and produce localized symptoms such as swelling, ulceration, or discomfort.
Diagnosis relies on culture, serologic testing, and coccidioidal skin testing. Accurate travel history is essential, particularly outside endemic areas. Serum IgM antibodies are detectable in approximately 75% of primary infections early in the course of illness. IgG antibodies develop later and usually decline if the infection resolves. False-positive serologic results are uncommon. Skin testing becomes positive soon after symptom onset in primary infection and rarely cross-reacts with other infections. Cerebrospinal fluid in meningitis typically shows mononuclear pleocytosis, elevated protein, and low glucose. Chest radiographs may demonstrate infiltrates, pleural effusion, or hilar adenopathy.
The role of antifungal therapy in mild or moderate primary pulmonary infection remains uncertain. Treatment decisions are individualized. Oral fluconazole (400 mg daily) or itraconazole (200 mg twice daily) may be given for 3–6 months, particularly in patients with severe symptoms, high antibody titers, extensive lung involvement, significant weight loss, persistent symptoms, or increased host susceptibility. Disseminated disease always requires prolonged antifungal therapy.
Fluconazole and itraconazole are the drugs of choice for meningeal disease. Lifelong suppressive therapy may be required in some cases. Amphotericin B is reserved for patients who fail azole therapy or have severe disseminated infection. Surgical intervention may be necessary for complications such as severe hemoptysis, enlarging cavities, empyema, bronchopleural fistula, or restricted lung expansion.
Approximately 5–10% of infections result in residual sequelae. Early diagnosis of meningitis is critical, as untreated cases carry a 90% mortality within 12 months. Chronic pulmonary disease may develop, particularly in diabetic or immunocompromised patients.
Complications are more common and severe in immunocompromised individuals, especially those with extrapulmonary disease. Organ transplant recipients are at highest risk during the first year after transplantation. Meningitis may occur within six months of primary infection and may lack classic meningeal signs seen in bacterial meningitis. Symptoms can include headache, fever, confusion, seizures, diplopia, ataxia, vomiting, and focal neurologic deficits.
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