Coccidioidomycosis (Valley Fever)

Coccidioidomycosis is a systemic fungal infection caused by inhalation of arthroconidia of Coccidioides immitis (primarily California) or C. posadasii (Arizona, Texas, Mexico, Central and South America), dimorphic fungi that grow as soil molds in arid regions and convert to parasitic spherules in tissue. Annual incidence has tripled over past decade with climate change, with approximately 150,000 infections estimated annually in the United States, predominantly in Arizona, California, New Mexico, Texas, Utah, and Nevada, also endemic in northern Mexico, parts of Central America, and Argentina.

Pathogenesis involves inhalation of airborne arthroconidia from disturbed soil (construction, archaeology, military training, dust storms) that lodge in alveoli and convert to characteristic large spherules (40-80 μm) containing hundreds of endospores. Cell-mediated immunity controls infection in 60-70% of immunocompetent individuals (asymptomatic). Symptomatic primary disease (Valley fever) presents 1-3 weeks after exposure with influenza-like illness, fatigue, fever, dry cough, chest pain, headache, erythema nodosum, erythema multiforme, and arthralgias (desert rheumatism). Most resolve spontaneously, but 5-10% develop persistent pulmonary disease (cavitary or chronic progressive), and less than 1% develop extrapulmonary dissemination affecting skin, soft tissue, bone, joints, central nervous system (meningitis), or other organs.

Diagnosis includes serology (Coccidioides IgM and IgG by EIA, immunodiffusion confirmation, complement fixation titer), tissue or fluid culture (biohazard level 3 organism), histopathology with characteristic spherules, antigen detection in urine and serum, and PCR. Imaging shows pulmonary infiltrates, nodules, cavities, hilar lymphadenopathy, and disseminated disease findings. Treatment depends on disease severity: observation for asymptomatic primary disease in immunocompetent hosts, fluconazole 400 mg daily for symptomatic primary disease, itraconazole as alternative, lifelong fluconazole 400-800 mg daily for meningitis (or amphotericin B intrathecal as adjunct), amphotericin B for severe disease or failure, and posaconazole or voriconazole for refractory cases.