Coccidioides immitis and Coccidioides posadasii cause coccidioidomycosis. The clinical manifestations of disease caused by these two species are the same, but the geographical distribution differs. For simplicity, the original species name, C. immitis, will be used most often in this chapter.
Coccidioides species are dimorphic fungi that exist as a mold in soil and as a spherule in tissue (Figure 49–1). C. immitis and C. posadasii are distinguished by genotyping but not by routine diagnostic tests in the clinical laboratory.
Stages of Coccidioides immitis. A: Arthrospores form at the ends of hyphae in the soil. They germinate in the soil to form new hyphae. If inhaled, the arthrospores differentiate into spherules. B: Endospores form within spherules in tissue. When spherules rupture, endospores disseminate and form new spherules. (Reproduced with permission from Brooks GF, Butel JS, Ornston LN. Jawetz, Melnick & Adelberg’s Medical Microbiology, 20th ed. New York, NY: McGraw-Hill Education; 1995.)
Transmission & Epidemiology
The fungus is endemic in the soil of arid regions of the southwestern United States and Latin America. People who live in Central and Southern California, Arizona, New Mexico, Western Texas, and Northern Mexico, a geographic region called the Lower Sonoran Life Zone, are often infected. The organism is also found in the soil in areas of Central and South America. C. immitis is found in California, whereas C. posadasi is found in other southwestern states and in Latin America.
In soil, it forms hyphae with alternating arthrospores and empty cells (Figure 49–2). Arthrospores are very light and are carried by the wind. They can be inhaled and infect the lungs.
Coccidioides immitis—arthrospores. Barrel-shaped, rectangular arthrospores appear blue with lactophenol-cotton blue stain. Arthrospores are also called arthroconidia. (Used with permission from Dr. Hardin, Public Health Image Library, Centers for Disease Control and Prevention.)
In the lungs, arthrospores form spherules that are large (30 mm in diameter), have a thick, doubly refractive wall, and are filled with endospores (Figure 49–3). Upon rupture of the wall, endospores are released and differentiate to form new spherules. The organism can spread within a person by direct extension or via the bloodstream. Granulomatous lesions can occur in virtually any organ but are found primarily in bones and the central nervous system (meningitis).
Coccidioides immitis—spherule. Long arrow points to a spherule in lung tissue. Spherules are large thick-walled structures containing many endospores. Short arrow points to an endospore. (Used with permission from Dr. L. Georg, Public Health Image Library, Centers for Disease Control and Prevention.)
Dissemination from the lungs to other organs occurs in people who have a defect in cell-mediated immunity. Most people who are infected by C. immitis develop a cell-mediated (delayed hypersensitivity) immune response that restricts the growth of the organism. One way to determine whether a person has produced adequate cell-mediated immunity to the organism is to do a skin test (see later). In general, a person who has a positive skin test reaction has developed sufficient immunity to prevent disseminated disease from occurring. If, at a later time, a person’s cellular immunity is suppressed by drugs or disease, disseminated disease can occur.
Infection of the lungs is often asymptomatic and is evident only by a positive skin test and the presence of antibodies. Some infected persons have an influenza-like illness with fever and cough, resembling a community-acquired pneumonia. About 50% have changes in the lungs (infiltrates, adenopathy, or effusions) as seen on chest X-ray, and 10% develop erythema nodosum (EN) (see later) or arthralgias. This syndrome is called “valley fever” (in the San Joaquin Valley of California) or “desert rheumatism” (in Arizona); it tends to subside spontaneously.
Disseminated disease can occur in almost any organ; the meninges (meningitis), bone (osteomyelitis), and skin (nodules) are important sites. The overall incidence of dissemination in persons infected with C. immitis is 1%, although the incidence in Filipinos and African Americans is 10 times higher. Women in the third trimester of pregnancy also have a markedly increased incidence of dissemination. Patients with compromised cell-mediated immunity such as those with acquired immunodeficiency syndrome (AIDS), cancer chemotherapy, or drugs to prevent transplant rejection also have an increased risk of disseminated disease. Infected patients in these high-risk categories are often treated even though they do not have signs of disseminated disease.
EN manifests as red, tender nodules (“desert bumps”) on extensor surfaces such as the skin over the tibia and ulna. It is a delayed (cell-mediated) hypersensitivity response to fungal antigens and thus is an indicator of a good prognosis. There are no organisms in these lesions; they are not a sign of disseminated disease. EN is not specific for coccidioidomycosis; it occurs in other granulomatous diseases (e.g., histoplasmosis, tuberculosis, and leprosy).
In infected persons, skin tests with fungal extracts (coccidioidin or spherulin) cause at least a 5-mm induration 48 hours after injection (delayed hypersensitivity reaction). Skin tests become positive within 2 to 4 weeks of infection and remain so for years but are often negative (anergy) in patients with disseminated disease.
In tissue specimens, spherules are seen microscopically. The presence of spherules is pathognomonic for Coccidioides infection.
Cultures on Sabouraud’s agar incubated at 25°C show septate hyphae with arthrospores (see Figure 49–2). (Caution: Cultures are highly infectious; precautions against inhaling arthrospores must be taken.)
Serologic testing is a common procedure for diagnosing Coccidioides infection. IgM antibodies are detected by a tube precipitin test, and their presence indicates an acute infection. IgG antibodies are detected by a complement fixation (CF) test, and their presence indicates a long-standing infection or a disseminated infection. A titer of 1/16 or greater is common in coccidioidal meningitis. Enzyme-linked immunosorbent assays (ELISA) are also used to detect IgM and IgG antibodies to Coccidioides.
A polymerase chain reaction (PCR) assay that detects nucleic acids of Coccidioides is available.
No treatment is needed in asymptomatic or mild primary infection. Fluconazole or itraconazole is used for persisting lung lesions or mild disseminated disease. Severe disseminated disease including bone lesions should be treated with amphotericin B. If meningitis occurs, fluconazole is the drug of choice. Intrathecal amphotericin B may be required and may induce remission, but long-term results are often poor.
There is no vaccine. Prevention involves avoiding travel to endemic areas. Patients with Coccidioides infection who are significantly immunocompromised (e.g., organ transplant patients) should receive fluconazole. Patients who have recovered from coccidioidal meningitis should receive long-term suppressive therapy with fluconazole.