What is coccidioidomycosis?

Causes and Symptoms

Coccidioidomycosis is an infection caused by the soil-based fungi Coccidioides immitis (C. immitis) and Coccidioides posadasii (C. posadasii). These fungi are found only in the Western hemisphere, and they prefer dry, alkaline soils. C. immitis and C. posadasii are endemic to the southwestern United States (south-central California, Nevada, Arizona, New Mexico, and western Texas), those regions of Mexico that border the western United States, parts of Central America (Guatemala, Honduras, and Nicaragua), and the desert regions of South America (Argentina, Paraguay, and Venezuela).

While in the soil, Coccidioides, like most fungi, grows as thin, branching filaments called hyphae. A collection of hyphae is called a mycelium. When it rains, the mycelium grows quite rapidly, but once the soil dries out, it forms resting cells called arthrospores. If disturbed by wind, earthquakes, or soil excavation, these arthrospores become airborne and, if inhaled, can cause coccidioidomycosis.

Once inhaled, the arthrospore transforms into a thick-walled, spherical structure called a spherule that divides itself into hundreds of small endospores. When the spherule ruptures, it releases the endospores, which grow into spherules that form more endospores.

About 60 percent of patients show no symptoms, and the disease resolves spontaneously. Those patients who show symptoms suffer from fever, sore throat, headache, cough, fatigue, painful bumps on the skin (erythema nodosum), and chest pain approximately one to three weeks after inhaling arthrospores. About 95 percent of symptomatic patients recover without further problems after several weeks. If symptoms persist beyond three months, however, then the patient has chronic progressive coccidioidal pneumonia. Between 5 and 7 percent of patients with coccidioidal pneumonia form pulmonary nodules, which are areas of the lung where the immune system has walled-off the organism from the rest of the lung. On an X-ray, these nodules can look exactly like cancerous masses in the lung. A biopsy is often necessary to distinguish between lung cancer and coccidioidal pulmonary nodules. In 5 percent of patients with coccidioidal pulmonary
nodules, the nodules enlarge to form pulmonary cavities that can become infected, rupture, and bleed, causing the release of pus between the lungs and the ribs (empyema). Small cavities (less than 2.5 centimeters) can heal after one to two years, but larger cavities can persist and cause the patient to spit up blood (hemoptysis) and allow the growth of fungi throughout the cavity (mycetoma).

A minority of patients develop disseminated coccidioidomycosis, in which the organism penetrates blood vessels, invades the bloodstream, and infects any organ in the body. Disseminated coccidioidomycosis occurs weeks or months after the primary pneumonia and can even develop in cases where there is no previous evidence of respiratory disease. Particular ethnic groups such as Filipinos and African Americans show increased risk of developing disseminated disease, as do pregnant women in the third trimester of their pregnancy, infants younger than one year old, diabetics, patients with Acquired immunodeficiency syndrome (AIDS), or those taking drugs or suffering from diseases that suppress the immune system.

Treatment and Therapy

Asymptomatic or symptomatic infections are usually self-limited and require little more than supportive care. Patients with coccidioidal pneumonia require fluconazole or itraconazole treatment for at least twelve months and intravenous amphotericin B for stubborn cases. Pulmonary nodules are typically not treated, but they may require surgery. Pulmonary cavities are only treated with antifungal drugs if the patient shows symptoms. Surgical removal might also be warranted if the infection resists treatment. Disseminated coccidioidomycosis requires higher doses of fluconazole, and very sick patients may require amphotericin B or a combination of fluconazole and amphotericin B. Amphotericin B is preferred for pregnant women, since other drugs harm the developing fetus.

Perspective and Prospects

Coccidioidomycosis was first described in 1892 by Roberto Johann Wernicke and Alejandro Posadas in South America. The first case in the United States was reported in California in 1894. Two years later, Emmet Rixford and Thomas Caspar Gilchrist reported several clinical infections that were caused by an organism that, they thought, resembled the protozoan Coccidia. Therefore they named it Coccidioides, which means “Coccidia-like.” In 1905, William Ophüls described the fungal life cycle and pathology of C. immitis. Charles E. Smith studied the epidemiology of coccidioidomycosis in the San Joaquin Valley of California and went on to develop the coccidioidin skin test and serological testing for the disease.

The Centers for Disease Control and Prevention released a study in 2013 that showed an increase in cases of coccidioidomycosis in the southwestern United States between 1998 and 2011. Cases in the states of Arizona, California, Nevada, New Mexico, and Utah increased from 2,265 reported in 1998 to 22,000 reported in 2011.

New treatments under investigation for coccidioidomycosis include posaconazole, voriconazole, caspofungin, and a new lipid-dispersal formulation of amphotericin B that reduces its kidney toxicity. Nikkomycin Z is another experimental agent that is very active against Coccidioides in culture and infected animals.

Bibliography:

Anstead, Gregory M., and John R. Graybill. “Coccidioidomycosis.” Infectious Disease Clinics of North America 20, no. 3 (September, 2006): 621–43.

Centers for Disease Control and Prevention. "Valley Fever Increasing in Some Southwestern States." CDC, Mar. 28, 2013.

Galgiani, John N. “Changing Perceptions and Creating Opportunities for Its Control.” Annals of the New York Academy of Sciences 1111 (September, 2007): 1–18.

Kohnle, Diana. "Coccidioidomycosis." Health Library, Nov. 26, 2012.

Kwon-Chung, K. J., and John E. Bennett. Medical Mycology. Philadelphia: Lea and Febiger, 1992.

Parish, James, M., and James E. Blair. “Coccidioidomycosis.” Mayo Clinic Proceedings 83, no. 3 (March, 2008): 343-348.