Coccidioides immitis and Coccidioides posadasii
These agents are species of dimorphic fungi that propagate as mycelial moulds in soil and as spherules bearing endospores in mammalian tissue. Mature hyphal filaments of the mycelial form develop arthroconidia which detach and may then become airborne. Arthroconidia are lightweight, barrel-shaped cells measuring approximately 3 μm x 6 μm that are stable to drying.
The fungus occurs in soil, especially in arid and semi-arid regions of South-western United States, northern Mexico and focal areas of central and South America. A substantial percentage of cattle, swine, sheep, dogs and humans in endemic regions have had asymptomatic infections, as revealed by skin testing.
Reservoirs: Soil, in particular arid regions of the western hemisphere.
Mode of transmission
Infection usually takes place by inhalation of arthroconidia. A dust storm originating in an endemic region of California in 1977 caused an elevated incidence of the disease over an area of thousands of square kilometres.
Mammals, including humans, inhaling even a single arthroconidium may become infected. Once within the host, arthroconidia undergo a morphological change into spherules. These are round, segmented structures of 30–60 μm. Within these are hundreds of 2–3 μm ovoidal endospores which themselves may develop into endosporebearing spherules, spreading the disease throughout the body.
Incubation period: The incubation period is usually 1–3 weeks.
In endemic areas, the majority of infections are asymptomatic, but may be detected by skin tests. The percentage of persons residing in endemic areas found to react positively to skin tests ranges from 5% to more that 50%.
For those developing clinical disease, the initial symptoms resemble those of other upper respiratory infections, and include cough, fever, night sweats, chills, chest pain, sputum production and headache. Less often, there may also be various skin manifestations, including erythema nodosum or erythema multiforme with or without joint aches.
The initial form of the disease usually resolves without therapy within several weeks, although occasional patients have a more protracted convalescence.
Persistent symptomatic coccidioidomycosis of the lungs occurs in a small percentage of patients and is more frequent in patients with diabetes mellitus. It is characterized by progressive destructive pulmonary disease with continuous low-grade fever, weakness, cough with sputum production, dyspnoea, haemoptysis and pleuritic chest pain.
Extrapulmonary dissemination is seen in approximately 1% of all infected persons, and usually becomes evident weeks to months after primary disease. It is characterized by involvement of the skin, subcutaneous tissues, bones, joints and the central nervous system Patients with AIDS or other deficiencies in cellular immunity are especially susceptible to these complications.
Without treatment, the disseminated form, which may follow a rapid or a prolonged course, has a mortality rate of more than 50%, approaching 100% if meningitis develops. Recovery from clinical disease appears usually to be accompanied by lifelong immunity, and most individuals with asymptomatic infection also develop lifelong immunity.
Spherules and endospores may be visualized with calcafluor, Papanicolaou, haematoxylin–eosin and Gomori methenamine staining in sputum samples, pus and biopsy tissue. The organism is rarely identified in cerebrospinal fluid. Direct microscopic examination of sputum samples placed in 10% potassium hydroxide reveals spherules and endospores in fewer than 30% of cases and may be complicated by the presence of spherule-like artefacts, such as pollen.
Skin tests for hypersensitivity to preparations derived from the fungal mycelia (with coccidioidin) or from spherules (with spherulin) have been useful for epidemiological studies but may give false-negative results in individual cases, especially if the disease is advanced. Skin testing reagents are not currently commercially available.
Medical management and public health measures
As the disease is not contagious, quarantine and patient isolation are not indicated. As the arthroconidia easily become airborne and are highly infective, manipulation of clinical specimens and sporulating cultures should be conducted under Biosafety Level 3 conditions. Contaminated specimens and materials may be sterilized by autoclaving or by treatment with iodine or glutaraldehyde-based disinfectants.
Prophylaxis and therapy
No vaccine against coccidioidomycosis is available at the present time. Recombinant coccidioidal antigens have been identified as protective in experimental infections and efforts are under way to develop them as vaccine candidates for clinical studies. For serious or persistent cases, prolonged therapy with amphotericin B or oral azole antifungal agents (ketoconazole, fluconazole, itraconazole) is moderately effective. Lifelong administration of fluconazole is recommended for coccidioidal meningitis.