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School of Molecular & Biomedical Science
The University of Adelaide
AUSTRALIA 5005

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Dr David Ellis
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Coccidioidomycosis

Description:

Coccidioidomycosis is initially, a respiratory infection, resulting from the inhalation of conidia, that typically resolves rapidly leaving the patient with a strong specific immunity to re-infection. However, in some individuals the disease may progress to a chronic pulmonary condition or to a systemic disease involving the meninges, bones, joints and subcutaneous and cutaneous tissues. Coccidioides immitis is a soil inhabiting fungus endemic in south-western U.S.A., northern Mexico and various centres in South America. Several cases have now been diagnosed in Australia, all in patients with a history of travel to endemic areas.

Clinical manifestations:

60% of individuals suffer a benign and transient chest infection that does not require medical attention. Of the 40% who develop symptoms, most will have an acute febrile "flu-like" illness starting 7-28 days (average 10-16 days) after exposure and most patients will recover completely. The main symptoms are fever, pleuritic chest pain, cough, malaise, headache, myalgia, night sweats and loss of appetite. Many patients also develop a mild, diffuse erythematous or maculopapular rash on the trunk and limbs. However, 5-10% of patients that do develop symptoms are left with pulmonary residual nodule or cavity that is usually detected several months or years later. Another 5% of patients may develop metapulmonary dissemination to the meninges, bones, joints and subcutaneous and cutaneous tissues, within the first few weeks to months after the onset of primary infection .

lesions of the face, neck and chin
Chronic cutaneous coccidioidomycosis showing granulomatous lesions of the face, neck and chin (Courtesy of John Rippon, USA).

large superficial, ulcerated plaque
Extension of pulmonary coccidioidomycosis showing a large superficial, ulcerated plaque (Courtesy of John Rippon, USA).

Laboratory diagnosis:

1. Clinical material: Skin scrapings, sputum and bronchial washings, cerebrospinal fluid, pleural fluid and blood, bone marrow, urine and tissue biopsies from various visceral organs.

2. Direct Microscopy: (a) Skin scrapings should be examined using 10% KOH and Parker ink or calcofluor white mounts; (b) Exudates and body fluids should be centrifuged and the sediment examined using either 10% KOH and Parker ink or calcofluor white mounts, (c) Tissue sections should be stained using PAS digest, Grocott's methenamine silver (GMS) or Gram stain.

Histopathology is especially useful and is one of the most important ways of alerting the laboratory that they may be dealing with a potential pathogen.

Direct microscopy of skin scrapings
Direct microscopy of skin scrapings from a cutaneous lesion mounted in 10% KOH and Parker ink solution showing characteristic endosporulating spherules (sporangia) of Coccidioides immitis. The presence of spherules with endospores is diagnostic.

Tissue section
Tissue section showing typical endosporulating spherules of Coccidioides immitisYoung spherules have a clear centre with peripheral cytoplasm and a prominent thick walled. Endospores (sporangiospores) are later formed within the spherule by repeated cytoplasmic cleavage. Rupture of the spherule releases endospores into the surrounding tissue where they re-initiate the cycle of spherule development.

Interpretation: As a rule, a positive direct microscopy demonstrating spherules (10-80um) with endospores (2-5um) from any specimen should be considered significant.

3. Culture: Clinical specimens should be inoculated onto primary isolation media, like Sabouraud's dextrose agar and Brain heart infusion agar supplemented with 5% sheep blood.

Culture
Culture of Coccidioides immitis showing a suede-like to downy, greyish white colony with a tan to brown reverse.

Interpretation: A positive culture from any of the above specimens should be considered significant.

WARNING: Cultures of Coccidioides immitis represent a severe biohazard to laboratory personnel and must be handled with extreme caution in an appropriate pathogen handling cabinet. .

4. Serology: Immunodiffusion and/or complement fixation tests for the detection of antibody have proven to be useful in the diagnosis of Coccidioidomycosis especially in immunocompetent patients. However, detection of antibodies in immunosuppressed patients is often difficult, with between 20-50% of patients testing negative.

5. Identification: In the past microscopic morphology, conversion from the mould form to the yeast or spherule form, and animal pathogenicity have all been used; however exoantigen tests are now the method of choice for identifying isolates of Coccidioides immitis.

Causative agents:

Coccidioides immitis

Treatment Guidelines

 

Further reading:

Ajello L and R.J. Hay. 1997. Medical Mycology Vol 4 Topley & Wilson's Microbiology and Infectious Infections. 9th Edition, Arnold London.

Chandler FW., W. Kaplan and L. Ajello. 1980. A colour atlas and textbook of the histopathology of mycotic diseases. Wolfe Medical Publications Ltd. London.

Kwon-Chung KJ and JE Bennett 1992. Medical Mycology Lea & Febiger.

Richardson MD and DW Warnock. 1993. Fungal Infection: Diagnosis and Management. Blackwell Scientific Publications, London.

Rippon JW. 1988. Medical Mycology WB Saunders Co.