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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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Histoplasmosis

Description:

Histoplasmosis is an intracellular mycotic infection of the reticuloendothelial system caused by the inhalation of conidia from the fungus Histoplasma capsulatum. Histoplasmosis has a world wide distribution, however, the Mississippi-Ohio River Valley in the U.S.A. is recognized as a major endemic region. Africa, Australia and parts of East Asia, in particular India and Malaysia are also endemic regions. Environmental isolations of the fungus have been made from soil enriched with excreta from chicken, starlings and bats. Two varieties of H. capsulatum are recognized, depending on the clinical disease: var. capsulatum is the common histoplasmosis, and var. duboisii is the African type. The two varieties are identical in their saprophytic mould form but differ in their parasitic tissue morphology.

Clinical manifestations:

Approximately 95% of cases of histoplasmosis are inapparent, subclinical or benign. Five percent of the cases have chronic progressive lung disease, chronic cutaneous or systemic disease or an acute fulminating fatal systemic disease. All stages of this disease may mimic tuberculosis.

lower gum showing an ulcer
Histoplasmosis of the lower gum showing ulcer around base of the teeth.

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.

H. capsulatum var. capsulatumH. capsulatum var. duboisii
Tissue morphology of H. capsulatum var. capsulatum (left) showing numerous small narrow base budding yeast cells (1-5um diam) inside macrophages and H. capsulatum var. duboisii (right) showing larger sized budding yeast cells (5-12 um in diam).

Interpretation: As a rule, a positive direct microscopy demonstrating characteristic yeast-like cells 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.

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

Culture
Culture of Histoplasma capsulatum.

WARNING: Cultures of H. capsulatum 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 Histoplasmosis, especially in immunocompetent patients. However, detection of antibodies in immunosuppressed patients is often difficult, with between 20-50% of patients testing negative.

5. Identification: Two varieties of H. capsulatum are recognized, depending on the clinical disease: var. capsulatum is the common histoplasmosis, and var. duboisii is the African type. Histoplasma isolates may also resemble species of Sepedonium and Chrysosporium. Traditionally, positive identification required conversion of the mould form to the yeast phase by growth at 37C on enriched media, however culture identification by the exoantigen test is now the method of choice.

Causative agents

Histoplasma capsulatum

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.