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School of Biological Sciences
The University of Adelaide

Dr David Ellis

Histoplasma capsulatum

WARNING: RG-3 organism. Cultures of Histoplasma capsulatum represent a severe biohazard to laboratory personnel and must be handled with extreme caution in a Class II Biological Safety Cabinet (BSCII).

Histoplasma capsulatum has a worldwide distribution, however the Mississippi-Ohio River Valley in the USA is recognised as a major endemic region. Environmental isolations of the fungus have been made from soil enriched with excreta from chicken, starlings and bats. Histoplasmosis is an intracellular mycotic infection of the reticuloendothelial system caused by the inhalation of the fungus. Approximately 95% of cases of histoplasmosis are inapparent, subclinical or benign. The remaining 5% of cases may develop chronic progressive lung disease, chronic cutaneous or systemic disease or an acute fulminating fatal systemic disease. All stages of this disease may mimic tuberculosis. Sporadic cases have been reported in Australia.

Morphological Description: Histoplasma capsulatum exhibits thermal dimorphism growing in living tissue or in culture at 37C as a budding yeast-like fungus and in soil or culture at temperatures below 30C as a mould.

Colonies at 25C are slow growing, white or buff-brown, suede-like to cottony with a pale yellow-brown reverse. Other colony types are glabrous or verrucose, and a red pigmented strain has been noted (Rippon, 1988). Microscopic morphology shows the presence of characteristic large, rounded, single-celled, 8-14 µm in diameter, tuberculate macroconidia formed on short, hyaline, undifferentiated conidiophores. Small, round to pyriform microconidia, 2-4 µm in diameter, borne on short branches or directly on the sides of the hyphae may also be present.

Colonies at 37C grown on brain heart infusion (BHI) agar containing blood are smooth, moist, white and yeast-like. Microscopically, numerous small round to oval budding yeast-like cells, 3-4 x 2-3 µm in size are observed.

Three varieties of Histoplasma capsulatum are recognised, depending on the clinical disease: var. capsulatum is the common cause of histoplasmosis; var. duboisii is the African type and var. farciminosum causes lymphangitis in horses. 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 for laboratory safety, culture identification by either exoantigen test or DNA sequencing is now preferred.

Key Features: Clinical history, tissue morphology, culture morphology and positive exoantigen test or DNA sequencing.

Molecular Identification: A probe for species recognition is commercially available (Padhye et al. 1992, Chemaly et al. 2001) and Elias et al. (2012) developed a multiplex-PCR for identification from cultures. Scheel et al. (2014) developed a loop-mediated isothermal amplification (LAMP) assay for detection directly in clinical samples which is affordable and useful in resource poor facilities. ITS sequencing may also be used for accurate identification (Estrada-Bárcenas et al. 2014, Irinyi et al. 2015).

References: McGinnis (1980), Chandler et al. (1980), George and Penn (1986), Rippon (1988), de Hoog et al. (2000, 2015).

Culture of Histoplasma capsulatum
Culture of Histoplasma capsulatum.

rounded tuberculate macroconidia
Large, rounded, single-celled, tuberculate macroconidia and small microconidia of H. capsulatum.




Mycosis: Histoplasmosis

Further reading:

Rippon, J.W. 1988. Medical Mycology. 3rd Edition. W.B. Saunders Co., Philadelphia, USA.