Histoplasma capsulatum

Histoplasma capsulatum
Histopathology of Histoplasma capsulatum, histiocytes .
Scientific classification
Kingdom:	Fungi
Division:	Ascomycota
Class:	Eurotiomycetes
Order:	Onygenales
Family:	Ajellomycetaceae
Genus:	Histoplasma
Species:	H. capsulatum
Binomial name
Histoplasma capsulatum Darling (1906)

Histoplasma capsulatum is a species of dimorphic fungus. Its sexual form is called Ajellomyces capsulatus. It can cause pulmonary and disseminated histoplasmosis.

H. capsulatum is "distributed worldwide, except in Antarctica, but most often associated with river valleys"^[1] and occurs chiefly in the "Central and Eastern United States"^[2] followed by "Central and South America, and other areas of the world".^[2] It is most prevalent in the Ohio and Mississippi River valleys. It was discovered by Samuel Taylor Darling in 1906.

Growth and morphology

H. capsulatum is an ascomycetous fungus closely related to Blastomyces dermatitidis. It is potentially sexual, and its sexual state, Ajellomyces capsulatus, can readily be produced in culture, though it has not been directly observed in nature. H. capsulatum groups with B. dermatitidis and the South American pathogen Paracoccidioides brasiliensis in the recently recognized fungal family Ajellomycetaceae.^[3][4] It is dimorphic and switches from a mould-like (filamentous) growth form in the natural habitat to a small, budding yeast form in the warm-blooded animal host.

Like B. dermatitidis, H. capsulatum has two mating types, "+" and "–". The great majority of North American isolates belongs to a single genetic type,^[5][6] but a study of multiple genes suggests a recombining, sexual population.^[6] A recent analysis has suggested that the prevalent North American genetic type and a less common type should be considered separate phylogenetic species, distinct from H. capsulatum isolates obtained in Central and South America and other parts of the world. These entities are temporarily designated NAm1 (the rare type, which includes a famous experimental isolate designated "the Downs strain") and NAm2 (the common type).^[6] As yet, no well-established clinical or geographic distinction is seen between these two genetic groups.

In its asexual form, the fungus grows as a colonial microfungus strongly similar in macromorphology to B. dermatitidis. A microscopic examination shows a marked distinction: H. capsulatum produces two types of conidia, globose macroconidia, 8–15 µm, with distinctive tuberculate or finger-like cell wall ornamentation, and ovoid microconidia, 2–4 µm, which appear smooth or finely roughened. Whether either of these conidial types is the principal infectious particle is unclear. They form on individual short stalks and readily become airborne when the colony is disturbed. Ascomata of the sexual state are 80–250 µm, and are very similar in appearance and anatomy to those described above for B. dermatitidis. The ascospores are similarly minute, averaging 1.5 µm.

The budding yeast cells formed in infected tissues are small (about 2–4 µm) and are characteristically seen forming in clusters within phagocytic cells, including histiocytes and other macrophages, as well as monocytes. An African phylogenetic species, H. duboisii, often forms larger yeast cells to 15 µm.

Geographic distribution

H. capsulatum is "distributed worldwide, except in Antarctica, but most often associated with river valleys"^[1] and occurs chiefly in the "Central and Eastern United States"^[2] followed by "Central and South America, and other areas of the world"^[2] It is most prevalent in the Ohio and Mississippi river valleys.

The

Histoplasmosis is usually a subclinical infection that does not come to the attention of the person involved. The organism tends to remain alive in the scattered pulmonary calcifications; therefore, some cases are detected by emergence of serious infection when a patient becomes immunocompromised, perhaps decades later. Frank cases are most often seen as acute pulmonary histoplasmosis, a disease that resembles acute pneumonia but is usually self-limited.[7]^[20] It is most often seen in children newly exposed to H. capsulatum or in heavily exposed individuals. Erythematous skin conditions arising from antigen reactions may complicate the disease, as may myalgias, arthralgias, and rarely, arthritic conditions. Emphysema sufferers may contract chronic cavitary pulmonary histoplasmosis as a disease complication; eventually the cavity formed may be occupied by an Aspergillus fungus ball (aspergilloma), potentially leading to massive hemoptysis.^[20] Another uncommon form of histoplasmosis is a slowly progressing condition known as granulomatous mediastinitis, in which the lymph nodes in the mediastinal cavity between the lungs become inflamed and ultimately necrotic; the swollen nodes or draining fluid may ultimately affect the bronchi, the superior vena cava, the esophagus or the pericardium. A particularly dangerous condition is mediastinal fibrosis, in which a subset of individuals with granulomatous mediastinitis develop an uncontrolled fibrotic reaction that may press on the lungs or the bronchi, or may cause right heart failure. There are a number of other rare pulmonary manifestations of histoplasmosis.

Histoplasmosis, like blastomycosis, may disseminate haematogenously to infect internal organs and tissues, but it does so in a very low proportion of cases, and half or more of these dissemination cases involve immunocompromisation. Unlike blastomycosis, histoplasmosis is a recognized AIDS-defining illness in people with HIV infection; disseminated histoplasmosis affects approximately 5% of AIDS patients with CD4+ cell counts <150 cells/µL in highly endemic areas.^[21] The incidence of this condition dropped significantly after introduction of current anti-HIV therapies.^[20] Other conditions very uncommonly associated with H. capsulatum include endocarditis and peritonitis.^[7][22]

Ecology and epidemiology

H. capsulatum appears to be strongly associated with the droppings of certain bird species as well as bats.

Histoplasmosis outbreaks are typically associated with cleaning guano accumulations or clearing guano-covered vegetation, or with exploration of bat caves. In addition, however, outbreaks may be associated with wind-blown dust liberated by construction projects in endemic areas: a classic outbreak is one associated with intense construction activity, including subway construction, in Montreal in 1963.[24]

As with blastomycosis, a good understanding of the precise ecological affinities of H. capsulatum is greatly complicated by the difficulty of isolating the fungus directly from nature. Again, the mouse passage procedure originally devised by Emmons^[25] must be used. A direct PCR technique for detection of H. capsulatum in soil has been published.^[26] H. capsulatum appears particularly likely to cause clinical disease in young children, persons working in sites contaminated by conducive bird or bat droppings, persons exposed to construction dust raised from contaminated sites, immunocompromised patients, and emphysema sufferers. Elimination of the agent from contaminated soils typically involves the use of toxic fumigants with limited success.^[27]

Etymology

In 1905, Samuel Taylor Darling serendipitously identified a protozoan-like microorganism in an autopsy specimen while trying to understand malaria, which was prevalent during the construction of the Panama Canal. He named this microorganism Histoplasma capsulatum because it invaded the cytoplasm (plasma) of histiocyte-like cells (Histo) and had a refractive halo mimicking a capsule (capsulatum), a misnomer. ^[28]

Additional images

• 
  Histopathology of Histoplasma capsulatum,

  GMS stain

  , showing narrow budding yeast
• 
  H. capsulatum. Methenamine silver stain.
• 
  Histoplasma (bright red, small, circular).

  PAS diastase

  stain
• 
  Histoplasma. PAS diastase stain.
• 
  Histoplasma in a granuloma. PAS diastase stain.
• 
  Histoplasma in a granuloma.

  GMS stain

  .

See also

• Blastomyces
• Coccidioides

References