Signalment:  
Eight year-old female baboon (
Papio sp.)Multiple ulcerated skin lesions were noted on the limbs, tail, and sex skin of an 8 year-old female baboon
from the Southwest National Primate Research Center at the Texas Biomedical Research Institute. Impression
smears were taken and submitted for cytology. The animal was euthanized following the identification of organisms
and evidence of extensive infection.
Gross Description:  
The animal was thin with decreased body fat. Multiple irregular-shaped, slightly raised, firm
and frequently ulcerated skin lesions were present on all four limbs, feet, sex skin, and the tail, ranging in size from
<0.5 cm to >4 cm. On section the dermis was expanded by pink-tan nodules.
Histopathologic Description:
Skin: There is a focally extensive area of epidermal ulceration,
hemorrhage and in some sections, overlying serocellular crust. The remaining epidermis is mildly to moderately
thickened (acanthosis). The dermis is markedly expanded by granulation tissue and coalescing nodular aggregates of
mixed inflammatory cells consisting of variable numbers of neutrophils, plump macrophages, multinucleated giant
cells and fewer lymphocytes and eosinophils. Within the cytoplasm of many of the macrophages and multinucleated
giant cells are numerous round to oval, pale staining organisms (yeast), which are 8-15 microns in diameter, with a
clear, refractile, ~1-2 micron-thick cell wall, a 1-2 micron, basophilic nucleus, and rare narrow-based budding,
morphologically consistent with
Histoplasma capsulatum var.Â
duboisii. Lymphohistiocytic perivascular cuffs are
present at the periphery of the lesion.
Morphologic Diagnosis:  
Haired skin: Dermatitis, granulomatous, nodular, multifocal, moderate,
with ulceration, hemorrhage, epidermal hyperplasia, and numerous intrahistiocytic yeasts, baboon (
Papio sp.),
nonhuman primate.
Condition:  
Histoplasma capsulatum var. duboisii
Contributor Comment:  
African histoplasmosis is a chronic progressive fungal infection endemic in Western and
Central Africa and caused by
Histoplasma capsulatum var.Â
duboisii. Natural infection is rare and has been reported
only in baboons and humans. In 1988, the first reported animal case in the United States was diagnosed in an adult
red baboon at the Southwest Foundation for Biomedical Research (currently the Texas Biomedical Research
Institute) in San Antonio, Texas. Imported from Senegal, this animal was in the United States for approximately 2
years prior to diagnosis(2). In 1991 this same research institute experienced an epizootic of
H. capsulatum var.
duboisii involving over 20 cases in both wild-caught and native-born baboons(3).
Although the ecology and pathogenesis of infection remain unclear, soil is believed to be the natural reservoir of
H.
capsulatum var.Â
duboisii, with inhalation, ingestion, and possibly dermal contact the most likely methods of
transmission. Inhalation and ingestion of the organism are thought to initially infect the lung or intestinal tract, with
subsequent hematogenous spread to the skin, for which the organism appears to have a predilection. Infected
animals may remain asymptomatic for a year or more before clinical symptoms become apparent(3,4).
Grossly, the lesions are typically nodular, ulcerated and/or exudative and commonly found on the face, ears, digits,
tail, scrotum and buttocks(3,4). Draining regional lymph nodes may become enlarged. Osteomyelitis caused by
H.
capsulatum var.Â
duboisii has been reported, presumably by extension from skin to subjacent bone. Lesions have also
been reported in nasal turbinates and testis.
Although
Histoplasma capsulatum var.Â
duboisii. stains well with Gomoris methenamine silver or Gridleys fungal
stains, identification can usually be made from standard histology sections by its unique morphologic appearance
which often includes organization in pairs and short chains, combined with the characteristic granulomatous
inflammation(6). The organism can be easily distinguished from the more common
Histoplasma capsulatum var.
capsulatum which presents as small oval yeast only 2-4 um in diameter.Â
Blastomyces dermatitidis is similar in size
and shape to
H. capsulatum var.Â
duboisii, but can be differentiated by its broad-based budding and lack of chain
formation.Â
Cryptococcus neoformans typically incites much less inflammation in tissues compared with
H.
capsulatum var.
duboisii, and morphologically the yeast phase is slightly smaller with a thin cell wall and a wide,
clear, unstained capsule that stains positive with mucicarmine. The immature or non-endosporulating spherules of
Coccidioides immitis can be similar in shape but are often slightly larger (5-25 um) than
H. capsulatum var.
duboisii; and are accompanied by the presence of larger mature spherules containing endospores(5,6).
The disease in humans is rare and generally limited to people in or from Africa. Epidemiologic data reveal the
organisms predilection for lymph nodes, skin and bone. In humans, pulmonary involvement is more common in
HIV-negative individuals while the incidence of disseminated disease is increased in HIV-positive patients(5). It is
unclear what role immunosuppression plays in the risk of infection. The reported incidence of disease remains very
low despite the high incidence of HIV infection in endemic regions, and is much lower compared with reports of
opportunistic infections with
Histoplasma capsulatum var.Â
capsulatum from the same areas(5).
JPC Diagnosis:  
Glaborous skin: Dermatitis, pyogranulomatous, focally extensive, severe, with numerous
intracytoplasmic yeasts.
Conference Comment:  
This is an excellent example of African histoplasmosis in a baboon and the contributor
provides a thorough overview of the disease. Conference participants discussed the list of rule outs mentioned by the
contributor, as well as
Lacazia lobo and cutaneous
Paracoccidioides brasiliensis, which have similar morphology.
Lobos disease has only been reported in humans and dolphins and is characterized morphologically by 10 um in
diameter yeast which bud to form chains that resemble a string of pearls. Cutaneous paracoccidiomycosis is
characterized by pyogranulomatous inflammation and multibudding yeast mother cells approximately 60 um in
diameter with a 1 um thick refractile cell wall surrounded by 2-10 um spherical daughter cells(1,4).
References:
1. Brummer E, Castaneda E, Restrepo A. Paracoccidioidomycosis: an update. Clin Microbiol Rev. 1993 Apr;6(2):89-117.
2. Butler TM, Gleiser CA, Bernal JC, Ajello L. Case of disseminated African histoplasmosis in a baboon. J Med Primatol. 1988;17(3):153-161.
3. Butler TM, Hubbard GB: An epizootic of Histoplasma duboisii (African histoplasmosis) in an American baboon colony. Lab Anim Sci 1991;41(5):407-410.
4. Durden WN, St Leger J, Stolen M, Mazza T, Londono C. Lacaziosis in bottlenose dolphins (Tursiops truncatus) in the Indian River Lagoon, Florida, USA. J Wildl Dis. 2009;45:849-856.
5. Loulergue P, Bastides F, Baudouin V, et al. Literature review and case histories of Histoplasma capsulatum var. duboisii infections in HIV-infected patients. Emerg Infect Dis. 2007;13(11):1647-1652.
6. Migaki G, Hubbard GB, Butler TM: Histoplasma capsulatum var. duboisii infection, baboon. In: Nonhuman Primates II: Monographs on Pathology of Laboratory Animals, ed. Jones TC, Mohr U, Hunt RD, Springer-Verlag, New York, NY 1993