Veterinary Medicine - May 2008 - (Page 251) Histoplasmosis PEER-REVIEWED The biological basics of Histoplasma species Life cycle Histoplasma capsulatum, a dimorphic fungus, exists in a mycelial stage in soil and transitions to a yeast phase in susceptible hosts. The sources of infection are macroconidia (15 to 18 µm) and microconidia (2 to 5 µm), which are produced in the mycelial stage. While moisture, humidity, and ambient temperatures of 71 to 84.2 F (21.6 to 29 C) are ideal for this organism to thrive, the mycelial stage of H. capsulatum is environmentally resistant and can survive wide variations in temperature.10 For example, H. capsulatum is endemic in the dry, desertlike region near El Paso, Texas,59 and California’s San Joaquin Valley.41 Inhaled microconidia are small enough to reach the bronchioles and alveoli, and the microconidia transition to a yeast phase in the body at 98.6 F (37 C). The yeast form is 2 to 4 µm18,21,35 and is surrounded by a 4-µm wall.24 The yeast reproduce by budding.10 31 of the 48 continental states10 and has been reported in domestic, wild, and zoo animals. Affected domestic animals include dogs, cats, horses, cattle, and swine. Many other mammalian species are reportedly susceptible, including baboons, badgers, bats, bears, chinchillas, foxes, mice, opossums, raccoons, rats, shrews, skunks, ferrets, guinea pigs, and squirrels.4 Histoplasma capsulatum’s survival in soil is enhanced in the presence of bird and bat excrement,7,10,11,61 which contain carbohydrates, nitrogen, phosphates, and cationic salts.4 These nutrients accelerate sporulation and, thus, enhance the organism’s growth.61 Cationic salt concentrations are also increased in the soil of the aforementioned river valleys.4 Areas of increased risk of exposure to histoplasmosis include bat caves, chicken coops, and the roosts of starlings and other avian species.11 Even after roosting sites have been cleared, soil samples may remain contaminated for up to 10 years.86 Soil disruption enhances the possibility of exposure to H. capsulatum and may occur through building or road construction, demolition, renovation, or farm work.4 Infection in both people and animals can occur through exposure to the same environmental source.82,87 In addition, systemic histoplasmosis has occurred in exclusively indoor cats,41 suggesting that potting soil or house dust may also be sources of transmission. Transmission of H. capsulatum from person to animal, animal to animal, or person to person does not normally occur.85 The primary route of transmission is by inhaling H. capsulatum spores from the environment.10,11,61,62,85 Dogs may also be infected by ingesting the spores.3,10,11 Rarely, infection in people may be acquired through the skin secondary to accidents such as contaminated needle puncture. In these scenarios, infection usually remains localized to the skin.4 The first confirmed case of canine disseminated histoplasmosis in Japan was recently reported.65 Previous Japanese cases of canine histoplasmosis were cutaneous in origin, including dogs with surgical wounds contaminated with the organism64,88 and cutaneous lesions confined to the interdigital regions of the paws.29,65 These findings lend support to the percutaneous entry of H. capsulatum organisms as a possible route of transmission. There are no reported cases of primary feline cutaneous histoplasmosis. Pathogenesis Inhaled organisms are engulfed primarily by macrophages of the mononuclear phagocyte system,10 where they grow as facultative intracellular organisms.4,10,11,89 Infection may be limited to the lungs, but lymphatic and hematogenous spread may occur during the first two weeks of infection, before specific host immunity develops.10,61 The host’s cell-mediated immune response is instrumental in determining the severity of clinical disease.10,89 Histoplasma capsulatum uses several mechanisms for survival and proliferation within its host. Inhibition of phagolysosomal fusion has been reported.89 While H. capsulatum can survive across a vast pH range, the acidic pH within the phagolysosome is not optimal for survival.89 Yeast organisms modify phagolysosomal pH to a relatively neutral 6 to 6.5, presumably decreasing lysosomal enzyme activity.10,90,91 Histoplasma capsulatum produces siderophores, small compounds that chelate extracellular iron, and the neutral pH facilitates iron acquisition.92 Histoplasma capsulatum also releases calciumbinding protein, and chelated calcium is reserved for fungal utilization.93 Epidemiology While initially considered a rare disease, globally, histoplasmosis is likely the most common human systemic mycosis2 and has been isolated on every continent except Antarctica.10,85 Multiple variants of H. capsulatum occur in different parts of the world. For example, H. capsulatum var capsulatum occurs in people and animals in North and South America, eastern Asia, Australia, and parts of Africa and is rarely reported in Europe.4 Histoplasma capsulatum var duboisii occurs in Africa,2,4,10 and H. capsulatum var farciminosum has been documented in Japan and Africa.10,11,28,65 Histoplasmosis is the most common human endemic mycosis in the United States.4 The areas of highest endemicity include the drainage and tributary system of the Ohio, Mississippi, and Missouri river valleys.10,11,28,59 Histoplasma capsulatum var capsulatum has been isolated from the soil in VETERINARY MEDICINE May 2008 251
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