Histoplasma capsulatum is a dimorphic soil-borne fungus that is endemic in the Midwest and Southern United States. Dogs inhale H capsulatum microconidia found in the environment. At body temperature, within the lungs, microconidia convert to the yeast form. Clinical illness can be isolated to the lungs, or H capsulatum yeast can disseminate within macrophages via the lymphatics and bloodstream to other organs or systems, including the liver, spleen, bone marrow, gastrointestinal tract, eye, lymph nodes, skin, bone, oral cavity, and CNS.1–10 Ingestion is another possible route of infection, given that experimental oral inoculation of dogs with the organism results in disseminated histoplasmosis, and this route might explain infections in dogs isolated to the gastrointestinal tract.3,11,12
Although dogs of all ages can become infected, most dogs are < 5 years old at the time of diagnosis.3,5,13 Both sexes are susceptible. Sporting, working, terrier, and hound breed groups as well as Brittany, English Pointer, and Weimaraner breeds might be at increased risk of histoplasmosis relative to other groups or breeds.1,7,13 Affected dogs typically have chronic nonspecific signs such as pyrexia, lethargy, decrease in appetite, and weight loss, although many have additional specific signs related to infected organs, such as cough or increased respiratory effort, diarrhea, or lymphadenopathy.3,5
The gold standard for diagnosis is cytologic or histologic confirmation of H capsulatum organisms.6 A urine Histoplasma EIA, which detects the fungal antigen galactomannan, is highly specific and sensitive for diagnosing histoplasmosis in dogs, and this assay might aid in diagnosis when more invasive testing (such as cytologic evaluation of a lung aspirate sample) is deemed unsafe or results are considered nondiagnostic.14
The treatment of choice for dogs with histoplasmosis is currently itraconazole, although no studies have been conducted to compare the efficacy of various antifungal agents for this purpose.6,7 Fluconazole is suggested for ocular or CNS involvement owing to its excellent penetration into these tissues.15,16 In addition, fluconazole might be more cost effective than itraconazole, averaging a third of the cost of itraconazole in a recent blastomycosis study.17 Duration of treatment with azole medication is typically at least 4 to 6 months; adverse effects can include nausea, vomiting, anorexia, and hepatotoxicosis; and drug interactions need to be considered such as with gastric acid suppression treatment (itraconazole) and cytochrome P450 metabolism (both itraconazole and fluconazole).7,8,17,18
Prognosis for dogs with pulmonary histoplasmosis is reported to be fair to excellent, whereas prognosis for dogs with disseminated or gastrointestinal disease varies from guarded to good, depending on organ involvement and severity.6–10 Research regarding histoplasmosis in humans has allowed antifungal treatment and supportive care to be carefully tailored on the basis of specific prognostic factors, including organ involvement, disease chronicity, and host immunocompetence19–22; the identification of more specific prognostic factors could help target treatment in dogs as well.
The objectives of the study reported here were 3-fold. The first objective was to describe the clinical manifestations of histoplasmosis in a large number of dogs treated at 2 veterinary teaching hospitals. The second objective was to compare outcomes of dogs treated with fluconazole versus itraconazole. Our hypothesis was that there would be no significant difference in survival or clinical remission rates. The third objective was to evaluate variables for which information was available at the time of diagnosis for prognostic value. Our hypothesis was that the need for oxygen supplementation and the presence of disseminated disease would be associated with lower survival and clinical remission rates than in dogs without these characteristics.
Partial thromboplastin time
Histoplasma quantitative EIA test, Miravista Diagnostics, Indianapolis, Ind.
SAS, version 9.4, SAS Institute, Cary, NC.
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