Histoplasmosis Update


Histoplasmosis is a disease which all of us heard about in the Small Animal Medicine courses in veterinary school, and it was discussed as one of the systemic fungal diseases of interest that we might encounter in practice. It was presented as primarily being a disease seen in the geographical regions of the Ohio River and Mississippi River Valley drainages, with sporadic incidence, and as a fungal agent that can occasionally infect humans. We further learned that it presented as a granulomatous disease that can infect multiple organs and systems, and a few other facts that we all dutifully memorized prior to taking the National Veterinary Board Examination, as well as various state board exams.  Later, some of us actually did see the disease in a dog or cat, and the more astute of us correctly diagnosed it. Most of us, however, probably never encountered it nor diagnosed it.
Histoplasmosis is present (and probably endemic) in New Mexico, based on a number of cases (both dogs and cats) diagnosed at Veterinary Diagnostic Services.  VDS has diagnosed histoplasmosis in a number of canines and felines (8 in past few years), ranging from Las Cruces to Carlsbad/Roswell in the south, and to Farmington and Four Corners areas in the north.  Based on these cases, we at VDS opined that perhaps a brief review of histoplasmosis might be appropriate.
Briefly, what is histoplasmosis?
It is a chronic, noncontagious, disseminated granulomatous disease of animals and humans caused by the fungus Histoplasma capsulatum.  The organism is commonly found in soil that contains bird droppings or bat guano.  It is found worldwide, is endemic in much of the United States, primarily the Ohio and Mississippi River Valleys, but with expansion in recent years into Texas and New Mexico of the Southwestern US.  It is transmitted commonly via aerosol contamination, with the respiratory system and thoracic lymph nodes being primary sites of infection; however, the gastrointestinal system may also be the primary site of infection (particularly in dogs), presumably via an ingestion route.  Organisms enter the blood stream via the primary site of infection, and become disseminated throughout the body.  This latter feature may ultimately result in localization in eyes, with subsequent endophthalmitis.
What are the clinical signs seen with histoplasmosis?
As above, this is commonly a multisystemic disease, and, as such, clinical signs vary and are non-specific, reflecting the various organs involved.  Canines may have a protracted course of weight loss, chronic cough, persistent diarrhea, splenomegaly, hepatomegaly, lymphadenopathy, visual impairment, and occasional “weeping” skin lesions.  Felines commonly have disseminated histoplasmosis, and severe respiratory signs are more consistent, as well as fever, depression, anorexia, and chronic weight loss.  Splenomegaly, a variety of ocular disease conditions, lymphadenopathy, and cutaneous nodules or ulcerations are also seen in the cat.
Since histoplasmosis is “expanding” its territory, can I expect to encounter it frequently? 
No, and yes.  In the big picture of day-by-day clinical practice in New Mexico, histoplasmosis will still be an unusual and infrequent occurrence clinically.  However, it is established here in New Mexico based on the cases diagnosed at VDS; as such it should be part of the differential diagnoses menu in animals with seemingly refractory cases of respiratory or gastrointestinal disease, and/or chronic weight loss.
How do I diagnose definitively histoplasmosis?
The disease should be considered in differential diagnoses when an animal is presented with signs of respiratory distress, persistent diarrhea, pulmonary nodules, and enlarged bronchial lymph nodes.  As the organisms are commonly numerous in affected tissues,  diagnosis may be achieved by fine needle aspirates and/or exfoliative cytology. Wedge biopsy is most accurate. The organism may be seen with routine H&E stains, but is easily seen with special stains that delineate fungi (i.e., PAS, GMS, etc.).  It may also be cultured from fresh tissue specimens, FNAs, and body fluids.
Can I diagnose histoplasmosis by serological findings?
Serology is strictly a screening test that verifies or negates the animal having responded serologically to an antigenic challenge by Histoplasma capsulatum at some time in its past.  A rising titer via paired samples taken 14+ days apart may be suggestive (but not absolutely diagnostic of) active infection.  Many animals (and humans) have been exposed to the agent, have seroconverted, and never develop overt signs of clinical disease.
If I have an animal with a suspect case of histoplasmosis that dies or is euthanized, are there gross pathologic lesions that can confirm the diagnosis?
No—for reasons cited above.  The lesions are non-specific in nature; they include lymphadenopathy, splenomegaly, hepatomegaly, and granulomas that occur irregularly in lungs, intestines, liver, spleen, and elsewhere.  Pathologic confirmation of the disease is best accomplished by having a complete necropsy procedure and appropriate  histopathology conducted by a pathologist at a veterinary diagnostic laboratory. If submission of the entire animal to a diagnostic laboratory is not possible, call the laboratory and speak with a pathologist about appropriate sample selection and submission.
Since histoplasmosis affects animals, birds, and humans, does a dog or cat diagnosed with the disease have zoonotic implications for the owner/family (or attending veterinarian)?
No—humans commonly get the disease via aerosol transmission from contaminated soil, as do animals.  There is no animal to-human-transmission, or animal-to-animal transmission.  Both humans and animals that are immunocompromised for some reason are more “at risk” for this disease. 
Is there an effective treatment for histoplasmosis?
According to the Merck Manual, Itraconazole (10 mg/kg/day) is the treatment of choice for disseminated histoplasmosis in dogs and cats.  Ketaconazole @ 10-15 mg/kg BID for 4-6 mo. may be effective in early or mild cases in dogs.  For severe cases, concurrent treatment with Amphotericin B is suggested.  Recurrence is commonly seen in severe cases, even after protracted treatment; as such, prognosis is always guarded with this disease.
Ref:  Merck Veterinary Manual, 9th Ed., (2005)
        Pathology of Domestic Animals (5th Ed.), Maxie, Jubb, Kennedy, and Palmer (2007)
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