Histoplasma spp

From Cat
Anterior uveitis may be due to histoplasmosis
Lateral view of feline thorax showing fine, diffuse interstitial pattern in the lungs, containing nodules
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Histoplasma capsulatum yeasts in the cytoplasm of two of three neutrophils (dog, blood smear, Wright-Leishman stain).
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Histoplasma capsulatum yeasts are present in the cytoplasm of a macrophage and in the background of a cytologic smear (dog, lymph node, fine-needle aspirate, Wright-Leishman stain)
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A 4 year old cat had been inappetant for 3 weeks with normal CBC/ CHEM. It was treated with Depo-Medrol and 2 weeks later was severely dyspneic and had anisocoria. On postmortem, lung showed multifocal to coalescing granulomas and Histoplasma was isolated
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Brain from above cat showing diffuse meningitis
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Cytology of fluid aspirate from brain in above cat: Intracellular fungi

Feline histoplasmosis is a soil-borne fungal disease caused by the dimorphic fungus Histoplasma capsulatum and is found in tropical and subtropical areas[1].

This organism has been isolated from the soil in 31 of the continental United States; however, most clinical cases of disease occur in the Mississippi, Missouri, and Ohio River areas. H. capsulatum lives in the soil and thrives in moist and humid environments. It is present in particularly high concentrations where birds and bats congregate due to the high nitrogen concentration in their faeces. Histoplasmosis is not contagious from animal to animal[2].

Exposure to the mycelial stage of development in the soil is required for fungal infection to occur. While most cases of histoplasmosis are subclinical, the fungus can replicate and cause severe local or disseminated infection. There is no sex predilection and it affects animals of all ages, however animals under the age of four are most commonly affected with severe disease. Immunodeficiency has been identified as a predisposing factor for severe infection since T-cell immunity is critical to clear the disease, yet in cats there has been no correlation to date between feline leukaemia virus associated immunosuppression and histoplasmosis. There appears to be no breed predilection in cats. Exposure of young animals with immature immune systems and exposure to large amounts of the fungus are the most common predisposing factors[3].

H. capsulatum is a dimorphic fungus, which resides in the soil or decaying organic matter during the free living mycelial stages. It produces fruiting bodies in the form of micronidia (2-5 µm) and macronidia (5-18 µm). Infection occurs via inhalation of micronidia, which can reach the lower respiratory tract. It is also thought that primary fungal infection also can occur by ingestion of the organism, but this has not been demonstrated experimentally. The incubation period is 12 to 16 days during which the micronidia convert to the yeast phase and replicate by budding. These yeasts are subsequently phagocytosed by macrophages. The fungal infection either is cleared or the organism continues to reproduce intracellularly and disseminates throughout the body via lymphatic and hematogenous circulation[4].

Clinical signs

Infection with H. capsulatum usually is asymptomatic. When clinical signs of histoplasmosis are present, they may be limited to the lung or appear as a variety of non-specific systemic symptoms, which vary slightly between dogs and cats. Cats with disseminated histoplasmosis often have a fever that is unresponsive to antibiotic therapy. Tachypnoea, dyspnoea, and abnormal lung sounds are common findings in cats, but coughing is rare cough. Respiratory signs can be the only signs if the infection is limited to the lungs. Weight loss, depression, inappetence, and pallor of mucous membranes also may be observed. Other common signs of disease include peripheral lymphadenomegaly, splenomegaly, and hepatomegaly. Ocular involvement is slightly more common in cats than in dogs and may include conjunctivitis, granulomatous blepharitis, chorioretinitis, retinal detachment, and optic neuritis. Nodular to ulcerated skin lesions are rare. Osseous infections with lameness and soft tissue swelling also are rarely observed[5].

Radiographic evidence of histoplasmosis includes a linear or diffuse pulmonary interstitial pattern. Pulmonary infiltrates may appear miliary or nodular. Abdominal radiographs may reveal an enlarged liver, spleen, or ascites. Barium contrast studies in the dog may reveal thickened intestinal walls and mucosa. Bony lesions appear as osteolysis with subperiosteal proliferation of new bone[6].

Complete blood cell count findings are non-specific. Normocytic, normochromic, non-regenerative anaemia is commonly present with chronic disease, bone marrow involvement, or gastrointestinal blood loss. Leukocytosis or leukopenia may be present. Pancytopenia (decreased leukocyte, erythrocyte, and platelet counts) has been observed in some cats with disseminated fungal infection. H. capsulatum may be identified infrequently in monocytes, neutrophils, and eosinophils during examination of the stained blood film. The biochemical profiles and urinalysis usually are unremarkable[7].

Diagnosis

A definitive diagnosis of histoplasmosis is made by identifying the organism in tissue samples obtained for cytologic or histologic evaluation. Histoplasmosis causes extensive granulomatous inflammation. Macrophages frequently contain yeasts of H. capsulatum that appear as "clusters of grapes" in the cytoplasm of these cells. Organisms also may be scattered in the background of cytologic preparations. The organism is most easily identified in cytologic aspirates of lung, liver, lymph nodes, spleen, and bone marrow that are stained with Romanowsky stains (Wright, Giemsa, or Leishman stains). The yeasts are 2-4 µm in diameter with a round body, basophilic centre, and surrounding halo caused by shrinkage of the organism during staining. Infrequently, H. capsulatum also may be identified in macrophages, monocytes, or neutrophils in smears of blood, body cavity effusion fluid, and transtracheal wash or bronchoalveolar lavage fluid[8].

Granulomatous inflammation and the proliferation of yeasts results in organomegaly and organ failure. Tissue biopsies may be necessary to demonstrate H. capsulatum if cytologic studies are equivocal. Histologic sections can be stained by the Periodic Acid-Schiff, Gomori’s methenamine silver (GMS), or Gridley techniques to demonstrate the organism more effectively, especially if low numbers of yeasts are present. Fungal isolation can be done using fine-needle aspirates, tissue biopsies, blood, or body cavity fluids. However, fungal isolation is not recommended in routine veterinary practice because the organism is highly pathogenic when grown in culture. Serologic testing has been done historically, but is very inaccurate and not used currently[9].

Treatment

Various oral antifungal drugs have been used to treat histoplasmosis, including:

  • Amphotericin B - 0.10 - 0.25 mg/kg IV every 24 hours until cumulative dose of 4.0 - 8.0 mg/kg is reached
  • Itraconazole - 5 mg/kg orally every 12 hours for 4 - 6 months
  • Fluconazole - 5 mg/kg orally every 12 - 24 hours for at least 4 months
  • Ketoconazole - 5 - 20 mg/kg orally every 12 - 24 hours for at least 6 months

The pulmonary form of disease is often self-limiting. Disseminated histoplasmosis can be difficult to treat, requiring a long course of combination drug therapy. Prevention of disease is based upon avoidance of areas with heavy bird and bat faecal contamination. Small areas of fungal contamination can be disinfected with 3% formalin solution.

References

  1. Cook, AK et al (2012) Clinical evaluation of urine Histoplasma capsulatum antigen measurement in cats with suspected disseminated histoplasmosis. JFMS 14(8):512-515
  2. Edison, L., Latimer, KS., Bain, PJ & Roberts EJ (2007) www.vet.uga.edu
  3. Clinkenbeard KD, Wolf AM, Crowell RL, Tyler RD (1989) Feline disseminated histoplasmosis. Compend Cont Educ Pract Vet 11:1223-1233
  4. Wolf AM (1989) Systemic mycosis. J Am Vet Med Assoc 194:1192-1196.
  5. Davies C, Troy GC (1996) Deep mycotic infections in cats. J Am Anim Hosp Assoc 32:380-391
  6. Wolf AM: Histoplasmosis. In: Green CE: Infectious Diseases of the Dog and Cat. WB Saunders, Philadelphia, 1998, pp. 378-383.
  7. Jones TC, Hunt RD, King NW (1997) Veterinary Pathology. Williams & Wilkins, Baltimore, pp. 519-522.
  8. Hawkins EC, DeNicola DB (1990) Cytologic analysis of transtracheal wash specimens and bronchoalveolar lavage fluid in the diagnosis of mycotic infection in dogs. J Am Vet Med Assoc 197:79-82
  9. Gionfriddo JR (2000) Feline systemic fungal infections. Vet Clin North Am Small Animal Pract 30:1029-1050