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Histoplasmosis

ISSN 2398-2950

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Introduction

  • Cause: systemic fungal infection caused by Histoplasma capsulatum  Histoplasma capsulatum  .
  • Endemic in many temperate and subtropical regions of the world.
  • Organism is soil-borne; microconidia of the mycelial form are infectious
  • Signs: nonspecific debilitation, respiratory signs, ocular signs, cutaneous lesions, lameness, occasional gastrointestinal signs.
  • Diagnosis: cytology, histopathology.
  • Treatment: itraconazole Itraconazole, ketoconazole Ketoconazole, fluconazole   Fluconazole, amphotericin B Amphotericin B.
  • Prognosis: good for localized and poor for generalized infections.

Presenting signs

  • Anorexia, weight loss, fever, lethargy, dehydration, depression are the most common signs.
  • Tachypnea, dyspnea.

Less commonly

  • Blepharospasm, change in appearance of the eye, blindness, eyelid nodules.
  • Cutaneous nodules, ulcerative lesions.
  • Diarrhea, vomiting, icterus, ascites, oral ulceration, nasal discharge.

Geographic incidence

  • Found throughout the United States, Central and South America.
  • Most common in the Ohio, Mississippi and Missouri River valleys.
  • Prefers nitrogen-rich, moist soil and often colonizes locations with high concentrations of bird and bat dung

Age predisposition

  • Clinical disease usually seen in young cats < 4 years of age.
  • Can affect any age of cat.

Public health considerations

  • People may acquire the disease from the same sources as animals.
  • The microconidia are infectious, so cultures are a potential source of the disease. Only specialized laboratories should undertake culturing.

Cost considerations

  • Expensive to diagnose and treat.

Special risks

  • Affects outdoor cats most often.

Pathogenesis

Etiology

Predisposing factors

General

  • Many animals may be exposed, develop subclinical infections and spontaneously recover.
  • Overwhelming infection and compromise of the immune system may lead to disseminated infection.

Specific

  • Living in an endemic area.
  • Travel history in endemic area.
  • Most affected cats are not positive for feline leukemia or feline immunodeficiency viruses

Pathophysiology

  • Infection occurs via inhalation of microconidia. Once in the lungs, the organism converts to an intracellular yeast phase and spreads within mononuclear phagocytes to regional lymph nodes and other organs of the body.
  • Most common organs affected are the lungs, lymph nodes, bone marrow, liver, spleen, eyes and bones.
  • Organs affected occasionally are the intestines, mouth, nose, and central nervous system.
  • Organisms are engulfed by phagocytic white blood cells. If host immunity is overwhelmed the organism replicates with the reticuloendothelial system, resulting in widespread disease and death.

Timecourse

  • Incubation = 12 - 16 days.
  • Duration = weeks to months.

Diagnosis

Presenting problems

  • Generalized systemic debilitation.
  • Respiratory distress.

Less commonly

  • Ocular signs.
  • Cutaneous lesions.
  • Lameness.
  • Vomiting, diarrhea

Client history

  • Gradual, progressive weight loss.
  • Decreased appetite and activity level.
  • Changes in the appearance of the eyes.
  • Occasional vomiting, diarrhea.

Clinical signs

Diagnostic investigation

Complete blood count

  • Nonregenerative anemia.
  • Leukocytosis with neutrophilia, monocytosis.
  • Neutropenia, pancytopenia.

Buffy coat smear

  • Organism sometimes found in white blood cells

Biochemistry profile

  • Hypoalbuminemia.
  • Hyperglobulinemia.
  • Elevated blood glucose, liver enzymes and bilirubin.
  • Hypercalcemia.

Cytology

  • Aspirates of bone marrow, lymph nodes, lungs, bronchoalveolar lavage Bronchoalveolar lavage and subcutaneous nodules.
  • May reveal the organism.

Radiography, Ultrasonography

  • Thoracic radiography Radiography: thorax : nodular to linear, diffuse interstitial pattern, hilar lymphadenopathy.
  • Abdominal radiography: hepatomegaly, splenomegaly.
  • Abdominal ultrasonography: thickening of intestines, hyperechoic pattern to the liver, splenomegaly, mesenteric lymphadenopathy.
  • Radiography of long bones Radiology: appendicular skeleton (long bones): osteolytic lesions in the metaphysis with periosteal proliferation; predilection for bones of carpal and tarsal joints and those adjacent to them.

Endoscopy of gastrointestinal tract

  • Thickening and increased friability of the mucosa.
  • Organisms may be identified on impression smears or biopsies.

Serology

  • Unreliable.

Confirmation of diagnosis

Discriminatory diagnostic features

  • Radiographic changes.
  • Ocular findings.

Definitive diagnostic features

  • Culture of organism not recommended due to human health risk.
  • Identification of the organism on cytology or histopathology - in the cat the bone marrow, lung and lymph node are the best areas to detect organisms.

Gross autopsy findings

  • Focal to diffuse discoloration, consolidation of hilar regions of the lungs.
  • Diffuse enlargement of tracheobronchial and mesenteric lymph nodes, liver, spleen.
  • Subretinal effusion, retinal detachment, thickening of the iris.
  • Thickening of the walls of the intestines.
  • Enlargement of metaphysis of long bones.

Histopathology findings

  • Pyogranulomatous inflammation.
  • Intracellular location of the organism in macrophages within infected tissues.
  • Cells are often packed with small (2-4 um), round organisms with a basophilic center, surrounded by a clear halo.
  • Walls of the organism are best seen with PAS, Gomori methenamine silver or Gridley stains.

Differential diagnosis

Treatment

Initial symptomatic treatment

  • Severely ill cats often need supportive care, depending upon their clinical signs:
    • Intravenous crystalloid and colloid therapy.
    • Blood transfusion.
    • Oxygen therapy.
    • Bronchodilator therapy.
    • Parenteral nutrition.

Standard treatment

  • Itraconazole: treatment of choice, dosage = 5-10 mg/kg PO BID for 2 - 4 months; dosage may be decreased to 5 mg/kg PO BID if liquid form is given Itraconazole.
  • Ketoconazole: effective in only about 30% of cats, dosage = 5 - 15 mg/kg PO BID for 4 - 6 months Ketoconazole.
  • Fluconazole: penetrates CNS and eyes better, but efficacy unknown for this disease in cats, dosage = 2.5 - 5.0 mg/kg PO, IV SID Fluconazole.
  • Amphotericin B: may be combined with itraconazole or ketoconazole for treatment of severe disseminated disease, dosage = 0.25 mg/kg IV as a slow IV infusion in 5% dextrose/water every other day until maximum dose of 4 mg/kg or renal function deteriorates Amphotericin B.

Monitoring

  • Initial 10 - 14 days are critical as a positive response may not be seen to antifungal therapy for 7- 14 days.

Subsequent management

Treatment

  • Treatment is prolonged. Administer antifungal drugs for 3-6 months, or for at least 30 days beyond resolution of all clinical signs.

Monitoring

  • Once cat is improving, recheck at monthly intervals. Repeat CBC, biochemistry profile and chest x-rays on a monthly basis.
  • Monitor for one year after termination of therapy, as relapses may occur within 6 - 10 months.

Prevention

Control

  • Prevent cat contact with soil containing bid or bat excreta.

Outcomes

Prognosis

  • Guarded to good.

Expected response to treatment

  • Eyelid granulomas, focal cutaneous disease, localized pulmonary infections usually respond well to treatment.
  • Posterior ocular changes do not respond as well, because penetration of the imidazole compounds is not very good within the posterior segment.
  • Response of animals with disseminated disease or with cacchexia is very poor.

Reasons for treatment failure

  • Severe, disseminated disease.
  • Inadequate dosage or length of therapy.
  • Premature termination of therapy due to expense.

Further Reading

Publications

Refereed papers

  • Recent references from PubMed and VetMedResource.
  • Aulakh H K, Aulakh K S & Troy G C (2012) Feline histoplasmosis: a retrospective study of 22 cases (1986-2009). JAAHA 4(3), 182-187 PubMed.
  • Clinkenbeard K D, Wolf A M & Cowell R L et al (1998) Feline disseminated histoplasmosis. Compend Contin Educ Pract Vet 11, 1223-1232.
  • Hodges R D, Legendre A M & Adams L G et al (1994) Itraconazole for the treatment of histoplasmosis in cats. J Vet Intern Med (6), 409-413 PubMed
  • McCalla T, Collier L & Wigton D et al (1992) Ocular histoplasmosis in the cat. Vet Pathol 29, 470.
  • Wolf A M (1988) Successful treatment of disseminated histoplasmosis with osseous involvement in two cats. JAAHA 24 (5), 511-516 VetMedResource.

Other sources of information

  • Wolf A M (1998) Histoplasmosis. In: Greene CE (ed) Infectious diseases of the Dog and Cat.2nd Ed. WB Saunders, Philadelphia, pp. 378-383.
  • Taboada J (2002) Systemic mycoses. In: Morgan RV, Bright RN, Swartout MS (eds) Handbook of Small Animal Practice. 4th Ed. WB Saunders, Philadelphia, pp.1075-1089.