How is histoplasmosis (infection caused by Histoplasma) endocarditis (inflammation of the heart valves) diagnosed and treated?

Diagnosis of Histoplasma Endocarditis

Histoplasma endocarditis is diagnosed through a combination of blood cultures, serological testing, histopathological examination of valve tissue, and molecular diagnostic techniques, with pathological examination of resected valve tissue being the gold standard for definitive diagnosis.

Clinical Presentation and Risk Factors

• Symptoms typically present for a median of 7 weeks before diagnosis 1

• Common symptoms include:

  • Fever (temperature >38°C)
  • Fatigue
  • Weight loss
  • Night sweats
  • Dyspnea
  • Hypotension
  • Near-syncope

• Risk factors:

  • Prosthetic heart valves (especially aortic valve) 1, 2
  • Residence in endemic areas (Ohio and Mississippi River valleys) 3, 2
  • Immunosuppression
  • End-stage renal disease 4
  • External cardiac devices 2

Diagnostic Algorithm

1. Blood Cultures

• Obtain at least three sets of blood cultures
• Blood cultures are positive in only 43% of Histoplasma endocarditis cases 1
• Use lysis-centrifugation blood culture system for higher sensitivity 3
• Cultures may require up to 6 weeks to grow 3

2. Serological Testing

• Histoplasma antigen detection in:
  • Urine (highest sensitivity)
  • Serum
  • CSF (if CNS involvement suspected)
  • Bronchoalveolar lavage fluid (if pulmonary involvement)
• Antigen testing provides rapid diagnosis and can be detected before culture positivity 3
• Anti-Histoplasma antibody testing (positive in 75% of cases) 1

3. Echocardiography

• Transesophageal echocardiography (TEE) is preferred over transthoracic (TTE)
• Look for:
  • Vegetations (often large and friable) 1
  • Valvular regurgitation
  • Abscess formation
  • Prosthetic valve dehiscence

4. Molecular Diagnostic Techniques

• PCR of blood or valve tissue
• Cell-free DNA testing (e.g., Karius test) 5
• Particularly useful in blood culture-negative cases

5. Histopathological Examination

• Pathological examination of resected valve tissue remains the gold standard 3
• Collect tissue in sterile container without fixative or culture medium 3
• Look for:
  • Granulomatous inflammation
  • Yeast forms (2-4 μm budding yeast)
  • Hyphal forms may also be present 1

Diagnostic Pitfalls and Caveats

1. Blood culture limitations: Histoplasma is often missed in routine blood cultures, with positivity in less than half of cases 1

2. Delayed diagnosis: The nonspecific presentation often leads to delayed diagnosis and treatment 4

3. Prior antibiotic use: May result in blood culture-negative endocarditis (BCNIE) 3

4. Prosthetic valve considerations:

   • Higher risk of fungal endocarditis 2
   • May have lower sensitivity on imaging studies 3

5. Cardioplegia interference: Intraoperative cardioplegia can affect cultivation of microorganisms from valve tissue 3

   • Avoid direct contact of cardioplegic solution with prosthesis and infectious material

Diagnostic Criteria

According to modified Duke criteria 3:

Major Criteria:

• Positive blood cultures (if obtained)
• Evidence of endocardial involvement on echocardiography
• Histopathological confirmation

Minor Criteria:

• Predisposing heart condition
• Fever >38°C
• Vascular phenomena (emboli, infarcts)
• Immunological phenomena
• Serological evidence of Histoplasma infection

Key Recommendations for Diagnosis

1. In patients with suspected endocarditis and negative blood cultures at 48 hours, consult with microbiology and infectious disease specialists 3

2. For blood culture-negative cases, perform systematic serological testing for Histoplasma and other fastidious organisms 3

3. Collect all excised valve tissue in sterile containers without fixative for optimal recovery of organisms 3

4. Perform both culture and histopathological examination of valve tissue, along with PCR when available 3

5. Consider Histoplasma endocarditis in patients with appropriate risk factors and exposure history, even outside of highly endemic regions 2, 5