Aspergillosis

Aka: Aspergillosis, Aspergillus, Aspergillus Fumigatus, Aspergilloma

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II. Pathophysiology

  1. Aspergillus are highly aerobic fungi that grow as molds
    1. Aspergillus genus (Phylum Ascomycota, Family Trichocomaceae) contains 100 of species
    2. Aspergillus Fumigatus is the most common human pathogen of Aspergillus species
      1. Other uncommon Aspergillus species in human disease: A. niger, A. flavus, A. terreus
  2. Aspergillus fungi cause pulmonary or systemic infections
    1. Occurs in debilitated or Immunocompromised patients
    2. Aspergillus mold spores are ubiquitous throughout the environment
  3. Aspergillus infections present in one of 3 ways
    1. Allergic Bronchopulmonary Aspergillosis (ABPA)
      1. See Allergic Bronchopulmonary Aspergillosis
      2. Asthma-like reaction to Aspergillus spores (Type 1 Hypersensitivity Reaction)
      3. Bronchiectasis (Type 4 Hypersensitivity Reaction)
    2. Aspergilloma (Lung Lesions)
      1. Fungal ball develops in preexisting lung cavitations (e.g. Tuberculosis, Lung Cancer)
      2. Risk for erosion into pulmonary vessels with life-threatening Hemoptysis
    3. Invasive Aspergillosis (Immunocompromised patients)
      1. Invasive Pneumonia
      2. Disseminated Aspergillosis (includes endocarditis)
  4. Other pathogenesis
    1. Aflatoxin
      1. Mycotoxin produced by Aspergillus
      2. Hepatotoxin and liver cancer risk
      3. Common contaminant in peanuts, grains and rice in some regions of the world (e.g. Africa)

III. Risk Factors

  1. Long term use of Antibiotics
  2. Longterm high dose Corticosteroids or Immunosuppressants
    1. Solid Organ Transplant
    2. Stem Cell Transplant
  3. Prolonged Neutropenia
    1. Acute Leukemia
    2. Myelodysplastic Syndrome
  4. AIDS (with CD4 Count <50 cells/uL)
  5. Pre-existing lung cavitations (e.g. Tuberculosis, Lung Cancer, Radiation Therapy)
    1. Aspergilloma risk

IV. Findings: Pulmonary or Aspergilloma

  1. Symptoms (slowly progressive)
    1. Dyspnea
    2. Cough
    3. Hemoptysis (occurs with pulmonary vessel wall invasion)
  2. Signs
    1. Low grade fever
    2. Purulent Sputum

V. Findings: Systemic or Disseminated Infection (Invasive Aspergillosis)

  1. Symptoms
    1. Skin eruption
    2. Arthralgias
    3. Mental status change
  2. Signs
    1. Skin eruption
    2. Infection of ears, eyes, sinuses

VI. Lab

  1. Serum Aspergillus Antibodies
    1. Test Sensitivity: 61-89%
    2. Test Specificity: 72-88%
  2. Sputum Culture

VII. Differential Diagnosis

  1. See Fungal Lung Infection

VIII. Imaging: Chest

  1. Pulmonary Aspergillosis or Aspergilloma
    1. Unique crescentic radiolucency surrounding a circular shadow on Chest XRay
    2. Multinodular Lung Lesions
    3. Cavitary lesions
    4. Pulmonary vascular interruption

IX. Management: Aspergillosis

  1. See Allergic Bronchopulmonary Aspergillosis
  2. First-line Antifungals
    1. Voriconazole
      1. Load: 6 mg/kg IV or Oral every 12 hours on Day 1, THEN
      2. Next: 4 mg/kg IV or Oral every 12 hours
      3. Target trough on Day Four: 1 to 5.5 mg/L
      4. Caution in renal dysfunction
    2. Isavuconazonium Sulfate
      1. Load: 372 mg oral or IV every 8 hours for 6 doses, THEN
      2. Next: 372 mg oral or IV daily
  3. Alternative Antifungals
    1. Posaconazole
      1. Extended Release (preferred) 300 mg orally twice daily for 2 doses, then 300 mg orally daily
      2. Suspension 200 mg orally four times daily, then once stable, 400 mg orally twice daily
      3. Intravenous 300 mg IV twice daily on day 1, then 300 mg IV daily (infuse over 90 minutes)
    2. Amphotericin B
      1. Liposomal Amphotericin B (L-AmB) 3-5 mg/kg/day IV
      2. Amphotericin B Lipid Complex (ABLC) 5 mg/kg/day IV

X. Management: Aspergilloma

  1. Asymptomatic, Stable Single Lesion
    1. May be observed for progression
  2. Symptomatic Single Lesion in Good Surgical Candidates
    1. Surgical resection is preferred
  3. Symptomatic Lesions in Poor Surgical Candidates
    1. Amphotericin B intracavitary instillation may be considered
    2. Bronchial artery embolization may be considered in significant Hemoptysis

XI. References

  1. Gladwin, Trattler and Mahan (2014) Clinical Microbiology, Medmaster, Fl, p. 209
  2. (2025) Sanford Guide, accessed on IOS 4/7/2025
  3. Cadena (2021) Infect Dis Clin North Am 35(2):415-34 +PMID: 34016284 [PubMed]
  4. Kanaujia (2023) Curr Fungal Infect Rep +PMID: 37360858 [PubMed]

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