• Clinical science



Aspergillosis is the collective term for diseases caused by mold species in the genus Aspergillus. Aspergillus spores are ubiquitous but do not usually cause infection in immunocompetent individuals. Risk factors for Aspergillus infection include immunosuppression (e.g., HIV, hematologic malignancies, transplant recipients) and underlying pulmonary conditions (e.g., cavernous tuberculosis, COPD). Infections may be localized, causing asymptomatic pulmonary aspergilloma, or symptomatic, complicated infiltrates (e.g., with cavitation, fibrosis, or necrosis). In immunocompromised patients, invasive aspergillosis is common, which manifests as severe pneumonia and septicemia with potential involvement of other organs. In patients with pre-existing bronchopulmonary conditions (e.g., asthma, cystic fibrosis), Aspergillus may cause allergic bronchopulmonary aspergillosis (ABPA), which presents with asthmatic symptoms or sinusitis. Elevated serum IgE levels and eosinophilia indicate a fungal infection. Tissue biopsy followed by histopathology and culture is used to confirm the diagnosis. Medical treatment for aspergillosis infection includes voriconazole, caspofungin, or amphotericin B. An aspergilloma, on the other hand, must be surgically removed. ABPA is primarily managed with glucocorticoid therapy. Immunocompromised patients should receive prophylactic posaconazole.



Clinical features

Clinical features of aspergillosis
Lung manifestations Other manifestations [2][3]
ABPA [4]
Chronic pulmonary aspergillosis [5]
Invasive aspergillosis [6]

Invasive aspergillosis mostly infects the bronchioles of the lungs, but can also manifest as a disseminated infection (e.g., skin, CNS).


Diagnostics of aspergillosis
Laboratory tests Chest x-ray and CT Tissue biopsy and/or culture
ABPA [4]
  • N/A
Chronic pulmonary aspergillosis [5]
  • Positive Aspergillus IgG serology
  • Culture and/or histopathology
    • Specimen are collected via:
      • Bronchoalveolar lavage via bronchoscopy
      • In patients with peripheral nodular lesions on imaging: endobronchial lung biopsy via bronchoscopy or CT-guided percutaneous biopsy
    • Staining: Gomori methenamine silver stain or PAS stain
    • Findings: monomorphic and/or septate hyphae branching dichotomously at 45°
Invasive aspergillosis [6]
  • Multiple nodules
  • Halo sign: hemorhagic ground glass opacities around nodules
  • Sickle-shaped air crescents around the fungal colony
  • Cranial MRI
    • Perform if CNS infection is suspected
    • Most commonly shows abscess formation

The most important diagnostics for the different aspergillosis types are:
ABPA: increased IgE and eosinophil count.
Aspergilloma: positive culture or serology and fungus ball seen on chest imaging.
Invasive aspergillosis: positive culture or biopsy showing septate hyphae.

Differential diagnoses

Differential diagnosis of pulmonary fungal infections
Mycoses Etiology Clinical features Diagnosis Treatment


Coccidioidomycosis (Valley fever)
  • Pathogen: Coccidioides immitis
  • Risk factors:
    • Travel to Southwestern United States, California
    • Immunosupression (e.g., HIV)
  • Chest x-ray: normal or infiltrates/lymphadenopathy/pleural effusion
  • Serology: IgM is initially increased, IgG increases after 1–3 months
  • KOH/calcofluor staining on smears or silver/PAS-staining on tissue biopsy: dimorphic fungus and spherules filled with endospores
  • Confirmatory: culture
  • Pathogen: Paracoccidioides species
    • Paracoccidioides brasiliensis
    • Paracoccidioides lutzii
  • Risk factors: travel to South and Central America
  • Infected patients often asymptomatic
  • Acute pneumonia
  • Painful nasal, pharyngeal, and laryngeal mucosal ulcerations
  • Lymphadenopathy (usually cervical)
  • Extrapulmonary manifestations (e.g., verrucous skin lesions)
  • KOH/calcofluor staining on smears or silver/PAS-staining on tissue biopsy: budding yeast with “captain's wheel” appearance
  • Cultures have a low sensitivity
  • Pathogen: Blastomyces dermatitidis
  • Risk factors: travel to states East of Mississippi River and Central America
  • Infected patients often asymptomatic
  • Pneumonia with flulike symptoms
  • Extrapulmonary manifestations
    • Verrucous skin lesions
    • Lytic bone lesions
    • Genitourinary involvement
    • CNS lesions
  • KOH/calcofluor staining on smears or silver/PAS-staining on tissue biopsy: broad-based dimorphic fungus
  • Confirmatory: culture
  • Pathogen: Histoplasma capsulatum
  • Risk factors:
    • Immunosupression (e.g., HIV)
    • Exposure to bird or bat droppings especially in Mississippi and Ohio river valleys
  • Infected patients often asymptomatic
  • Acute pneumonia
  • Extrapulmonary manifestations (e.g., ulcerative oral lesions)
  • Best initial: positive urine and serum polysaccharide antigen test
  • Chest x-ray:
  • Silver/PAS-staining on bronchoalveolar lavage or biopsy: macrophages filled with dimorphic fungus with septate hyphae
  • Confirmatory: culture
Pneumocystis pneumonia
  • Chest x-ray/CT: diffuse, bilateral ground-glass opacities
  • Silver stain and immunofluorescence on bronchoalveolar lavage (or lung biopsy if sputum is negative): disc-shaped yeasts
  • Cannot be cultured

The differential diagnoses listed here are not exhaustive.


Treatment of aspergillosis [3][8][9]
General measures Medical therapy Surgical therapy
ABPA [4]
  • Avoid aspergillus exposure
  • Oral glucocorticoids
  • For acute or recurrent ABPA: itraconazole
Chronic pulmonary aspergillosis [5]
  • Asymptomatic patients without disease progression
    • Do not require treatment
    • Should undergo regular follow-ups (imaging and Aspergillosis antibody titer tests)
  • Aspergilloma
  • Other types: In the case of severe disease, surgical resection may be required.
  • All types: bronchial angiography and embolization for temporary stabilization in the event of massive hemoptysis
Invasive aspergillosis [6]
  • Protective measures: See “Prevention” below.
  • N/A


Prophylactic therapy

Reduction of mold exposure

The following measures reduce the risk of indoor mold exposure according to the CDC guidelines:

  • Protective measures taken at home:
    • Use a ventilation hood while cooking
    • Add mold inhibitors to wall paint
    • Use mold killers in bathrooms
    • Ensure regular ventilation (complete opening of the windows for 5–10 min) and adequate heating (especially in winter) in order to keep the humidity as low as possible.
    • Avoid drying laundry indoors, use of humidifiers, and carpets in bathrooms.
  • Protective measures taken during the construction of buildings, both indoors and outdoors:
    • Adequate insulation
    • Sealing of the floor to prevent moisture from the soil from entering and pervading it
    • Protection from driving rain
    • Regular re-roofing
    • Ensuring the floors and roofs are watertight.
    • Adequate dust cover measures need to be incorporated during construction and restoration work so that there is reduced exposure to the mold present in the dust that is normally stirred up.