Aspergillosis

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.

• Allergic bronchopulmonary aspergillosis (ABPA): a hypersensitivity reaction caused by exposure to Aspergillus that mostly occurs in patients with cystic fibrosis or asthma
• Chronic pulmonary aspergillosis: a long-term Aspergillus infection of the lung which can manifest as:
  • Aspergilloma: an opportunistic infection of a pre-existing cavitary lesion (e.g. from previous tuberculosis)
  • Aspergillus nodule: single or multiple nodules with possible cavitation
  • Chronic cavitary pulmonary aspergillosis: extensive fibrosis with tissue destruction of at least two lung lobes
  • Fibrotic pulmonary aspergillosis
  • Chronic necrotizing pulmonary aspergillosis: a subacute and semi-invasive form of chronic pulmonary aspergillosis characterized by localized, slowly progressive, inflammatory destruction of lung tissue and commonly associated with alcohol use disorder
• Invasive aspergillosis: a severe form of Aspergillus infection which manifests with severe pneumonia and septicemia with potential involvement of other organs (e.g., skin, CNS) and mostly occurs in immunocompromised individuals

• Pathogen
  • Aspergillus, a genus including over 200 species
  • Most common: Aspergillus fumigatus and Aspergillus flavus
• Transmission: airborne exposure to mold spores
  • Aspergillus spores (also referred to as conidia) are ubiquitous indoors, as they enter with the normal flow of air.
  • The spores can also settle on easily accessible sources of nutrition (e.g., water), dust, cellulose (e.g., in wallpaper), and indoor plants
  • Aspergillus spores may also be found in intensive care units
• Risk factors
  • Severe immunosuppression (e.g., due to HIV/chemotherapy, after organ transplantation) or neutropenia (e.g., due to chronic granulomatous disease) can facilitate the development of invasive aspergillosis
  • Destructive pulmonary pathology may lead to chronic pulmonary aspergillosis
    • Scar tissue or lung cavities (e.g., from tuberculosis)
    • Sarcoidosis
    • Pneumocystis pneumonia
    • COPD, emphysema
  • Aspergillus can trigger hypersensitivity reactions (ABPA) in patients with preexisting bronchopulmonary conditions (e.g., asthma, cystic fibrosis) ^[1]
  • Alcohol use disorder and steroid-dependent COPD are associated with chronic necrotizing pulmonary aspergillosis

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

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.

The differential diagnoses listed here are not exhaustive.

Prophylactic therapy

• Indication: severely immunocompromised patients
• Drug of choice: posaconazole (IV loading dose followed by oral maintenance therapy)
• Alternatives: inhaled amphotericin B, itraconazole, micafungin

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.