• Macrophage phagocytic response is the first and main line of defense against infection with Aspergillus.
• Relative lack of importance of cell-mediated immunity in host defense for this infection (therefore, not a common infection in patients with acquired immunodeficiency syndrome)
• The lung is the most common site of both noninvasive and invasive Aspergillus infection.

• Allergic bronchopulmonary aspergillosis is characterized by periodic episodes of wheezing, low-grade fever, eosinophilia on peripheral smear, transient infiltrates on chest x-ray film, and a cough productive of brown mucus plugs. It occurs when patients with chronic respiratory disease trap Aspergillus spores in mucus, which leads to an immune response and a worsening of respiratory symptoms.
• Paranasal sinusitis and otomycosis in healthy hosts in warm, wet climates
• Aspergillomas are noninvasive pulmonary fungus balls that grow in bronchogenic cysts or other lung cavities. They are the most frequent form of pulmonary aspergillosis.
• Invasive aspergillosis occurs in the immunocompromised host, most commonly in patients treated with long-term broad-spectrum antibiotics, cytoxic chemotherapy, or immunosuppressive therapy, or in patients with an underlying disease that causes neutrophil or macrophage dysfunction (i.e., acute leukemia or chronic granulomatous disease). In the immunocompromised host, invasion of blood vessels by Aspergillus leads to infarction, necrosis, and hematogenous dissemination.

• Aspergillus species are ubiquitous and worldwide, growing in soil, grain, dung, bird droppings, and decaying plant matter.
• Spores are resistant to desiccation, lightweight, and easily dispersed in air currents.
• Main route of transmission is via inhalation of airborne spores; person-to-person spread does not occur.
• Other than those with otomycosis or allergic bronchopulmonary disease, most patients infected with Aspergillus are immunocompromised in some way (see above).
• Nosocomial outbreaks have occurred when ventilation or heating systems become contaminated, or when large numbers of spores become airborne during building construction or renovation.
• The incubation period in the human host has not been defined.

• Disseminated infection: defined as infection of two or more organs, and can involve any of the previously discussed sites, as well as the CNS, heart, bones, or skin. Invasiveness depends on the immune state of the host, as well as the period of time and number of spores in the exposure.
• Patients with underlying diseases that predispose them to pulmonary cavitations, blebs, or cysts (such as asthma, chronic bronchitis, TB, sarcoid, histoplasmosis, and bronchiectasis) may develop an aspergilloma (fungus ball) after seeding their pulmonary secretions with Aspergillus. When the mass is large enough to be demonstrated on chest x-ray study, serum levels of IgG antibody to Aspergillus will be characteristically high. Patients may present with hemoptysis, exacerbation of their underlying disease, or rarely, invasion or dissemination.

• Good in noninvasive disease, such as simple otomycosis or paranasal sinusitis
• Immunosuppressed or severely neutropenic patients can have rapid extension or dissemination of disease; prognosis is often very poor. Early recognition and aggressive treatment and debridement are necessary.

• Other overwhelming systemic infections, both bacterial and fungal
• Allergic pneumonitis (other causes)
• Neoplasm

• Otomycosis is characterized by a mass of black spores (A. niger ) that start close to the eardrum and eventually fill the external canal, pain on tragal movement, and occasionally a purulent discharge. It is only rarely an invasive disease.
• Invasive sinus aspergillosis may present with severe pain, proptosis, monocular blindness, and bony destruction on x-ray films, with evidence of direct extension to the anterior fossa or orbit, or with widespread dissemination.

• Isolation of Aspergillus species by culture is required for definitive diagnosis.
• Aspergillus can be recovered from samples of blood, CSF, sputum, urine, BAL sample, or tissue biopsy. Types of specimens collected are guided by history and physical examination.
• Microscopic examination of specially stained tissue samples, or of 10% potassium hydroxide wet preparation samples, that are positive for branching, septate hyphae are suggestive of Aspergillus or other fungal invaders.
• Elevated serum IgE eosinophilia, serum antibody for Aspergillus, and an immediate-type skin test response to Aspergillus antigen are often present in patients with allergic aspergillosis and are helpful in establishing the diagnosis.
• Recent developments in early diagnosis include the use of: high-resolution chest CT, new rapid stain techniques and monoclonal antibodies for BAL samples, and serum ELISA for Aspergillus galactomannan.
• Aspergillus can be a contaminant of laboratory stains or other preparative agents, but a positive culture or a microscopic examination positive for hyphae in an immunocompromised patient should be considered of likely clinical significance.

• Allergic bronchopulmonary aspergillosis is frequently managed with oral or inhaled corticosteroids.
• If paranasal sinusitis is noninvasive, surgical drainage or debridement usually results in clearance of the infection.
• Otomycosis (most commonly secondary to A. niger ) is often found in association with a bacterial external otitis. Debridement of the external canal and treatment of underlying bacterial external otitis usually produces a good therapeutic response.
• Invasive or systemic disease is treated with amphotericin B, with recommended doses ranging from 0.5 to 1.5 mg/kg/d (after initial test dose and subsequent incremental increases in therapeutic doses until total daily dose is reached; see hospital pharmacy protocol).
• The addition of flucytosine or rifampin to amphotericin B therapy is sometimes recommended.
• Itraconazole has been used as an alternative in patients unable to tolerate amphotericin B, but adequate therapeutic trials in invasive aspergillosis have not been performed.
• Surgical excision, in addition to amphotericin B, is sometimes required for localized debridement in invasive disease.

• Any immunocompromised patient with persistent fevers or signs of invasive infection not improving on treatment with broad-spectrum antibiotics must be evaluated for fungal infection and the empiric use of antifungal medications considered.
• The rare finding of diffuse nodular pneumonia in children may be indicative of an underlying diagnosis of chronic granulomatous disease and aspergillosis.

Q: What are rare complications of aspergillosis?
A: Endocarditis, osteomyelitis, and cutaneous disease.