Aspergillosis is a disease caused by pathogenic Aspergillus species. The primary mode of infection is through inhalation of fungal spores, which commonly involve the lungs but may also affect the skin and mucous membranes. In severe cases, septicemia may occur, spreading the infection to other tissues and organ systems. The disease is more common in immunocompromised individuals but may also develop in otherwise healthy people.
Etiology and Pathogenesis
Aspergillus species are filamentous fungi and represent common opportunistic pathogens. These fungi are widely distributed in the natural environment, particularly in soil, air, plants, and on the fur of wild animals, domestic poultry, and birds. They may also colonize the skin and upper respiratory tract of healthy individuals. Currently, Aspergillus includes 18 groups, 132 species, and 18 variants, with the most common species causing human diseases being Aspergillus fumigatus, Aspergillus niger, and Aspergillus flavus.
Infection generally occurs through the inhalation of Aspergillus conidia, which are airborne fungal spores. Inhalation of these spores can trigger IgE-mediated hypersensitivity reactions in individuals with allergic predispositions, leading to bronchial spasms. In cases of compromised host immunity, Aspergillus present on the skin or mucosal surfaces may germinate into hyphal forms, causing localized infection or entering the bloodstream, subsequently disseminating to various organs.
Clinical Manifestations
Pulmonary Aspergillosis
Pulmonary aspergillosis is the most common presentation and is classified into two types:
Aspergillus Bronchopneumonia
Acute disease begins with high fever or irregular fever, cough, shortness of breath, and production of green purulent sputum. Chronic cases manifest as recurrent coughing or hemoptysis, resembling symptoms of tuberculosis. Lung signs may be subtle, occasionally accompanied by coarse crackles. Chest X-rays reveal increased pulmonary markings or diffuse patchy infiltrates.
Aspergilloma (Fungus Ball)
Most patients are asymptomatic or exhibit symptoms related to underlying conditions. Some present with fever, cough, dyspnea, and productive sputum containing green particles, often accompanied by recurrent hemoptysis. Chest X-rays may show a spherical fungal mass suspended within a pulmonary cavity, surrounded by a crescent-shaped radiolucent area, a feature of diagnostic significance.
Allergic Aspergillosis
Patients with allergic predispositions may experience asthma, coughing, and sputum production a few hours after inhaling large amounts of Aspergillus-contaminated dust. Fever may also occur. Symptoms typically resolve within 3–4 days but may recur with subsequent exposure. Examination of sputum often reveals abundant eosinophils and fungal hyphae, and culture typically shows the growth of Aspergillus fumigatus. Laboratory findings include elevated blood eosinophil counts (>1.0 × 109/L) and serum IgE levels exceeding 1,000 ng/mL.
Disseminated Aspergillosis
The clinical manifestations vary depending on the affected organs. Fever, systemic toxicity, and embolic symptoms are the most common presentations. Cardiac involvement may result in endocarditis, myocarditis, or pericarditis, leading to suppuration, necrosis, and granuloma formation. Central nervous system involvement may cause meningitis or brain abscesses. Hepatic involvement is the most common gastrointestinal presentation. Chronic infections of the ear, nose, and paranasal sinuses may extend to the orbit, eyeball, optic nerve, or meninges as the lesions progress.
Diagnosis
Pathogen Examination
Direct smears of specimens taken from the affected site may reveal fungal hyphae or spores. Cultures from samples such as sputum, blood, or localized tissues may grow Aspergillus. Since Aspergillus is a common environmental contaminant in laboratories, the isolation of the same species on multiple occasions, combined with clinical findings, is significant for diagnosis.
Histopathological Examination
Biopsies of affected tissues or lymph nodes can confirm the diagnosis based on the morphology of the fungi. This method is particularly valuable for diagnosing disseminated aspergillosis.
Serological Detection of Galactomannan (GM) Antigen
The GM test detects galactomannan, a component of the Aspergillus cell wall. A positive GM test indicates invasive aspergillosis.
Treatment
Antifungal therapy is the primary approach for treating aspergillosis. Voriconazole is the first-line treatment. Liposomal amphotericin B, amphotericin B lipid complexes, caspofungin, posaconazole, and itraconazole are suitable alternatives. Treatment typically continues until imaging studies show significant resolution of the lesions, often requiring 6–12 weeks or longer.
Voriconazole
This triazole antifungal is recommended at a dosage of 7 mg/kg every 12 hours for children aged 2–14 years. Administration may be oral or intravenous.
Lipid-Based Amphotericin B
This includes amphotericin B lipid complex (ABLC), amphotericin B cholesterol sulfate complex (ABCC), and liposomal amphotericin B (L-AmB). Recommended doses are as follows: ABLC, 5 mg/kg; ABCC, 3–4 mg/kg; and L-AmB, 3–4 mg/kg, administered via slow intravenous infusion.
Caspofungin
This echinocandin antifungal is not recommended for central nervous system infections due to its low cerebrospinal fluid concentrations. In neonates less than 3 months old, the recommended dose is 25 mg/m2 or 1 mg/kg. In children aged 3 months to 17 years, a loading dose of 70 mg/m2 is given on the first day, followed by a maintenance dose of 50 mg/m2 from the second day onward, not exceeding the adult dose (adult loading dose is 70 mg on the first day, followed by 50 mg daily). Slow intravenous injection is administered once daily.
Posaconazole
This orally-administered triazole antifungal is a derivative of itraconazole with a broader spectrum of activity. It is particularly effective for prophylaxis in severely immunocompromised patients. In children aged 8 months to 12 years, the dosage is 4 mg/kg three times daily.