What is the rate of aspergillosis (invasive fungal infection) post-influenza (flu)?

Rate of Aspergillosis Post-Influenza

Invasive pulmonary aspergillosis (IPA) occurs in approximately 19% of patients admitted to intensive care with severe influenza, with diagnosis typically occurring within a median of 3 days after ICU admission. 1

Incidence and Risk Factors

• The incidence of influenza-associated pulmonary aspergillosis (IAPA) ranges from 14% in non-immunocompromised patients to 32% in immunocompromised patients with severe influenza requiring ICU admission 1
• A systematic review and meta-analysis found that IAPA occurs in 28.8% of critically ill influenza patients 2
• The incidence appears similar between influenza A and influenza B infections 1
• IAPA can develop in patients without traditional risk factors for invasive fungal infections, representing a distinct clinical entity 3, 1

Risk Factors for Post-Influenza Aspergillosis

• Male sex is associated with higher risk of developing IAPA 1
• Corticosteroid use significantly increases the risk of developing aspergillosis following influenza infection 1, 4
• Higher APACHE II scores (indicating greater disease severity) correlate with increased risk 1
• Viral-induced lymphopenia is present in approximately 86% of cases and may be a contributing factor 3
• Severe influenza causes respiratory epithelium disruption and impaired immune function, creating conditions favorable for Aspergillus invasion 3, 1

Diagnostic Considerations

• Bronchoalveolar lavage (BAL) sampling for culture, galactomannan testing, and PCR forms the cornerstone of diagnosis 5
• Visual examination of the tracheobronchial tract during bronchoscopy is essential to detect invasive Aspergillus tracheobronchitis 5
• Patients may present with nonspecific symptoms and be unresponsive to treatments for bacterial pneumonia 6
• Early and extensive use of diagnostic tools, especially bronchoscopy, is critical for timely diagnosis 6

Clinical Outcomes and Mortality

• The 90-day mortality rate is significantly higher in influenza patients who develop IPA (51%) compared to those without IPA (28%) 1
• The overall mortality rate for IAPA is approximately 33.4%, but can exceed 50% despite antifungal therapy 2, 5
• Patients with IAPA require longer duration of mechanical ventilation (mean 17.3 vs 10.5 days) compared to influenza patients without aspergillosis 2
• IAPA is associated with longer ICU stays (mean 26.8 vs 12.8 days) and hospital length of stay (mean 38.7 vs 27.0 days) 2
• Patients with IAPA more frequently require vasopressor support (76.4% vs 57.9%), renal replacement therapy (45.7% vs 19.1%), and ECMO (25.9% vs 12.8%) compared to influenza patients without aspergillosis 2

Emerging Trends

• There has been an increasing number of reported cases of influenza-associated aspergillosis since 2010 3
• Similar patterns of fungal superinfection have been observed with COVID-19, termed COVID-19-associated pulmonary aspergillosis (CAPA), with diagnosis rates of 10-20% in severe cases 5
• Approximately 65% of patients who develop post-viral aspergillosis lack classic underlying conditions that typically predispose to invasive fungal infections 3

Management Considerations

• Azoles (particularly voriconazole) are the first-choice antifungal drugs for treatment 5
• Liposomal amphotericin B is an alternative in settings where azole resistance is prevalent 5
• Prompt diagnosis and initiation of antifungal therapy are critical given the high mortality rates 3