Global epidemiology of influenza and IAPA
Although figures vary depending on geographic region, season and vaccination rates, approximately 0.1% of influenza patients require hospital admission with 5–10% of these requiring ICU admission [13, 14]. The mortality in patients admitted for influenza is 4% and 20–25% for those admitted to ICU [14–16]. Bacterial superinfection is common, affecting 10–35% of cases, typically with Streptococcus pneumoniae or Staphylococcus aureus [16]. However, a recent Dutch–Belgian multicenter study over seven influenza seasons in seven institutes demonstrated influenza as an independent risk factor of IPA (adjusted odds ratio 5.19, 95% confidence interval (CI) 2.63–10.26, p < 0.001) [9]. Results also showed that the 90-day mortality rate for ICU patients with IAPA was almost double that of ICU influenza patients without IAPA (51% vs. 28%, adjusted odds ratio 1.87, 95% CI 1.05–3.32). IAPA was initially thought to be associated with influenza A/H1N1pdm09 only [7, 17], but it became clear that IAPA is also associated with other influenza A and influenza B viruses [9]. The median time between influenza diagnosis and IAPA was short, often in the first 5 days [7, 8, 18]. Studies have shown considerable variation in rates of IAPA in different countries, with high rates in the Netherlands, Belgium and Taiwan, but lower rates in other countries [19], and in some we do not know the incidence (e.g., USA) [20–22]. Potential reasons for these regional differences are related to the underlying conditions, concomitant exposure to corticosteroids, environmental factors, including exposure to Aspergillus, use of non-culture-based diagnostic tests for Aspergillus (e.g., galactomannan (GM)) and differences in awareness of IAPA [23–25]. Autopsy rates are very low, which results in a considerable underdiagnosis in many countries [26]. Other factors that might contribute to regional differences in IAPA rates include influenza vaccination rates, with different policies in different countries, and differences in influenza antiviral treatment strategies with oseltamivir or zanamivir [27]. Annual vaccination reduces influenza-associated complications (hospitalization, ICU admission, severity of illness, superinfection) and improves the outcome in transplant recipients and COPD patients [28, 29].