Mixed Influenza and Aspergillus Infections

Mixed Influenza and Aspergillus Infections common and have high death rates

Worldwide, about 5 million people develop severe influenza infections each year, leading to several hundred thousand annual deaths (1). The severity and mortality of influenza infections are often worsened by concomitant infections of bacteria and fungi. In recent years, there is an increasing appreciation that mixed infections of both influenza virus and Aspergillus fungi are quite common and such mixed infections have higher death rates than either infection by themselves (2-6).

A study of 7 ICUs (Intensive Care Units) in Netherlands and Belgium between 2009-2016 reported that invasive pulmonary aspergillosis was found in 83 out of 432 patients (19%) admitted for influenza (2).  Among immunocompromised patients aspergillus infection was found in 32% of the influenza patients (38 of 117 immuncompromised patients) as compared to 14% in non-immunocompromised patients (45 of 315 non immunocompromised patients) (p=0.001 for difference) (2). Mortality rates were significantly higher in influenza patients with concurrent Aspergillus infection (51% of 83 patients) as compared to influenza patients without Aspergillus infection (28% of 432 patients) (p=0.001 for difference) (2).

A similar study in a Taiwan hospital reported that Aspergillosis was present in 21 of 124 (17%) hospitalized influenza patients, with in-ICU death rates of 67% among the Aspergillus coinfected influenza patients as compared to only 15% of those with influenza alone (p<0.001) (3).

Hospitalized patients who develop lower respiratory symptoms should have rapid clinical evaluation including EKG, echocardiography, galactomannan assay for Aspergillus infection, chest CT, and bronchoscopsy studies for viruses, bacteria, and fungi(6). If invasive aspergillosis is suspected, treatment should be begin immediately, with primary treatment with azoles like isavuconazole or voriconazole and secondary treatment with echinocandins like caspofungin (6). Lung sputum samples should be cultured for Aspergillus and other fungi and resistance to antifungal drugs noted to provide optimal antifungal drug treatment.

Use of HEPA (High Efficiency Particulate Air) filters in hospitals have been associated with significantly lower rates of hospital Aspergillus infections.  A meta-analysis of 6 published studies reported that use of HEPA air filters in hospital rooms was associated with significantly lower rates of fungal infections (RR 0.29, 95% CI 0.15-0.54) (7).

Research/Resources

1. Vanderbeke L, Spriet I, Breynaert C, Rijnders BJA, Verweij PE, Wauters J. Invasive pulmonary aspergillosis complicating severe influenza: epidemiology, diagnosis and treatment. Curr Opin Infect Dis. 2018;31(6):471-80.

2. Schauwvlieghe A, Rijnders BJA, Philips N, Verwijs R, Vanderbeke L, Van Tienen C, et al. Invasive aspergillosis in patients admitted to the intensive care unit with severe influenza: a retrospective cohort study. The Lancet Respiratory medicine. 2018;6(10):782-92.

3. Ku YH, Chan KS, Yang CC, Tan CK, Chuang YC, Yu WL. Higher mortality of severe influenza patients with probable aspergillosis than those with and without other coinfections. J Formos Med Assoc. 2017.

4. Huang L, Zhang N, Huang X, Xiong S, Feng Y, Zhang Y, et al. Invasive Pulmonary Aspergillosis in Patients with Influenza Infection: A Retrospective Study and Review of the Literature. The clinical respiratory journal. 2019.

5. Vanderbeke L, Spriet I, Breynaert C, Rijnders BJA, Verweij PE, Wauters J. Invasive pulmonary aspergillosis complicating severe influenza: epidemiology, diagnosis and treatment. Curr Opin Infect Dis. 2018.

6. Koehler P, Bassetti M, Kochanek M, Shimabukuro-Vornhagen A, Cornely OA. Intensive care management of influenza-associated pulmonary aspergillosis. Clin Microbiol Infect. 2019.

7. Eckmanns T, Ruden H, Gastmeier P. The influence of high-efficiency particulate air filtration on mortality and fungal infection among highly immunosuppressed patients: a systematic review. J Infect Dis. 2006;193(10):1408-18.