Aspergillosis, An Emerging Complication of Severe Flu Infections

During IDWeek 2016, Nancy Crum-Cianflone, MD, MPH, from the Scripps Mercy Hospital in San Diego, California sat down with Infectious Disease Advisor to discuss aspergillosis as an emerging complication of severe influenza infections.

Dr Crum-Cianflone conducted a retrospective study at a large academic hospital from 2015 to 2016.  The study encompassed 48 patients who were admitted to the intensive care unit with 8 patients diagnosed with influenza infection.  Six of the 8 patients had Aspergillus sp isolated from respiratory cultures. No patient with Aspergillus was immunosuppressed. 

To find out more, please see video below and scroll down to view the text transcript beneath the video.

Video Transcript

Michael Tapper, MD: This is Dr Michael Tapper from Lenox Hill Hospital and the Hofstra Northwell School of Medicine in New York City, reporting to you from the annual meeting of the Infectious Diseases Society of America (IDWeek 2016) in New Orleans, Louisiana. I’m joined by Dr Nancy Crum-Cianflone from the Scripps Clinic in San Diego, California.

You just presented some very interesting data on Aspergillus as a complication of influenza infection. Would you fill us in on some of the data that you reported?

Nancy Crum-Cianflone, MD, MPH: Sure, thank you very much. The influenza season is rapidly approaching. One thing we noticed this last influenza season is that many of our patients with influenza who were hospitalized then became infected with Aspergillus.  We have always known that influenza sets you up for bacterial superinfections like Streptococcus pneumoniae and Staphylococcus aureus, but we were surprised to see this last year that some of these patients also developed Aspergillus, typically A fumigatus invasive pulmonary infection, along with their influenza. This happened in patients who were in the intensive care unit (ICU); patients who were very sick with influenza. Initially, we thought this may just be a contaminant or not a real pathogen. But we found in our study that it was the influenza patients who were developing it, and it was invasive. The patients did have positive fungal serology markers in most cases. Patients who underwent bronchoscopy often had invasive-looking disease. So, we ended up treating them. Despite our treatment, we saw a 60% mortality rate in this group. So, we put together this work and presented it at IDWeek to increase recognition that people with influenza who are not getting better or who have severe forms of the disease, may have a suppurative infection with not only bacteria but also fungi like Aspergillus. One may want to look for it and if discovered, consider doing further workup to see if it is invasive and consider prompt treatment.

Dr Tapper: Aside from the influenza, were these patients otherwise not considered immunosuppressed? They were not cancer patients or patients with stem cell transplants, correct?

Dr Crum-Cianflone: That is entirely correct. These were normal hosts. The median age was in the 50s, but the youngest patient was in their 40s. None of them had any classic risk factors for Aspergillus. There were no transplant patients nor were any on immunosuppressives or chemotherapy. No one in our group had HIV. This was a group of patients typically thought not to be at risk for Aspergillus. We hypothesized that by compromising the immune system and causing lymphopenia (as many of our patients had lymphopenia around the time of their influenza infection), the influenza set our patients up for potentially developing Aspergillus in this setting. So, this may be a new group where there are now novel risk factors for Aspergillus in an otherwise normal host.

Dr Tapper: Were there any other commonalities? Did any of these patients receive corticosteroids—either inhaled, parental, or oral—that might explain this peculiar susceptibility? As you say, this is a very unusual case and to have a cluster like this raises the question of nosocomial infection, which they probably acquired within the hospital. I am curious if there are any other medication histories that might have predisposed them, as this would then serve as a warning for other people. Steroids are sometimes given to people with acute respiratory distress syndrome, who have severe pneumonia, as a desperation move.

Dr Crum-Cianflone: Only one of our patients received steroids prior to the diagnosis of Aspergillus. All the patients received broad-spectrum antibiotics, which also may be considered a risk factor because you are killing off normal flora and providing an avenue for Aspergillus to not only colonize, but then to also become an invasive infection. One of the lessons this teaches us is that unless you have to administer steroids or broad-spectrum antibiotics in influenza cases, it may be better to avoid them because of an increased risk for Aspergillus. We did not see any Aspergillus cases in our hospital setting in patients who did not have influenza.

Dr Tapper: So, no new construction going on, none of the things we technically associate with aspergillosis outbreaks?

Dr Crum-Cianflone: Right. We thought that there was a real correlation between influenza and Aspergillus because we saw this only in these patients. In addition, because we originally thought this might be just a contaminant and not a real finding, we did a thorough literature review of other similar cases. We found 52 other cases described in PubMed and analyzed them. We were unable to tease out risk factors for why this happened in these specific people.

Dr Tapper: Or in clusters like in this specific instance.

Dr Crum-Cianflone: Right, and there were not a lot of clusters either. So, we need better studies, including case-control studies, to look at this further to decipher the true risk factors. We were unable to identify an exact link to why these patients developed Aspergillus.

Dr Tapper: Fascinating and scary. Thanks so much for sharing with us today.

Dr Crum-Cianflone: Thank you.

Reference

Crum-Cianflone N. Invasive aspergillosis associated with severe influenza infection. Presented at: IDWeek 2016. New Orleans, LA; October 26-30, 2016. Poster 1272.