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Severe Influenza May Be a Risk Factor for Aspergillosis

Over one-third of patients with invasive aspergillosis lacked a documented immunosuppressive condition.

Although rare, invasive aspergillosis may be a risk factor for patients with severe influenza, according to the results of a recent study presented in a Poster Abstract Session at ID Week 2018, held this year in San Francisco, California.

In the study, Mitsuru Toda, MS, PhD, from the US Centers for Disease Control and Prevention (CDC) Mycotic Diseases Branch, along with her team, shared documented evidence that more than one-third of patients with invasive aspergillosis lacked documented immunosuppressive conditions.

Past research has suggested that Aspergillus infections can result in invasive disease in the setting of severe influenza, including in patients without classic risk factors. Pathogenesis of the infection in this setting could include viral disruption of the respiratory epithelium as well as impaired local immunity.

“Our colleagues in the Netherlands and Belgium were seeing one-fifth of influenza patients admitted to the intensive care units developing a complication of a fungal disease called invasive aspergillosis. We often think invasive aspergillosis as a disease that only affects people with weakened immune systems,” Dr. Toda told Contagion® in an exclusive interview.

“What was concerning to us was that our colleagues were seeing both immunocompromised and previously healthy people developing invasive aspergillosis after severe influenza,” she added. “The extent of which this problem occurs in the United States was unknown, and we wanted to look at our national influenza surveillance system to look for answers.”

Dr. Toda and her team postulated that severe influenza infection could be a lesser-known risk factor for invasive aspergillosis. As such, they set out to determine the frequency of invasive aspergillosis-associated hospital discharge codes in a national surveillance database of influenza hospitalizations. The database, referred to as FluSurv-NET, includes active surveillance for laboratory-confirmed influenza cases in adults and children in 13 states.

The investigators looked at invasive aspergillosis discharge codes from 2005 to 2017 and evaluated data pertaining to underlying conditions and clinical course that were gathered via medical chart abstraction.

Invasive aspergillosis cases were defined as influenza hospitalizations with 1 or more of the following International Classification of Diseases (ICD) 9th or 10th Clinical Modification discharge diagnosis codes for invasive aspergillosis: aspergillosis (117.3), pneumonia in aspergillosis (484.6), invasive pulmonary aspergillosis (B44.0), tonsillar aspergillosis (B44.2), and disseminated aspergillosis (B44.7).

From 2005 to 2017, invasive aspergillosis ICD codes were rare (0.1%) in patients who were hospitalized with influenza; of 92,671 influenza hospitalizations, 94 cases had aspergillosis ICD codes. However, according to Dr. Toda, despite the fact that this seems like a low number, the findings were striking.

“This is notable because aspergillosis in influenza patients is not well described in the United States, and only 57 cases have been described in the literature in the past 60 years,” Dr. Toda added.

Of the identified cases, 60% (56/94) were male, 72% (60/83) were white, and the median age of the patients was 58 years [interquartile range (IQR) 41-67]. Influenza A accounted for the majority of cases (80%, 75/94); 79% (74/94) received antiviral therapy.

The investigators noted the following underlying conditions among patients with invasive aspergillosis: immunocompromising condition (63%, 59/94), chronic lung disease (51%, 48/94), renal disease (22%, 21/94), and asthma (15%, 14/94).

Patients with aspergillosis ICD codes experienced more severe outcomes compared with those who did not have the codes. Almost half, (48%, 45/94) of the patients required intensive care, according to the investigators. Sixty percent (56/94) had been diagnosed with pneumonia at discharge and 14% (13/94) of patients died.

Dr. Toda and her team concluded that more than one-third of the patients with invasive aspergillosis did not have a documented immunosuppressive condition. and that ICD codes may be “an imperfect” way to identify invasive aspergillosis, as not all cases of Aspergillus infection are coded as such, and some patients with codes for Aspergillus infection may not actually have the infection.

A prospective study looking at laboratory data (eg, culture and antigen) could offer more robust data, the authors write. Additional studies are needed to characterize risk factors and verify diagnoses for invasive aspergillosis in patients with severe influenza.

“We would like clinicians to be aware that invasive aspergillosis can not only occur in immunocompromised patients but also in previously healthy patients with severe influenza,” Dr. Toda said. “We would like clinicians to think of fungal infections when patients do not get better with treatment, and we would like to them to look out for invasive aspergillosis in the coming flu season.”