# Invasive aspergillosis complicating severe influenza

> **NIH NIH R21** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2021 · $194,789

## Abstract

Project Summary
Invasive infections by Aspergillus fumigatus and other Aspergillus species are leading causes of mortality and
morbidity among profoundly immunosuppressed hosts. Recently, invasive aspergillosis has been described as
a complication of severe influenza infection, predominantly among patients who lack traditional aspergillosis risk
factors. Despite an increasing number of case reports of influenza-associated aspergillosis (IAA), the incidence
and clinical features of the disease in the United States (US) are unknown. Whereas risk factors for aspergillosis
are well described in immunosuppressed populations, they have not been defined for patients with severe
influenza. In the largest studies of IAA to date, investigators retrospectively diagnosed the disease in 14%-19%
of intensive care unit (ICU) patients with influenza at 7 European hospitals from 2009-16; the mortality rate of
IAA was 50%. Comparable incidence has been described in retrospective reports from single ICUs, but rates of
Aspergillus superinfections in most multi-center studies of severe influenza have been lower. In the absence of
systematic testing for aspergillosis among patients with severe influenza, it is possible that IAA is under-
recognized by US clinicians and under-reported in the literature. At the same time, incidence may be overstated
in the retrospective European studies by liberal acceptance of serum or bronchoalveolar lavage fluid (BALf)
galactomannan as definitive markers of disease. Our objectives in this project are to define the incidence, clinical
characteristics, and risk factors of IAA by conducting the first prospective study of the disease in the US. We will
employ strict IAA case definitions and systematic serum and BALf galactomannan diagnostic testing of ICU
patients with severe influenza. We hypothesize that we will demonstrate rates of IAA in the US that are
comparable to those reported in Europe, and that a novel point-of-care galactomannan lateral flow assay (LFA)
will demonstrate strong sensitivity and specificity for diagnosing IAA. In aim 1, we will conduct a prospective,
observational clinical study of IAA in ICUs at 4 large medical centers from different regions of the US. In aim 2,
we will evaluate the performance of serum and BALf galactomannan LFA for diagnosing IAA. Our findings will
allow us to develop strategies for rapidly and accurately identifying patients with IAA. This study addresses
fundamental gaps in understanding of the epidemiology and clinical aspects of an under-appreciated form of
invasive aspergillosis. It will lead to clinical trials in which improved understanding of IAA and its diagnosis are
used to guide early antifungal treatment strategies, as well as to future laboratory studies of IAA pathogenesis.
The project is feasible due to the multidisciplinary expertise of our collaborative team of pre-eminent physician-
investigators. Finally, the study has the support of the US Centers for Disease Control and P...

## Key facts

- **NIH application ID:** 10180901
- **Project number:** 5R21AI153575-02
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** M. Hong Thi NGUYEN
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $194,789
- **Award type:** 5
- **Project period:** 2020-06-04 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10180901

## Citation

> US National Institutes of Health, RePORTER application 10180901, Invasive aspergillosis complicating severe influenza (5R21AI153575-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10180901. Licensed CC0.

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