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Volume 26, Number 4—April 2020
Research Letter

Knowledge of Infectious Disease Specialists Regarding Aspergillosis Complicating Influenza, United States

Mitsuru TodaComments to Author , Susan E. Beekmann, Philip M. Polgreen, Tom M. Chiller, Brendan R. Jackson, and Karlyn D. Beer
Author affiliations: Centers for Disease Control and Prevention, Atlanta, Georgia, USA (M. Toda, T.M. Chiller, B.R. Jackson, K.D. Beer); University of Iowa, Iowa City, Iowa, USA (S.E. Beekmann, P.M. Polgreen)

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Abstract

In an online survey, we found that nearly one fifth of physicians in the United States who responded had seen or heard about a case of invasive pulmonary aspergillosis after severe influenza at their institution. However, <10% routinely used galactomannan testing to test for this fungus in patients with severe influenza.

Invasive pulmonary aspergillosis (IPA) occurs primarily among immunocompromised patients with a history of organ or stem cell transplantation, chemotherapy, or immunosuppressive medications. However, a multicenter retrospective study in the Netherlands and Belgium suggested that patients with severe influenza (i.e., requiring intensive care unit [ICU] admission) are also at risk for IPA (1). In that study, 19% patients with severe influenza showed development of IPA. More than half of these patients were not immunocompromised, and mortality rates were twice as high among ICU patients with IPA compared with those without IPA.

Corticosteroids, which have been associated with higher mortality rates and are used for influenza patients (2), are a known risk factor for IPA and have been associated with IPA in severe influenza (3). However, 44% of patients who showed development of IPA in the study in the Netherlands and Belgium had not received these medications (1). Although case reports exist (4,5), clinicians might not consider IPA as a cause of worsening respiratory function or sepsis because influenza is not considered a classical risk factor for IPA and because of the complexity inherent in diagnosis (6). In the study in the Netherlands and Belgium, IPA cases were diagnosed by galactomannan antigen testing of bronchoalveolar lavage fluid (1). Although galactomannan testing might be useful in the ICU setting (7), it is unclear how often galactomannan testing is performed in the United States.

To clarify clinical practices regarding diagnosis of IPA in patients with severe influenza, the Emerging Infections Network (EIN) surveyed infectious disease specialists in the United States. EIN is a provider-based emerging infections sentinel network supported by the Centers for Disease Control and Prevention and the Infectious Diseases Society of America (8). During May‒June 2018, EIN distributed a 6-question poll to its >1,500 member listserv (https://ein.idsociety.org); 114 responded.

Twenty-nine (26%) respondents were familiar with reports of aspergillosis after severe influenza, and 21 (18%) had seen or heard about >1 case at their institution (Table). Among 108 responding clinicians, 33 (31%) always or very often used lower respiratory tract specimens for diagnostic testing in patients with severe influenza. Only 8 (8%) of 107 clinicians always or very often used lower respiratory specimens and galactomannan testing in patients with severe influenza in the ICU and worsening respiratory function.

Most respondents were unaware of concerns about IPA in severe influenza, suggesting that physicians might not consider it in their differential diagnosis. In addition, most respondents reported infrequent use of galactomannan testing in patients with severe influenza, which might limit ability to detect IPA.

Although our response rate and possible selection bias might limit our ability to draw conclusions, ≈20% of respondents had seen or heard about an IPA case at their institution. IPA in patients with severe influenza might be more common than appreciated based on small numbers of previously published cases in the United States (4,5). Additional research and surveillance are needed to understand the association between IPA and severe influenza and performance of galactomannan testing in patient with severe influenza. Nonetheless, it is essential for clinicians to consider IPA in patients with severe influenza who do not improve with treatment, even in those who are not immunocompromised.

Dr. Toda is an epidemiologist in the Mycotic Diseases Branch, Division of Foodborne, Waterborne, and Environmental Diseases, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA. Her primary research interests are improving disease surveillance and outbreak response for fungal diseases domestically and globally.

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Acknowledgments

This study was supported by Cooperative Agreement 1 (U50 CK000477) funded by the Centers for Disease Control and Prevention.

All coauthors contributed to study design. S.E.B. and P.M.P. collected data; M.T. and S.E.B. analyzed data; M.T., B.R.J., and K.D.B. interpreted data; M.T., T.M.C., B.R.J., and K.D.B. wrote the paper; and S.E.B. and P.M.P. supervised the study.

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References

  1. Schauwvlieghe  AFAD, Rijnders  BJA, Philips  N, Verwijs  R, Vanderbeke  L, Van Tienen  C, et al.; Dutch-Belgian Mycosis study group. Invasive aspergillosis in patients admitted to the intensive care unit with severe influenza: a retrospective cohort study. Lancet Respir Med. 2018;6:78292. DOIPubMed
  2. Rodrigo  C, Leonardi-Bee  J, Nguyen-Van-Tam  JS, Lim  WS. Effect of corticosteroid therapy on influenza-related mortality: a systematic review and meta-analysis. J Infect Dis. 2015;212:18394. DOIPubMed
  3. 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. Clin Respir J. 2019;13:20211. DOIPubMed
  4. Shah  MM, Hsiao  EI, Kirsch  CM, Gohil  A, Narasimhan  S, Stevens  DA. Invasive pulmonary aspergillosis and influenza co-infection in immunocompetent hosts: case reports and review of the literature. Diagn Microbiol Infect Dis. 2018;91:14752. DOIPubMed
  5. Crum-Cianflone  NF. Invasive aspergillosis associated with severe influenza infections. Open Forum Infect Dis. 2016;3:ofw171. DOIPubMed
  6. De Pauw  B, Walsh  TJ, Donnelly  JP, Stevens  DA, Edwards  JE, Calandra  T, et al.; European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group; National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Clin Infect Dis. 2008;46:181321. DOIPubMed
  7. Meersseman  W, Lagrou  K, Maertens  J, Wilmer  A, Hermans  G, Vanderschueren  S, et al. Galactomannan in bronchoalveolar lavage fluid: a tool for diagnosing aspergillosis in intensive care unit patients. Am J Respir Crit Care Med. 2008;177:2734. DOIPubMed
  8. Pillai  SK, Beekmann  SE, Santibanez  S, Polgreen  PM. The Infectious Diseases Society of America emerging infections network: bridging the gap between clinical infectious diseases and public health. Clin Infect Dis. 2014;58:9916. DOIPubMed

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Table

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Cite This Article

DOI: 10.3201/eid2604.190953

Original Publication Date: March 11, 2020

Table of Contents – Volume 26, Number 4—April 2020

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Mitsuru Toda, Centers for Disease Control and Prevention, 1600 Clifton Rd NE, Mailstop H24-9, Atlanta, GA, 30329-4027, USA

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Page created: March 17, 2020
Page updated: March 17, 2020
Page reviewed: March 17, 2020
The conclusions, findings, and opinions expressed by authors contributing to this journal do not necessarily reflect the official position of the U.S. Department of Health and Human Services, the Public Health Service, the Centers for Disease Control and Prevention, or the authors' affiliated institutions. Use of trade names is for identification only and does not imply endorsement by any of the groups named above.
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