Myocardial Injury and Bacterial Pneumonia Contribute to the Pathogenesis of Fatal Influenza B Virus Infection

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J Infect Dis. (2012) doi: 10.1093/infdis/jir861 First published online: January 30, 2012



Myocardial Injury and Bacterial Pneumonia Contribute to the Pathogenesis of Fatal Influenza B Virus Infection

Christopher D. Paddock1,
Lindy Liu1,
Amy M. Denison1,
Jeanine H. Bartlett1,
Robert C. Holman2,
Marlene DeLeon-Carnes1,
Shannon L. Emery3,
Clifton P. Drew1,
Wun-Ju Shieh1,
Timothy M. Uyeki4 and
Sherif R. Zaki1

1Infectious Diseases Pathology Branch
2Office of the Director, Division of High-Consequence Pathogens and Pathology
3Viral Surveillance and Diagnostic Branch
4Epidemiology and Prevention Branch, Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia

Correspondence: Christopher D. Paddock, MD, MPHTM, Infectious Diseases Pathology Branch, Mailstop G-32, Centers for Disease Control and Prevention, 1600 Clifton Rd, Atlanta, GA 30333 (cdp9{at}cdc.gov).

Abstract

ARTICLE

Background. Influenza B virus infection causes rates of hospitalization and influenza-associated pneumonia similar to seasonal influenza A virus infection and accounts for a substantial percentage of all influenza-related hospitalizations and deaths among those aged <18 years; however, the pathogenesis of fatal influenza B virus infection is poorly described.

Methods. Tissue samples obtained at autopsy from 45 case patients with fatal influenza B virus infection were evaluated by light microscopy and immunohistochemical assays for influenza B virus, various bacterial pathogens, and complement components C4d and C9, to identify the cellular tropism of influenza B virus, characterize concomitant bacterial pneumonia, and describe the spectrum of cardiopulmonary injury.

Results. Viral antigens were localized to ciliated respiratory epithelium and cells of submucosal glands and ducts. Concomitant bacterial pneumonia, caused predominantly by Staphylococcus aureus, was identified in 38% of case patients and occurred with significantly greater frequency in those aged >18 years. Pathologic evidence of myocardial injury was identified in 69% of case patients for whom cardiac tissue samples were available for examination, predominantly in case patients aged <18 years.

Conclusions. Our findings suggest that bacterial pneumonia and cardiac injury contribute to fatal outcomes after infection with influenza B virus and that the frequency of these manifestations may be age related.

Received March 28, 2011.
Accepted May 2, 2011.

Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2012.

http://jid.oxfordjournals.org/content/early/2012/01/28/infdis.jir861.abstract

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Re: Myocardial Injury and Bacterial Pneumonia Contribute to the Pathogenesis of Fatal Influenza B Virus Infection

J Infect Dis. (2012) doi: 10.1093/infdis/jir865 First published online: January 30, 2012

Fatal Influenza B Infections: Time to Reexamine Influenza Research Priorities

Jonathan A. McCullers1 and
Frederick G. Hayden2,3

1Department of Infectious Diseases, St. Jude Children?s Research Hospital, Memphis, Tennessee
2Department of Medicine, Division of Infectious Diseases and International Health, University of Virginia School of Medicine, Charlottesville
3International Activities, Wellcome Trust, London, United Kingdom

Correspondence: Jonathan A. McCullers, MD, St. Jude Children?s Research Hospital, 262 Danny Thomas Pl, Memphis, TN 38105 (jon.mccullers{at}stjude.org).

ARTICLE

Influenza A viruses (IAVs) are zoonotic pathogens that sometimes establish long-term lineages in humans and other mammalian hosts. New introductions of influenza genes or whole viruses from animal reservoirs can result in viruses with an exceptionally virulent phenotype. After a period of adaptation and development of population immunity, however, the descendents of pandemic viruses rarely cause severe illness and mortality through direct viral damage in immunocompetent hosts [1, 2]. Instead, exacerbation of a preexisting, chronic illness or virus-mediated impairment of host defenses facilitating bacterial superinfection account for most fatalities. Selwyn Collins of the US Public Health Service, who refined the terms by which we classify outcomes after influenza, expressed this view as, ?In fact, influenza may well be thought of as not a killing disease except by the intervention of pneumonia or the presence of chronic disease in a patient? [3].

Influenza B viruses (IBVs) are stably adapted to humans, having diverged from IAVs at some point in the distant past. IBVs were first isolated from humans in 1940 and have caused seasonal epidemics since at least 1935 but likely have been endemic in humans for centuries. Although IBVs can establish lineages in seals, they are not known to have a stable animal reservoir from which new variants could emerge [4]. Over the last several decades, rates of hospitalization and mortality attributed to IBVs have been lower than those associated with H3N2 subtype IAVs but higher than those linked to the less virulent seasonal H1N1 strains. During the 2010?2011 season, 38% of all influenza-associated pediatric deaths were attributed to IBVs, despite only 26% of all circulating viruses being of this type [5]. Half (49%) of these children who died had no known high-risk medical condition, and only 50% received any ?

http://jid.oxfordjournals.org/content/early/2012/01/28/infdis.jir865.extract