Deaths from Bacterial Pneumonia during 1918–19 Influenza Pandemic

Brundage, John F.; Shanks, G. Dennis

doi:10.3201/eid1408.071313

Cited by 341 publications

(331 citation statements)

References 29 publications

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“…One of the likely outcomes of such modulation is increased susceptibility to subsequent bacterial superinfection, which accounts for an important portion of morbidity and mortality associated with influenza infection. Indeed, clinically, the majority of flu patients diagnosed with bacterial superinfection were found to have just recovered or were still recovering from the flu (19,27). However, the underlying mechanisms have remained largely to be elucidated.…”

Section: Discussionmentioning

confidence: 99%

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Influenza Infection Leads to Increased Susceptibility to Subsequent Bacterial Superinfection by Impairing NK Cell Responses in the Lung

Small

Shaler

McCormick

et al. 2010

The Journal of Immunology

194

160

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Influenza viral infection is well-known to predispose to subsequent bacterial superinfection in the lung but the mechanisms have remained poorly defined. We have established a murine model of heterologous infections by an H1N1 influenza virus and Staphylococcus aureus. We found that indeed prior influenza infection markedly increased the susceptibility of mice to secondary S. aureus superinfection. Severe sickness and heightened bacterial infection in flu and S. aureus dual-infected animals were associated with severe immunopathology in the lung. We further found that flu-experienced lungs had an impaired NK cell response in the airway to subsequent S. aureus bacterial infection. Thus, adoptive transfer of naive NK cells to the airway of prior flu-infected mice restored flu-impaired antibacterial host defense. We identified that TNF-α production of NK cells played an important role in NK cell-mediated antibacterial host defense as NK cells in flu-experienced lungs had reduced TNF-α expression and adoptive transfer of TNF-α–deficient NK cells to the airway of flu-infected mice failed to restore flu-impaired antibacterial host defense. Defected NK cell function was found to be an upstream mechanism of depressed antibacterial activities by alveolar macrophages as contrast to naive wild-type NK cells, the NK cells from flu-infected or TNF-α–deficient mice failed to enhance S. aureus phagocytosis by alveolar macrophages. Together, our study identifies the weakened NK cell response in the lung to be a novel critical mechanism for flu-mediated susceptibility to bacterial superinfection.

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Section: Discussionmentioning

confidence: 99%

“…1). The 7 d time point postflu infection for the onset of bacterial superinfection was chosen also based on the clinical evidence that most bacterial superinfections in humans occur within the first 2 wk of influenza infection (19,27). The mice were then infected i.t.…”

Section: Prior Flu Infection Causes Increased Susceptibility To Bactementioning

confidence: 99%

Influenza Infection Leads to Increased Susceptibility to Subsequent Bacterial Superinfection by Impairing NK Cell Responses in the Lung

Small

Shaler

McCormick

et al. 2010

The Journal of Immunology

194

160

View full text Add to dashboard Cite

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“…However, any of these organisms can move up and down the respiratory tract quite freely, especially if the cilial ladder mechanism that constantly wafts debris from the lungs to the mouth to be swallowed (and destroyed by the stomach acid) is damaged. This is one mechanism by which an initial viral infection can lead to the more serious secondary bacterial infections that may have caused the majority of deaths in the 1918 and subsequent influenza pandemics (Brundage & Shanks 2008;Morens et al 2008).…”

Section: Generation Of Fomites In the Air And Their Microbiological Cmentioning

confidence: 99%

Airborne transmission of disease in hospitals

Eames

Tang

et al. 2009

J. R. Soc. Interface.

170

126

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Hospital-acquired infection (HAI) is an important public health issue with unacceptable levels of morbidity and mortality, over the last 5 years. Disease can be transmitted by air (over large distances), by direct/indirect contact or a combination of both routes. While contact transmission of disease forms the majority of HAI cases, transmission through the air is harder to control, but one where the engineering sciences can play an important role in limiting the spread. This forms the focus of this themed volume.In this paper, we describe the current hospital environment and review the contributions from microbiologists, mechanical and civil engineers, and mathematicians to this themed volume on the airborne transmission of infection in hospitals. The review also points out some of the outstanding scientific questions and possible approaches to mitigating transmission.

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“…Bacterial pneumonia is a serious complication of infl uenza infection and was likely a major cause of the excess deaths seen during the 1918 infl uenza pandemic (4)(5)(6)(7)(8). Even today, though the overall disease mortality rate due to infectious diseases is declining in the United States, death from pneumonia and infl uenza remains one of the top 10 causes of death overall (9,10).…”

mentioning

confidence: 99%