Tuesday, September 20, 2011

mBio: Lethal Synergism of H1N1 Pandemic Influenza & Bacterial Pneumonia




PHIL Image 2111

CDC PHIL - Photomicrograph of Streptococcus (Diplococcus) pneumoniae bacteria


# 5856



While the vast majority of people who contracted the H1N1 pandemic flu of 2009 recovered without incident, a very small minority saw severe – sometimes fatal – illness. 


Often during 2009 we saw reports of severe lung damage. Damage that in some cases was compared to what has been seen in H5N1 bird flu and during the great pandemic of pandemic of 1918.


A few of the stories from back then include:


In early September of 2009, in Pathology Of Fatal H1N1 Lung Infections, we looked at a report by Helen Branswell that looked early autopsy results.



Lung damage in fatal swine flu cases more bird flu than seasonal flu: expert

By Helen Branswell Medical Reporter (CP) 

TORONTO — The lungs of people who have died from swine flu look more like those of the victims of H5N1 avian influenza than those of people who succumb to regular flu, the chief of infectious diseases pathology at the U.S. Centers for Disease Control says.


Study of about 70 fatal H1N1 cases so far also reveals there may be more incidences of co-infections with bacteria than was earlier thought, Dr. Sherif Zaki told The Canadian Press in an interview.


A couple of weeks later in More On The Pathology Of Novel H1N1, we saw a report by Maggie Fox, then Health and Science Editor for Reuters, who brought us more details of this  story, including comments by Dr. Sherif Zaki of the U.S. CDC who  stated that "This is almost exactly what we see with avian flu. This looks like avian flu on steroids."


That same month, I wrote about the use of ECMO (Extracorporeal Membrane Oxygenation) in the treatment of severe lung injury in H1N1 victims in The ECMO Option.


In early December (see NIH: Post Mortem Studies Of H1N1) the NIH announced the results of a series of autopsies conducted on H1N1 victims in New York City over the summer, which are chronicled in the Archives of Pathology & Laboratory Medicine.


The NIH put together a press release, which provided highlights of the study.


Monday, Dec. 7, 2009

Media Contact: Anne A. Oplinger
(301) 402-1663

New York Autopsies Show 2009 H1N1 Influenza Virus Damages Entire Airway

In fatal cases of 2009 H1N1 influenza, the virus can damage cells throughout the respiratory airway, much like the viruses that caused the 1918 and 1957 influenza pandemics, report researchers from the National Institutes of Health (NIH) and the New York City Office of Chief Medical Examiner. The scientists reviewed autopsy reports, hospital records and other clinical data from 34 people who died of 2009 H1N1 influenza infection between May 15 and July 9, 2009. All but two of the deaths occurred in New York City. A microscopic examination of tissues throughout the airways revealed that the virus caused damage primarily to the upper airway—the trachea and bronchial tubes—but tissue damage in the lower airway, including deep in the lungs, was present as well. Evidence of secondary bacterial infection was seen in more than half of the victims.


The team was led by James R. Gill, M.D., of the New York City Office of Chief Medical Examiner and New York University School of Medicine, and Jeffery K. Taubenberger, M.D., Ph.D., of the National Institute of Allergy and Infectious Diseases (NIAID) at NIH. The findings are reported in the Archives of Pathology & Laboratory Medicine, now available online and scheduled to appear in the February 2010 print issue.


This pattern of pathology in the airway tissues is similar to that reported in autopsy findings of victims of both the 1918 and 1957 influenza pandemics,” notes Dr. Taubenberger.


While many people continued to insist that swine flu was no worse than seasonal flu, obviously something was different in the way it produced severe lung damage.  


A year into the pandemic, I summarized many of the ways that the 2009 H1N1 virus differed from seasonal flu in There’s No Flu Like A New Flu.


While the overall incidence of these complications was relatively low, those who suffered from them often experienced extremely severe illness.



All of which serves as prelude to an open access study, published today in mBio, called:


Lethal Synergism of 2009 Pandemic H1N1 Influenza Virus and Streptococcus pneumoniae Coinfection Is Associated with Loss of Murine Lung Repair Responses

John C. Kasha, Kathie-Anne Waltersb, A. Sally Davisa, Aline Sandouka, Louis M. Schwartzmana, Brett W. Jaggera, Daniel S. Chertowa, Qi Lia, Rolf E. Kuestnerb, Adrian Ozinskyb, and Jeffery K. Taubenbergera



The entire study is available, and is well worth reading, but briefly:


Scientists at NIAID and the Institute for Systems Biology (ISB) infected experimental mice with both seasonal flu and the 2009 H1N1 pandemic flu, and after 48 hours exposed some of them to Streptococcus pneumoniae, one of the main causes of pneumonia.


Mice that were exposed only to the two flu strains showed expected flu symptoms, but all survived.

Mice that were exposed to seasonal flu and S. pneumoniae experienced minor lung damage, but once again, all survived.


But all of the mice infected with the pandemic H1N1 virus, and S. pneumoniae showed severe weight loss, lung damage, and 100% mortality


Excerpts from the press release below explain what else they found:


American Society for Microbiology


2009 H1N1 pandemic flu more damaging to lungs, opens opportunities for bacterial infection


The lung tissues of the dead mice revealed that the alveoli were severely inflamed and the surfaces of the bronchioles were wiped clean of the protective layer of cells called the epithelium. There was also increased bacterial replication in the lungs of the co-infected mice, a sign that the bacteria were thriving there.


Looking at the mouse genes that were expressed during infection revealed more details about how the pandemic influenza virus sets the stage for lethal bacterial infections. Mice infected with the pandemic flu virus and S. pneumoniae had a similar inflammatory response as the other mice, but they lack responses that would repair and regenerate their damaged epithelial cells, those protective tissues that would otherwise keep bacteria from penetrating to deeper layers of tissue.


All these factors add up to big problems in the lung: as compared with seasonal flu, infection with the pandemic strain of flu was associated with more extensive damage to the epithelium that requires more extensive tissue repair. This opens the body up to attack from bacterial invaders, including Streptococcus pneumoniae.

(Continue . . . )


So not only did this duel infection lead to greater lung damage, and increased bacterial replication, it also disabled the lung’s ability to repair itself.


Since it can take 6 months or longer to develop a vaccine for a novel influenza virus, these results may suggest a bigger role for the 23-valent Pneumonia vaccine (PPVSV) during a future pandemic. 


More than a year after the end of the 2009 pandemic, scientists are still uncovering basic information about how pandemic flu differs from seasonal flu. 


With luck, work like this will provide better ways for us to deal with an outbreak, when the next one arrives.

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