Pandemic influenza and bacterial pneumonia-yet again

Reuters decided that the news about 1918′s H1N1 bacterial pneumonia presentation hadn’t yet received enough play.

Bacteria a big killer in 1918 flu pandemic: study

Tue Aug 19, 2008 12:56pm EDT [excerpt]

WASHINGTON (Reuters) – Bacterial pneumonia may have killed most people during the 1918 flu pandemic, and antibiotics may be as crucial as flu drugs to fight any new pandemic, U.S. researchers reported on Tuesday.

Samples of lung tissue taken from soldiers who died in the pandemic, the worst of the 20th century, showed evidence of damage both by the flu virus and by pneumonia-causing bacteria.

Such so-called co-infections also cause many influenza-related deaths today.

“In essence, the virus landed the first blow while bacteria delivered the knockout punch,” Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, which conducted the study, said in a statement.

Writing in The Journal of Infectious Diseases, Fauci, Dr. Jeffery Taubenberger and colleagues said preparations for future pandemics should include stockpiling antibiotics as well as antiviral drugs and vaccines.

I quoted the following paper when I first blogged on the information released above:

Influenza Virus Neuraminidase Contributes to Secondary Bacterial Pneumonia

Ville T. Peltola, et al.

Secondary bacterial pneumonia is a common cause of death during influenza epidemics. We hypothesized that virus-specific factors could contribute to differences in annual excess mortality. Recombinant influenza viruses with neuraminidases from representative strains from the past 50 years were created and characterized. The specific level of their neuraminidase activity correlated with their ability to support secondary bacterial pneumonia. Recombinant viruses with neuraminidases from 1957 and 1997 influenza strains had the highest level of activity, whereas a virus with the neuraminidase from a 1968 strain had the lowest level of activity. The high level of activity of the neuraminidase from the 1957 strain, compared with that of other neuraminidases, more strongly supported the adherence of Streptococcus pneumoniae and the development of secondary bacterial pneumonia in a mouse model.

Influenza A virus causes epidemics annually and pandemics several times a century. Two subtypes of influenza A virus, H3N2 and H1N1, are presently circulating in the human population. Epidemics caused by H3N2 are associated with higher mortality in human populations than are epidemics caused by H1N1 or influenza B virus. Viruses that cause pandemics are defined as those that acquire a new hemagglutinin (HA), have a high attack rate, and spread globally. Infection with them is generally considered to result in high mortality. Understanding what factors are associated with increased mortality will help us prepare for the next influenza pandemic.

There is no arguing pneumonia is a problem with influenza.  The influenza virus itself sets the body up for what I think of as a “bacterial bloom”, my mind’s eye seeing something akin to the coastal red tides.  In our seas and oceans the local ecology causes and supports the bacterial blooms of red tide and in the lungs the “local ecology” of influenza infected lungs support the bacterial growth.

The Peltola paper continues…

It has been suggested that antigenic novelty accounts for increased mortality during pandemics, but a comparison of mortality estimates between different pandemic years and between interpandemic years indicates that other factors are also involved. The capability of influenza viral strains to predispose to bacterial superinfection may be a factor that determines mortality during an epidemic. Secondary bacterial pneumonia is an important cause of influenza-associated death during both pandemic and interpandemic periods. Results of studies performed during the influenza pandemics of 1957 and 1968 revealed that there was a bacterial etiology in 70% of patients with fatal or life-threatening pneumonia. During interpandemic periods, 44%–57% of patients hospitalized with influenza have bacterial pneumonia, and—although the estimate varies from year to year, depending on the viral strain that is circulating—on average, 25% of all influenza-associated deaths are due to secondary bacterial pneumonia. 

We are learning more and more as time passes, as research matures and is published, and these findings about bacterial pneumonia are likely to be of vital importance, because as I said above, pneumonia is a problem with influenza.  Pneumonia is a problem that can, and does, kill.  Pneumonia kills the very young, the old, and those with pre-existing health problems.  It also can kill healthy young adults, as was demonstrated when Australia had its recent epidemic of H3N2 seasonal influenza, A/Brisbane, a few days past a year ago [here].

It isn’t that we were ignorant of the problems of bacterial pneumonia, but what underlies every bit of what I have quoted here tonight, bacterial pneumonia needs to take its place among the many other threats a pandemic strain might present us with.  

There are things we can do now to protect ourselves.  We can all get a pneumonia vaccine.  Everyone in my family received theirs in 2005 for the potential pandemic threat mitigation it [hopefully] will offer us.   Frustratingly, in the three years I have been involved in the cyber flu community I have read many a Flubie say that their health care provider refused them an pneumonia vaccine.  

I did not have a problem when I sought the vaccines for my family in 2005, even for my 20-something son and daughter-in-law.  I went armed with printouts of relevant research and confidence in the “why” of why I was making the request.  My physician, being not only a wonderful human being, but also a most thorough and caring doctor, double checked efficacy and contraindications for the ages of three of the four of us and found none.  After a bit of discussion, yes my doctor and I have actual conversations, it came out that I and my 20-somethings were the youngest healthy individuals he had vaccinated against pneumonia.  

I have assumed over the intervening years that the difference between my successful outcome and the failure of many others attempts was that I was informed and brought research papers with me.  These papers, of which there are any number, are available on the internet for anyone who searches them out.  Some carry a price but many are open access and free.  The other thing that likely played into my success was the fact that my physician and I had an existing Doctor/Patient relationship so I and my family were not strangers to him.  He knew me to be a woman of at least a certain intelligence and proactive when it comes to my family’s health.  Lastly, I suspect that my demeanor played a small part, I did not humbly ask that my physician do this “strange and out of the ordinary” thing for me and my family because I believed in some hypothetical but remote threat, I asked him to provide a service and product that I was going to pay for.  Perhaps something from my success would prove helpful if seeking a pneumonia vaccine.

Lastly, as has become my habit, I would like to mention another bit of research, this one about specific to vaccines, that has shown that the over the counter and prescription anti-inflammatory medications many of us take (myself included) can hinder the body’s production of antibodies.  It is production of antibodies that we are after when we get any vaccine so refraining from anti-inflammatories for about two weeks after a vaccination is probably a prudent thing to do.

Although the following paper references the human papillomavirus the mechanisms at work would hold for any immunization.

The Journal of Immunology, 2006, 177: 7811-7819. [Abstract, but full paper is available at link]
Copyright © 2006 by The American Association of Immunologists, Inc. 

Cyclooxygenase-2 Inhibition Attenuates Antibody Responses against Human Papillomavirus-Like Particles

Elizabeth P. Ryan, et al.

Vaccination to generate protective humoral immunity against infectious disease is becoming increasingly important due to emerging strains of virus, poorly immunogenic vaccines, and the threat of bioterrorism. We demonstrate that cyclooxygenase-2 (Cox-2) is crucial for optimal Ab responses to a model vaccine, human papillomavirus type 16 virus-like particles (HPV 16 VLPs). Cox-2-deficient mice produce 70% less IgG, 50% fewer Ab-secreting cells, and 10-fold less neutralizing Ab to HPV 16 VLP vaccination compared with wild-type mice. The reduction in Ab production by Cox-2^–/– mice was partially due to a decrease in class switching. SC-58125, a structural analog of the Cox-2-selective inhibitor Celebrex reduced by 70% human memory B cell differentiation to HPV 16 VLP IgG-secreting cells. The widespread use of nonsteroidal anti-inflammatory drugs and Cox-2-selective inhibitory drugs may therefore reduce vaccine efficacy, especially when vaccines are poorly immunogenic or the target population is poorly responsive to immunization. 

For those who do not believe in vaccinations, well, I obviously don’t agree, and I make no apology for it.  I do however have a small sliver of hope that perhaps one or three might change their minds, at least in the case of a pneumonia vaccine [pneumo 23] specifically targeting the 23 most common bacteria that cause bacterial pneumonia.  Unfortunately, there is no vaccine to help protect against viral pneumonia, and yes, there is a difference, but that’s a topic for another evening….

SZ