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AFD - Bacteria & Pandemic Influenza

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  • sharon sanders
    Re: AFD - Bacteria & Pandemic Influenza

    Viral-Bacterial Copathogenesis

    # 2241

    Over the past couple of weeks we've heard a good deal about the role of secondary bacterial pneumonia in the 1918 Spanish Flu, and speculation on how that may affect us during the next influenza pandemic.

    Some of these studies I've recently covered are here, here, and here.

    Today we have another study, this time in The Journal of Infectious Diseases, by Morens, Taubenberger, and Fauci that looks at the predominant role of bacterial pneumonia in the high death toll of 1918.

    (highlighting and reparagraphing mine)

    Predominant Role of Bacterial Pneumonia as a Cause of Death in Pandemic Influenza: Implications for Pandemic Influenza Preparedness

    David M. Morens,
    Jeffery K. Taubenberger, and
    Anthony S. Fauci

    National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland

    Background. Despite the availability of published data on 4 pandemics that have occurred over the past 120 years, there is little modern information on the causes of death associated with influenza pandemics.

    Methods. We examined relevant information from the most recent influenza pandemic that occurred during the era prior to the use of antibiotics, the 1918?1919 ?Spanish flu? pandemic. We examined lung tissue sections obtained during 58 autopsies and reviewed pathologic and bacteriologic data from 109 published autopsy series that described 8398 individual autopsy investigations.

    Results. The postmortem samples we examined from people who died of influenza during 1918?1919 uniformly exhibited severe changes indicative of bacterial pneumonia. Bacteriologic and histopathologic results from published autopsy series clearly and consistently implicated secondary bacterial pneumonia caused by common upper respiratory?tract bacteria in most influenza fatalities.

    Conclusions. The majority of deaths in the 1918?1919 influenza pandemic likely resulted directly from secondary bacterial pneumonia caused by common upper respiratory?tract bacteria.

    Less substantial data from the subsequent 1957 and 1968 pandemics are consistent with these findings. If severe pandemic influenza is largely a problem of viral-bacterial copathogenesis, pandemic planning needs to go beyond addressing the viral cause alone (e.g., influenza vaccines and antiviral drugs).

    Prevention, diagnosis, prophylaxis, and treatment of secondary bacterial pneumonia, as well as stockpiling of antibiotics and bacterial vaccines, should also be high priorities for pandemic planning.

    The take away lesson from this and other studies we've seen over the past few weeks is that while antivirals may be valuable during a pandemic, they won't be enough by themselves.

    Antibiotics will be needed to combat what are likely to be rampant secondary bacterial pneumonias.

    Governments who have been thus far focusing on antiviral stockpiling must now consider expanding their stockpiles to include a wide variety of antibiotics as well.

    Complicating matters greatly will be the wide variety of bacteria capable of causing secondary pneumonias.

    Typical community acquired pneumonias (CAP) are usually caused by Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis. While these strains generally respond well to penicillin's or other common antibiotics, drug resistant strains of S. pneumoniae are increasingly common.

    Other, atypical pneumonias, and nosocomial infections such as caused by S. aureus, further complicate matters. Once rarely seen outside of hospitals, S. aureus pneumonia has, in recent years, been occasionally seen in the community as well.

    Unlike antivirals, there is no one-pill-fixes-all solution here. What works on one bacteria is often ineffective on another.

    Undoubtedly, getting the right antibiotics into the hands of patients who will need them will be one of the biggest challenges facing the medical system during a pandemic crisis.

    Posted by FLA_MEDIC at <a class="timestamp-link" href="" rel="bookmark" title="permanent link"><abbr class="published" title="2008-08-19T12:13:00-04:00">12:13 PM</abbr>

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  • sharon sanders
    Re: AFD - Bacteria &amp; Pandemic Influenza

    Influenza's One-Two Punch

    # 2237

    For the past few years many scientists have subscribed to the idea that the unusually high fatality rate during the 1918 Spanish Flu was due, at least in part, to it having been a novel virus that provoked a devastatingly strident immune response in healthy victims.

    This so-called `cytokine storm', where the body unleashed antibodies and cytokines at an unrecognized virus, was believed to have overwhelmed the victim and resulted in their deaths.

    This, it was felt, helped explain why young healthy adults (many in their mid-20's) fell victim to the virus.

    While the cytokine storm theory hasn't completely fallen out of favor, recent research has indicated that secondary bacterial pneumonias were one of the major factors in the high fatality rates seen in the 1918-1919 pandemic.

    According to recently published research by Brundage and Shanks, 5% of the deaths attributed to the 1918 pandemic occurred in the first 3 days of infection, while the majority of them occurred after about 2 weeks.

    Clinical Courses of Fatal Cases Highly Variable and Often Prolonged

    In most affected populations, <5% of deaths occurred within 3 days of illness onset, median time from illness onset to death was 7?10 days, and significant numbers of deaths occurred >2 weeks after initial symptoms.

    This, they believe, indicates that bacterial pneumonias, and not an over active immune response, were the leading cause of death during the 1918 pandemic.

    While the availability of common antibiotics far exceeds that of antivirals, today many of the common pneumonia's no longer respond to the the older tier of antibiotics.

    As Dr. Fauci points out, new antibiotics are needed. But of course, that takes time. Years, in fact.

    This from the Los Angeles Times.

    New strategy for flu pandemic

    Bacterial infections killed most victims of 1918 flu, scientists say
    By MARY ENGEL, Los Angeles Times
    First published: Monday, August 18, 2008

    Most deaths in the 1918 influenza pandemic were caused not by the virus alone, but by common bacterial infections that overwhelmed victims' weakened immune systems, according to two new studies that could change the strategy against the next pandemic.

    "We have to realize that it isn't just antivirals that we need," said Dr. Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases and co-author of one of the studies.

    "We need to make sure that we're prepared to treat people with antibiotics," said Fauci, whose study will be released online this month by the Journal of Infectious Diseases.

    In both studies, scientists analyzed a trove of historical documents from around the world, examining firsthand accounts, medical records and autopsy reports.

    Writing about the 1918 influenza outbreak in the August issue of the journal Emerging Infectious Diseases, researchers reported that few of the deaths were swift.

    Instead, they found that most of the deaths occurred a week to two weeks later -- indicating opportunistic bacterial infections.

    Most of the samples collected from patients, dead or alive, were bacteria common to the noses and throats of healthy people, according to co-authors Dr. John F. Brundage, a medical epidemiologist at the U.S. Armed Forces Health Surveillance Center in Silver Spring, Md., and Dr. G. Dennis Shanks, director of the Australian Army Malaria Institute in Queensland, Australia.

    So far, public health officials around the world have focused on producing and stockpiling vast quantities of antiviral drugs to combat future pandemic flu strains.

    Fauci said scientists also need to develop new antibiotics and vaccines against bacteria, especially against a virulent strain of Staphylococcus aureus that has been linked to seasonal flu deaths worldwide and is resistant to many antibiotics.
    (Continue . . .)
    Posted by FLA_MEDIC at <a class="timestamp-link" href="" rel="bookmark" title="permanent link"><abbr class="published" title="2008-08-18T07:01:00-04:00">7:01 AM</abbr>

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  • sharon sanders
    started a topic AFD - Bacteria & Pandemic Influenza

    AFD - Bacteria & Pandemic Influenza

    EID Journal: Bacterial Pneumonia and Pandemic Planning

    # 2201

    This month's Journal of Emerging Infectious Diseases, from the CDC, has a good article on the need to plan for treating secondary bacterial pneumonia during a pandemic.

    Here is the abstract, and then some discussion.

    Volume 14, Number 8?August 2008

    Bacterial Pneumonia and Pandemic Influenza Planning

    Ravindra K. Gupta,* Robert George,? and Jonathan S. Nguyen-Van-Tam?
    *John Radcliffe Hospital, Oxford, UK; ?Health Protection Agency, London, UK; and ?University of Nottingham, Nottingham, UK

    Abstract (Reparagraphed for Readability)

    Pandemic influenza planning is well under way across the globe. Antiviral drugs and vaccines have dominated the therapeutic agenda.

    Far less work has been conducted on stockpiling and planning for deployment of antimicrobial drugs against secondary bacterial pneumonia, a cause of substantial illness and death in previous pandemics and epidemics.

    In the event of a pandemic, effective antimicrobial drug measures are expected to substantially benefit public health. We address issues regarding use of antimicrobial drugs as stocks of individual agents are diminished and the role of resistance surveillance in informing such policy.

    Furthermore, vaccination with polysaccharide and conjugate pneumococcal vaccines is considered as part of a pandemic strategy.

    Most illness and death from influenza are likely to occur in developing countries, where neuraminidase inhibitors and vaccines may be neither affordable nor available; thus, compared with industrialized countries, the benefits of treating bacterial complications in developing countries may be substantially greater.

    (Continue Reading . . . )

    There is a good deal here to read, and is worth your time to follow the link.

    This article is basically a companion piece to a historical review I blogged about on July 18th - If you missed the comments section on that piece, there is a lengthy commentary left by a doctor that is well worth reading.

    Brundage JF, Shanks GD. Deaths from bacterial pneumonia during 1918?19 influenza pandemic. Emerg Infect Dis. 2008 Aug; [Epub ahead of print]

    The authors of today's article go on to recommend government stockpiling of specific antibiotics, and a vaccination strategy using the various pneumonia vaccines available.

    * * * * * *

    The last great pandemic (1918) occurred years before the virus theory had been accepted by the scientific community. Bacteria, we knew about - but the existence of viruses had barely been recognized.

    It would take another 15 years before the influenza virus would be identified.

    While there are theories about a virus induced cytokine storm being responsible for many of the deaths during the Spanish Flu, gradually that idea has been falling out of favor - or at least has been modified.

    Today, many scientists believe that a good deal of the excess mortality experienced in the 1918 pandemic was due, not so much to the viral infection itself, but to secondary bacterial pneumonia.

    Granted, with no knowledge of viruses, just about all of the contemporaneous accounts of complications due to the Spanish Flu were attributed to `influenzal pneumonia' or `purulent bronchitis'. Both were believed to be of bacterial origin.

    Here is how the Lancet described an outbreak of purulent bronchitis in Europe, the year before the Spanish Flu broke out. It is very similar to other accounts from the 1918 pandemic:

    Clinically, the prominent signs were the characteristic yellow purulent or mucopurulent sputum, tachycardia, and cyanosis.

    The pathological findings were thick purulent material in the smaller bronchi from which frequently air was excluded; in some cases secondary broncho-pneumonia, edema, and emphysema. The lungs were almost always bulky.

    And this does indeed sound like an aggressive bacterial infection.

    Many of us carry, in our lungs or nasopharynx, colonies of bacteria that - under normal circumstances - remain dormant. When we get a viral infection, we set up ideal conditions in our lungs for these bacteria to grow.

    When that happens, a secondary bacterial pneumonia can set up.

    While the Cytokine Storm theory hasn't been completely abandoned, we do know that millions of people each year develop secondary bacterial pneumonia as a direct result of developing a viral infection. Many of the `flu fatalities' each year are really the result of a secondary bacterial pneumonia.

    This is an observable, and well documented, correlation.

    The need for antibiotic stockpiles during a pandemic, therefore, is readily apparent. Antivirals, alone, won't do the trick.

    The call for a vaccination strategy with with polysaccharide and conjugate pneumococcal vaccines (23-valent and 9-valent pneumonia vaccines) also makes a good deal of sense. Prevention is always preferable to trying to cure.

    All of this proves that there are no easy solutions, no one-pill-fixes-all treatment during a pandemic. And while we can draw much value from looking at past pandemics, the old epidemiologist's lament holds true:

    "If you've seen one pandemic . . . you've seen one pandemic"

    Past performance is no guarantee of future results.

    We could very well find ourselves dealing with unforeseen problems during the next pandemic.

    Hopefully, those that go through the `pandemic-after-next' will have a lot more hard science behind their preparedness efforts than we have behind ours.

    posted by FLA_MEDIC @ 2:19 PM