J Infect Dis. Pneumococcal Surface Protein A Contributes to Secondary Streptococcus pneumoniae Infection after Influenza Virus Infection.

[Giuseppe]

J Infect Dis. 2009 Jul 8. [Epub ahead of print]

Pneumococcal Surface Protein A Contributes to Secondary Streptococcus pneumoniae Infection after Influenza Virus Infection.

King QO, Lei B, Harmsen AG. Veterinary Molecular Biology, Montana State University, Bozeman.


We compared the growth of Streptococcus pneumoniae mutants with a disruption in the gene for either pneumococcal surface protein A (PspA(-)), neuraminidase A (NanA(-)), or hyaluronidase (Hyl(-)) to that of the parental strain D39 by means of a competitive growth model in mice with and those without prior influenza virus infection. The numbers of total bacteria recovered from mice with prior influenza virus infection were significantly greater than those recovered from mice without prior influenza virus infection. Although the Hyl(-) and NanA(-) mutants did not display attenuation in mice with or without prior influenza virus infection, the PspA(-) mutant exhibited attenuation both in mice with and in mice without prior influenza virus infection. This defect was severe in influenza virus-infected mice, for which growth of the PspA(-) mutant was 1800-fold lower than that of the parental strain D39. Furthermore, PspA immunization significantly reduced secondary bacterial lung burdens and concentrations of specific markers of lung damage in mice receiving serotypes 2, 3, and 4 pneumococci. Our findings indicate that PspA contributes to secondary S. pneumoniae infection after influenza virus infection and that PspA immunization mitigates early secondary pneumococcal lung infections.

PMID: 19586418 [PubMed - as supplied by publisher]
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[kiwibird]

Re: J Infect Dis. Pneumococcal Surface Protein A Contributes to Secondary Streptococcus pneumoniae Infection after Influenza Virus Infection.

Is a laymans summary of this: you have a higher bacterial load if you have had an influenza infection previously? This is a vehicle of "original antigenic sin"?

 

[gsgs]

Re: J Infect Dis. Pneumococcal Surface Protein A Contributes to Secondary Streptococcus pneumoniae Infection after Influenza Virus Infection.

if you are a mouse

 

[the doctor]

Re: J Infect Dis. Pneumococcal Surface Protein A Contributes to Secondary Streptococcus pneumoniae Infection after Influenza Virus Infection.

Is a laymans summary of this: you have a higher bacterial load if you have had an influenza infection previously? This is a vehicle of "original antigenic sin"?

No.

The message is all children (and adults) need to be vaccinated against pneumococcus now before they get influenza. Doing so is the best and perhaps only way to prevent post-influenza pneumococcal pneumonia, the most common case of bacterial infections after influenza.

Don't wait. Do it now. If your insurance company won't pay for it, pay for it yourself.

You need a doctor's Rx for this vaccine. Beg him or her to give it to you or your child the prescription. Explain that you are very concerned about the flu and getting pneumococcal pneumonia afterward.

They may listen better now that we are in a pandemic.

GW

 

[mixin]

Re: J Infect Dis. Pneumococcal Surface Protein A Contributes to Secondary Streptococcus pneumoniae Infection after Influenza Virus Infection.

I recently told my doctor I'd like to have a pneumonia shot and she didn't hesitate.

Otoh, snips from that NEJM study on pneumonia and respiratory failure in Mexico,

During the 1918 pandemic, a large number of deaths were associated with bacterial infection; but concurrent bacterial infection does not appear to be a major contributing factor to the severity of illness in our patients, possibly in part because most received antibiotics before hospitalization.

In most of our patients, lung damage was most likely due to the primary effect of infection with influenza virus. Possible mechanisms of damage include direct injury to the respiratory epithelium with a secondary cytokine storm. We do not currently know whether our patients, especially those who died, had viremia, as was reported in association with H5N1 infection, a very aggressive variety of influenza.

We really do need more up to date information on patients.

 

[kiwibird]

Re: J Infect Dis. Pneumococcal Surface Protein A Contributes to Secondary Streptococcus pneumoniae Infection after Influenza Virus Infection.

if you are a mouse

No worries there! LOL!

Thank you for the clarification everyone. The pneumovax vaccine is available here - you have to pay for it (around $50 + nurse charge).

 

[the doctor]

Re: J Infect Dis. Pneumococcal Surface Protein A Contributes to Secondary Streptococcus pneumoniae Infection after Influenza Virus Infection.

I recently told my doctor I'd like to have a pneumonia shot and she didn't hesitate.

Otoh, snips from that NEJM study on pneumonia and respiratory failure in Mexico,

We really do need more up to date information on patients.

This is true. What the young are dying of is cytokine storm.

What those who don't succumb to cytokine storm are most likely to die from is dehydration. The next cause will be bacterial pneumonia with pneumococcal pneumonia being the most likely cause.

GW

 

[the doctor]

Re: J Infect Dis. Pneumococcal Surface Protein A Contributes to Secondary Streptococcus pneumoniae Infection after Influenza Virus Infection.

No worries there! LOL!

Thank you for the clarification everyone. The pneumovax vaccine is available here - you have to pay for it (around $50 + nurse charge).

Dearest Kiwibird,

The study on mice was done with pneumococcus because that bacteria is the most common cause of human death after flu infection.

The study was done to shed light on what might happen to us not mice during a pandemic. The mouse is simply a model for us.

GW

 

[kiwibird]

Re: J Infect Dis. Pneumococcal Surface Protein A Contributes to Secondary Streptococcus pneumoniae Infection after Influenza Virus Infection.

Thank you for your kindness - I really don't deserve you all! I was just being naughty!

 

[St Michael]

Re: J Infect Dis. Pneumococcal Surface Protein A Contributes to Secondary Streptococcus pneumoniae Infection after Influenza Virus Infection.

From the Fedson study:

Bacterial pneumonia cannot account for the majority of deaths in the 1918 pandemic

An added level of complexity has been introduced recently by the suggestion that secondary bacterial pneumonia was the primary cause of mortality in the 1918 pandemic.20 Support for this notion comes from recent experiments showing that antecedent influenza virus infection greatly increases the risk of death following subsequent pneumococcal pneumonia.21 In a recent report, Morens et al. reviewed almost 8400 bacterial cultures of specimens taken from patients who died during the 1918 pandemic.20 After considering their findings and related epidemiological evidence, they found little to implicate the influenza virus as the sole cause of mortality. Instead, they concluded 'the vast majority of influenza deaths resulted from secondary bacterial pneumonia'. This conclusion has led to recommendations for pre-pandemic stockpiling of antimicrobial agents as well as antivirals and vaccines.

Morens et al. have written that the 'copathogenic properties of the 1918 influenza virus may have been generic and not specific to the 1918 virus or to influenza viruses in general.22 They have found support for their view in the measles epidemics that affected US Army training camps in 1917?1918. Like the influenza pandemic 1 year later, most measles deaths were associated with bacterial pneumonia. The measles outbreaks were 'the result of an unfortunate 'natural experiment' in which young men from remote rural areas, many of whom had escaped measles virus infection in childhood, were brought together in crowded barracks during the winter/spring season of measles circulation.22 This explanation may be sufficient to explain why trainees became infected, but it does not explain why they died.

Clinicians have known since the time of Osler that not all people who die with pneumonia necessarily die because of pneumonia.23 In patients with H5N1 influenza, virtually all who have come to medical attention have received antibiotic treatment, yet the mean duration of illness before death has been 10 days,18 as it was in 1918,24 For patients with H5N1 influenza who have presented late in the course of illness, bacterial pneumonia should have been evident, yet it has rarely been mentioned. Instead, most have gone on to develop acute respiratory distress syndrome (ARDS) and multi-organ failure.

In the studies of bacterial pneumonia in the 1918 pandemic, one important epidemiologic feature has received little attention: children had higher influenza attack rates than young adults, yet they seldom developed bacterial pneumonia and their case fatality rates were much lower (Figure 1).20,23,24 There is nothing to suggest that the experience of children with measles in 1917?1918 was any different from that of children in earlier years.22 Virulence factors inherent in the 1918 influenza virus and the cytokine dysregulation caused by infection might help explain the increased mortality of younger adults, but there is no good reason to place the burden of 'pathogenic responsibility' entirely on the virus. Doing so overlooks a more important question: why did children live?

In attempting to understand the high mortality in the 1918 pandemic, influenza scientists have focused their attention on young adults.25 Previous exposure to 1918-like viruses in the late 19th century seems to have given older adults a degree of protection that spared them the mortality experienced by younger adults. For children, however, there has been no satisfactory explanation for why the same virus failed to cause most of them serious harm.

 

[the doctor]

Re: J Infect Dis. Pneumococcal Surface Protein A Contributes to Secondary Streptococcus pneumoniae Infection after Influenza Virus Infection.

In college I did a paper on the 1918 flu and while that was in the 1970s and I really remember very little about it, the one thing I do recall was a bit of the microbiology. The pathologists then had almost everything we have today in terms of basis stains and regular microscopy. They did not have the electron microscope nor did they know about L form bacteria therefore could not stain or culture mycoplasma and clamidya. Of course they did not know the cause of flu and had not identified the virus, that came 12 years later when classical H1N1 was recovered from s*w*i*n*e.

What I remember most was how frustrated the microbiologists were trying to identify the cause of the pulmonary pathological findings. They could not find very many bacterial organisms at all but one that did turn up fairly commonly but not widely enough to explain the event was a bug they named Hemophylus Influenza. Of course this is a bacteria and not a virus and certainly not the cause of what happened in 1918 but since it was found in the lung tissue of some of the young adults who died in 1918 and is a pathogen that should not be there, post-influenza pneumonia was happening.

However, the quantity of H. Flu found in the lungs of these people was not very great or at least not what you would expect to cause death in most of them so, they died from something else before they could died from H. Flu pneumonia.

I agree with Dr. Fedson on this, cytokine storm was the probable cause of death in most of these young adults but I also think that those who lived long enough might have then developed bacterial pneumonia dying from that.

I also agree with Morens that it is a good idea for the US to add more antibiotic to the strategic stockpile but not his opinion regarding the reason so many young adults died from the 1918 pandemic.

Grattan Woodson, MD

GW

 

[tyto]

Re: J Infect Dis. Pneumococcal Surface Protein A Contributes to Secondary Streptococcus pneumoniae Infection after Influenza Virus Infection.

Here's another piece of the puzzle why influenza and s. pneumonia are partners in crime.

In the May 15th, 2009 edition of J Infectious Disease, there was an article about how sialic acid acts as a signal for pneumococcal biofilm formation, colonization, and invasion of the host.

http://www.journals.uchicago.edu/doi/abs/10.1086/598483

Neuramindase from influenza frees up sialic acid from newly formed virus particles and from host cell receptors. The levels of free sialic acid acts as a signal for s. pneumonia to form biofilms and become invasive.

In the Jan 1, 2009 edition of the New England Journal of Medicine an article explained how bacteria grown in vitro don't exhibit full virulence like when grown in vivo. Bacteria in vivo will interrogate their environment with proteins and virulence genes will turn on when certain signals from their environment are detected.

http://content.nejm.org/cgi/content/extract/360/1/83