Sisyphus and the Conjugate Vaccines III

March 27, 2008 by
Filed under: Vaccine/Disease Analysis 

Part III of a three part series. Parts one and two can be found here and here.

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The big question with these conjugate vaccines is “What is the overall effect?”

How many fewer cases of invasive bacterial disease are happening after replacement is accounted for?

The more narrowly you look, the better these conjugate vaccines look. The more broadly you look, the more the apparent effects melt away to nothing. With Hib and “replacement disease”, if you just compare h influenza serotype B to serotype A, it would appear that killing off Hib via mass vaccination was extremely successful in the grand scheme of things. When you look at nontypeable (also known as “non capsulated”) h influenzae plus Hia and Hif, that’s when you start seeing that we’re not really any better off now than we were before the Hib conjugate vaccine.

For Prevnar and s pneumo, the situation is similar, but it’s by looking at “interspecies competitions” that we see the futility of the mass vaccination programs against these vaccine-serotype bacterial diseases. The replacement that happens with Prevnar is stunning, but it’s more than just some strains of s pneumo replacing vaccine-strains of s pneumo.

For example, this paper says in the abstract that:

Conclusions. Hospital discharge rates for persons admitted with invasive pneumococcal disease, including meningitis, have decreased since introduction of the heptavalent pneumococcal conjugate vaccine. The decrease was driven in part by the reduction of invasive pneumococcal disease–associated hospitalizations in the subgroup aged 65 years.

Sounds like a slam dunk for the pneumococcal conjugate (Prevnar, aka PCV7) vaccine, doesn’t it? It’s true that pneumococcal disease went down, but when you look at the overall picture, with the interspecies competitions taken into account, a different picture emerges.

This chart from the same study shows that although pneumococcal bacteremia went down, other species of bacteria filled in the ecological niche, plus some, resulting in an overall increase in bacteremia.

The argument could be made that perhaps Prevnar is preventing bacterial meningitis, the nastiest of the invasive bacterial diseases. But this chart from the same study shows that, no, Prevnar hasn’t done anything to curb overall bacterial meningitis after replacement effects are taken into account.

The most alarming of the replacement effects with Prevnar is how staph moves in when pneumo is taken out. Described here:

“A trial with a 7-valent pneumococcal-conjugate vaccine in children with recurrent acute otitis media showed a shift in pneumococcal colonisation towards non-vaccine serotypes and an increase in Staphylococcus aureus-related acute otitis media after vaccination”

“These findings suggest a natural competition between colonisation with vaccine-type pneumococci and S aureus, which might explain the increase in S aureus-related otitis media after vaccination. “

How does it work?

The bactericidal activity of Streptococcus pneumoniae towardStaphylococcus aureus is mediated by hydrogen peroxide. Catalaseeliminated this activity. Pneumococci grown anaerobically orgenetically lacking pyruvate oxidase (SpxB) were not bactericidal,nor were nonpneumococcal streptococci. These results providea possible mechanistic explanation for the interspecies interferenceobserved in epidemiologic studies.

S pneumo poisons staph with hydrogen peroxide.

So what does that mean?

This study concludes:

Conclusions
Streptococcus pneumoniae carriage, specifically of vaccine-type strains, is negatively associated with S aureus carriage in children. The implications of these findings in the pneumococcal vaccine era require further investigation.

You can’t lock out pneumo with the vaccine without opening a window for staph. The change in the “ecosystem” extends beyond those who are vaccinated with Prevnar, as well. Because of herd immunity, the phenomenon can be seen in the whole population.

This study says:

If the association is causal and acquisition of S. pneumoniae eradicates S. aureus carriage, then use of pneumococcal vaccines may eliminate the “protective” effect of S. pneumoniae against S. aureus carriage and an increase in S. aureus carriage will follow. Increased S. aureus otitis media has been observed among vaccinees in a pneumococcal conjugate vaccine randomized trial (23). Whether the current increase in severe community-acquired S. aureus infections, including methicillin-resistant S. aureus (6), is partially caused by the recent introduction of the pneumococcal conjugate vaccine is yet to be determined.

Now, I don’t know about you guys, but I’d say causing or contributing to the CA-MRSA epidemic is one heck of an adverse event. Confirming and determining the role these vaccines played in the staph epidemic should be a top priority.

Comments

3 Comments on Sisyphus and the Conjugate Vaccines III

  1. Mary on Sun, 19th Sep 2010 7:15 am
  2. It’s begun already.

    “Staph Infections Growing Exponentially In Children”

    http://www.11alive.com/news/local/story.aspx?storyid=154043&catid=3

    “Renee Watson, Director of Infection Control at Children’s Healthcare of Atlanta said the staph infection, which is resistant to most common antibiotics, has been creeping into the pediatric population and has been growing exponentially every year.

    … Watson said doctors at Children’s Healthcare of Atlanta are treating children with MRSA on a daily basis.”

  3. Peter on Sun, 1st May 2011 3:41 pm
  4. other interesting study about the impact of serotype replacement for adults:

    Exposure to children as a risk factor for bacteremic pneumococcal disease: changes in the post-conjugate vaccine era, http://www.ncbi.nlm.nih.gov/pubmed/20421560:

    “RESULTS:

    During the study period, the annual rate of disease due to vaccine serotypes declined by 29% per year, but the rate of disease due to nonvaccine serotypes increased 13% per year, yielding an overall 7% increase in the annual rate of disease among adults.”

  5. Peter on Sun, 1st May 2011 3:46 pm
  6. list of new vaccines in the pipeline includes of course staph:

    # Japanese Encephalitis vaccine
    # Staphylococcus aureus vaccine
    # Pseudomonas vaccine
    # Clostridium difficile vaccine
    # Hepatitis C virus vaccine
    # Pandemic Influenza vaccine patch
    # Travelers’ Diarrhea vaccine patch
    # IC31® Seasonal Influenza vaccine
    # Tuberculosis vaccine
    # Pneumococcus vaccine
    # Group A Streptococcus vaccine
    # Bacterial vaccine
    # Lyme Borreliosis vaccine
    # Anti-infective monoclonal antibodies (mAbs)

    http://www.intercell.com/main/forvaccperts/products/

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