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A case against Hib Serotype Replacement?

post #1 of 29
Thread Starter 
http://www.medscape.com/viewarticle/413130_8


It's a 34 page slide presentation.. you might have to log in to read it all

Here is where it starts
http://www.medscape.com/viewarticle/413130_1



And just for some info on the author:

http://www.med.ubc.ca/research/Resea...hools/paed.htm


Quote:
Dr. David Scheifele is a prominent clinician scientist leader in our faculty [University of British Columbia]. He is Professor of Paediatrics in the Division of Infectious and Immunological Diseases and Sauder Family Professor of Pediatric Infectious Diseases. He is Director of the Vaccine Evaluation Centre in the B.C. Research Institute for Children’s and Women’s Health. He is an exceptional researcher and teacher whose focus is on applied vaccinology. Dr. Scheifele has built an outstanding laboratory for the study of new vaccines and vaccine-related problems.

Although this PPT presentation appears to be a presentation and compilation of several people.
post #2 of 29
I can't read it, but can you give us a summary? are they arguing that serotype replacement is not happening? or is happening? is a problem or is not?
post #3 of 29
oh wait I got it reading it now
post #4 of 29
This is very like a lot of other material I have been reading that seems to say there is not the serotype replacement going on in the case of the Hib vaccine that we see with prevnar.
post #5 of 29
Thread Starter 
I would be incapable of summarizing it! *lol*

Though it is actually quite a readable presentation. I hope those who can dissect this better will come along (mamakay ).

I need to sit down to focus on it but they mentioned later vaccinated to unvaccinated studies....
post #6 of 29
Quote:
Now I think we're all very familiar with the idea that Hib conjugate vaccines protect against acquisition of carriage, but it's important to remind ourselves that this was not an expected finding of these vaccines, and it actually was something that was somewhat stumbled upon and led to evaluation of invasive disease among children who were not vaccinated with conjugate vaccines. Because this was not an expected phenomenon, studies were not designed specifically during the prelicensure era of Hib conjugate vaccines to really evaluate this question.
Underlining mine - and yes this is my bias. It did strike me that scientists were going in blind. Still reading - only got to pg 7 of 34

ETA: From p8
Quote:
So, although we do believe, of course, that Hib vaccination does confer protection, it's not quite as simple as just running around and vaccinating everybody.
post #7 of 29
Quote:
Originally Posted by ema-adama View Post
Underlining mine - and yes this is my bias. It did strike me that scientists were going in blind. Still reading - only got to pg 7 of 34

ETA: From p8

So can you break it down a little more for me? lol Sorry I'm kind of slow. Are "they" saying the vaccine isn't quite as effective as once believed? And who are they (who conducted this research?)

Thanks!!
post #8 of 29
Katherine O' Brien, MD, MPH is presenting slides and I am quoting the transcript. This is from 2001

The list of authors and their disclosures

Still from pg. 8
Quote:
So the mechanism of vaccine-induced protection against carriage is really quite unclear. It's important to recognize that we're giving a parenteral vaccine product, and we're talking about protecting against mucosal acquisition of organism.
There is much more interesting stuff too.... I am just drawn to the bits where it is admitted that scientists do not know what they are doing. admittedly 8 years later they might have a better idea.... who knows.
post #9 of 29
Thread Starter 
Right, she presented part of the presentation. Others did other parts. I should have said he was on the introduction, not author as it was a compilation.
post #10 of 29
http://www.medscape.com/viewprogram/223_authors

Quote:
David Scheifele, MD
Sander Family Professor of Pediatric Infectious Diseases, University of British Columbia, Director, Vaccine Evaluation Center, British Columbia Children's Hospital, Vancouver, Canada

Disclosure: David Scheifele, MD receives grant and/or research support from Aventis Pasteur and SmithKline Beecham Pharmaceuticals. He is also consultants for SmithKline Beecham Pharmaceuticals, Aventis Pasteur, and Wyeth Lederle Vaccines.
Quote:
Katherine O'Brien, MD, MPH
Assistant Research Professor, Johns Hopkins University, School of Hygiene and Public Health, Baltimore, Maryland

Disclosure: Katherine O'Brien, MD, MPH receives grant and/or research support from, is a consultant for, and is a member of the Speakers Bureau at Wyeth Lederle Vaccines.
The disclosures are pretty much all the same
post #11 of 29
They only looked at serotypes e and f.

NTHi is the predominant replacing type.
post #12 of 29
Have you seen theis, anewmama?
They go over the case against replacement, and explain what's wrong with only looking at serotypes e and f.

http://insidevaccines.com/wordpress/...e-vaccines-ii/

(no copyright, plus author permission to distribute in full)

Quote:
The general thinking on what has happened with Hib is summarized here:

“Serotype replacement has not been detected since the introduction of Hib conjugate vaccines. Studies of H. influenzae carriage in 700 children in Finland (21) and 364 families in the United Kingdom (15,22) found no evidence of increased carriage of non-b H. influenzae as a result of vaccination. Although increases in invasive disease from other nasopharyngeal bacteria have been reported since Hib vaccination began (23,24), no evidence of a causal link to Hib vaccination has been observed.”

Two claims here: let’s break this down.
__________________________________________________ ___

1) “Serotype replacement” didn’t happen with the Hib vaccine.
__________________________________________________ ___

Well actually, it says “has not been detected”, and that’s probably correct. “Replacement disease” has happened, although the bulk of it was not with an actual serotype of h. influenzae, but rather a type of h. influenzae without a “cap” to give it a a corresponding letter. It wasn’t Hia, or Hif (for example) that primarily filled the ecological niche the Hib conjugate vaccine left behind (although those serotypes have, in fact, taken off to some extent in recent years) but rather it was a ‘type’ that’s not a serotype; it’s a species known as “non-typeable haemophilus influenzae” (NTHi) or “nonencapsulated haemophilus influenzae” that filled in most of the gap.

The degree of the replacement is explained here:

“In addition to the proportional increase in cases of non-type b Haemophilus influenzae disease in the post-H. influenzae type b vaccine era, the incidence of invasive H. influenzae disease was found to be approaching the rates of H. influenzae type b disease that were documented in the prevaccine period. Fifty-six percent of invasive disease now occurs in individuals aged >10 years.”

This is mirrored in the CDC’s Pink Book, Appendix G, where you can clearly see how the cases of invasive h. influenzae dip down until 1996, when they begin climbing again, until they start approaching pre-Hib vaccine levels in recent years.

On to the second claim about the Hib conjugate vaccine:

__________________________________________________ _____

2) “Although increases in invasive disease from other nasopharyngeal bacteria have been reported since Hib vaccination began, no evidence of a causal link to Hib vaccination has been observed .“
__________________________________________________ _____

This is completely meaningless. When you see terms like “has been observed” you need to realize that not looking is a good way to avoid observing. Besides that, it is biologically implausible. The claim is that the increase in s. pneumo (which is a member of our bacterial flora much of the time) had nothing to do with the removal of Hib (which was another member of our bacterial flora) is very unlikely in light of recent research showing that:

“More recent studies have shown increases in the proportion of Haemophilus influenzae and Moraxella catarrhalis in the middle-ear fluid of PCV7-immunized children.”

Remove pneumo and you get an increase in h-flu. I doubt anyone will disagree with that. But we’re supposed to assume that removing h-flu conversely does not increase pneumo?
That’s very unlikely, as there is an interspecies competition between pneumo and h-flu, the details of which remain to be elucidated.
You can get to the original research they're discussion by clicking the link.

post #13 of 29
The method of trying to detect replacement by looking only at the rare serotypes e and f, makes me think of this. This is the best articulation of what can be wrong with even randomized, controlled, blinded trials I've ever read:

http://covertrationingblog.com/gener...ls-and-breasts

Quote:
The sad truth is that the results of RCTs are invariably dependent on the bias built into their design, and even if internally they are statistically legitimate, they can often send us down the wrong path.

Those who design RCTs (the smart ones, at least) know this. They are like smart trial attorneys, in that they know the answer before they ever dare to ask the question. So they tailor their “question” in such a way as to yield the answer they want to get. Indeed, if a lawyer should end up asking a question that produces an unexpected answer, he or she is completely incompetent and ought to be sued for legal malpractice. In more cases than one might think, the same is true for those who design RCTs.
post #14 of 29
Quote:
Originally Posted by carriebft View Post
This is very like a lot of other material I have been reading that seems to say there is not the serotype replacement going on in the case of the Hib vaccine that we see with prevnar.
What are you reading, and what are they looking at?
post #15 of 29
Quote:
Originally Posted by ema-adama View Post
Katherine O' Brien, MD, MPH is presenting slides and I am quoting the transcript. This is from 2001

The list of authors and their disclosures

Still from pg. 8


There is much more interesting stuff too.... I am just drawn to the bits where it is admitted that scientists do not know what they are doing. admittedly 8 years later they might have a better idea.... who knows.
Yeah, I think I said in another thread that they are just making it up as they go along.
post #16 of 29
So, are they saying that serotype replacement isn't happening? The CDC hasn't ruled it out...

http://www.cdc.gov/EID/content/14/1/48.htm

Quote:
...serotype replacement with non–type b strains may result in a reemergence of invasive disease in children...Among 88 typeable isolates, 42 (48%) were H. influenzae type a (Hia)... Serotype a is now the most common H. influenzae serotype in the North American Arctic; the highest rates are among indigenous children.
post #17 of 29
From what I understood in this presentation from 2001 was that they were not seeing Hib serotype replacement (mamakay has addressed this), but they were seeing serotype replacement with the Pneumococcal vaccine.

They are also talking about the reemergence of Hib in highly vaccinated populations on pg 7.
post #18 of 29
The Prevnar trials have been really well designed to detect replacement of all types. Some of then even took note of carriage and disease caused by other species of bacteria, like h-flu and staph.
The Hib trials weren't designed like that. Then again, they had no idea the vax would prevent carriage. No carriage prevention, no possibility of replacement.
So it's sort of a mess.
post #19 of 29
However, the fact that the Prevnar trials were well-designed and that they spotted replacement problems, hasn't stopped the roll-out of Prevnar I and the planned roll-out of Prevnar II. All it means is that the powers that be know they are screwing things up.
post #20 of 29
I realize this is a bit OT but does any of the research indicate how long these vaxes ares supposed to last? Are they effective for a lifetime or do they wear off? Has that been determined?
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