Sisyphus and the Conjugate Vaccines – II
Part one can be found here.
Wipe out some s. pneumo with Prevnar, and more s. pneumo fills in the gap, along with some staph.
The great and shining hope with this situation all along has been an idealistic vision that perhaps the bacteria that filled in the gap would be much milder, or ideally, that nothing would fill in the gap at all. It was hoped that we could just eliminate those bacteria, and horrible diseases like bacterial meningitis would fade into distant memory, along the lines of what supposedly happened with invasive Hib disease, the ultimate conjugate vaccine success story.
Hib meningitis was at one time a disease that many an ER doc was familiar with. When people got bacterial meningitis, the bacteria found in their cerebrospinal fluid was very often, if not usually, Hib.
And the Hib conjugate vaccine is widely thought to have eliminated the problem of invasive h. influenzae disease. But is that what has actually happened?
Well, sort of, in a way. It depends on where one sets their goalposts.
If you develop a case of epidemiological tunnel vision and only look at h. influenzae, specifically and only serotype B, then yes, the Hib conjugate vaccine was and is a complete success.
Hib is gone, not just from its life as an invasive pathogen, but it is gone as a commensal, as well. Before kids were routinely vaccinated with the Hib conjugate vaccine, about 5% of us were commonly carrying Hib around without symptoms at any given time, but now Hib is no more.
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.
Another example of an interspecies competition is the relationship between pneumo and staph, which we will explore next time….