September 2012, Week 2


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Sun, 9 Sep 2012 20:32:48 -0400
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Pertussis Outbreaks And Vaccine Effectiveness
Posted by Orac
Respectful Insolence
September 5, 2012

[moderator: to view the informative graphics which
accompany this article please use the link above]

About a month ago, I deconstructed a typically dishonest
and deceitful attempt by that Overlord of Quackery on
the Internet (in my opinion, of course), Joe Mercola, to
claim that the acellular pertussis vaccine doesn't work.
It was a typical Mercola bit of prestidigitation that,
as so much antivaccine propaganda does, took a grain of
truth (that there have been outbreaks among vaccinated
populations) and ran with it to construct a fantasy
world in which pertussis outbreaks are somehow an
indictment of all vaccines, which, of course, don't work
at all, ever, under any circumstances, anywhere at least
in the minds of antivaccinationists.

Perhaps the biggest difference between science-based
doctors and quacks is a very simple one. When a
treatment or preventative measure isn't working as well
as it should, we science-based physicians ask why. We
try to find out what is not working optimally. We try to
figure out how to make things better. So it is with the
acellular pertussis vaccine. It's no secret that recent
outbreaks have been notable for a large contingent of
vaccinated children being involved. Indeed, I cited two
studies that both basically agreed that there appears to
be a hole in the vaccination schedule that leaves
children in the 10-12 year age range inadequately
protected, such that the attack rate is nearly equal in
vaccinated and unvaccinated or undervaccinated children
during the outbreaks was nearly the same.
Antivaccinationists love to cite these studies, but what
they always leave out is the finding that the acellular
pertussis vaccine is effective in protecting younger
children and also in protecting teens who have received
the recommended booster at age 11 or 12.

In other words, antivaccinationists willfully invoke the
fallacy of the perfect solution (also known as the
Nirvana fallacy), which I like to liken to an old sketch
Mike Myers back when he was on Saturday Night Live in
which he played a Scotsman who would loudly say, "If
it's not Scottish it's crap." Basically, under this
fallacy, if a vaccine doesn't work perfectly 100% of the
time, it's crap. If it isn't absolutely, positively,
100% safe, it's crap. If it fails, even just once, to
protect against the disease it's designed to protect
against, it's crap. Never mind that nothing in medicine
is 100% effective and safe and the only certainty in
medicine (and life) is that all of us will one day die.

None of this is to say that we shouldn't strive to
improve the acellular pertussis vaccine or improve the
vaccine schedule, and that was the topic of a recent
paper in the New England Journal of Medicine by Dr.
James D. Cherry, a pediatrician at the David Geffen
School of Medicine, University of California at Los
Angeles, Los Angeles entitled Epidemic Pertussis in 2012
- The Resurgence of a Vaccine-Preventable Disease. He
begins by noting that we are currently experiencing what
may turn out to be the largest outbreak of pertussis in
50 years, asking the question: Why has this
theoretically vaccine-preventable disease been on the
upswing? Several answers are forthcoming, but here's a
graph of pertussis versus time:

It's first noted that whooping cough is a cyclical
disease. In the pre-vaccine era, there were epidemics
every two to five years. Although vaccination was wildly
successful in reducing the incidence from 157 per
100,000 in the 1940s to 1 per 100,000 in 1973, infection
does not, contrary to the claims of antivaccinationists
that "natural immunity" is permanent, produce lifelong
immunity; neither does the vaccine. Cherry notes that
this is in marked contrast to, for example, measles, for
which immunity due to the vaccine is much longer. So
now, even though there isn't as high an incidence of
whooping cough, the causative organism, Bordetella
pertussis is still circulating in a manner similar to
the way it did in the pre-vaccine era. Until recently,
it just wasn't causing epidemics the way that it did

Cherry tells us that there are actually two relevant
issues to consider: The epidemiology of reported
pertussis cases and the epidemiology of pertussis
infection. He notes that existing studies suggest that
13 to 20% of prolonged coughs in adolescents and adults
are likely due to B. pertussis infection, and studies
examining antibody titers suggested an infection rate
between 1% and 6%. In other words, there's a lot of
mildly symptomatic pertussis out there, which leads
Cherry to ask:

    So what are the causes of today's high prevalence of
    pertussis? First, the timing of the initial
    resurgence of reported cases (see graph) suggests
    that the main reason for it was actually increased
    awareness. What with the media attention on vaccine
    safety in the 1970s and 1980s, the studies of DTaP
    vaccine in the 1980s, and the efficacy trials of the
    1990s comparing DTP vaccines with DTaP vaccines,
    literally hundreds of articles about pertussis were
    published. Although this information largely escaped
    physicians who care for adults, some pediatricians,
    public health officials, and the public became more
    aware of pertussis, and reporting therefore

Antivaccinationists will no doubt scoff at this
suggestion the same way that they scoff at any
suggestion that the increased prevalence of autism over
the last 20 years could possibly be due to greater
awareness and intensive screening programs, but as I've
pointed out before, it's a truism in medicine that
whenever you look for a disease you will find more of
it-sometimes a lot more, particularly if you use more
sensitive tests or broaden the diagnostic criteria (the
latter of which was done for autism in the early 1990s).

Even though I've used this example within the last six
months, it bears repeating because it's in my specialty
and it illustrates the concept. Basically, the same sort
of thing happened when mass mammography screening
programs were undertaken with an entity called ductal
carcinoma in situ (DCIS). This is a premalignant
precursor of breast cancer, some proportion of which
will progress to full-blown cancer. Basically, it's
cancerous cells that haven't broken out of the breast
ducts yet to invade the surrounding tissue. A few
decades ago, DCIS was fairly rare because by the time it
grew large enough to be a palpable mass, it almost
always had become invasive cancer. Now, thirty years or
so after mass mammographic screening programs began,
DCIS is common. In fact, it's the most common diagnosis
of breast cancer made, making up approximately 40% of
breast cancer diagnoses Once again, I'll cite a recent
study that reported that DCIS incidence rose from 1.87
per 100,000 in the mid-1970s to 32.5 in 2004. That's a
more than 16-fold increase over 30 years. There's no
reason to suspect that the "true" incidence of breast
cancer is increasing. (Indeed, it's not.) So that
implies that this increase was pretty much all due to
the introduction of mammographic screening. Other
examples abound in medicine, including hypertension,
hypercholesterolemia, and others.

Cherry suggests that one factor behind the rise in
pertussis lately is similar:

    Moreover, during the past decade, polymerase-chain-
    reaction (PCR) assays have begun to be used for
    diagnosis, and a major contributor to the difference
    in the reported sizes of the 2005 and 2010 epidemics
    in California may well have been the more widespread
    use of PCR in 2010. Indeed, when serologic tests
    that require only a single serum sample and use
    methods with good specificity become more routinely
    available, we will see a substantial increase in the
    diagnosis of cases in adults.

In other words, some of what's going on here might just
be overdiagnosis, in which mildly symptomatic cases or
cases that aren't that serious are picked up that once
might have been dismissed as a persistent "crud."
Clearly, though, that's not the only thing going on. Two
other issues are likely also contributing. The first is
the issue that I discussed before, namely waning
immunity from the acellular pertussis vaccine. Cherry
cites five studies showing that the old DTP (the whole
cell pertussis vaccine combination with the tetanus and
diphtheria vaccine) was more efficacious than the DTaP
(the acellular pertussis vaccine combination), as well
as the California studies whose misuse by Mercola I
discussed before. One needs to remember that the switch
from the DTP combination vaccine to the DTaP combination
vaccine was largely due to concerns about the safety of
the DTP back in the 1980s that led to the rise of
Barbara Loe Fisher and her antivaccine group the
National Vaccine Information Center (NVIC) over reports
of encephalopathy after the vaccine, fears that later
studies failed to confirm. So, in essence, we traded a
highly effective vaccine for one that's effective, but
not quite as effective.

Finally, there's this:

    Finally, we should consider the potential
    contribution of genetic changes in circulating
    strains of B. pertussis.4 It is clear that genetic
    changes have occurred over time in three B.
    pertussis antigens - pertussis toxin, pertactin, and
    fimbriae. In fact, changes in fimbrial agglutinogens
    related to vaccine use were noted about 50 years
    ago. Studies in the Netherlands and Australia have
    suggested that genetic changes have led to vaccine
    failures, but many people question these findings.
    If genetic changes had increased the rates of
    vaccine failure, one would expect to see those
    effects first in Denmark, which has for the past 15
    years used a vaccine with a single pertussis antigen
    (pertussis toxin toxoid). To date, however, there is
    no evidence of increased vaccine failure in Denmark.

These are the observations behind the claims by cranks
like Mercola that vaccines are "causing dangerous
mutations." While it is possible that the B. pertussis
bacteria is developing "resistance" to the vaccine
through natural selection, the evidence that it is doing
so strikes me as rather weak and preliminary. Even if it
were, the answer would be to change the vaccine in order
to include the altered antigens. After all, do we decide
that antibiotics don't work when bacteria evolve
resistance or that chemotherapy doesn't work when tumors
manage to do the same? That's a rhetorical question, of
course. Some segments of the alt-med world do, but
reasonable scientists do not. They work to overcome that

Leaving aside that hypothetical problem that might be
contributing to pertussis epidemics in the era of the
acellular vaccine, what can be done to bring these
epidemics under control? Some of what Cherry mentions
are the same things I mentioned the last time I
discussed this issue. First, he notes that the purpose
of vaccination against B. pertussis is not to eliminate
all disease. It's to prevent serious disease with its
potentially horrific complications, up to and including
death, particularly among young infants. One possible
approach would be to start DTaP at a younger age with
shorter intervals between doses. Another strategy is to
immunize pregnant women in order to reduce the risk that
the mother will acquire pertussis around the time of
delivery, with the added bonus that it would give the
infant some protection for a month or two through
maternal antibodies.

The point of course is that these recent epidemics,
while they point to problems with the current
vaccination schedule, do not by any means demonstrate
that the vaccine doesn't work or that it's failed.

I also have one final point. While the evidence that
pockets of unvaccinated children are the nidus for
measles outbreaks is very clear, these latest pertussis
outbreaks do not appear to be strongly related to
pockets of unvaccinated children. There's no doubt that
having pockets of unvaccinated children doesn't help.
They are, after all, at a 23-fold increased risk of
catching whooping cough, which allows for the
degradation of herd immunity at the very least as well
as providing a reservoir for the offending bug, and even
the latest studies out of California indicate that for
most age ranges unvaccinated and undervaccinated
children are at a significantly higher risk of catching
pertussis than fully vaccinated children; the problem is
primarily at one age range where waning immunity from
the DTaP leaves a gap in immunity. However, in this
case, as far as I've been able to tell, they do not
appear to be the primary drivers of these most recent
epidemics, as they are for measles outbreaks. We as
science-based supporters of vaccination have to be
careful not to overstate our case.

Would that antivaccinationists would do the same.
Actually, would that antivaccinationists would actually
stop spreading misinformation. The difference between
science-based supporters of vaccination and
antivaccinationists is simple. We face reality. Evidence
and science matter to us. When vaccines do not function
as well as we would like and try to fix it. As Cherry
reminds us, even with these new epidemics, today's
incidence of pertussis is still about one twenty-third
what it was during a typical epidemic year in the 1930s.
Indeed, a reader sent me a link to a presentation by
Thomas Clark, MD, MPH about pertussis epidemiology and
vaccination. This slide set includes a slide that takes
the slide above and puts it in context:

That rather puts the antivaccinationists' attacks on the
acellular pertussis vaccine into perspective, doesn't
it? Indeed, I can't help but note that the graph above
shows the total number of cases. Because the U.S.
population has grown considerably over the last 90
years, if it were graphed by incidence, the effect of
the vaccine would be even more striking. In any case,
this graph illustrates quite clearly that the pertussis
epidemics over the last few years are mere blips on the
curve compared to what we saw in the past, before there
was a vaccine available to combat pertussis. Still,
although this is good, it is not nearly good enough. We
can do better. Contrary to what antivaccinationists tell
us, recent outbreaks of pertussis do not mean that
vaccines don't work. They mean that we need to use the
vaccine we have better and possibly develop newer
vaccines that overcome the shortcomings of the existing


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