Pertussis outbreaks and vaccine effectiveness

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 before.

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 improved.

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 resistance.

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 vaccine.