Whooping cough vaccination, pertussis and parapertussis: forty times more likely to be misunderstood?

Two Bordetella species of bacteria regularly cause the disease known as whooping cough in humans, Bordetella pertussis and Bordetella parapertussis. Of the two, B. pertussis causes much more severe disease, with a rate of about 1 fatality per 125 cases in infants aged less than six months. As such, there has been widespread vaccination against pertussis starting in the 1940s. However, the early ‘whole cell’ pertussis vaccine (wP) was eventually replaced by the ‘acellular’ pertussis vaccine (aP), which contains proteins from B. pertussis. The aP component is typically given with diphtheria and tetanus toxoids, such as in the DTaP shot.

Those of you who follow the online exploits of various anti-vaccine groups have probably come across the factoid that a study in mice showed receipt of the acellular pertussis vaccine increases susceptibility to infection with Bordetella parapertussis to forty times compared to the unvaccinated.

For example, here’s The Refusers’ take on it:

Vaccinators’ maniacal insistence on multiple boosters of pertussis vaccine may be the culprit behind the so-called increase in whooping cough.  According to this 2010 study vaccination led to a 40-fold enhancement of B. parapertussis colonization.’ In other words, the vaccine stimulates the growth of a bacterial strain that is not included in the shot. The scientific term for this phenomena [sic.] is vaccine failure.

And here the president of the Australian (anti-)Vaccination Network states

…it has been found that mice who are vaccinated against pertussis (whooping cough) are more likely to contract parapertussis – 40 times more likely – and parapertussis causes symptoms that are clinically indistinguishable from whooping cough. Interesting, eh?

So ’40x’ seems to be a recurring theme, however, whether it’s increasing susceptibility to or stimulating the growth of a whooping cough-causing bacterium depends of which anti-vax source you go to. What did the study actually find?

Well, let’s look at the study, Acellular pertussis vaccination facilitates Bordetella parapertussis infection in a rodent model of bordetellosis, full text freely available on PubMed Central.

In order to study how aP vaccination influenced the course of pertussis/parapertussis infection the researchers took two equal groups of mice and immunised half with a commercial aP vaccine, and the other half with saline and an adjuvant (the placebo group). About a quarter of the mice in each group were infected with B. pertussis, another quarter with B. parapertussis, a further quarter with both bacteria, and the remaining quarter were sham-infected with saline. Then, at various time points following infection 4-5 mice from each group were euthanized, their lungs removed and the amount of each of the bacteria tested for.

The results of this experiment are summarised in this figure, and I’ll go through the four panels one by one, explaining what they represent and what it means.

Amount of pertussis bacteria in the lungs of mice either immunised (open squares) or unimmunised (closed squares) prior to infection. Horizontal dashed line represents the limit of detection.

We’ll start with (a). As you can see, the horizontal axis is time, in days post-infection, while the vertical axis is ‘CFUs’ or colony-forming units, a measure of the amount of viable pertussis bacteria present. The filled (black) squares represent mice that received sham vaccination. As you can see, in these unimmunised mice the number of bacteria increases as the infection progresses, then as the immune response catches up, the number of bacteria falls. Now compare this to the open squares, representing aP-immunised mice. Despite all mice being infected with similar amounts of B. pertussis bacteria, you’ll notice that on day 0 there is already a ~10-fold difference in bacterial load. This means that by the time the researchers had infected all the mice (there was about 200), got that experiment cleared away, and got around to sacrificing their first lot of mice (maybe a few hours all up) the numbers of pertussis bacteria were already on the decline. This trend continues until the infection is cleared. In the unimmunised mice however, the number of pertussis bacteria increases for a few days, before the immune response catches up and brings the infection under control.

So what does this tell us? Well the fact that the immune response was protecting mice right from the time they were infected suggests that the aP vaccine reduces susceptibility to infection with B. pertussis – which has certainly been the experience with human trials. This is no surprise and is consistent with the currently available research: aP vaccination reduces susceptibility to pertussis infection and aids in the clearance of the bacterium from the respiratory tract.

What about panel (b)?

So yeah, pertussis vaccine protects against pertussis. Stop the presses.

Average amounts of pertussis bacteria present in the lungs of immunised (open squares) and sham-immunised (closed squares) mice for the day 3 to 35 time points. ‘Single’ – mice that were only infected with B. pertussis; ‘Mixed’ – mice that were also infected with B. parapertussis.

The panel shows the average counts of B. pertussis bacteria from day 3-35 post infection. The two sides represent average B. pertussis counts in mice infected only with B. pertussis (left) and infected with both species (right) (This was included as the researchers wanted to test whether the two species interfered with one another in a mixed infection). As you can see, regardless of the presence of parapertussis, there is ~700 times less pertussis bacteria in those that were given the aP vaccination.

Okay, so panels (a) and (b) show aP vaccination primes the mouse immune system to be immediately ready to combat pertussis infection. So what? Why did I include them if they don’t cover the 40x figure? Well, for two reasons:
One: To familiarise readers with the format of the figure. It’s not all that approachable to those that haven’t studied some bacteriology, so before going to the parapertussis-specific data I want people to be comfortable with it, and understand what susceptibility should look like; and

Two: That data shows just how effective the aP vaccine was in combating pertussis infection, and I want everyone to enjoy just how supportive of aP immunisation this study is, and just how thoroughly it demonstrates the intellectual dishonesty of those who cite this paper, while simultaneously claiming that there’s no evidence that aP vaccination does anything to prevent/combat pertussis infection.

So now let’s look at panel (c). This is in the same format as panel (a), except the triangles indicate levels of B. parapertussis infection (that’s the one not included in the vaccine). Again, open shapes represent aP-immunised mice, closed shapes sham-immunised.

Remember, this time we’re looking at B. parapertussis:

Amount of parapertussis bacteria in the lungs of mice either immunised (open triangles) or unimmunised (closed triangles) against pertussis prior to infection. Horizontal dashed line represents the limit of detection.

So what do we notice? Well in both the immunised and un-immunised the bacterial load increases, peaks at day 3, then decreases. You’ll notice that at the first two time points there is not much difference in the bacterial load of the immunised and unimmunised cohorts, but beyond then the clearance of B. parapertussis occurs more quickly in the unimmunised. It would appear that some aspect of the immune response, attributable to the aP vaccine, is interfering with the clearance of the bacterium. As a result, from days 7-35 the amount of parapertussis bacteria in the lungs of aP immunised mice is greater than in those of the unimmunised. As you can see in panel (d), from days 3-35 this difference averages at a factor of about 40x:

Average amounts of parapertussis bacteria present in the lungs of aP immunised (open triangles) and sham-immunised (closed triangles) mice for the day 3 to 35 time points.

So we’ve finally found the ‘40x’ figure. But is this really a measure of increased susceptibility? Well look again at panel (a), comparing pertussis infections in mice that have or have not been immunised against pertussis. Those mice that are more susceptible (the unimmunised; closed squares) show a drastically increased frequency of pertussis in their lungs compared to the immunised, which is evident from day 0. Look back to panel (c), and see that the bacterial load in parapertussis infection is indistinguishable between vaccine and sham groups for the first three days (in fact on day 3 it’s marginally lower in the aP immunised). In other words, the capacity to fend of parapertussis was uninfluenced by aP immunisation for at least 3 days following infection. So, did this study find “…that mice who are vaccinated against pertussis (whooping cough) are more likely to contract parapertussis – 40 times more likely…”? No, it did not.

That said, the time taken to clear the parapertussis infection is longer in the aP immunised. Even if susceptibility to infection if not increased, clearly something is not right. So what about The Refusers’ take, “According to this 2010 study vaccination led to a 40-fold enhancement of B. parapertussis colonization.’ In other words, the vaccine stimulates the growth of a bacterial strain that is not included in the shot.”?

…not quite. Again, look at panel (c). By the time the effect is apparent, bacterial load is decreasing, regardless of vaccination status, and the only difference if the rate of the decrease. Rather than “stimulating the growth” of B. parapertussis, the effect of the vaccine is to somehow interfere with the clearance seen in the sham-immunised group. If The Refusers had looked through the article themselves and not just based their commentary on a cherry-picked quote from the press release then perhaps they wouldn’t have described bacteria whose levels are decreasing as having stimulated growth. But then again, if they based their opinions on the actual data from these studies, I guess they wouldn’t be anti-vaxxers.

So what is happening? Surely you’d expect that antibodies against B. pertussis should offer some cross protection against the related B. parapertussis?

Well, as it turns out they don’t, thanks to part of the parapertussis outer membrane called the O antigen. It seems some time in its evolutionary history, B. parapertussis resigned itself to being the less-common Bordetella species, and to try and avoid the widespread anti-Bordetella immunity in the human population induced by its more-prominent cousin, it developed an O antigen that fights antibodies.  Mouse studies have shown that when the O antigen is missing, antibodies induced by both aP and wP vaccination bind parapertussis more efficiently, but when the antigen is present the binding of these antibodies is largely blocked. Luckily (perhaps ironically) the O antigen itself can be targeted by antibodies, which is important for inducing anti-parapertussis immunity.

Okay, so the O antigen research explains how aP-induced immunity is rendered ineffective against parapertussis, but the study in question didn’t just show no effect on parapertussis from aP immunisation, it showed an impairment of the clearance of the bacterium. The researchers asked why, and found less neutrophils were recruited to the lungs of parapertussis-infected mice when they’d received aP immunisation.

Neutrophils are the most common white blood cell in the blood, and are the first to flood to the scene of an infection, where they effectively destroy microbial invaders. Recruitment of these cells to the respiratory tract and targeting to Bordetella cells by antibodies is critical for the optimal clearance of both pertussis and parapertussis.

So why were less neutrophils recruited to the lungs of parapertussis infected mice that previously received aP vaccination? Well the researchers looked into the type of immune responses, and found that unvaccinated mice exposed to either bacterium developed more of an inflammatory response, which is more effective in recruiting neutrophils, while the immune memory induced by the aP immunisation favoured a less-inflammatory response.

While this bias in the kind of immune response induced is not a problem in pertussis infection (just look at panel (a) again – it is clearly protective) it seems that this has actively impaired the response to B. parapertussis.

While the researchers did not divine the exact mechanism behind the impaired clearance of  parapertussis, these clues they found do allow for well-informed conjecture. It would appear that the less-inflammatory response the vaccine pushes the specific immune response towards impaired neutrophil recruitment. While that isn’t a problem in subsequent pertussis infection, parapertussis uses its O antigen to further impair immune responses, buying the bacterium a little more time.

The authors note that this study was done in mice, and should not be simply extrapolated to humans, though I answer the question of whether this effect is seen in humans here. In short, our biggest prospective trials of aP vaccines come up negative when it comes to the question of aP immunisation in any way enhancing parapertussis infection.
I’d like to finish this post with one last observation. Last month, PLOS Medicine published a study examining how ‘spin’ on a research article can be translated to inaccurate reporting, by comparing the abstracts, press-releases and finally media reports on those articles to see where the exaggerations were introduced. For a plain-language summary, I’d suggest reading Dr Novella’s coverage of the paper on Neurologica. Not unsurprisingly, it was found that scientists’ overselling of their own findings in the abstracts of their articles was highly correlated with spin in the subsequent reports in the media.

When it comes down to it, the ultimate message I take from the PLOS Medicine study is that scientists need to frame their findings and conjecture carefully when writing abstracts. Over-hyping results or their relevance might be eye-catching and possibly increase your chances of getting into a better journal, but is ultimately a dishonest act and should be avoided.

I felt the entire body of the parapertussis study was a good assessment of the results and their implications. However, this was the abstract:

Despite over 50 years of population-wide vaccination, whooping cough incidence is on the rise. Although Bordetella pertussis is considered the main causative agent of whooping cough in humans, Bordetella parapertussis infections are not uncommon. The widely used acellular whooping cough vaccines (aP) are comprised solely of B. pertussis antigens that hold little or no efficacy against B. parapertussis. Here, we ask how aP vaccination affects competitive interactions between Bordetella species within co-infected rodent hosts and thus the aP-driven strength and direction of in-host selection. We show that aP vaccination helped clear B. pertussis but resulted in an approximately 40-fold increase in B. parapertussis lung colony-forming units (CFUs). Such vaccine-mediated facilitation of B. parapertussis did not arise as a result of competitive release; B. parapertussis CFUs were higher in aP-relative to sham-vaccinated hosts regardless of whether infections were single or mixed. Further, we show that aP vaccination impedes host immunity against B. parapertussis—measured as reduced lung inflammatory and neutrophil responses. Thus, we conclude that aP vaccination interferes with the optimal clearance of B. parapertussis and enhances the performance of this pathogen. Our data raise the possibility that widespread aP vaccination can create hosts more susceptible to B. parapertussis infection.

I was flabbergastered on re-reading the abstract, specifically the last line; “Our data raise the possibility that widespread aP vaccination can create hosts more susceptible to B. parapertussis infection.

The only point in the article such a concept is raised is in the introduction, where they discuss hypothetical mechanisms by which parapertussis could have an advantage over pertussis in an aP-immunised population. The data certainly do not raise this possibility, which would explain why the authors do not mention it when interpreting their data. The inclusion of that sentence at the end of the abstract is a perfect example of over-hyping results to sell your study.

Even worse is the press release, written by one of the study’s authors:

“…vaccination led to a 40-fold enhancement of B. parapertussis colonization in the lungs of mice…”

“…these data suggest that the vaccine may be contributing to the observed rise in whooping cough incidence over the last decade by promoting B. parapertussis infection”

I do not have a problem with that first sentence; an enhancement of colonisation or an impairment of clearance, either way it’s a matter of semantics, though I do feel ‘impaired clearance’ more accurately describes the observed effect. As for the second sentence, the only place in the study that possibility is implied is the abstract; the data show nothing of the sort.

Looking at the two sentences together it’s easy to see how the misconceptions were bred. It’s just a shame that second sentence is simply untrue.

Scientists should know better.

Posted in acellular pertussis, Acellular pertussis vaccine, Australian Vaccination Network, Australian Vaccination Skeptics Network, AVSN, Bordetella parapertussis, Bordetella pertussis, Pertussis, Pertussis immunisation, Pertussis vaccination, Vaccination, Whooping cough, whooping cough immunisation, whooping cough vaccine | 4 Comments

Hepatitis B vaccine: Preventing cancer, except for when it’s not actually given…

One of the commentors over on the Australian Anti-Vaccination Network’s facebook page challenged the group’s president – Meryl Dorey – to comment on a hypothetical scenario as a way of discussing the utility of vaccination against Hepatitis B (Hep B). A conversation ensued and commentor’s question was never answered, however just last night Dorey posted the following comment on the AVN page:

Dorey’s condescending post – ‘5 minutes’ seems to be a recurring theme. (And how considerate to ensure the post she thinks is evscerating all Kellie’s points with evidence is easy to find at the top of the page! Just a shame she still hasn’t actually managed to get around to giving Kellie a direct answer)

…with this chart of liver cancer incidence in the United Kingdom:

Liver cancer rates in the UK by gender from 1993-2009 (Cancer Research UK)

Right now I’m going to focus on the claim of increasing liver cancer rates thanks to Hep B vaccination.

But first the rationale behind using the Hep B vaccine to prevent liver cancer:

  • Hepatitis B is a virus that chronically infects liver cells.
  • This chronic infection naturally leads to prolonged inflammation.
  • A continual inflammatory state is conducive to cancer formation.

(The virus also seems to be able to integrate its DNA into host cells to cause cancer)

Therefore prevention of infection through vaccination should also prevent the resultant cancer.

Nice in theory – but is this borne out by the evidence?

In July 1984, Taiwan launched a vaccination program to cover infants born to Hep B carrying mothers. Then in 1986 the program was extended to all infants under 12 months, and over the coming seven years was extended up the age groups to cover adults 20 years and older. It just so happens that since 1979 Taiwan has also had a national cancer registry (with an unregistered rate estimated to be as low as ~4%). Some canny researchers utilised this database to determine the influence of the country’s Hep B immunisation policy on liver cancer rates over the 20 years it was in place. So what did they find?

Well, the relative risk of liver cancer for the vaccinated compared to the unvaccinated was calculated to range from 0.31-0.38, meaning the unimmunised were about three times more likely to develop the cancer.

So that’s pretty clear cut, using data that spans a country’s entire population, but what about other risk factors? Well firstly boys had a risk ratio for the cancer of 2.5 compared to girls, and having a Hep B positive mother was also a big predisposing factor. Notably, the number of doses of the vaccine also played a role, with those that received less than three doses having a greater incidence of the cancer (odds ratio = 4.32), further indicating the protective effect of the vaccine against liver cancer.

So, in our biggest, longest-running ‘phase 4’ trial of the vaccine, it’s clear the vaccine has succeeded in preventing liver cancer. So what about Meryl Dorey’s data?

Well let’s look at her figure, from the UK.

Liver cancer rates in the UK by gender from 1993-2009 (Cancer Research UK)

Yup, it definitely shows rising incidence of liver cancer. Not all that surprising, since (unlike in Australia or Taiwan) the UK’s National Health Service only recommends Hep B immunisation for high-risk groups. In fact, the link where Dorey got the figure from says [bolding mine]:

Trends over time

Liver cancer incidence rates have overall increased in Great Britain since the mid-1970s (Figure 1.2).1-3 For both men and women, European AS incidence rates increased by around three times between 1975-1977 and 2007-2009.

Much of this increase can probably be attributed to past changes in the prevalence of major risk factors for liver cancer, such as heavy alcohol consumption and infection with the hepatitis B and C viruses.7,8 Alcohol consumption increased in Britain during the 1990s, particularly in women, but the proportion of men and women drinking more than 21 and 14 units/week, respectively, has fallen since 2002.9 A corresponding fall in alcohol-related diseases, including liver cancer, might take a number of years to become apparent, due to the lag between alcohol consumption and related illness. For example, alcoholic liver disease takes approximately ten years to develop.10

In fact, I had a search for Hep B incidence rates in the UK and got this study. It looks at the rate of testing for various diseases during pregnancy in London, and the results of those tests. Sure, it’s not absolute prevalence rates, but it gives us an idea of the way the trend is heading.

Yep, you guessed it, it shows the rate of Hep B infection as being on the rise.

Prevalence of Hep B in London 2000-2008; results of widespread antenatal testing

So I’m not exactly sure what Meryl Dorey was trying to prove with this one, other than that countries which haven’t implemented a large enough immunisation policy to control Hep B rates continue to see an increase in liver cancer – sort of the opposite of what she was saying. Also, it’s not surprising she failed to pass on the nuance regarding alcohol consuption causing liver cancer, or the lag between cause and effect – firstly Dorey is notorious for not reading her own sources, and personally I’ve found she only seems to understand nuance when it involves some convoluted justification of an anti-vaccine claim.

So what about Dorey’s ‘paper’? Well, as outlined in more detail in this facebook post, it’s a collection of references supposedly showing the dangers of Hep B and the vaccines against it. I started reading the papers (at least those that were actually on PubMed, and in English – hey, three out of six ain’t bad) and got three in. So far they were just case studies – in other words, a doctor noticed the rare, usually unexplained, disease they were treating occurred within a week after receiving a vaccine, so they write in to a journal, just so that information is out there. In short, the citations demonstrated that 1-2 people worldwide came down with some pretty bad illnesses following Hep B immunisation – rates that pretty much guarantee no association other than temporal. I didn’t read any more of the so-called ‘paper’, and instead satisfied myself by once more reading the RationalWiki entry on ‘Gish Galloping’.

However, I am now much more sympathetic to Meryl’s position. She said in 2009 she had been studying this issue for twenty years, and looking at the age of the references in this ‘paper’ it’s clear she simply just hasn’t had the time to get her hands on any new journals over the last two decades. I’m sure when the AVN release their next financial statement there’ll be the cost of a subscription to Vaccine or the New England Journal of Medicine on there, and Dorey’s posts will actually start to reflect the trials and research that have been published the last few decades.

To sum up, of the Hep B vaccine we can say that it is effective in preventing liver cancer, as well as Hep B infection; more doses give superior protection to fewer doses, and both are superior to no doses. Maybe someone should pass the memo to the NHS.

Of Meryl Dorey, what can we say? Well, her evidence of harm from the Hep B vaccine demonstrated to me that some very rare and very unpleasant conditions occur so infrequently after the shot that they simply don’t seem to be associated with it. As for Dorey’s knowledge on the Hep B vaccine… Well, her unfamiliarity with the many controlled studies of the shot, her apparent ignorance that the UK does not immunise all infants, and her belief that the vaccine increases your odds of liver cancer… Well, let’s just say that maybe Dorey was revealing more than she intended regarding her research technique when she told Kellie it would only take five minutes to look this all up.

Posted in Australian Vaccination Network, Hepatitis B, Vaccination | 3 Comments

Here’s that booster shot I promised…

Just a quick follow up from the last post. Here’s that booster shot I said I’d get.

While waiting the required 15 minutes before leaving my local community health centre I read the package insert, and I can tell you that I am:

  • one of the ~72% of adults who experience pain at the injection site for a short time following the immunisation; and
  • one of the estimated only ~11% of Australian adults up to date on their pertussis boosters

Whooping cough is a vaccine preventable illness. Do your bit to protect yourself and your community from it, as well as from diphtheria, and yourself from tetanus.

Call your doctor and book an appointment for YOUR booster shot today.

And Remember: Real guys immunise.

Posted in Pertussis, Vaccination | 1 Comment

Has Whooping Cough Evolved Around The Current Vaccine? Reflections On The (Then) Current Scientific Evidence

Before reading this post be aware that as of April 2014 we now know that Australian strains of B. pertussis have largely lost expression of the protein whose variation is a key feature of this piece. An explanation of that study can be found here.


Whooping cough is a potentially deadly infectious disease. While vaccination against it has managed to significantly reduce the incidence of the disease, it still remains a global presence.

Recent coverage in the mainstream media and from anti-vaccine proponents has suggested that the whooping cough bacterium has evolved around the current acellular vaccine. Such reports occurred following publication of a paper attributing over 80% of Australian cases to a new strain apparently not well covered by the vaccine.

This review analyses these claims. Careful examination of the current literature indicates that while the bacterium’s genome does appear to have changed in response to pressure from the vaccine, none of these changes appear to give it any significant advantage over the immunity the vaccine induces. Thus, reports that the current vaccine is ineffective are misleading and inaccurate. Each of the factors that could potentially influence vaccine-induced immunity are discussed.

You may remember about a fortnight ago in the news there were references to a new study which looked at an emerging strain of whooping cough and raised some questions about the current vaccination campaign. Intrigued, that very day I downloaded and read the paper in question, as well as the previous paper from the same group. What followed was a fortnight in which my spare time was taken up by reading as many journal articles as possible about whooping cough and the vaccine.

Then, just a few days ago, Meryl Dorey, president of the Australian Vaccination Network, wrote a blog post attacking the current whooping cough vaccination program, in which she cited this new, fascinating research (funnily enough, with an explanation that suggests she hasn’t actually read it). It strikes me that a reply to this blog post would be an ideal format for a piece discussing the history, efficacy and new insights into the whooping cough vaccine, so here goes.

It seems that the president of the anti-vaccine lobby group The Australian Vaccination Network is at it again, vilifying people who have suffered from vaccine-preventable diseases and misrepresenting the state of medical research.

In a new ironically named blog post, ‘the fear that transcends logic’, Ms Dorey attacks a mother living “in the heart of the avn’s kingdom… surrounded by anti vac people” whose family contracted both whooping cough and chicken pox, despite being fully vaccinated. The open letter explains the terrible circumstances the family has gone through dealing with whooping cough, in an attempt to give others some insight into coping with the disease.

However, neither the contents of this letter, nor how Ms Dorey treats the writer are the focus of this post. This post will deal with the incorrect information Dorey has provided about the whooping cough vaccine.

Right off the bat Dorey sets the scene:

“Our biggest problem is that both the government and the medical community have painted parents who don’t vaccinate or who vaccinate selectively as ‘the enemy’. They are intentionally vilifying the unvaccinated without any evidence that we are the problem. In fact, they are consciously choosing to ignore the medical research proving that the pertussis or whooping cough vaccine is almost completely ineffective against the strain of the disease circulating in Australia today (84% of all whooping cough cases are being caused by bacteria that is not contained in our current vaccine and it is possible that the vaccine itself was responsible for this change in the strain of bacteria which is now responsible for whooping cough).”

Is this the case? Has the bacterium responsible for causing whooping cough mutated so much that it’s not affected by vaccine-induced immunity, and all because of the vaccine?

First, some background. In the 1950s a whooping cough vaccine was introduced, and saw a massive drop in cases all around the world. However, the vaccine had a high rate of side-effects such as seizures, dizziness and fainting, which led to decreased uptake of the vaccine, and a subsequent resurgence of disease. This vaccine contained whole, killed cells of Bordetella pertussis, the whooping cough bacterium, and it seems that the fact that the entire organism was in there was behind the severity of the reactions. In order to reduce the rate of adverse events, a new vaccine was introduced. The new ‘acellular’ vaccine, which replaced the whole-cell vaccine in Australia in 2000, contains just a few proteins produced by B. pertussis, one being the pertussis toxin (chemically inactivated, of course), and the other two (which I’ll call Prn and FHA for now) being adhesion molecules, which basically help the bacterium cling to the host’s respiratory tract.

Here it’s worth noting that there exist other formulations of acellular pertussis vaccines, which contain two more adhesion molecules, as well as formulation with just one or two components. But, as the three-component vaccine is the most commonly used form in Australia it’s what I’ll be referring to when I use the term ‘acellular pertussis’ or aP vaccine.

So what is the efficacy of the acellular pertussis vaccine? Well, in an attempt to answer that question, the Cochrane Collaboration put together a review of all the existing literature, entitled “Acellular vaccines for preventing whooping cough in children”. The review, updated in March of 2012, considered only double-blind randomised placebo controlled trials in which participants were actively followed up and cases of pertussis were laboratory verified – in other words, only the very best evidence. In the end, they included six studies of aP vaccine efficacy, which investigated vaccines with a variation of 1-5 acellular pertussis components. They found:

“This updated review included six efficacy trials with a total of 46,283 participants… The efficacy of multi-component (≥ three) acellular vaccines varied from 84% to 85% in preventing typical whooping cough (characterised by 21 or more consecutive days of paroxysmal cough with confirmation of B. pertussis infection by culture, appropriate serology or contact with a household member who has culture-confirmed pertussis) and from 71% to 78% in preventing mild pertussis disease (characterised by seven or more consecutive days of cough with confirmation of B. pertussis infection by culture or appropriate serology). One- and two-component acellular vaccines were less effective.

So the vaccine is quite effective, and quite logically, the fewer pertussis proteins included, the less effective the shot in preventing the disease.

One of the concerns about using a vaccine with only a few components is that it should be easier for the microbe to evolve around. That is, when an entire pertussis cell is in the vaccine, then potentially every molecule in the bacterium could hypothetically be the target of an immune response; when just three pertussis molecules are in the vaccine, protection is less broad. If the bacterium mutates its three vaccine-targeted molecules enough then eventually they’ll be so different that aP vaccine-induced immunity won’t recognise them, whereas with the whole cell vaccine there’s far more vaccine targets to mutate, making that version of the vaccine so much harder to evade.

Another issue with the current vaccine is the waning of vaccine induced immunity. A recent literature review put the duration of vaccine-induced immunity at 4-12 years (although it looks like the figure can be optimised by careful timing of booster shots), as opposed to 4-20 years for naturally acquired infection. This is something that will need to be sorted out with the next generation of pertussis vaccines as people are notoriously bad at getting their boosters, to the point where only an estimated 11.3% of the adult population of Australia is up to date on their whooping cough shots.

So, has B. pertussis managed to mutate its pertussis toxin, Prn and FHA proteins to the point where the immunity induced by the vaccine versions of them is seriously impacted, making our current estimates of aP vaccine efficacy wrong?

Well, no.

In fact, the bacterium has only mutated two of the three proteins – the FHA most commonly used by B. pertussis in Australia is the same as the kind in the vaccine. However, FHA is one of the less important vaccine targets involved in protection from pertussis, and so the fact that they still match isn’t all that big a deal. Let’s get onto the mismatches.

Firstly, pertussis toxin. Acellular pertussis vaccines include the active subunit of pertussis toxin, referred to as PtxA. Genetic variants in PtxA are then numbered, eg: PtxA1, PtxA4 etc. Studies have shown that pertussis toxin is the most important pertussis protein to include in the vaccine for inducing a protective immune response, with some experts even suggesting that a one-component pertussis toxin vaccine is all that would be necessary to induce effective immunity.

The current Australian aP vaccines contain PtxA2, while all samples of B. pertussis isolated recently from Australia express PtxA1 – definitely a mismatch. But how does that impact the current statistics? Well, from what I can tell, not at all.

“What?” I hear you ask, “How on earth can you think that efficacy data from a vaccine containing pertussis toxin variant 2 can be generalised to a country in which the endemic pertussis strains carry toxin variant 1?”

“Well,” (I would respond) “because those efficacy trials were *done* in populations where the endemic pertussis strains carry toxin variant 1!”

That’s right. There is a mismatch between the vaccine type pertussis toxin and the type our wild strains carry, but that doesn’t change the efficacy data because that same mismatch existed in the population it was collected from. Looking at the three studies the Cochrane Collaboration included that studied three or more component vaccines, the countries and years they took place in, there is an at or near 100% rate of PtxA1 in the wild B. pertussis population. [See Note 1]

So what about the last remaining protein in the Australian aP vaccine, pertactin, or Prn? After all, in the recent study of Australian Bordetella pertussis samples, 86% of the 194 collected were positive for a specific non-vaccine Prn variant, Prn2, whereas the vaccine contains Prn1. These two forms of the protein differ by only a few amino acids (the building blocks of proteins) in an area of the protein called ‘variable region 1’. Apart from this, the proteins are identical.

Pertactin is a cell-surface protein of B. pertussis which assists in bacterial adherence to host cells. A study in mice demonstrated that antibodies to pertactin, but not other pertussis proteins were essential for efficient opsonisation (the process where antibodies bind a bacterium or virus and mark it for destruction by white blood cells). So, surely a mismatch between vaccine and circulating variants of Prn could have an effect on vaccine efficacy?

A study using an animal model of pertussis infection published in 2001 suggest this could indeed be the case. In this paper the researchers found that the Dutch whole cell pertussis vaccine (which includes Prn1) was significantly more protective against Prn1 strains than Prn2 strains. Two years later a study looking at human serum samples (serum being the fraction of blood that contains proteins such as antibodies) tried to see if they could find Prn1-specific antibodies in serum from people who’d received booster shots, and from people who’d been infected with Prn2-carrying pertussis. Of course, they found Prn1-specific antibodies in 68-84% of children who’d received booster shots, but only in 0-6% of kids that had had a Prn2-type pertussis infection.

So there is type-specificity in the human immune response to pertactin. Does this mean that the estimate of vaccine efficacy we currently use is likely not to apply to these currently circulating Prn2-carrying strains?

Well no, because the human immune response to pertactin is almost entirely directed against parts of the protein that are the same between Prn1 and Prn2. A study published in 2008 took human serum samples and measured how well they react to different parts of the pertactin protein, and found that two of the thirty seven samples they collected showed significant reactivity to variable region 1, compared to 36 of the 37 reacting to the N-terminus of the protein, which is a region that is identical in Prn1 and Prn2. These results don’t make the previous study wrong. What the first study found was that pertactin induces type-specific antibodies. What the second study found was that yeah, it does, but those antibodies are pretty insignificant compared to the amount induced against type-indifferent parts of the protein. The authors conclude:

“Combined, these results suggest that variation in Prn will probably not constitute a problem in highly immune individuals, as we were unable to measure any antibody differences in this group. However, in individuals with low antibody [levels] and waning immunity this has to be investigated further.”

So in other words, if you’ve just got your booster, the response you’re developing doesn’t care whether any invading B. pertussis is Prn1, Prn2, or whatever Prn type, but it’s possible that these type specific antibodies might play a bigger role once vaccine-induced immunity begins to wane.

Okay, so neither of the individual variations in vaccine-targeted proteins seems to suggest that any considerable change to our current estimation of vaccine efficacy is needed, but what about the combination of the two mutations? Well, a paper published in May 2010 wanted to establish how these new, non-vaccine variations in PtxA and Prn could be impacting vaccine efficacy. They immunised mice with a current PtxA2 and Prn1-containing aP vaccine, and then infecting them with four different varieties of B. pertussis. All four were derived from the same strain as the vaccine, except three were genetically modified so that:

  • In one PtxA2 was replaced with PtxA1
  • In another, Prn1 was replaced with Prn2
  • And in the third, both PtxA2 and Prn1 were replaced with PtxA1 and Prn2, respectively.

As you might expect, the authors found a statistically significant difference between the number of pertussis bacteria in the lungs of the immunised mice challenged with the vaccine strain, and those challenged with the double mismatch mutants. However, it’s worth noting that while the double mismatch challenged mice had ~10 times more pertussis bacteria in their lungs compared to those challenged with the vaccine strain, they still had 100 times fewer pertussis bacteria than the unvaccinated controls.

However, that doesn’t inform the current question of whether the varieties currently circulating in Australia might warrant a change in the current efficacy estimate, since the aP vaccine trials were done in human populations challenged with a pertussis toxin mismatch. So, in the mouse study, was there a difference between the bacterial loads of immunised mice challenged with pertussis toxin single mutants and the bacterial loads of immunised mice challenged with toxin/pertactin double mutants? Yes, there was a slightly greater bacterial load in the mice challenged with the double mutants, but the observed difference was not statistically significant.

So, what effect do the mismatches between the vaccine-strain and circulating pertussis strains have on our current estimates of vaccine efficacy? Well, the pertussis toxin mismatch has no effect, since the efficacy data was done in populations with this mismatch, while the animal and human data suggest that the pertactin mismatch gives the pertussis bacterium at best a negligible advantage, and even then most likely only manifesting in any considerable manner in the population with waning (either vaccine-induced or wild Prn1-carrying pertussis-induced) immunity.

So as well as attributing her claim that the vaccine is almost useless against the emerging pertussis variants to this new paper (the paper does not say that – it is just not true), Dorey also cites the paper, saying:

“The new strain of pertussis (whooping cough) is far more dangerous than the older strain. It produces much higher levels of pertussis toxin and it is the toxin that determines how bad the symptoms will be. (Newly Emerging Clones of Bordetella pertussis Carrying prn2 and ptxP3 Alleles Implicated in Australian Pertussis Epidemic in 2008–201; The Journal of Infectious Diseases 2012;205:1220–4)

Funnily enough, none of this over-hyped fear-mongering actually appears in the paper she’s citing as a source. But before I get into the data regarding possible enhanced virulence of this new emergent variant, I’d like to address a minor point of pertussis bacteriology Ms Dorey butchers here.

“…and it is the toxin that determines how bad the symptoms will be.”

While the pertussis toxin is one of the major virulence factors of B. pertussis, it is not the only one. In fact, it is not the only toxin the bacterium produces. In fact, the closely related species B. parapertussis is capable of producing a pertussis-like syndrome, despite the fact that it is incapable of producing pertussis toxin. What’s more, comparing genome sequences of pertussis bacteria with and without this new mutation has revealed that it is associated with mutations in at least two other virulence-associated genes, the reactivation of a gene that was previously mutated to the point where it was inactive, the inactivation of two more genes, as well as a deletion of a chunk of the genome encoding eighteen genes. Ascribing a change in virulence to just one mutation when there are this many other mutations also present in these same strains seems premature, especially since the significance of any or all of them really hasn’t been established yet.

Just keep an eye out for such over-simplifications of complex scientific issues, as Ms Dorey has done here. More often than not, they’ll turn out to be wrong.

So this claim of Dorey’s relates to this new paper I mentioned, which looked at 194 Australian pertussis samples from 2008-2010 and found that 86% of them carried the mutation ptxP3. This mutation is a change in one DNA base in the pertussis toxin promoter (the part of the genome that controls how much pertussis toxin is made). How dangerous is this mutation? Well, a 2009 paper looked at toxin production of ptxP3-carrying pertussis cells in culture, and compared the frequency of pertussis hospitalisations and deaths from two time periods where ptxP3 frequency went from 1.6% to 54.5% in the pertussis population. The researchers cultured pertussis cells with different ptxP variants for 48, 54 and 60 hours on agar plates (on a solid jelly-like growth medium in petrie dishes) and found that ptxP3 variants produced 1.62 times the amount of pertussis toxin that other strains did. It’s unclear exactly how this relates to toxin production in humans, though it seems reasonable to assume that ptxP3 strains will also express more pertussis toxin in an infection than non-ptxP3 strains. Is 1.62x ‘much higher levels’ of toxin production? Well, the term’s subjective, but in this context, I’d say it doesn’t warrant the hyperbole Meryl attributes to it, especially since we don’t even know what the rate of secretion is like in an actual infection.

So what about the hospitalisation and death data? Well, the authors calculated ‘lethality’, the number of deaths divided by the number of hospitalisations, and found that in 1981-1992 lethality was 0.00041 deaths per hospitalisations compared to 0.00299 in 1993-2004. And while those numbers may seem small, that equates to a seven-fold increase in lethality. Sounds pretty bad, right? Well, it may be. While I expect there would be an increase in the number of cases and deaths from whooping cough associated with this ptxP variation, the 95% confidence interval (basically a measure of the possible error within certain parameters, like error bars) for the lethality figure varies from 0.93-56.07 – all the way from a slight decrease in lethality, to a ridiculously over-the-top increase. What’s more, there’s more factors involved in the numbers of hospitalisations and deaths from pertussis than just which ptxP variant is most common. At this stage there just isn’t enough data to allow a confident estimation of how much more virulent ptxP3 strains are. Are they more virulent? Probably, in my opinion. Can we reasonably say they’re ‘far more dangerous’? Not just yet.

Meryl Dorey also claims the vaccine isn’t effective, and even goes on to say

“In fact, there is a great deal of evidence that not only won’t these vaccines prevent the diseases they are meant to – but that those who are vaccinated and catch the diseases may have worse symptoms than those who are unvaccinated and contract them (the exact opposite of what the medical community claims).”

Wow. Ms Dorey claims her authority comes from 20 years of researching vaccines, yet despite this, she can’t provide a single reference to support her assertions. In all of the efficacy trials the Cochrane Collaboration considered acceptable for inclusion in their aP vaccine review, in every single one, the rate of laboratory confirmed pertussis infection is lower in the vaccinated. So, from reading the best evidence available, one could easily be forgiven for thinking that acellular pertussis vaccines are effective at preventing pertussis infections, and certainly not at causing it. But, luckily for anyone who was foolish enough to base their opinion on that kind of evidence, Meryl Dorey is here to correct that impression with her collection of unsourced, uncited statements. While she may not actually provide any studies to back these claims up, if you’re lucky she’ll tell you just how numerous such studies are.

She finishes her screed against the pertussis vaccine by saying

“Healthy, unvaccinated children are no more likely to spread infectious diseases than healthy vaccinated children”

Whether they’re healthy or not isn’t the point, the point is whether they’re more susceptible to contracting pertussis or not, which the efficacy trials have been quite definitive about, but let’s read on.

“And being fully vaccinated – or even being immune (which is a totally different situation altogether) cannot prevent you from carrying and transmitting infectious diseases even if you yourself are not showing the symptoms as Dr Larry Palevsky so clearly demonstrated in his blog.”

So what does this blog post, from December 2011, say? Well, Dr Palevsky begins by discussing the outbreak of pertussis in Suffolk County, New York State. He begins by rightly stating that the actual number of cases of whooping cough is likely higher than the ~200 reported at the time. He then goes on to lament the fact that the health department is reporting the number of cases but – shock and horror – they are not also reporting the vaccination status of each case!

Simply reporting the total number of cases of pertussis without reporting their vaccination status is also incomplete, and misleading to the public.” [bolding mine]

If Dr Palevsky honestly believes that, during the outbreak of a deadly disease, the health department should be prioritising data collection and analysis over, say, I don’t know, co-ordinating a response to the outbreak, then he should get his head out of his rear-end, or at least out of his private clinic, and go work in public health for a while.

Interestingly, he then goes on to state that an outbreak of ~200 cases really isn’t all that bad, and that it’s an over reaction to tell people to go out and get their boosters. Yes, I know this seems to contradict his first point, which says that the actual number of cases will actually be higher than the reported number, but we’ll just skip past that for now.

He then states the current pertussis vaccination rate for 19-35 month and 13-17 year old children in the area of the outbreak, and there’s a range of 75-95% vaccination uptake across the age groups and areas. So he has up-to-date pertussis immunisation rates. Does he use these figures to do a back-of-the-envelope calculation of how many susceptible kids there should hypothetically be in the area of the outbreak? No. he ignores those figures and instead cites a 1995-2001 telephone survey which attempted to quantify and analyse the numbers, counties and various details (race, reasons for exemption etc.) of completely unvaccinated 19-35 month olds in America. He takes the average rate of completely unvaccinated kids across the country from the survey, 0.3%, and applies it to the county the outbreak is in. When he discovers that this rate is so absurdly low that it can’t possibly explain the outbreak (by some unstated criterion), he decides this must mean that it’s mathematically impossible for unvaccinated children to have some big role in the spread of pertussis.

All that Dr Palevsky demonstrates with this is his own ignorance of the whooping cough vaccine. It is not just the unvaccinated that are more susceptible to catching, and therefore spreading pertussis, it is also those who have been vaccinated, but not against pertussis, as well as those who have been vaccinated against pertussis, but whose immunity has since waned, not to mention the vaccinated that are still susceptible to disease (remember, the vaccine doesn’t work 100% of the time, it has an estimated efficacy of ~71-85%). The idea that only the unvaccinated are susceptible to pertussis is a strawman, which Dr Palevsky clearly finds it easier to attack than the actual efficacy data.

He then goes on to say:

“Pertussis bacteria live in the air. They get blown around along with the other trillions of bacteria that live in the air. Because pertussis bacteria live in the air, we breathe them in along with the other trillions of bacteria swirling around. They end up inhabiting our noses, airways, and lungs. We can be harboring pertussis bacteria in our airways simply by breathing the air.”

Well, no. B. pertussis is an obligate human pathogen. That is, it has to inhabit a person to survive, replicate and grow. What is true is that an infected person can spread pertussis to another person by respiratory droplets – that is, they hitch a ride on the microscopic drops of moisture released when an infected person coughs. What is not true is the picture Dr Palevsky paints of ­B. pertussis as the aerial equivalent of plankton. They don’t just swirl around on the breeze, inhabiting every square meter of the air around us. It’s a finicky organism that requires some very specific conditions in order to be able to grow and survive. If you’re in a room with an infected person, then it may be a more accurate representation (in the unvaccinated there is an ~80% transfer rate of pertussis to household contacts), but pertussis bacteria are not just always swirling around us in our every day lives.

At last, he finally raises a point that might actually be valid, that is, asymptomatic carriage of pertussis. It is possible for B. pertussis to colonise someone’s respiratory tract and not cause disease. It’s even possible for a vaccinated person to be colonised by B. pertussis, and then come down with whooping cough once their immunity wanes. During the time they are carrying it they could potentially pass it on and infect other people. Because of this Dr Palevsky equates the vaccinated and unvaccinated in their potential to carry and pass on pertussis.

While it’s true that the effect of asymptomatic or mild cases in the vaccinated on transmission remains to be established, it’s not like we’re clueless. Take for example this paper, the first hit if you search PubMed for ‘pertussis outbreak asymptomatic’. The study looked at an outbreak of pertussis in a daycare, in which all four unvaccinated children contracted the pertussis, whilst of the remaining 27 vaccinated children, two contracted pertussis, one with milder symptoms than the unvaccinated cases, the other with no symptoms. Here there was one vaccinated child found to be asymptomatically harbouring pertussis. Does this mean we need to re-evaluate our estimates of vaccine efficacy, because this skews the stats? Well, no, because when pertussis is detected in an asymptomatic vaccinated individual it’s still considered to be a ‘case’. It doesn’t skew the stats, because in more recent studies where all exposed individuals are tested for the presence of the whooping cough bacterium, asymptomatic cases are identified, and so far no studies have come out saying that the rate of asymptomatic cases they’ve found is inconsistent with the current estimates of vaccine efficacy. In fact, the World Health Organisation specifically note that “chronic carriers of B. pertussis are uncommon“. In other words, there’s not currently any good evidence that a high rate of asymptomatic pertussis carriage is occurring in vaccinated kids and somehow making them as likely to pass on pertussis as the unvaccinated, and studies, such as the one above, where the exposed are tested regardless of symptoms or not, are evidence against this ludicrous argument, as is the frankly low rate of this carriage.

So, in short, all Dr Palevsky’s blog post proves is that he didn’t do any background reading into the bacteriology of Bordetella pertussis or into the vaccine against it. Dorey’s claim that “being fully vaccinated – or even being immune (which is a totally different situation altogether) cannot prevent you from carrying and transmitting infectious diseases even if you yourself are not showing the symptoms” is fallacious; the rate of asymptomatic carriage in the vaccinated is low enough that vaccinated children can’t be considered equally as likely as the unvaccinated to spread pertussis, especially since the efficacy studies demonstrate they are less likely to contract the infection than unvaccinated controls.

And Meryl Dorey finishes with a corker:

“Vaccines create antibodies – they do not create immunity. So when a vaccinated person gets a disease they are supposed to have been protected against, the vaccine has failed in its job. The community has not failed – the vaccine has. And if vaccines can’t protect individuals – they can’t protect at all.

Let’s break it down.

“Vaccines create antibodies – they do not create immunity.

Actually, aP vaccines have been demonstrated to induce strong both T and B cell responses against pertussis, and what do you call a lower infection rate in vaccine recipients compared to placebo recipients if not evidence of immunity?

“…when a vaccinated person gets a disease they are supposed to have been protected against, the vaccine has failed in its job. The community has not failed – the vaccine has. And if vaccines can’t protect individuals – they can’t protect at all.

So according to Meryl Dorey, unless the aP vaccine protects 100% of recipients 100% of the time, it’s worthless. This is an astonishingly ignorant statement from her that makes me wonder: does she wear a seatbelt?

The huge disconnect between the literature I’ve read over the last fortnight and what I’ve read in Ms Dorey’s blog post was astonishing, and to be honest, I felt embarrassed reading it, when it became obvious that she hadn’t even read the one paper she cites for support. As well as attributing to it frankly hyperbolic doomsaying, the phrase of hers:

“84% of all whooping cough cases are being caused by bacteria that is not contained in our current vaccine”

…is clearly meant to relate to this paper, and is also clearly wrong. Firstly, the paper states that 100% of the pertussis samples taken are caused by bacteria not in the vaccine, right in the introduction, when it notes that PtxA1 is the only variant of the pertussis toxin active subunit found in Australian B. pertussis. If, instead, she were going by the Prn mismatch, the figure would have been 86%, not 84%. The 84% figure is actually the percentage of B. pertussis samples that had both the Prn2 and ptxP3 variants; I expect that’s the sort of nuance you would miss if you didn’t actually read the paper you were citing and got your interpretation of it from newspaper headlines.

And lastly, for the claim by Ms Dorey I am yet to address: is the vaccine responsible for the observed changes in which strains are predominant (that is, the observed shift to Prn2 and ptxP3)? Well, from my reading of the literature, the general consensus seems to be along the lines of ‘yeah, that seems to make sense’. Vaccination against B. pertussis provides strong selective pressure, as demonstrated by the severe reductions in the genetic diversity of the species when a vaccine is introduced, and both of these mutations contribute, each in a small way, to evasion of our immune responses. Firstly, as mentioned, it looks like, in a population vaccinated with Prn1, immunity to Prn2 wanes sooner, giving pertussis cells carrying this version a very slight advantage over Prn1 pertussis. The vaccine doesn’t select for Prn2, it selects against all Prn types – just a little less effectively against Prn2 cells than Prn1. Secondly, greater production of pertussis toxin (a la ptxP3) should theoretically give pertussis a little extra leeway time to set up its infection, replicate and get passed on to a new host, thanks to the suppressive effects the toxin has on our immune responses. However, this should not be advantageous in the recently immunised, as they have existing anti-toxin antibodies that can simply mop up the toxin and allow clearance of the bacteria; this would be most advantageous during the infection of someone without prior pertussis infection or immunisation, or whose immunity has waned.

So, both of these adaptations by the whooping cough bacteria sound like a win for them and a lose for us, right? Well, not so. In researching this I made some observations which I think are actually quite heartening. Firstly, in a mouse model of pertussis infection, Prn2 was found to be associated with decreased respiratory colonisation. Secondly, the closely related species B. parapertussis and B. bronchoseptica both carry the genes for making pertussis toxin, but in both species the promoter region is so mutated that they are unable to produce it. What this tells us is that there is a cost to producing pertussis toxin, a cost high enough that both of these species don’t do it any more. And yet, across the world, B. pertussis is moving toward increased pertussis toxin production.

This species has made two changes that before vaccination would be considered maladaptive, probably in order to try and evade vaccine-induced immunity, and yet the advantages it has received for these changes are, as I’ve discussed, relatively small.

The pressure that vaccination has put on this species is immense, to the point where it is making otherwise maladaptive changes in order to try and evade the vaccine.

We have Bordetella pertussis on the ropes. These recent developments on the side of the bacterium are desperate, but most importantly, they are not working.

We can send this species the way of smallpox. We can send it the way of rinderpest.

In the long run we’re going to need a vaccine with longer lasting immunity, and as I type this, research around the world into such vaccines is continuing, but for now, the acellular pertussis vaccine remains our best way of preventing B. pertussis infection. Right now, you can do your bit to help protect yourself, your family and your community from whooping cough. My last booster was in August 2005, seven years ago. Chances are I’m about to be entering the period in which my anti-Prn2 immunity begins to wane, before the anti-Prn1 immunity starts to go too. This week I will be calling up my local medical clinic and booking in an appointment for my adult booster shot. You can do the same thing too, and together we can help relegate this pathogen to the sands of time, where it belongs.

[Note 1: The three studies mentioned were conducted in Germany, Italy and Sweden. The PtxA1 prevalence data across Europe is summarised in this review, with specific figures for each country here: Germany, Italy, Sweden.]

(P.s. You may notice that in the Blog post by Meryl Dorey she also attacks the Chicken Pox/Shingles vaccine. The reasons I didn’t address that part of her blog post were twofold. The minor reason was length, as clearly this was a long post with just the pertussis-relevant sections. The major reason was that every single one of her incorrect/misleading claims about the shot were effectively answered by the ‘Varicella’ and ‘Zoster’ sections of the Australian Immunisation Handbook, and so there wasn’t really any fun background reading to do.)

Posted in Australian Vaccination Network, Pertussis, Vaccination | 18 Comments

Meryl Dorey’s Talk at the Woodford Folk Festival – What’s in a Title?

As is quickly shaping up as somewhat of a popular issue within the Skeptiverse, Meryl Dorey (president of the anti-vaccine lobby group the Australian Vaccination Network) will be giving a talk at this year’s Woodford Folk Festival.

This fact has been widely denounced, with Meryl Dorey’s unsuitability to comment on vaccines echoing throughout the blogosphere, as well as on the radio and television. For those unfamiliar with the AVN, the Network was the subject of a year-long investigation by the New South Wales Health Care Complaints Commission (NSW HCCC) which found that the AVN:

  • provides information that is solely anti-vaccination
  • contains information that is incorrect and misleading
  • quotes selectively from research to suggest that vaccination may be dangerous.

The report finishes by stating that “the AVN provides information that is inaccurate and misleading”. Given these findings, there have been several complaints to the local council and state government (who sponsor the festival) that they are effectively allowing Meryl Dorey to peddle incorrect and misleading information that a government report has found represents a danger to public health and safety.

More recently, however, Executive Director of the Festival, Bill Hauritz, has defended the decision to include Meryl Dorey in the festival line-up, ultimately defending the move with the statement “Everyone has the right to their opinion”, though without commenting on his interviewer’s inquiry as whether that right extends to their own facts. Meryl Dorey has been shown to disseminate misinformation in seminars before, and already, we can see she plans to in the upcoming presentation.

The title of Dorey’s talk is billed as “Autism Emergency – 1 Child in 38 with Meryl Dorey”. This title is derived from a study which attempted to estimate the true prevalence of autism spectrum disorders (ASDs) with a comprehensive 5 year survey of South Korean schoolchildren. The study estimated the prevalence of children with ASDs amongst the general population to be one child in thirty eight, or a prevalence of 2.64 percent. Even ignoring the large drop-out rate and the increased likelihood of parents of children with ASD symptoms to complete the survey, this represents a significant increase from the previous 1:100 estimate of the prevalence of ASDs in the general population. But does this study indicate a recent increase in the prevalence of ASDs, as Dorey’s alarmist title for her talk seems to suggest? Not according to the authors:

“It doesn’t mean all of a sudden there are more new children with [autism spectrum disorders],” said co-author Dr. Young-Shin Kim of the Yale Child Study Center. “They have been there all along, but were not counted in previous prevalence studies.”

Neurologist Stephen Novella, whose discussion of the study I highly recommend, is of a similar opinion. It seems that science is simply getting better at estimating the prevalence of ASD-associated traits in the general population. It doesn’t mean society is experiencing an ‘Autism Emergency’ but rather that there are many people in the general population who fall onto the autism spectrum, yet suffer no severe impairments, who are identified when a more rigorous search for them is performed. The prevalence rates appear to be dependent upon the current diagnostic criteria and the rigour of the study, with no good evidence yet out to suggest a real increase in ASD prevalence.

Perhaps someone should tell Meryl Dorey, so that she knows not to jump into an alarmist ‘ZOMG! Autism epidemic!’ rant?

Oh, wait, I already did. Soon after Meryl Dorey tweeted about this study:

“S. Korean study shows Autism 1:38 – up from 1:10,000 25 years ago. Vaccines implicated as well as antibiotic overuse and env. chemicals” (Interestingly vaccines, antibiotics and environmental chemical are not actually mentioned in the study)

I alerted her to the author’s comment, which neatly pointed out that Meryl’s statement that the rate is ‘up’ was incorrect:

@nocompulsoryvac ‘”It doesn’t mean all of a sudden there are more new children with (ASDs),” said co-author Dr. Y-S K (link to article with quote)”

Her immediate response? To block my twitter account:

Meryl Dorey is aware her characterisation of the study is incorrect, yet continues to repeat it. It seems that she can’t even get past the title of her talk without lying to her audience.

Posted in Australian Vaccination Network, Vaccination | 5 Comments

02 – Innate immunity

In order for the immune system to respond to microbes like viruses or bacteria, and not to our own tissues, it needs to recognise them as foreign. How does our immune system do this, and what are the consequences?

Throughout the body are immune surveillance cells that are constantly on the lookout for invading microorganisms. In order to discuss the early immune response to a microbe I will first introduce you to one of these cells, the macrophage.

The cell in the middle is a monocyte. It becomes a macrophage when it matures, leaves the blood and treks to the site of inflammation. The ring-like cells are red blood cells and the little splodges are platelets.

Macrophages are a kind of white blood cell found throughout the body, in slightly different forms depending on the kind of tissue they’re in. As the name ‘macrophage’ (literally ‘big eater’) suggests, they are experts at gobbling up microbes. But what tells the macrophage to eat the microbe? How does the macrophage recognise it as foreign?

The key is in recognising molecules commonly made by microorganisms, but not people. These are often structural, or essential for the microbe to survive or cause disease. Bits of bacterial cell wall provide structural support to the cell and are often essential for bacterial survival, while flagella  (whip-like ‘tails’ used for movement, below) are not essential to survive, but are often critical for setting up a successful infection. Concentrated samples of either of these are enough to induce a strong immune response, even without the rest of the microbe present.

Flagella on a bacterial cell. Flagella are long filaments that spin. Bacteria use them to move around, and they are often critical for the bacterium to set up an infection.

It’s not only completely foreign molecules that are recognised, but also familiar molecules organised in a foreign way. For example, the DNA of bacterial genomes may chemically resemble that produced by humans, but may encode combinations of bases uncommon in humans. Another example is RNA. Our cells use single strands of RNA to ‘read off’ the code in our DNA, while a lot of viruses use double-stranded RNA. This double stranded form can trigger an immune response, while our own single-stranded type does not. There are a wide range of molecular patterns that differentiate foreign microbes from our own cells and tissues.

These molecular patterns are the ‘danger signals’ that let the macrophage know it has found something foreign. You may remember this video from the last post:


(Om nom nom)

In this case the bacterial sugar ‘mannose’ is the danger signal, which activates the macrophage, telling it to eat and destroy the bacterium.

The sensor on the immune cell that recognises the danger signal is called the pattern recognition receptor (PRR). In the example above mannose is the danger signal and the mannose receptor is the PRR. Not all pattern recognition receptors are expressed on the cell surface, because not all microbes turn up there. Many different PRRs are expressed in many places throughout the cell. For example, viruses replicate inside our cells, so that’s where we can find lots of receptors for double-stranded RNA and other viral products. As you can see, even the location in or on the cell where a PRR is expressed is fine-tuned for the kind of microbe it will recognise.

Recognising a wide array of molecules and looking for them inside and outside cells acts like a broad net, ensuring that potentially any infection can be recognised by our immune system.

So now our macrophage has found a microbe and recognised what it is, and hopefully destroyed it. What if there are more? He alone may not be able to deal with all of the invaders, and so calls for backup, bringing other white blood cells to the area. The way he does this is by triggering inflammation.

Sure, we all know inflammation, that annoying reaction you get around a wound when you accidentally cut your finger while chopping veggies. It is triggered by immune cells that recognise a potential infection, to call for other immune cells. It’s also triggered by tissue damage, that way if you do get a cut you will have some white blood cells there, ready to fight any microbes that try and enter through the wound.

*sigh* Bad girl, Luna. At least you're properly house trained.

inflammation around some cat scratches. Note that the areas around the scratch marks have become red and slightly raised.

There are five key signs which tend to accompany inflammation – heat, pain, redness, swelling and loss of function – but why are they occurring? How does a bit of bacterial cell wall lead to these symptoms, and how does it help bring immune cells to the area?

Receiving the danger signal has not only made our macrophage much better at eating and destroying microbes, but also caused him to produce pro-inflammatory chemical messengers. These molecules diffuse through the tissue and trigger changes in the nearby blood vessels. The vessels dilate (expand) and the cells that line them change shape slightly, opening up small gaps between them. They also start to express more ‘adhesion molecules’, which are kind of like Velcro to white blood cells. The normal (non-inflamed) levels of these molecules mean that white blood cells which bump into the vessel walls during circulation will stick and roll along the edges for a while, but can still dislodge.

During inflammation more and stronger-binding adhesion molecules are produced which mean that some cells will actually stick so strongly that they stop there. These cells then creep between the gaps and out into the tissue. Once out of the blood stream the newly recruited white blood cell can follow the trail of chemical messengers to the site of infection, and help out our macrophage. This is a video of the entire process occurring in a mouse, beginning with an explanatory cartoon.


The dilation of the blood vessel also allows for some of the smaller soluble components of blood to leak into inflamed tissue. Some of these molecules bind microbes, attracting macrophages to them, and making them easier to gobble up, while others are capable of directly puncturing the cell wall, killing the microbial invader.


It is this increase in the permeability of the blood vessels that allows blood components to flow out into the tissue, causing the macroscopic signs we recognise as inflammation: blood is at core body temperature, so the tissue its components leak into will get warmer, while the introduction of fluid causes swelling. These symptoms may be irritating, but they also allow the immune system to recruit white blood cells to the site of an infection, which is critical to our body’s defences against microbes.

The immune system recognises microbes by the presence of molecular ‘danger signals’ that activate its cells. The immune cells that are activated this way can then tell the cells lining nearby blood vessels to change, helping bring while blood cells in from the blood stream. We recognise this on the macroscopic level as inflammation.

Next time I will discuss the later, more specific immune response mediated by the adaptive immune system, and how it produces the phenomenon known as ‘immunological memory’ in which the body is better able to fight of previously encountered microbes.

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01 – What is the immune system?

The immune system is the collective term for the many mechanisms the body uses to protect us from infection. It isn’t one thing, but rather a complex system of many molecules, cells and organs which interact in very specific ways to prevent and combat infection.

Given the prevalence of herbs, exercise programs and even bottles of water that are marketed as being able to ‘boost the immune system’, and the fact that little immunology is taught in schools outside of biology subjects, it is understandable that many people picture the immune system as a kind of vague, ethereal shield.

In reality the immune system has many different components throughout the body, from specialised cells and molecules capable of combating infection, to whole organs whose main function is to develop specific immune responses. Apart from these highly specialised systems there are organs and cells that primarily perform other functions – and so are not strictly considered part of the immune system – but which still play a part in preventing infection, such as skin cells that produce proteins that kill bacteria.

One of the key features of the immune system is memory, which manifests as a resistance to repeated infections with the same microbe. This lets us consider the immune system in two parts – as the adaptive and innate immune systems. The innate immune system responds the same way to the same infection each time it is encountered. The adaptive immune system takes longer to respond, but is much more effective at combating infections, and also produces memory cells. Memory cells remember an infection and if a person is infected with the same microbe then these cells allow the adaptive immune system to respond much quicker than the first encounter – in most cases you won’t even know you’ve been infected the second time.

The footsoldiers in this army are white blood cells, which are responsible for most of the activities of the innate and adaptive arms of our body’s defences.

White blood cells are produced from bone marrow stem cells. Some mature in the marrow, while others head to other tissues to mature before being able to properly function. Some white blood cells live in specific tissues, whilst others circulate in the bloodstream, and can be recruited to the site of an infection. While there can be a lot of variability between the cell types produced, there are two basic mechanisms by which they kill invading organisms.

One of these mechanisms is the gobbling up of microbes to destroy them. Some white blood cells specialise at this. The process of phagocytosis (literally ‘cell eating’) involves the white blood cell binding the microbe by specialised receptors, followed by the extension of the cell’s own membrane around the microbe. This leads to the cell engulfing the microbe which is now held in an internal compartment. This compartment is fused with others containing harmful enzymes. Other enzymes assemble at the edge of the compartment and produce highly reactive chemicals to help destroy the microbe.

Once the microbe has been killed, the left over parts can be used to activate the adaptive immune system, so that the body can fight the infection more efficiently, and once it is cleared, remember it in case of future infection.

After some more processing, molecules from the microbe can be used to stimulate an adaptive immune response, or re-activate memory cells from a previous infection with the same microbe.


This animation illustrates each of the steps involved in phagocytosis. In this example the way the bacterium is recognised as foreign is by expression of the bacterial sugar mannose.


Here we can see a white blood cell chasing and then phagocytosing bacteria. Nom nom nom.

The other major mechanism of destroying microbes is the process of releasing a granule of harmful molecules, a process known as degranulation. This is especially useful for attacking organisms too big to be gobbled up, such as parasitic worms. Some cells release granules that specialise in killing host (own) cells – which can be important in protecting the body from intracellular parasites like viruses, and from cancers, which develop from our own cells.

Phagocytosis, degranulation and memory are a few of the basic mechanisms by which cells of the immune system combat invading microorganisms.

The immune system is a complex arrangement of molecules, cells and tissues which exists throughout the body, and which helps to prevent and combat infection. The major cellular processes for destroying invading microorganisms are performed by white blood cells, and include phagocytosis and degranulation.

Next time I will discuss how the innate immune system recognises things as foreign, and the role of inflammation in an immune response.

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Welcome to the LymphoSite

Hi there. I’m an immunology student who is repeatedly disappointed by the amount of mis-information about the immune system on the web. I’m starting this blog not to talk about myself or any ‘deep musings’ but instead to try and to my bit to inform the general public.

I love immunology, and I love explaining concepts – especially given how often you learn new things when explaining them to others – and I love the feeling when suddenly it all makes sense, and you get that click, followed by a sudden rush of understanding and appreciation – the joy of learning.

I’m going to try and do my best to take what I’ve learned over the last three years, with the help of my text-books, some researchers, and the scientific literature, to explain to you, the reader, how the immune system works in as accessible language as possible, using examples and visual cues.

If at any point something I’ve discussed is unclear, let me know, and I’ll re-work it until it’s understandable. Immunology is relevant to all our lives, and shouldn’t just be for those who spend all day in the labs and know the jargon like it’s their native tongue. I’ll also do my best to try and explain new findings developments in immunology.

The first series of articles will be entitiled Introduction to the immune system, and will begin by detailing the basic mechanisms used by our body to recognise and combat infection, and from there will hopefully expand into such concepts in immunology as allergy, transplantation and cancers.

Enjoy, and let me know if you’re not learning.


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