Friday, May 15, 2009

Worrying about vaccines

Being the parent of a toddler means, among other things, giving the kid immunisation shots against various diseases at regular intervals. Understandably, this is not something kids enjoy. Moreover, some vaccines cause temporary reactions, that in rare cases can be quite severe. And while some vaccines are universally administered, others are very much at the discretion of paediatrician (and, in theory, the parents). So one tries to keep well informed.

So I read with interest a recent blog post where Dan Summers, a paediatrician, takes apart the anti-vaccine crowd, and in particular, this article by Jim Carrey.

The anti-vaccine movement is primarily driven by claims that vaccines are linked with childhood autism-spectrum disorders. There are at least two versions of this claim: first, that the MMR (measles-mumps-rubella) combined vaccine is linked with autism (a claim that caused particular scare in the UK); second, that thimerosal, a now-discontinued mercury-based preservative, is linked to autism (a continuing source of scare in the US). Both these are supported, at best, by anecdotal evidence. There are also claims that combined vaccines increase the shock to an immature immune system, leading to possibly undesirable side-effects.

Lots of peer-reviewed studies have, supposedly, refuted links between either MMR or thimerosal, and autism. This article reviews the situation. And only a few fringe loonies would argue that we would be better off without vaccines. It is wonderful to be in a world without smallpox, and to look forward to one without polio. Various once-common childhood killer diseases have now become rarities. Dr Summers says he has never even seen a single case of measles, still a common (if rarely fatal) disease in India. What's not to like about vaccines?

Dr Summers also exposes the bogus nature of Jim Carrey's "supporting" links. Like most conspiracy theorists, Carrey does not link to actual scientific literature, only to paranoid-sounding sites like "Generation Rescue".

Here's the problem though: I find Dr Summers unconvincing not for the things he refutes and exposes, but for the things he ignores in Carrey's article. And if I, a strong skeptic on most "alternative medicine" views, am unconvinced, I am sure millions of others will be even less persuaded.

First of all, Dr Summers says, "Indeed, I have never seen a single case of smallpox, polio, tetanus, measles or a handful of other once-common childhood illnesses..." But Carrey entirely agrees with the need to vaccinate against "the most serious threats including measles and polio"; I'm sure he would agree that tetanus is more serious than measles, and nobody vaccinates against smallpox anymore. So this is a strawman at the outset.

Dr Summers says "the advent of vaccinations has been as close to an unalloyed good as is likely ever to occur." If he merely refers to the eradication of smallpox, the near-eradication of polio, and the success against several other serious diseases, few should argue. But his article suggests something stronger: every approved vaccine is close to an unalloyed good. I think few doctors would agree with that (and he himself does not quite say it, only implies it).

Carrey says that there are 36 vaccines in the current US immunisation schedule; the version I saw only included 15 (as I discuss below), but perhaps he includes optional approved vaccines. He continues that there have been "no tests for cumulative effect or vaccine interaction" of all these vaccines, let alone the 100 or so in development. If there is such a test, Dr Summers doesn't supply a link to one.

Carrey claims that "American children are being given twice as many vaccines on average, compared to the top 30 first world countries". I don't know the true numbers, but Dr Summers doesn't refute this. I will return to this topic below.

Carrey says that "Paul Offit, the vaccine advocate and profiteer, who helped invent a Rotavirus vaccine is said to have paved the way for his own multi-million dollar windfall while serving on the very council that eventually voted his Rotavirus vaccine onto our children's schedule", and quotes strong words on this topic from a Congressional committee. Dr Summers does not address this.

Carrey says that "Veterinarians found out years ago that in many cases they were over-immunizing our pets, a syndrome they call Vaccinosis. It overwhelmed the immune system of the animals, causing myriad physical and neurological disorders." He also says veterinarians removed thimerosal from animal vaccines in 1992, and wonders why human vaccines lagged behind. Summers does not address this (or refute these claims).

Carrey admits that vaccines are good and bad, but says "One thing is certain. We don't know enough to announce that all vaccines are safe!" Summers, and the CDC in the US, seem to be announcing precisely that.

Now, here's the main bothersome issue that Summers entirely ignores: if vaccines were such an "unalloyed good", why do US children reportedly receive twice as many vaccines as children in other developed countries?

In my developing country, India, the National Immunisation Schedule lists the following vaccines up until 6 years: BCG (tuberculosis), OPV (polio), DTP (diphtheria, tetanus, pertussis), Hepatitis B, Hib (Haemophilus influenzae B), Measles, MMR (measles, mumps, rubella), and various boosters for these. That's seven vaccines for ten diseases. (Source: IAP Guidebook on Immunisation, 2009, available here.)

The US schedule that I can find for children below 6, here, lists vaccines for a total of 15 diseases: in addition to the above, there are rotavirus, pneumococcal, influenza, varicella, hepatitis A, and meningococcal (while BCG is missing). The UK schedule lacks several of the US vaccines: namely, rotavirus, influenza, varicella, hepatitis A and B are missing.

Many children in India receive more vaccines than the immunisation schedule recommends, and the same may be true in the developed world. The Indian Academy of Paediatrics recommends typhoid in addition to the ones in the immunisation schedule, and also suggests that pneumococcal, rotaviral, Hepatitis-A and Varicella "can be given after discussion with parents". Needless to say, such discussion rarely occurs.

But why does no country include all 36 vaccines in its schedule, and why are other countries omitting so many vaccines included in the US schedule? Are other countries being perverse and regressive in ignoring the "unalloyed good" provided by all those US vaccines? Or are there other factors to consider?

What are the possible drawbacks of vaccines? One is obvious: cost. This is relevant not only in India but very much also in the US, whose health coverage leaves much to be desired. It is the reason DTaP (the newer form of DPT, with an acellular pertussis vaccine that has milder side-effects) is not yet officially favoured in India. (Vaccines in India's National Immunisation Schedule are delivered free of cost via the public health system.)

Another is side-effects. Most vaccines have side effects; for the smallpox vaccine, one in a thousand have severe rashes, and about one in a hundred thousand had more severe, life-threatening complications. The risk was acceptable compared to the dangers of contracting smallpox when it was widespread. But as smallpox got effectively eradicated, the risk was judged unacceptable and the vaccine is no longer administered.

A third is an unknown and controversial factor: the effect of administering many vaccines simultaneously. More and more frequently, vaccines are "bundled" with five or more often administered in a single shot. Skeptics argue that the effects of this sort of "shock" on an immature and developing immune system are at best questionable. Defenders think there is little danger and an infant, of whatever age, is exposed to many more antigens and possible pathogens every day than what are administered in a vaccine. But few doctors or immunologists, I think would assert that there is no danger whatever.

Unfortunately medical science is not an exact science: despite the most exhaustive clinical trials, certain side-effects, interactions and allergic reactions from drugs can take years or decades to discover.

Unfortunately, also, patient mistrust of doctors and medicine seems to be rising all over the world, and not only are "alternative medicine" therapies of various levels of dubiousness rising, but proven medical therapies and treatments are being ignored by patients who read scare-mongering half-truths. Vaccines are an example: today's young parents have never encountered smallpox, polio, diphtheria, tetanus or many other dangerous diseases, but do encounter the reactions to the vaccines and read frightening but unsubstantiated stories on the internet; therefore many reject vaccines.

But how to tackle this? I think Dr Summers' approach is not the answer.

I know many committed, sincere doctors who are concerned with nothing except the welfare of the patient. I believe this is true of the majority of doctors, around the world (though perhaps not the majority of high-profile, headline-grabbing doctors.) They are aware of the limitations of medical science, are willing to prescribe alternative methods (ayurveda, yoga, acupuncture) when appropriate, but prescribe powerful drugs when required. It is a pity when patients do not trust such advice, and assume that all antibiotics must be bad regardless of circumstance -- or that vaccines for certain diseases are not required because you don't run into those diseases any more.

But patient mistrust is not limited to the doctors: it extends to the pharmaceutical companies. And, here, I think the mistrust is merited.

Carrey cited the example of the rotavirus vaccine, included -- allegedly under the pressure of the developer -- in the US schedule but not in most other countries. But this is only one of their many crimes.

Pharmaceutical firms are routinely accused of focussing their efforts on "lifestyle drugs" that are directly marketed to the public, with minimal consideration of side-effects. See, for example, this article in Nature Medicine.

Infant formula makers used to claim that their products are superior to breastfeeding; when such advertising was banned in most countries, they resorted to more indirect claims that planted the same impression in the minds of the public. (See this article by George Monbiot, for example.)

Dr Summers talks about the importance of peer-reviewed research, and challenges skeptics on vaccines to publish their work in peer-reviewed journals. Unfortunately, pharmaceutical companies have done their best to pervert the scientific peer-review process too. It is mandatory for scientists to disclose sources of funding and potential conflicts of interest in their manuscripts, but this is not always kept above board. In a recent spectacular case of fraud, an anaesthesiologist who had built a significant international reputation turned out to have faked his clinical trials for over 10 years; his research was funded by pharmaceutical companies who produce many of the drugs that his papers promoted. And even more egregiously, Elsevier Science -- publisher of many leading journals in every discipline -- was found to have published fake journals, at the behest of pharmaceutical companies (in particular, Merck), that had every appearance of containing peer-reviewed research but in fact contained in-house research from the pharma giant presented in academic form.

I think this sort of thing hurts medicine and public health much more than a few conspiracy theorists ever do, because it undermines confidence in the entire medical system, and indeed, the scientific peer-review system.

Dr Summers writes that "Carrey wrote his post and appears as a spokesperson for Generation Rescue while affecting the posture of an informed and enlightened ambassador for truth." But when large swathes of peer-reviewed research is guilty of precisely the same crime, why should Carrey seem less credible? How are we to trust published research when it is so easily perverted by big money?

I tend to believe the published "basic research" that I read, because it is unlikely that the authors have hidden agendas. But in order to verify the claims that there is no statistical link between autism and MMR or thimerosal, I will not only have to read those papers, but verify that none of those authors had a conflict of interest in writing those papers. This is rather hard to do sitting at my desktop on the other side of the world. (I may also have to verify the statistics used: see this article on hypothesis-testing in the medical literature.)

So while I do not believe vaccines are bad, I am suspicious of mercury-based preservatives in vaccines, unwilling to believe disclaimers from the CDC, and unwilling to accept that every vaccine included in the US schedule (or being pushed on my son by a corporate hospital in Chennai despite its absence from the Indian schedule) is being considered on its merits alone. Take the hepatitis A vaccine: the WHO's recommendations say that large-scale childhood vaccinations should be "considered" only in regions of intermediate endemicity; but it is included in the US schedule (a low-endemicity country) and was recommended by our paediatrician in India (a high-endemicity country).

And I would like to see a lot more research on vaccine interactions, before administering five or more bundled vaccines in one shot to an infant.

And industry-funded research is unlikely to persuade me that my worries are unfounded.


Tabula Rasa said...

super post, thanks. fwded to relevant authority.

km said...

I came across this blog which quotes a report from 2006 about the use of mercury in vaccines in India.

ProVaccine said...

Try reading Respectful Insolence on the Scienceblogs. He has been writing on vaccines, their effectiveness and the myths of autism/vaccines for long time.
Hope that helps.

Sakshi said...

1. Why disbelieve CDC research? It is not industry funded and is under a lot of pressure to be as correct as possible.
2. Mercury in vaccines was removed after the anti-vaccers kept crying about the autism link, DESPITE, numerous studies that showed that such a link was a myth. It was to reassure the public but the goal posts have been moved again - now the concern is about "green" vaccines or "bundling" vaccines.
There is enough peer reviewed literature and well written articles that address all the the dubious claims that articles like Carey's make. How ever, it seems that people are more than ready to mistrust scientists than celebs who have no knowledge about science whatsoever but are willing to go on and on about dangers of vaccines.
Vaccines work due to herd immunity. If people start mistrusting valid, proven scientific opinion then the diseases we have conquered are going to come back.
3.What will it take for skeptics to believe in vaccines? I would like someone to explain that,lay out the points you want addressed and what will it take for you to believe in them. That way one can go about addressing the issues.

Rahul Siddharthan said...

Sakshi: the CDC mostly does not do research; it makes recommendations based on other people's research. The "no link between thimerosal and autism" studies that I have seen had nothing to do with the CDC.

Carrey claims that thimerosal was removed from animal vaccines in 1992. I have seen this claim elsewhere (and claims that Eli Lilly had evidence of its toxicity in the 1930s, but suppressed it). Is that true?

There are other peer-reviewed papers out there -- say, this one -- that suggest one cannot make firm claims about the safety of thimerosal.

I listed a large number of claims made by Carrey that are ignored by Summers, and by all the other debunking articles that I have seen. What would it take for me to trust thimerosal and combination vaccines, and the CDC recommendations? Addressing those claims would be a start. Explaining why, in the case of Hepatitis A, the CDC disagrees with the WHO's recommendations, would be useful too.

A lot of the vaccines under discussion -- influenza, hepatitis A, etc -- have nothing to do with "herd immunity": nobody is hoping to eliminate those diseases. Your comment, like so many of the posts out there, relies on such strawmen.

Sakshi said...

@Rahul - The flu vaccines might not "eliminate" the virus but it will go a long way to keep the epidemic in check. That is where the herd immunity comes from. The young and the old are the ones hit the hardest by flu. 38,000 people die in US each year of flu- it is not a minor disease.
Thimerosal's removal from human vaccines was bought about by a FDA act in 1997 and was removed from childhood vaccines in 2001.(Autism spike does not coincide with this - it keeps spiking even after the removal of thimerosal and hence the demand for "green" vaccines from the antivaccers crowd.)

Regarding its safety -
Thimerosal is metabolized in the body to ethyl mercury and thiosalicylate. While ethyl mecury is harmful in high dosage, there has been no studies that show effect on chronic low dosage of ehtyl mercury on neurological development (as far as I know, this is not my field of study and I could be wrong). And it also seems to cleared out of the blood quicker and more effectively than its more dangerous cousin methyl mercury.
I have seen nothing about thimerosal toxicity studies and autism links - the only claim was by Dr.Wakefield and lately it was shown that he faked the data.
The most significant study was done in 2001/2 (forgot by whom, published in Lancet) and the investigators monitored mercury elimination in vaccinated infants. They found that levels of mercury derivatives were below toxic levels. There is now a larger follow up study going on (Check here for more information)

The oldest study I found was in 1930, these animal studies used 20mg of thimerosal/kg (rabbits)- which is using a lot. And hence would have shown toxicity :)

I applaud your concern for your child's safety. My advice would be to read (as suggested above) Orac's blog and get in touch with him to address your questions. He is a doctor and hence would be able to deal with all your concerns about your child's vaccination. I dont know appropriate authorities in India but I am sure there are people like Orac in India too.

Rahul Siddharthan said...

Sakshi: we have given the kid every vaccine on the IAP schedule (which means every vaccine on the national schedule), plus a few; and have drawn the line at a few others, in consultation with our paediatrician. She herself seems skeptical about certain combination vaccines, but is helpless because the individual vaccines are no longer available.

I thought it was perfectly clear from my post that I am not anti-vaccine; your response confirms my suspicion that anyone who does not wholeheartedly endorse the recommendations of the CDC (including someone like Jay Gordon, who probably sees more kids in a week than your friend Orac sees in a lifetime) must be "anti-vaccine".

The paper I linked to shows clearly that previous ways of estimating toxicity of ethylmercury (by comparing with known toxicity levels of methylmercury) are unreliable. It was, notably, not from the medical community. Though I agree with Orac on several things, I find his brazenly confident defence of thimerosal quite off-putting. I'm still waiting for an answer on whether the thing was removed from animal vaccines in 1992, and if so, why. Also for why the CDC recommends so many more vaccines than other countries, and in the case I mentioned (Hep-A), goes against WHO recommendations.

The way the self-appointed pro-vacciners jump on the easy questions -- or worse, construct strawman questions that they then jump on -- and avoid the difficult ones does not inspire confidence.

Sakshi said...
This comment has been removed by the author.
Sakshi said...

@ Rahul - I did the quick Pubmed search and it is around the 94-95 that thiomerusal was removed from small animal vaccines. Large animal vaccines still contain it. A couple of papers indicated sensitivity to the compound. I did not come across neurotoxicity reports but it was a very quick search. I will look into it over the weekend

I am sorry if it came across as I was coming down on you as an antivaccer. It was not my intention. I do however dont understand the mistrust of CDC.

And FYI, I am not friends with Orac. Don't know the guy but have read him over the years. Since the antivaccination thing began.

I am willing to tackle your difficult questions but I would need time to do that. I am not an immunologist and would rather not make any claims that are wrong.

As I said before your concerns are not invalid. But I would ask an immunologist or a doctor to address my concerns - about the toxicity, necessity and the studies out there. And I would trust them to have my child's best interest at heart.

Sakshi said...
This comment has been removed by the author.
Sakshi said...

Pubmed will be too time consuming to go through now. So I did the next best thing - looked up ingredients for dog/cat vaccines and found that thimerosal is still present in them.

Hope that helps.

Rahul Siddharthan said...

Sakshi - thanks for your comments and sorry if I misunderstood you.

The trouble is, doctors are often not very familiar with the literature (the Ben Goldacre article that I linked in my posting mentions that a doctor would need 700 hours a month to keep abreast of the literature) and immunologists don't actually see kids and their reactions.

About animal vaccines, this article by RFK Jr says the FDA "considered" banning thimerosal from animal vaccines in 1991; perhaps that statement got exaggerated by Carrey and others. RFK's article too is alarming reading. Once again, while I have seen takedowns of it, they focus on only a few aspects (notably, misrepresentation of the Simpsonwood meeting). It quotes a huge number of important people by name.

About the "no link" studies, the more widely quoted ones (this one and this one) were done in the UK, where both the total number of vaccines administered and the number that contain thimerosal are much fewer than in the US. In fact, the second (retrospective) study only considers DTP and DT vaccines, which are administered in 4-5 doses, the first three being over a year or so, each containing about 20 micrograms of ethyl mercury. In contrast, this paper says (as quoted here -- I can't access it from home) that US infants in 2000 received nearly 200 micrograms in the first 14 days of life, which is at or above the toxicity limit.

Much of the pro-vaccine comment focuses on the presentation, and not the content, of arguments by RFK, Carrey, et al. That's my problem.

Rahul Siddharthan said...

Sorry, make "14 days" above "14 weeks".

RFK quotes the same number (187 micrograms) over 6 months, which he says is 40% over the EPA daily average limits. But these shots were not given as daily averages: individual shots could go as much as 99 times the EPA daily average limit. See clarifications at the bottom of the article.