Thursday, February 10, 2005

MMR vaccine and autism

I just got a suggestion to write about the putative link between the measles, mumps and rubella (MMR) vaccine and autism. I'm happy to oblige, as this is a subject that connects to science, public health, public perceptions of science and medicine, all things I find very interesting! This is a fairly long post, so quick summary: the MMR-autism link is bogus; the uncertainty that the MMR-autism claim has created has led to concrete harms in terms of public health; and the widespread acceptance of the claim is typical of modern skepticism about the "scientific establishment." Feel free to skip down to whichever section interests you most.

MMR vaccine does not cause autism

In 1998, a group of doctors led by Andrew Wakefield published a paper associating the MMR vaccine, gastrointestinal inflammation, and autism in a study of 12 children. The paper stated that in these children, intestinal inflammation and "neuropsychiatric dysfunction" (diagnosed as autism in 8 of the 12) followed MMR vaccination, usually within a week. Even though they were cautious enough to state that "We did not prove an association between measles, mumps, and rubella vaccine and the syndrome described," public fears of the MMR vaccine became widespread and MMR infant vaccination rates fell to record lows.

As it turns out, Andrew Wakefield received £55,000 (over US$100,000 at current exchange rates) from lawyers who were suing the manufacturers of the MMR vaccine. He found his patients through those lawyers, whose clients were the parents of many of the children in the study. He never disclosed this conflict of interest. 10 of the 13 original authors retracted the study when they found out. What's more, the study represents a few children that Wakefield selected precisely because of a temporal coincidence between MMR and autism (i.e., which caused parents to worry and join a lawsuit. This selection bias is a fatal flaw on top of the failure to disclose a critical conflict of interest.

As for methodologically valid studies: this one found that incidence of autism is equal among MMR-vaccinated and non-MMR-vaccinated children (498 autistic children analyzed from a survey of medical records). Incidence of autism in the UK steadily increased from 1988-1993 even though MMR vaccination rates were virtually constant at 95%. Within autistic children, neither "developmental regression" (meaning worsening of symptoms) nor bowel problems increased from 1979 to 1999. (The MMR vaccine was introduced in Britain in 1988 after a measles outbreak killed 17 people.) This study, covering 5773 people, also found no evidence for a link between MMR vaccine and autism.

Anti-vaccine movements lead to concrete harms

MMR infant vaccination rates in Britain are now about 80%. Before the 1998 MMR scare, vaccination rates approached 92%. 95% coverage is required for "herd immunity" to kick in, where so many people are immune to measles, mumps, and rubella that the viruses cannot spread in the country at all.

Before the MMR vaccine was introduced in 1988, a handful of children died of measles in the UK every year, and thousands contracted it. (The death rate from measles is pretty low for healthy children.) After 1992, there has not been a single death from measles in the UK. (Worldwide, it's estimated that almost 800,000 people died from measles in 2000, out of almost 40 million people who got the disease, mostly in Africa and Southeast Asia.)

But now, the percentage of unvaccinated children is high enough that measles is on the verge of becoming an endemic disease in the UK. In technical terms, the "reproductive number" (R) of the measles virus, or the chance that each infected person will transmit the virus to another uninfected person, rose sharply from 0.47 to 0.82 from 1995-98 to 1999-2002. Above R = 1.0, the disease is endemic (e.g., common cold); below 1, it occurs in isolated outbreaks. If reduced vaccination rates continue, the proportion of unvaccinated children will grow (after all, 1998 was only 6 years ago), and R will grow as well. I quote the original Science paper:
If the current low level of MMR vaccine uptake persists in the UK population, the increasing number of unvaccinated individuals will lead to an increase in the reproductive number and possibly the re-establishment of endemic measles and accompanying mortality. In their attempt to avoid the perceived risk associated with vaccination, parents' behavior collectively results in a substantial increase in the real risk of exposure to measles.
If you can access the paper, check out the figure - it's shocking how sharp the rise in both the frequency and size of measles outbreaks is, and how sudden the rise in reproductive number is.

Meanwhile, mumps is also on the rise. For example, in the last couple months there have been several outbreaks of mumps in UK universities, including Cambridge and Oxford. College students are vulnerable because they were born in the 1980's, before the MMR vaccine was introduced in Britain. But these mumps epidemics are happening now because of the loss of herd immunity in the general population.

For another example of anti-vaccine movements harming public health, see this paper, a cross-country comparison of incidence of pertussis (whooping cough), showing that countries with active anti-vaccine movements suffered increased incidence of pertussis shortly after vaccination rates dropped. This comparison is especially striking: (the gray on the England and Wales graph represents a period in the mid-1970's after a public health academic said the pertussis vaccine was not worth the risks, and before a national reassessment declared the vaccine to be of "outstanding value.")



Why do people still believe the MMR-autism link?

Autism first becomes apparent before the age of 3 - just about the same age as childhood vaccines like MMR are given. By sheer chance, you'll always have some kids who show the first signs of autism right after they get the MMR vaccine. Parents naturally worry over their kids, especially for a condition like autism that seems to parents to rob their child's heart and soul, and the first instinct is to find an explanation. Hence the continuing tragic personal testimonials, which unfortunately have no relevance to whether MMR really does increase the risk of autism.

The problem is that these personal testimonials really tug at the heartstrings ("Won't someone please think of the children! --Helen Lovejoy). And when parents are convinced that something harmed their child, they are (naturally) really, really vocal about it.

The second problem is that childhood immunization has been so spectacularly successful that it's become self-defeating in a sense. Smallpox is eradicated. No one in the developed world gets polio anymore. Measles, mumps, rubella, diptheria, pertussis - all are now extremely rare. Formerly widespread childhood diseases are now so rare that almost no one in the developed world thinks or cares about them. Because no one is afraid of these diseases anymore, people see vaccines as having a negligent marginal benefit. (Due to herd immunity, they're right - if everyone else is vaccinated, you're safe even if you're not. But if everyone thinks that way, we're in trouble.) Next to even the tiniest perceived risk, the benefits of vaccination suddenly doesn't seem worth it. This is the availability heuristic - people think something is more likely if it's more salient in their minds. Absence of childhood diseases + media reports of an MMR scare = an availability heuristic in exactly the wrong direction.

Perceptions of science, medicine, and the establishment

I was slightly shocked by this website, especially this bit (attacking this article in JAMA):
The information on the internet, thank goodness, is not peer reviewed by doctors like these authors or we wouldn't be able to believe what is on the internet anymore than we are able to believe what is published in JAMA.
This sort of complete distrust in the scientific and medical establishment is the third reason that the MMR-autism link has gone so far in public opinion. It doesn't do any good to report that "the overwhelming majority of experts have concluded there is no link between the MMR vaccine and autism," because scientific "expertise" (and science itself) has lost at least some of the patina of authority it once commanded. The anti-vaccine movement is thus intimately connected (as an intellectual and social phenomenon) to quack medicine, conspiracy theories, and even (loosely) creationism.

What to do about this? Some policy ideas do make sense - for example, the US government has a system where reporting adverse reactions to vaccines is required, and has a fund to compensate victims of the (extremely) rare complications of vaccines that stops them from suing the manufacturer. This last one stops pharmaceutical companies from halting manufacture of a critical vaccine because they're afraid of lawsuits. But these treat the symptoms of the anti-vaccine movement, not the root causes.

Meanwhile, I don't think we can turn back the clock to "just trust me, I have a white lab coat on," and a healthy distrust of "the scientific establishment" is probably a good thing, lest we end up with pseudoscientific theories like eugenics once again taking over the scientific community. In combating the excessive anti-science paranoia, I have little else to suggest other than continued efforts to explain to the public that vaccines are safe, and to do so not by appealing to expert authority but to demonstrate it transparently (e.g., publicize studies on vaccine safety). (I won't buy into the line that we need to do "more research" on vaccine safety - usually, there's plenty of research and the anti-vaccine activists just use it as a rhetorical technique, for there can never be enough research done in any field to definitively prove a negative - only to prove that the risk is lower than the very stringent limit of detection.)

Maybe the only thing that will cure us of anti-vaccine hysteria is a good old-fashioned reminder of how awful infectious diseases can be. That may be the one good thing to come out of the recent mumps outbreaks in Britain - the constant appeals to get vaccinated will be more convincing next to the actual risk of getting sick. (Availability heuristic, once again.)

There's more on this from Respectful Insolence (scroll down to the comment by "Dreaming again" for a personal testimonial of the what vaccines are good for.)

Update: I've now posted about resistance to polio vaccine in Nigeria, here

158 Comments:

Anonymous Anonymous said...

get the real story at www.whale.to

 

Posted by john

2/10/2005 09:40:00 PM  
Anonymous Anonymous said...

www.whale.to has exactly the kind of absurd conspiracy theories I'm talking about. Here's a quote: "It is naive to think the medical cartel are looking for the truth regarding autism and MMR, and wouldn't put themselves before the children.  For one thing allopathy is resting on shifting sand/lies, they fear if one is exposed the whole pack of cards will come down like Kissinger's domino effect.  They will lie, steal, cheat and kill, before that happens, as history shows clearly.  At the top the Illuminati run the show through their monopolies and corporations, and they create all the wars, run the illegal drug trade, and so on, and have been top of the dung heap, robbing the taxpayers blind, for 200 years."I am not sure that someone who truly believes this is susceptible to reasonable argument. It's like creationism or raving anti-Semitism. (Seriously. This conspiracy theory is in exactly the same form as the old "the Jews are running the world from behind the scenes" trope.) 

Posted by Andrew

2/11/2005 12:36:00 AM  
Anonymous Anonymous said...

Thank you for writing this article. The ugliness of the whole autism epidemic mindset and the related antivax hysteria has caused much damage. It allows for autism to become demonized and hated - as if autism can be separated from the people who are autistic.

Descriptions of autistic children sometimes sound like hate speech. I think everyone would benefit if all those involved with autism would just stop hyperventilating and realize that there are handicapped people in this world who need extra care.
In fact, given time we will ALL be such. I believe the morality of cultures can be judged by how much effort they are willing to expend on keeping the vulnerable among them safe. Currently the standard chant seems to be, "autistics are a burden and a curse, an epidemic, and they must not be allowed to be here".

I am not saying that there should be no treatment for autistic children, or saying that people should wish that their normal chldren were autistic. So far, there is little evidence for any major increase in autism and there is no "smoking gun" in the form of an environmnental cause. If an environmental cause were found to be the cause of some forms of autism, a kind of pollution for instance, then by all means clean up the pollution.

I am saying, lets do a reality check, If life gives parents an autistic child they don't have to scream about how horrible it is and that there should never be another one born. Parents don't have to push that child through extreme and unproven treatments in an effort to make him normal. At least one child has been killed by such efforts.

Camille - adults with an Asperger's diagnosis and parent of a disabled adult on the autism spectrum
 

Posted by Camille Clark

2/11/2005 06:12:00 AM  
Anonymous Anonymous said...

Camille,

I personally haven't come across any demonization of autism or autistic children, but I'll take your word for it and say that's really a shame.

For a satire of common views of autism, see the Institute for the Study of the Neurologically Typical . 

Posted by Andrew

2/15/2005 09:44:00 AM  
Anonymous Anonymous said...

I have two friends who dismissed the whole Wakefield fuss as just more of the usual silly scientific scare story activity, until they were half persuaded otherwise by the duplicitous behaviour of the P.M.concerning his own youngest. 

Posted by dearieme

2/19/2005 01:40:00 PM  
Anonymous Anonymous said...

I was going to go into the same diatribe I did on Respectful Insolence, then got to the end and realized ...oops ... don't have to.

I have a couple of pictures of my husband ...with clothes on so it's hard to see, it masks the severity of the scoliosis ...but it can be seen that there is scoliosis. If you want to see the picture of just how thin he is, just how much muscle atrophy has been caused by the polio... email me at PeggikayeE@aol.com  

Posted by Peggikaye

2/20/2005 12:41:00 AM  
Anonymous Anonymous said...

Ok, what I meant by if you want to see the picture, was if you've never seen the devastation that the childhood diseases like polio can wreak on a body! 

Posted by Peggikaye

2/20/2005 04:41:00 AM  
Anonymous Anonymous said...

Neuroscientists have found indications of structural problems
in the brains of autistic babies as young as three months old.
NY Times-Search for Autism's Cause 

Possibly publicizing these recent discoveries might shift
parental anxieties to considering other causes, such as
bith defects or genetics. 

Posted by Peggy

2/26/2005 03:50:00 AM  
Anonymous Anonymous said...

Possibly publicizing these recent discoveries might shift
parental anxieties to considering other causes, such as
bith defects or genetics.
 

Yes, I hope so! But I do still worry that irrational distrust of scientific expertise will lead anti-vaccine people to dismiss this kind of evidence as further nefarious "cover-ups" of MMR vaccine's notional harms. Let's hope that most people are reasonable enough to accept these new findings. 

Posted by Andrew

2/26/2005 05:52:00 AM  
Anonymous Anonymous said...

Since my wife and I chose not to vaccinate our children, I feel obligated to make a couple of points:

1) Some of these diseases are much worse than others. Smallpox and polio are frightful (but no longer widespread). Measles, on the other hand, does not kill healthy people. Pertussis can be treated with antibiotics. In other words, there is a wide range of risks we are assessing.
2) For many diseases the greatest part of the reduction in mortality can be attributed to improvements in health and nutrition rather than vaccination. The big difference in mortality for measles between the UK (pre-MMR) and various parts of Africa that are mentioned in the worldwide mortality figures is not due to vaccination. For some diseases such as tuberculosis (for which no really effective vaccine exists) the reduced incidence is entirely due to advances in the overall quality of life.
3) Because of 2), above, models that use historical data will tend to overrate the effectiveness of vaccines in preventing disease.
4) Perhaps most important, at least to me: vaccines are not generally studied for long-term ill effects. Two weeks observation, and if you're not obviously ill then the vaccine must not be harmful. Well, I like to be more cautious than that. The use of adjuvants like aluminum doesn't strike me as innocuous. Thimerosal may not have been proven to be linked to autism, but surely I can say that injecting mercury into my children represents a risk that is hard to quantify? In this case I am simply preferring the devil I know to the one I don't.
5) Your points about herd immunity and the risks to a healthy unvaccinated individual in a population that is otherwise 95% vaccinated make clear that in many cases it may be antisocial to refuse vaccination, but it is not irrational. Even absent conspiracy theories, a person could reason that they would avoid subjecting their children to a one in ten thousand chance of adverse vaccine reaction since everyone else's vaccinated state made the risk of the disease so low. This is sort of a special case of the tragedy of the commons (or something like it... not sure of the best analogy).
6) The guy who published the paper drawing a link between MMR vaccination and autism was clearly a shill for his lawyer buddies. However, I think that both sellers of vaccines and public health officials have plenty of reasons to downplay the dangers of vaccination (to the point of deception in some cases). In the former case of course there is money at stake. In the latter case the government has to contend with the people I describe in 5), above, who would like to free ride on the herd's immunity. It of course behooves them to paint vaccine refuseniks as crazy weirdos rather than rational actors who happen to put their children's health ahead of the general welfare. 

Posted by bbartlog

3/04/2005 08:35:00 PM  
Anonymous Anonymous said...

1) Polio isn't widespread anymore but its incidence is on the rise, as I said, precisely because of anti-vaccine movements. Measles does not kill healthy people but it can kill. And even diseases that don't kill can be pretty nasty. (Ask anyone who's had chicken pox, or mononucleosis, and so on.) Why allow easily preventable pain, suffering, and yes, death?
2) I didn't say that all disease can be cured or prevented with vaccines. My point was that if vaccines do exist, and they do work, and they are safe, raising irrational and unproven concerns about vaccines can really lead to more people dying or suffering from preventable diseases.
3) Please explain where I used historical data that is invalidated by your point. (If you are referring to the pertussis graphs, the only important part was showing that pertussis incidence rose sharply in England after uptake of the vaccine dropped.)
4) I agree that vaccines ought to be studied for their long-term effects - if only to convince people like you that they are safe. But I absolutely abhor the "devil you know over the devil you don't" mentality. In any case, there is always going to be a cost-benefit ratio. A vaccine that prevents certain diarrheal diseases may not be safe enough to use in the West, where lethal childhood diarrhea is very rare, but in many developing countries where diarrhea is common and kills millions of kids, it might be worth the risk to save those millions of lives.
5) Yes, riding free on herd immunity is a perfect example of the tragedy of the commons. That doesn't mean it is okay to spread unproven rumors that vaccines are harmful.
6) We may ignore the bias introduced by vaccine manufacturers, because it is obvious and it's easy to discount what they say. Public health officials are tricker. In fact, there are plenty of examples where officials decided that a particular vaccine was too dangerous to use, even despite its benefits (see #4 above). Public health officials aren't going to lie and say that a vaccine is safe if there is real evidence that it is dangerous enough that the risks outweigh the benefits. In the case of MMR/autism, there is no such evidence. 

Posted by Andrew

3/06/2005 12:01:00 AM  
Anonymous Anonymous said...

1) As regards polio, I agree that in this case the benefits far outweigh the risks. I am not sympathetic to the vaccine opponents in Africa and would agree that the containment of polio is a great medical achievement. If it were still prevalent in the US my children would have been vaccinated against it.
2) Long-term safety of vaccines is my main issue, though overestimates of effectiveness are also a concern when doing a cost-benefit analysis.
3) My comment was a general one, not directed at your graph specifically.
4) The only reason to study the long-term effects of vaccination is to convince people like me of the error of their ways? I hope that if such studies are done we can find someone motivated by the spirit of scientific inquiry and not someone who supposes the conclusion to be foregone. As for the precautionary principle, you may abhor it, but that's not an argument against it.
5) Well, the problem is an interesting one from an ethical standpoint. People are bad at evaluating costs and benefits when low probabilities are involved (like winning the lottery, or having a one in ten thousand chance of an adverse reaction to a vaccine...). So you can make a utilitarian case for a Straussian approach, where such risks are downplayed because they are not going to be assessed in a rational way. As for the ethics of spreading 'unproven rumors', I agree that there are cranks who have all sorts of unfounded ideas about vaccines. But it's a mistake to lump everyone who questions their value into the same category.
6) Yes; for example the rotavirus vaccine is not recommended. But a better example of the kind of thing I'm talking about is here  . The worst possible outcomes for diseases are emphasized, while discussion of any major adverse reactions is deferred to the doctor.

 

Posted by bbartlog

3/08/2005 02:50:00 PM  
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Anonymous allison said...

Mercury is one of the most deadly elements known to science. It does cause neurologic disorders ( including but not limited to autism,and MS )and it is also used as a preservative in vaccines. It is also found in "silver" or amalgam dental fillings.
There have been improvements. Less mercury is found in todays vaccines. And you can get composite fillings instead of "silver" which have more mercury than silver. You must be vigilant. The American Dental Association has patents on amalgams and they are a source of great income.
IMPORTANT: if your body can not eliminate mercury it will not show up in most tests. People who can not eliminate mercury are often the ones who develope problems. There is more than one kind of mercury. You could have a problem with one kind and not another.
For More info go to :
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12/29/2006 03:59:00 AM  
Anonymous Anonymous said...

While this is spinning off the topic of vaccines, as a dentist, I must respond to this belief that placing dental amalgams is seen as a way to make money and not as a scientifically proven method to treating dental decay.

In fact, I stand to make far more money by placing composite restorations as they cost more out of the patients' pocket, are often not covered by insurance, and need to replaced more frequently than amalgams! Yet I choose to continue placing amalgam fillings because I care about my patients' teeth and hope to give them the most long-lasting treatment that I can.

Furthermore, I am personally insulted by any critic or patient that believes I would knowingly place a substance in the body that I found to be harmful. That goes against every bit of the ethical code I swore to uphold. This ethical code begins with the promise to "do no harm." I would, and have, placed amalgam fillings in the teeth of my loved ones.

Trust the science, not the propaganda.

1/28/2007 02:57:00 AM  
Anonymous Anonymous said...

I am pleased that this website brings to light reasonable assurances that scientifically there is no link of MMR and Autism. My father and I are from immigrants that came to America from Germany. Both of us had families of fathers that did not spend time with children. From reading about aspargers syndrome, he and I are certain to have it in mild to severe form. No vaccine gave me asparger's. I was a supposed "Good baby" and left alone during early development. My vaccine shots came later when I already was odd to my school mates.
I'm certain that lack of early stimulation combined with generic factors are what caused my mild autism in the form of asparger's syndrome. Presently I am married and my family support me. Using the talent of being able to block out distractions and study technical data to a great degree, i am proudly a "A" student in a Masters of Science degree program.
I try to use Aspargers to enhance my life while my family constantly reminds me not to "float off in space" and forget I have a wife, a son, and loving daughter.

7/01/2007 06:52:00 AM  
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