American Family Physician, the journal of the American Academy of Family Physicians, has a feature called AFP Journal Club, where physicians analyze a journal article that either involves a hot topic affecting family physicians or busts a commonly held medical myth. In the September 15, 2010 issue they discussed “Vaccines and autism: a tale of shifting hypotheses,” by Gerber and Offit, published in Clinical Infectious Diseasesin 2009.
The article presented convincing evidence to debunk 3 myths:
- MMR causes autism.
- Thimerosal (mercury) causes autism.
- Simultaneous administration of multiple vaccines overwhelms and weakens the immune system, triggering autism in a susceptible host.
Gerber and Offit reviewed 13 large-scale studies that demonstrated no association between the MMR vaccine and autism. These included ecologic studies, retrospective observational studies and prospective observational studies. The findings were consistent; the only outlier in all the studies of MMR was Dr. Andrew Wakefield’s small, discredited 1998 study, which was fully retracted by The Lancet in early 2010.
They reviewed 7 large-scale studies (again, ecologic, retrospective, and prospective) that consistently demonstrated no association between thimerosal and autism. They showed that the hypothesis was not biologically plausible, since the symptoms of mercury poisoning are distinct from those of autism and are not produced by the thimerosal in vaccines.
They showed that the overload hypothesis is not credible because
- The immunologic load has dropped from 3000 components in the 7 vaccines used in 1980 to less than 200 in the 14 vaccines recommended today.
- An infant’s immune system is capable of handling the thousands of antigens it is exposed to early in life.
- Vaccinated children are not more susceptible to infections.
- Autism is not an autoimmune disease.
Not that this will settle anything, because science fact is not decided by arguments from popularity, but I think it is important to point this out. Many in the anti-vaccine community appeal to a “mommy knows best” argument, in which they will tell a very emotional story about how a mother saw their child fade away right after getting a vaccine. McCarthy herself has told her son’s story many times, telling us how she, to paraphrase, saw his soul fade away right after the vaccine. The implication is that mothers of autistic children know that their children’s autism is caused by vaccines.
Nevertheless, surveys do not support this notion. A survey of 62 families of autistic children found out that only 29% of parents of autistic children blame vaccines for their children’s autism (page 6). So if mothers know best, it appears McCarthy is in the minority within the community of parents of autistic children. It appears, at least from this survey, that about 70% of parents of autistic children do not blame vaccines for their children’s autism. So if the results of this survey hold, and can be extrapolated out to the entire population of parents of autistic children, which is quite a stretch to be honest, it would appear that for every mommy instinct blaming vaccines, there are two mommy instinct not blaming vaccines.
So what does this mean for the vaccines-autism “controversy”. Absolutely nothing; the correlation, or lack there of, between vaccines and autism is a scientific issue, not a popularity contest. The fact is what it is, regardless of what parents think, and I’m willing to say that even when parental opinion is on my side. Is Jenny McCarthy, and all the rest in the anti-vaccine community, willing to do the same? The answer to that question would shed so much light on their ability, and willingness, to find out the truth.
It is reasonable to ask how new vaccines are tested before they are cleared for public use. The National Institute of Allergy and Infectious Diseases explains the various studies that must be done before the new vaccine is approved by the FDA. There are various stages of testing a vaccine must undergo before it is cleared for use. They are as follows.
1) Animal Testing – Firstly, the new vaccine is tested in animals for safety and immunogenicity, meaning that is must be safe and induce enough of an immune response to justify moving on with human trials.
2) Phase I Study – After a promising animal test, the process moves to what is referred to as clinical trials, meaning testing in human subjects. The first step in this process is a Phase I study, which is the first setting in which an experimental vaccine is given to people. The trial, which can last up to 2 years, may enroll between 20 to 100 volunteers. A Phase I study primarily seeks information on safety, particularly looking for any vaccine-related side effects. The study can also provide data on the dose and administration schedule needed to achieve the optimal immune responses.
3) Phase II Study – Once Phase I studies show the experimental vaccine is safe, well tolerated, and appears promising, it can advance into Phase II. These studies, which can last longer than 2 years, enroll between 100 to 300 volunteers. In these studies researchers gather more data on safety and immunogenicity. These studies also test the effects of varying the doses, and are also referred to as dose-ranging studies.
4) Phase III Study – The most promising vaccine candidates move into Phase III, enrolling 10,000 or more people. A Phase III study, which can last up to 4 years, is typically designed to ensure enough data are collected on safety and effectiveness to support a license application to FDA.
An intermediary study, called a Phase IIb study is being considered, as a middle step between the Phase II and the Phase III studies. This study would enroll between 2,000 and 9,000 volunteers. It appears, as of the time of writing, that Phase IIb studies are not a requirement like the others.
Besides the required tests, the FDA may require additional testing and data at any point. Furthermore, the proposed manufacturing facility undergoes a pre-approval inspection during which production of the vaccine as it is in progress is examined in detail. Vaccine approval also requires the provision of adequate product labeling to allow health care providers to understand the vaccine’s proper use, including its potential benefits and risks, to communicate with patients and parents, and to safely deliver the vaccine to the public.
Until a vaccine is given to the general population, all potential adverse events cannot be anticipated. Thus, many vaccines undergo Phase 4 studies-formal studies on a vaccine once it is on the market. Also, the government relies on the Vaccine Adverse Event Reporting System (VAERS) to identify problems after marketing begins. The VAERS system and how it works is discussed further on this website.
NEW YORK — A new government study adds to the evidence that thimerosal, a mercury-based preservative until recently found in many vaccines, does not increase children’s risk of autism.
It shows kids who had been exposed as babies to high levels of the preservative — through vaccines they received or their mothers received while pregnant — were no more likely to develop autism, including two distinct subtypes of the condition.
“This study should reassure parents about following the recommended immunization schedule,” said Dr. Frank Destefano, director of the Immunization Safety Office at the Centers for Disease Control and Prevention (CDC) in Atlanta, and the study’s senior author.
Concerns about a link between vaccines and autism were first raised more than a decade ago by British physician Andrew Wakefield.
His report, based on 12 children, has since been discredited and was retracted earlier this year by the journal that published it. In the meantime, it sparked a fierce worldwide debate among scientists and a health scare that caused many parents to shy away from recommended vaccines like the one against measles, mumps and rubella.
Outbreaks of all three diseases followed.
One widespread worry has been that thimerosal might play a role in the development of autism, a condition that affects as many as one in 110 U.S. children, according to the CDC.
Most scientists consider autism a developmental disorder, likely influenced by genes.
Autism spectrum disorders range from mild Asperger’s Syndrome to severe mental retardation and social disability, and there is no cure or good treatment.
The CDC researchers used data for U.S. children born between 1994 and 1999, who were enrolled in one of three managed care organizations.
They found 256 children with an autism spectrum disorder and compared them with 752 children who did not have the condition, but were matched for age and sex.
No matter when a child had been exposed to thimerosal — before birth when the mother had a shot, or when the child itself was vaccinated as a baby or toddler — there was no increase in the risk of any type of autism spectrum disorder.
WASHINGTON — A federal appeals court on Friday upheld a ruling that vaccines are not to blame for autism.
The U.S. Court of Appeals for the Federal Circuit upheld a decision last year by a special vaccine court, which concluded there’s little if any evidence to support claims of a vaccine-autism link.
Scientist years ago reached that conclusion, but more than 5,500 families sought compensation through the government’s Vaccine Injury Compensation Program.
Friday’s ruling came in the case of Michelle Cedillo of Yuma, Ariz., who is disabled with autism, inflammatory bowel disease and other disorders that her parents blame on a measles vaccine given at 15 months.
The question of safety is the main vaccine concern. Are vaccines safe? If I vaccinate my child, will that have negative effects for their health? Of course, these questions are extremely broad to be answered all at once. Thus I will be breaking the answers in little bits. Today we will look at the MMR (Measles, Mumps & Rubella) vaccine and autism. Is the MMR vaccine correlated with autism? A quick PubMed search found this study from the June 12, 1999 Lancet (the same journal that originally published and recently retracted the Wakefield study that is widely credited with starting the MMR/vaccine hysteria):
Taylor B, Miller E, Farrington CP, Petropoulos MC, Favot-Mayaud I, Li J, Waight PA.
Department of Community Child Health, Royal Free and University College Medical School, University College London, UK
Study Summary: The authors looked at data about autism diagnoses since 1979 and data about MMR vaccinations, which started in 1988 in the UK, to try to see if there is any increase in autism diagnoses in or around the time when the MMR vaccine was introduced. They found that autism rates were steadily increasing every year and no “step-up” in autism diagnoses occurred when the vaccine was introduced, thus lending credibility to the conclusion that MMR does not seem to increase autism rates.
There was a steady increase in cases by year of birth with no sudden “step-up” or change in the trend line after the introduction of MMR vaccination. There was no difference in age at diagnosis between the cases vaccinated before or after 18 months of age and those never vaccinated. There was no temporal association between onset of autism within 1 or 2 years after vaccination with MMR (relative incidence compared with control period 0.94 [95% CI 0.60-1.47] and 1.09 [0.79-1.52]). Developmental regression was not clustered in the months after vaccination (relative incidence within 2 months and 4 months after MMR vaccination 0.92 [0.38-2.21] and 1.00 [0.52-1.95]). No significant temporal clustering for age at onset of parental concern was seen for cases of core autism or atypical autism with the exception of a single interval within 6 months of MMR vaccination. This appeared to be an artifact related to the difficulty of defining precisely the onset of symptoms in this disorder. INTERPRETATION: Our analyses do not support a causal association between MMR vaccine and autism. If such an association occurs, it is so rare that it could not be identified in this large regional sample.
Now, let us keep in mind that, one study never proves anything. At best one study points to a possible direction, no matter how well done, and how rock solid that one study may appear. What matters is the literature as a whole; what do all the studies done on the topic suggest. As such, given that this is the first study about vaccines & autism we’ve reviewed here, let us not interpret this as proof that the MMR vaccine is not correlated to autism. Only when we have found more studies, and only when all the studies appear to reach the same conclusion can we say with any level of certainty that it appears highly unlikely that the MMR vaccines causes an increase in autism levels.
May 3, 2010 — Researchers have discovered two new genes that may be involved with autism, the brain disorder marked by difficulty in communicating and relating to others.
The evidence for one of the two new “susceptibility genes” is stronger than that for the other, says Daniel Notterman, MD, the senior author of the study and a professor of pediatrics, biochemistry, and molecular biology at Penn State College of Medicine in Hershey.
One of the newly discovered gene mutations is in NCAM2 and the other is in PTPRD.
“We are more confident about NCAM2 and less about PTPRD,” Notterman tells WebMD.
The researchers announced the discovery Sunday at the Pediatric Academic Societies annual meeting in Vancouver, British Columbia.
Autism or autism spectrum disorder, involving less severe forms of the condition, affect one in 110 U.S. children, according to estimates from the CDC.
The new finding, Notterman says, adds to the growing evidence for genetic links for autism but doesn’t rule out a role for environmental factors. “Over the last couple of years, beginning in 2007, it’s become clear that some cases of autism, maybe up to 15%, will be caused by rare mutations, either occurring spontaneously or that can be inherited by a parent,” he says.
Tracking the Autism Genes
Notterman and his colleagues analyzed data from the Autism Genetic Resource Exchange (AGRE), a collaborative gene bank for autism, on 943 families, most of whom had more than one child diagnosed with autism. In all, they evaluated 3,742 family members.
They compared these with genetic data from 6,317 people without developmental or neuropsychiatric conditions.
Comparing genetic information on those affected with autism and those not, Notterman says, ”gave us a starting list of about 25 genetic mutations” found more commonly in those with autism.
Next, the researchers looked at whether the 25 were substantially different in the two groups, and in the process narrowed the list of suspect genes to four.
Two of the four had already been identified by researchers as linked with autism. The other two were new. “No one had shown this [link] statistically,” Notterman says.