Resource: multiple simultaneous vaccinations, immune compromise, and autism

Correction (6/12/2013): I originally referred to a vaccine containing multiple vaccinations as both “comcomitant” and “conjugate.” In fact, a “conjugate” vaccine is different; it is one where an antigen is attached to a protein from the same parent organism in an attempt to confer the immunological properties of the carrier protien to the antigen. This is not at all what is being assessed in the articles below, which are focused on concomitant vaccines – the intent of this post.

There was a decent review of the advances in understanding autism and its causes printed in the New York Times [1]. I thought it would be useful to remind folks that this is scientific evidence for a real set of causes (linked to the immune response of the mother during development of the fetus). In contrast, there is no consistent supporting scientific evidence for the long-discredited “vaccine hypothesis,” which holds that vaccination is the cause of autism.

One of the claims used to argue against childhood vaccination is that some of the vaccines are introduced using a single dose containing multiple vaccines (a concomitant vaccination). The claim goes on to state that the baby’s immune system, overwhelmed by the multiple diseases it must suddenly learn about, causes autism to then occur. However, this claim has been scientifically discredited because the underlying explanatory mechanisms do not hold water and because in a specific case, MMR, no evidence has been found in multiple independent peer-reviewed studies for a vaccine-autism link.

Here are resources to help understand why this is not considered a legitimate scientific claim.

Note: journals are uptight about paid access to research, a practice with which I STRONGLY disagree. If you need any of these articles, please comment below (use your real email address when entering your comment) and I will try o make copies of the articles available in a private way. Some of these articles do not have electronic versions, so you’ll have to make a trip to your local university library or town library and see if you can get a copy from inter-library loan or through their journal subscription (typical of university libraries). If you care about this subject, you won’t see this as a barrier.

• Overview article, published in Clinical Infectious Diseases, an international peer-reviewed journal on infectious diseases. This is merely a review article, which itself cites the key studies that disconfirm the conjugate vaccine/autism hypothesis (http://www.oxfordjournals.org/our_journals/cid/about.html): “Vaccines and Autism: A Tale of Shifting Hypotheses.” Gerber, J. and Offit, P. (section editor: Plotkin, S.). Clin Infect Dis.(2009) 48 (4): 456-461. doi: 10.1086/596476. http://cid.oxfordjournals.org/content/48/4/456.full
• 13 publications showing no link between the MMR conjugate vaccine and autism. Ten of these were conducted by independent authors. The studies span populations in North America and Europe. This is perhaps the strongest collection of evidence dis-confirming that conjugate vaccination causes autism, independent of any other studies, since no causation or correlation is detected at all, independent of the causal mechanisms hypothesized below. All of these were published in various peer-reviewed scientific journals.
  • Taylor B, Miller E, Farrington CP, et al. Autism and measles, mumps, and rubella vaccine: no epidemiological evidence for a causal association. Lancet 1999; 353:2026–9.
  • Farrington CP, Miller E, Taylor B. MMR and autism: further evidence against a causal association. Vaccine 2001; 19:3632–5.
  • Kaye JA, del Mar Melero-Montes M, Jick H. Mumps, measles, and rubella vaccine and the incidence of autism recorded by general practitioners: a time trend analysis. BMJ 2001; 322:460–3.
  • Dales L, Hammer SJ, Smith NJ. Time trends in autism and in MMR immunization coverage in California. JAMA 2001; 285:1183–5.
  • Fombonne E, Zakarian R, Bennett A, Meng L, McLean-Heywood D. Pervasive developmental disorders in Montreal, Quebec, Canada: prevalence and links with immunizations. Pediatrics 2006; 118:e139–50.
  • Fombonne E, Chakrabarti S. No evidence for a new variant of measles-mumps-rubella–induced autism. Pediatrics 2001; 108:e58.
  • Taylor B,Miller E, LingamR, Andrews N, Simmons A, Stowe J.Measles, mumps, and rubella vaccination and bowel problems or developmental regression in children with autism: population study. BMJ 2002;324: 393–6.
  • DeWilde S, Carey IM, Richards N, Hilton SR, Cook DG. Do children who become autistic consult more often after MMR vaccination? Br J Gen Pract 2001; 51:226–7.
  • Makela A, Nuorti JP, Peltola H. Neurologic disorders after measles-mumps-rubella vaccination. Pediatrics 2002; 110:957–63.
  • Madsen KM, Hviid A, Vestergaard M, et al. A population-based study of measles, mumps, and rubella vaccination and autism. N Engl J Med 2002; 347:1477–82.
  • DeStefano F, Bhasin TK, Thompson WW, Yeargin-Allsopp M, Boyle C. Age at first measles-mumps-rubella vaccination in children with autism and school-matched control subjects: a population-based study
    in metropolitan Atlanta. Pediatrics 2004; 113:259–66.
  • Peltola H, Patja A, Leinikki P, Valle M, Davidkin I, Paunio M. No evidence for measles, mumps, and rubella vaccine–associated inflammatory bowel disease or autism in a 14-year prospective study. Lancet
    1998; 351:1327–8.
  • Patja A, Davidkin I, Kurki T, Kallio MJ, Valle M, Peltola H. Serious adverse events after measles-mumps-rubella vaccination during a fourteen-year prospective follow-up. Pediatr Infect Dis J 2000; 19:1127–34.
• A theoretical exercise, based on data about the infant immune system, suggests that an infant immune response can handle thousands of infections at once before becoming “overwhelmed.” Published in “Pediatrics,” a major peer-reviewed journal (http://pediatrics.aappublications.org/site/misc/about.xhtml) and the official journal of the American Academy of Pediatrics. Offit PA, Quarles J, Gerber MA, et al. Addressing parents’ concerns: do multiple vaccines overwhelm or weaken the infant’s immune system? Pediatrics 2002; 109:124–9.
• A data-based study of multiple vaccinations, which agrees with the theoretical predictions made above in terms of immune response. The finding is that simultaneous multiple vaccines trigger an immune response similar to the introduction of a single vaccine. This paper was published in the Pediatric Infectious Disease Journal, a European publication and a peer-reviewed journal (http://edmgr.ovid.com/pidj/accounts/ifauth.htm)  King GE, Hadler SC. Simultaneous administration of childhood vaccines: an important public health policy that is safe and efficacious. Pediatr Infect Dis J 1994; 13:394–407. http://journals.lww.com/pidj/Citation/1994/05000/Simultaneous_administration_of_childhood_vaccines_.12.aspx
• A study of the natural level of exposure of urban American children to infectious disease finds that an average child is exposed to 4-6 diseases per year. The sample under study was a group of 86 Cleveland families (443 individuals)  in middle- and upper-level socio-economic groups. This study helps us to understand whether a vaccine containing 3-5 biological samples needed to train an immune response is atypical.  Dingle JH, Badger GF, Jordan WS Jr. Illness in the home: a study of 25,000 illnesses in a group of Cleveland families. Cleveland: Press of Western Reserve University, 1964. http://www.cabdirect.org/abstracts/19652703477.html;jsessionid=330136A8E5AF79032A96E065282DE773?freeview=true
• A related hypothesis is that multiple vaccinations weaken the immune system. Three studies suggest that there is no difference in the immune response of a vaccinated and un-vaccinated child (within some time period after administration of the vaccine). Here are the resources:
  • This article was published in the American Journal of Diseases of Children 1991.  (this journal changed its name in 1993 to “Archives of Pediatrics & Adolescent Medicine,” http://www.worldcat.org/title/american-journal-of-diseases-of-children/oclc/1480134). It is a journal of the American Medical Association, and uses peer-review. Black SB, Cherry JD, Shinefield HR, Fireman B, Christenson P, Lampert D. Apparent decreased risk of invasive bacterial disease after heterologous childhood immunization. Am J Dis Child 1991; 145:746–9. http://archpedi.jamanetwork.com/article.aspx?articleid=515725
  • This study looked at the rates of certain bacterial infections in a control group (prior to immunization) of about 100 people and in a post-vaccination group (also of about 100 people). No evidence was found for a weakening of immune response after application of the DTP combined vaccination. This was published in the same year as the previous article by independent researchers using a different population and technique, in the same peer-reviewed journal. This is independent confirmation of the null hypothesis (vaccines do not weaken immune response). Davidson M, Letson GW, Ward JI, et al. DTP immunization and susceptibility to infectious diseases: is there a relationship? Am J Dis Child 1991; 145:750–4. http://archpedi.jamanetwork.com/article.aspx?articleid=515726
  • This study in Sweden looked at an anomalous number of deaths in the ~year after they received pertussis vaccination. The study had no control group (e.g. unvaccinated children). The analysis of their immune responses showed nothing atypical, suggesting no immune compromise. The hypothesis that vaccination was the cause could not be ruled out, but also had no support from the data. This was published in the Pediatric Infectious Diseases Journal in 1988. This journal was mentioned above, and is a respected European peer-review journal. Storsaeter J, Olin P, Renemar B, et al. Mortality and morbidity from invasive bacterial infections during a clinical trial of acellular pertussis vaccines in Sweden. Pediatr Infect Dis J 1988; 7:637–45. http://ukpmc.ac.uk/abstract/MED/3050858/reload=0;jsessionid=tWDyMDPyTZkMwFtEcOYC.0

The authors of the overview article above note at the time of writing of their article that no study had yet been performed comparing autism rates in normally vaccinated (e.g. multiple simultaneous vaccinations), alternative vaccinations (a spread schedule), and non-vaccinated children. They attribute this to the difficulty in controlling factors in the three populations such as quality of health care, frequency of health care, and follow-up with the subjects of the study. For instance, undervaccinated children tend to be minority and poor; unvaccinated children tend to be caucasian and affluent. Controlling for these is extremely difficult, especially given the much stronger evidence that the mother’s immune response during pregancy appears to have a STRONG correlation with autism rates in children and that immune response depends on the mother’s environmental exposure to pathogens, etc. which vary with socio-economic status.

Here is a reference for a study of vaccination schedule and socio-economic status: Children Who Have Received No Vaccines: Who Are They and Where Do They Live? Philip J. Smith, Susan Y. Chu, and Lawrence E. Barker. Pediatrics 2004; 114:1 187-195; doi:10.1542/peds.114.1.187. http://pediatrics.aappublications.org/content/114/1/187.full

There are also not enough unvaccinated children in the U.S. to do such a study. In order to detect down to a ~few percent difference in autism rates between unvaccinated and vaccinated children, you need  several hundred THOUSAND children. This is because autism occurs in about 1 in 150 children. There are only a few tens of thousands of unvaccinated children in the U.S. Even a study that could control for the environmental factors would be statistically insignificant. With the sample available, if EVERY unvaccinated child could be studied, you’d only be able to detect a difference in rates as small at ~26% but not smaller. For some math, see Ref [2].

REMEMBER: one must keep in mind the following: in science, you don’t get to leap to the conclusion that “X causes Y” just because no one has yet been able to test whether or not X causes Y. A lack of knowledge is not knowledge at all. The weight of the evidence is strongly against the hypothesis that concomitant or conjugate vaccines cause autism (due to the proposed hypotheses of an overwhelmed immune system and/or a weakened immune system).

Also, just because someone hasn’t tried to test this, or hasn’t thought of a way to test this, does not mean it cannot be tested.

Autism is an emotionally stirring subject (as a scientist, even though I do not do medical research I am passionate about supporting researchers who DO search for real knowledge about such diseases). That means often the debate is laced with logical fallacies and charged language. If you truly care about the cause of autism, and where to spend your tax dollars or donations on research for this disorder, you need to consider the weight of the evidence. That weight is strongly against the vaccine hypothesis, while pointing instead to other factors. Regardless of how you feel about vaccines, you must consider the evidence against the vaccine-autism link when donating to organizations for research and lobbying. Otherwise, you are wasting precious money and doing a great disservice to all children with autism and families of children with autism.

Every dollar wasted on a discredited hypothesis is a dollar that could have been spent understanding, and maybe curing, this disorder.

[1] http://nyti.ms/U0bvU5

[2] http://photoninthedarkness.com/?p=154