Vaccine pseudo-controversy

1. Vaccine pseudo-controversy • Mark Crislip • 2010

2. Conflicts of Interest None I have been practicing Infectious Diseases in one form or another for 24 years.

3. shill • Am I a shill of the medical-industrial complex? • Nope. Although a common argument against the studies we will discuss is that they are funded by either big pharma or the government and both have a compelling financial reason to push vaccines.

4. Shill • It is true that funding source, in part, biases the outcomes. • But it is a subtle bias, it does not invalidate the results. • It is one of many factors to consider in evaluating clinical trials

5. JAMA. 2003 Aug 20;290(7):921-8. • Association of funding and conclusions in randomized drug trials: a reflection of treatment effect or adverse events? • CONTEXT: Previous studies indicate that industry-sponsored trials tend to draw proindustry conclusions. OBJECTIVE: To explore whether the association between funding and conclusions in randomized drug trials reflects treatment effects or adverse events. DESIGN: Observational study of 370 randomized drug trials included in meta-analyses from Cochrane reviews selected from the Cochrane Library, May 2001. From a random sample of 167 Cochrane reviews, 25 contained eligible meta-analyses (assessed a binary outcome; pooled at least 5 full-paper trials of which at least 1 reported adequate and 1 reported inadequate allocation concealment). The primary binary outcome from each meta-analysis was considered the primary outcome for all trials included in each meta-analysis. The association between funding and conclusions was analyzed by logistic regression with adjustment for treatment effect, adverse events, and additional confounding factors (methodological quality, control intervention, sample size, publication year, and place of publication). MAIN OUTCOME MEASURE: Conclusions in trials, classified into whether the experimental drug was recommended as the treatment of choice or not. RESULTS: The experimental drug was recommended as treatment of choice in 16% of trials funded by nonprofit organizations, 30% of trials not reporting funding, 35% of trials funded by both nonprofit and for-profit organizations, and 51% of trials funded by for-profit organizations (P<.001; chi2 test). Logistic regression analyses indicated that funding, treatment effect, and double blinding were the only significant predictors of conclusions. Adjusted analyses showed that trials funded by for-profit organizations were significantly more likely to recommend the experimental drug as treatment of choice (odds ratio, 5.3; 95% confidence interval, 2.0-14.4) compared with trials funded by nonprofit organizations. This association did not appear to reflect treatment effect or adverse events. CONCLUSIONS: Conclusions in trials funded by for-profit organizations may be more positive due to biased interpretation of trial results. Readers should carefully evaluate whether conclusions in randomized trials are supported by data. • PMID: 12928469

6. Age of Autism Generation Rescue

7. Growing rich Vaccinating? • Pediatrics. 2009 Dec;124 Suppl 5:S472-91. • Net financial gain or loss from vaccination in pediatric medical practice • OBJECTIVE: The goal was to determine the net return (gain or loss after costs were subtracted from revenues) to private pediatric medical practices from investing time and resources in vaccines and vaccination of their patients. METHODS: A cross-sectional survey of a convenience sample of private medical practices requested data on all financial and capacity aspects of the practices, including operating expenses; labor composition and wages/salaries; private- and public-purchase vaccine orders and inventories; Medicaid and private insurance reimbursements; patient population; numbers of providers; and numbers, types, and lengths of visits. Costs were assigned to vaccination visits and subtracted from reimbursements from public- and private-pay sources to determine net financial gains/losses from vaccination. RESULTS: Thirty-four practices responded to the survey. More than one half of the respondents broke even or suffered financial losses from vaccinating patients. With greater proportions of Medicaid-enrolled patients served, greater financial loss was noted. On average, private insurance vaccine administration reimbursements did not cover administration costs unless a child received > or = 3 doses of vaccine in 1 visit. Finally, wide ranges of per-dose prices paid and reimbursements received for vaccines indicated that some practices might be losing money in purchasing and delivering vaccines for private-pay patients if they pay high purchase prices but receive low reimbursements. CONCLUSIONS: We conclude that the vaccination portion of the business model for primary care pediatric practices that serve private-pay patients results in little or no profit from vaccine delivery. When losses from vaccinating publicly insured children are included, most practices lose money. • PMID: 19948579

8. Vaccines • Vaccines in my world are like clean water and fresh air? Who would be against them?

9. Vaccine

10. Vaccine

11. Vaccine

12. vaccines

13. Quite the hodegepodge • What good do they do? • Remember, the decreases in infectious diseases are multifactorial • Good nutrition, understanding of disease transmission, flush toilets, clean water, decreased crowding have all contributed to the decline in infections. • Tuberculosis has gone from 1 in 3 Europeans infected in the 1800’s to a rare disease today, all without a vaccine. • Often some antivaccers are binary in their approach: either the vaccines can be credited with all the results or nothing.

14. Quite the hodgepodge • Not only is the decrease in diseases multifactorial, the type and effects of the vaccines are variable. • there are live vaccines and killed vaccines • there are protein vaccines, carbohydrate (sugar) vaccines, and conjugate/adjuvant vaccines. • the goal of each vaccine is to prime the pump: giving the immune system prior exposure to part or all of a pathogen, so that when the host is exposed to the real deal, it can attack the infection immediately, rather than the delay it usually takes for the immune system to gear up to a new infection.

15. Those who do not remember the past are doomed to repeat it WHO Stats • Humans used to die in droves from infections and in the third world they still do.

16. What Good? JAMA, November 14, 2007—Vol 298, No. 18

17. What Good JAMA, November 14, 2007—Vol 298, No. 18

18. What good? • A greater than 92% decline in cases and a 99% or greater decline in deaths due to diseases prevented by vaccines recommended before 1980 were shown for diphtheria, mumps, pertussis, and tetanus. • Endemic transmission of poliovirus and measles and rubella viruses has been eliminated in the United States; smallpox has been eradicated worldwide. • Declines were 80% or greater for cases and deaths of most vaccine-preventable diseases targeted since 1980 including hepatitis A, acute hepatitis B, Hib, and varicella. • Declines in cases and deaths of invasive S pneumoniae were 34% and 25%, respectively. JAMA, November 14, 2007—Vol 298, No. 18

19. Who would object to Vaccines • As long as there have been vaccines, there have been those who are agin em. • Like all technologies, vaccines have been improved over time. So we are no longer injecting cowpox into incisions in an attempt to prevent small pox. • I am going to focus on the modern antivaccine movement. • Unlike them, I am constrained by the truth.

20. Vaccines contrversy • Since Jenner there have been objections to vaccines. • There is the philosophical/political viewpoint that institutions/governments should not and cannot mandate vaccines. • That is not a scientific question. The question is safety and efficacy, which are.

21. Vaccine controversy • Issue with vaccines vary with time and with society. • The French have worried about hepatitis B vaccine leading to the development of multiple sclerosis. • Nigerian Islamic clerics decided that the polio vaccine was actually a Western plot to sterilize people and spread HIV. • Consequently, polio was resurgent in Nigeria and spread to adjacent countries.

22. Polio • What happened in Nigeria was herd immunity declined as a result and there is a lot of HIV/immunodeficiency in Nigeria. • As a result, the live virus vaccine mutated (1% per year of its genome) and was able to perpetuate in the community. • Now the vaccine derived strain is circulating in Nigeria as well as wild type has caused almost 300 cases of paralytic polio. • Of the children with cVDPV in Nigeria, 40% had never been vaccinated; 87% were under-vaccinated (three or fewer doses).

23. Polio vaccine in perspective • In the past 10 years worldwide: • over 10 billion doses of OPV have been administered to more than 2 billion children; • 9 cVDPV outbreaks have occurred in 9 countries, in communities with low OPV coverage, resulting in under 200 polio cases; • during that period, more than 33,000 children were paralyzed by wild poliovirus while over 3.5 million polio cases were prevented by OPV. • cVDPVs in the past have been rapidly stopped with 2-3 rounds of high-quality immunization campaigns with OPV. 

24. The Big Three • Mercury and Autism • MMR and Autism • Too many too soon • Toxins in the vaccines • 5 out of 4 Americans do not understand math.

25. Autism • Autism spectrum is increasing as a diagnosis. • Why? Mostly due to expanded diagnostic criteria and increased awareness. • Do vaccines cause autism? Nope. But autism manifests around the time the vaccines start to be given. So there is an association, and association is not causation. • CDC: 25,000 heart attacks every week; 14,000 to 19,000 miscarriages every week; 300 severe allergic reactions called anaphylaxis every week. • Whenever large numbers of children are vaccinated, by random chance alone there will be a not insignificant number of instances of children regressing in reasonably close temporal proximity. Such a regression can appear all the world as though the vaccine caused it. • It is only on the population level, where no higher incidence of regression is observed with vaccination than without, where it is possible to see that apparent correlations between the timing of vaccination and timing of regression are in fact coincidences.

26. Autism • That is true of a lot of issues with vaccines: GBS and flu vaccine, anaphylaxis and HPV vaccine. • However, one good story is worth more than all the studies in all the journals; that’s human psychology. • The plural of anecdote is anecdotes not data.

27. Mercury and Vaccine • Mercury is a neurotoxin. • Elemental mercury. • Chlorine gas killed thousands in WW1, NaCl is table salt and is mostly harmless. • Mercury in vaccines was thimerosal, and was used as a preservative. • It was removed from most vaccines since about 2000

28. Hg • HOW MUCH MERCURY IS IN 6 OUNCES OF CHUNK WHITE TUNA? • MERCURY INGESTED = 8959 micrograms of methyl mercury • Before the reductions, the maximum cumulative exposure to mercury via routine childhood vaccinations during the first six months of life could have been 187.5 micrograms of ethyl mercury. • ethyl is not methyl

29. Thimerosal and Autism • Infants and toddlers in the United States were exposed to more of the ethylmercury-containing preservative, thimerosal, after recommendations in 1991 for universal administration of the hepatitis B virus and Hib vaccines. • They have been exposed to less thimerosal since at least the national recommendation in 1999 for its removal from childhood vaccines. • If thimerosal exposure is a primary cause of autism, then the prevalence of autism would be predicted to decrease as young children's exposure to thimerosal has sharply decreased to its lowest levels in decades.

30. The DDS data do not show any recent decrease in autism in California despite the exclusion of more than trace levels of thimerosal from nearly all childhood vaccines. The DDS data do not support the hypothesis that exposure to thimerosal during childhood is a primary cause of autism.

31. mercury and Autism • of course, that was an after the fact study. • the are at least 10 other epidemiological studies that have looked for a relationship between the thimerosal and autism. • None found. • Hg was been found to be a mostly non-starter and is starting to be supplanted by aluminum, an adjuvant in a few vaccines. Adjuvants are chemicals that make vaccines more effective. • There is much less aluminum and it is in only a few vaccines.

32. Hg downside • there are numerous labs that will measure hg and al in the urine and hair and these are used to guide chelation therapy, a bogus use of intravenous and sometimes even more bogus oral therapies that 'bind' the toxins so they are excreted. • a potentially dangerous treatment that does not work.

33. Death • Clin Toxicol (Phila). 2008 Dec;46(10):1083-4. • Pediatric fatality secondary to EDTA chelation. • BACKGROUND: Chelation therapy has emerged as a popular treatment modality to remove heavy metals that are thought to cause autism. We report a fatality that occurred as a consequence of chelation therapy for autism when the incorrect form of EDTA was administered. CASE REPORT: A five-year-old autistic male was being chelated in a physician's office. While receiving his third treatment he went into cardiac arrest. It was not determined until after the child's death that he had been given edetate disodium rather than edetate calcium disodium, causing profound hypocalcemia and triggering the cardiac events that led to his death. DISCUSSION: In 1991, the CDC recommended using only edetate calcium disodium, not edetate disodium, to children because edetate disodium may induce tetany and possible hypocalcemia as illustrated in this case. • CONCLUSION: The use of chelation therapy in autistic children has not been validated and can have tragic consequences. • PMID: 18949650 [PubMed - indexed for MEDLINE]

34. MMR and autism • in 1998 the Lancet published: Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children by Dr. Andrew Wakefield. • the study was a fairly minor molehill. • he had 12 kids with autism and he did extensive evaluations including colonoscopy and lumbar punctures and found • "We have identified a chronic enterocolitis in children that may be related to neuropsychiatric dysfunction. In most cases, onset of symptoms was after measles, mumps, and rubella immunization. Further investigations are needed to examine this syndrome and its possible relation to this vaccine."

35. mar and autism • the paper was circumspect: • We did not prove an association between measles, mumps, and rubella vaccine and the syndrome described. Virological studies are underway that may help to resolve this issue. • If there is a causal link between measles, mumps, and rubella vaccine and this syndrome, a rising incidence might be anticipated after the introduction of this vaccine in the UK in 1988. Published evidence is inadequate to show whether there is a change in incidence or a link with measles, mumps, and rubella vaccine.

36. Dr. Wakefield was less circumspect in public. He said the vaccines caused autism and that rather than one MMR kids should get three separate shots. • a conclusion not supported by the paper in any way

37. what was discovered later • two years before the paper he was hired by a lawyer to perform research to prove a link between autism and vaccines. almost 500,000 pounds. Never mentioned it to the lancet. • he received a patent for a single dose measles vaccine 9 mnths before the press conference calling for and end to the mar. • they then looked back at the records of the children and found that he altered the histories to support his contention. ie he lied. • because he lied and was unethical, the paper was retracted and his license to practice in England was yanked.

38. oddly enough • despite the fraud unearthed against Dr Wakefield, he is considered a hero in part of the autism world • "believe that the public lynching and shaming of Dr. Wakefield is unwarranted and overwrought, and that history will ultimately judge who was right and who was wrong about proposing a possible association between vaccination and regressive autistic spectrum disorder (ASD)." • David Kirby on the Huffington Post

39. and no one can confirm the results • There were several studies that asked the same questions and got answers that contradicted Wakfield's findings. • They found that bowel disease was not more common in autistics, that the alleged ilial-lymphonodular hyperplasia biopsy findings were not characteristic of autistics, • that MMR and autism were not correlated, and • that measles RNA was not detectable in autistics at a higher rate than in non-autistic children.

40. Lack of Association between Measles Virus Vaccine and Autism with Enteropathy: A Case-Control Study • The objective of this case-control study was to determine whether children with GI disturbances and autism are more likely than children with GI disturbances alone to have MV RNA and/or inflammation in bowel tissues and if autism and/or GI episode onset relate temporally to receipt of MMR. The sample was an age-matched group of US children undergoing clinically-indicated ileocolonoscopy. Ileal and cecal tissues from 25 children with autism and GI disturbances and 13 children with GI disturbances alone (controls) were evaluated by real-time reverse transcription (RT)-PCR for presence of MV RNA in three laboratories blinded to diagnosis, including one wherein the original findings suggesting a link between MV and ASD were reported. The temporal order of onset of GI episodes and autism relative to timing of MMR administration was examined. We found no differences between case and control groups in the presence of MV RNA in ileum and cecum. Results were consistent across the three laboratory sites. GI symptom and autism onset were unrelated to MMR timing. Eighty-eight percent of ASD cases had behavioral regression. • Conclusions/Significance • This study provides strong evidence against association of autism with persistent MV RNA in the GI tract or MMR exposure. Autism with GI disturbances is associated with elevated rates of regression in language or other skills and may represent an endophenotype distinct from other ASD.

41. most recent • Pediatr Infect Dis J. 2010 May;29(5):397-400. • Lack of association between measles-mumps-rubella vaccination and autism in children: a case-control study • Abstract • OBJECTIVE: The first objective of the study was to determine whether there is a relationship between the measles-mumps-rubella (MMR) vaccination and autism in children. The second objective was to examine whether the risk of autism differs between use of MMR and the single measles vaccine. DESIGN: Case-control study. STUDY POPULATION: The 96 cases with childhood or atypical autism, aged 2 to 15, were included into the study group. Controls consisted of 192 children individually matched to cases by year of birth, sex, and general practitioners. METHODS: Data on autism diagnosis and vaccination history were from physicians. Data on the other probable autism risk factors were collected from mothers. Logistic conditional regression was used to assess the risk of autism resulting from vaccination. Assessment was made for children vaccinated (1) Before diagnosis of autism, and (2) Before first symptoms of autism onset. Odds ratios were adjusted to mother's age, medication during pregnancy, gestation time, perinatal injury and Apgar score. RESULTS: For children vaccinated before diagnosis, autism risk was lower in children vaccinated with MMR than in the nonvaccinated (OR: 0.17, 95% CI: 0.06-0.52) as well as to vaccinated with single measles vaccine (OR: 0.44, 95% CI: 0.22-0.91). The risk for vaccinated versus nonvaccinated (independent of vaccine type) was 0.28 (95% CI: 0.10-0.76). The risk connected with being vaccinated before onset of first symptoms was significantly lower only for MMR versus single vaccine (OR: 0.47, 95% CI: 0.22-0.99). CONCLUSIONS: The study provides evidence against the association of autism with either MMR or a single measles vaccine.

42. consequences • England went from 95 to 80% vaccinated and measles and mumps took off • several thousand cases and 'only' one death. • measles is coming under control in the UK, but there are still more cases than the have been for 30 years.

43. consequences • the second M is for mumps. England has had over 7500 cases of mumps • there is an outbreak of mumps currently on the east coast that was traced to an unvaccinated child who went to England and brought it home • there have now been over 1500 cases of mumps, most spread in a religious community that doesn't vaccinate, but there has been spread into the local vaccinated community.

44. US • you need clusters of non immune people for infections to perpetuate. • it varies depending on the organism, but once immunity falls below about 95% many vaccine preventable diseases can spread. • Jackson county Oregon has a 15% unvaccinated rate and it is estimated that 25% of children in Ashland are not completely vaccinated. • Ashland (with a vaccine refusal rate of 25%) had 1.1% of their students with educational diagnoses of autism, the highest in Jackson County and higher than the Statewide average. • Do not inhale at the Shakespearian festival. • In the US most unvaccinated are clustered in private schools.

45. too many too soon • OK. Its not Hg or Al or the MMR. It is too many vaccines too close together. • 5 live attenuated or altered organisms and 21 different antigens by age 6. A couple of vaccines are added from age 7 to 18, but by then it is too late. • Maybe it would be easier on the child to give fewer vaccines, less often. And so there are alternative schedules, the most popular, perhaps, by Dr Bob Sears.

46. Ick • As a comparison, there are 10-100 times more bacteria in and on you than there are cells of you. • 100 billion bacteria representing several thousand species, most acquired in the first year of life and kept at bay by an immune response. • I also once counted a total 1374 potential pathogens we can be exposed to in life, counting Salmonella once. • The vaccine schedule is 5 live attenuated or altered organisms and 21 different antigens by age 6.

47. Not that many not that fast • Estimates of antibody specificities in an individual range between 1,000,000-100,000,000 (2). We have the ability to make 10 billion antibodies and, due to exposure to various germs and other foreign materials, we make between 1 million and 100 million different antibodies. • Lets say as an argument that you have most of your antigen exposure is by age 18. To get 1,000,000 antibodies, you must make 152 antibodies day. I cannot find how many antigens the average human has made by age 18, but one antibody a day would result in 2160 antibodies by age 6 or 6570 antibodies by age 18. We are exposed to far more antigens in the world than 6570. • If a child is exposed to 1 antigen a day and makes one antibody a day, a very conservative estimate, then the vaccines represent about 0.694 % (15/2160)x100 of the antigen exposure of a six year old. • If a child makes 152 antibodies a day, still a conservative estimate, then by age 6 the vaccine exposure would account for .004% of the antigen exposure of the child. • If a child is aiming for 100 million antibodies, the rough maximum, then to reach that number by age 18, then they have to be exposed to 15,520 antigens a day and made 15,520 new antibodies a day. By age 6 thats a total of 3,333,333 new antigenic exposures, and the vaccine schedule would account for 0.00045% of exposure.

48. too many too soon • The schedule looks like a lot of vaccines, but bear in mind it also represents the infection schedule. • does the alternative schedule prevent autism? No. • Not quite answering the question was a study in Pediatrics, • On-time Vaccine Receipt in the First Year Does Not Adversely Affect Neuropsychological Outcomes

49. too many too soon • Objectives: To determine whether children who received recommended vaccines on time during the first year of life had different neuropsychological outcomes at 7 to 10 years of age as compared with children with delayed receipt or nonreceipt of these vaccines. Methods: Publicly available data, including age at vaccination, from a previous VaccineSafety Datalink study of thimerosal exposure and 42 neuropsychological outcomes were analyzed. Vaccine receipt was defined as timely when each vaccine was received within 30 days of the recommended age. Associations between timeliness and each outcome were tested in univariate analyses. Multivariable regression models were constructed for further assessment of the impact of timeliness on neuropsychological outcomes after adjustment for potential confounders. Secondary analyses were performed on a subset of children with the highest and lowest vaccine exposures during the first 7 months of life. Results: Timely vaccination was associated with better performance on 12 outcomes in univariate testing and remained associated with better performance for 2 outcomes in multivariable analyses. No statistically significant differences favored delayed receipt. In secondary analyses, children with the greatest vaccine exposure during the first 7 months of life performed better than children with the least vaccine exposure on 15 outcomes in univariate testing; these differences did not persist in multivariable analyses. No statistically significant differences favored the less vaccinated children. Conclusions: Timely vaccination during infancy has no adverse effect on neuropsychological outcomes 7 to 10 years later. These data may reassure parents who are concerned that children receive too many vaccines too soon.

50. too many too soon • the only thing delay in vaccination does is increase the time the child is vulnerable to infections. • But the vaccines are not safe, they are filled with toxins. • "I do believe sadly it's going to take some diseases coming back to realize that we need to change and develop vaccines that are safe. If the vaccine companies are not listening to us, it's their f___ing fault that the diseases are coming back. They're making a product that's s___. If you give us a safe vaccine, we'll use it. It shouldn't be polio versus autism."