Vaccine critics have often demanded “vax-unvax” studies comparing health outcomes fully-vaccinated and never-vaccinated children. The CDC and orthodox medicine generally refuse to conduct or fund such research. They give irrational and unscientific reasons for refusing to look at health outcomes of children that have never received vaccines.

Vaccine promoters sometimes allege that vax-unvax studies have been performed, with results supporting vaccine safety claims. In this article, I review the alleged vax-unvax studies cited by vaccine promoters.

I define a “vax-unvax” study with these criteria:

1) includes a never-vaccinated control group. This control group has never received any vaccines.

2) includes a fully-vaccinated exposed group. This group must receive all or nearly all the vaccines in the CDC schedule.

3) measures long-term health outcomes, especially neurological and immune-related outcomes, such as autism, mental illnesses, learning disabilities, allergies, autoimmune disorders and the like. Follow-up period should be at least a couple years, because it takes this long for these health conditions to appear.

4) has enough subjects (i.e. has sufficient statistical power) to detect adverse outcomes at about the 1-2% level. This will require a few hundred subjects per group.

Randomization is not required. But of course randomization is preferred. Randomization requires withholding vaccines from the control group.

Vaccine promoters use 2 arguments to justify the refusal to study the never-vaccinated:

1) randomization is unethical, because vaccines would need to be withheld from some subjects. Vaccines are so wonderful that it would be unethical to withhold them, even temporarily.

2) observational studies are useless because of selection bias. The unvaccinated differ in many ways from those that choose to be vaccinated, rendering the results meaningless.

Concerning #1, I believe it is unethical to not perform randomized studies of the vaccine schedule. Vaccines do not need to be permanently withheld from subjects to have a randomized trial. They only need to be delayed by a few months, or perhaps a year (such a study will not be able to detect adverse effects occurring later). A recent study of the DTP vaccine and infant mortality had such a “delayed vaccination” design: http://vaccinepapers.org/high-mortality-dtp-vaccine/

Concerning #2, This argument is particularly hypocritical, because almost all studies of vaccine safety are observational and therefore vulnerable to selection bias (and other biases). Observational studies are done all the time, despite the selection bias problem. Concern about selection bias, while valid, is not a reason to not do research. All the MMR-autism studies are observational and have selection bias, for example. All 3 studies reviewed below are observational. Lots of useful research is affected by selection bias on some level. What matters is whether the research is designed to minimize, understand and control for the selection bias.

The first true vax-unvax study is Mawson 2017. This study used an anonymous survey and included hundreds of never-vaccinated subjects. The never-vaccinated subjects had dramatically lower rates of neurological and immune disorders. However, the researchers did not have access to medical records. This is a substantial weakness. However, it is unique and valuable because it is the first vax-unvax study. Read about it here: http://info.cmsri.org/the-driven-researcher-blog/vaccinated-vs.-unvaccinated-guess-who-is-sicker

Vaccine promoters also argue that vax-unvax studies have already been done, with results supporting the safety of the vaccine schedule. The “thoughtscapism” blog has perhaps the most-cited article on this topic. https://thoughtscapism.com/2015/04/10/myth-no-studies-compare-the-health-of-unvaccinated-and-vaccinated-people/

The thoughtscapism article provides this list of 5 alleged vax-unvax studies:



Above: List of alleged “vax-unvax” studies cited by vaccine promoters. Studies 4-5 are not vax-unvax studies (as defined here) because they only looked at the flu vaccine. Studies 1-3 are considered here.

Studies 4 and 5 are clearly not relevant because they are limited to the flu vaccine. The flu vaccine study results are almost certainly explained by healthy user bias: http://vaccinepapers.org/healthy-user-bias-why-most-vaccine-safety-studies-are-wrong/

Studies 1-3 are relevant, because they consider multiple vaccines. Lets look at studies 1-3 in detail.

1) Germany 2011. (Schmitz et al) Full paper: Vaccination Status and Health in Children and Adolescents

This is the well-known “KIGGS” study, which is a German acronym for “German Health Interview and Examination Survey for Children and Adolescents.” It is widely cited by vaccine promoters.

Study Characteristics:

Zero-vaccine group size: 94 total, comprising 50 age 6-17 and 44 age 1-5.

Vaccinated group size: 13,359

Group definitions:

———- unvaccinated: Zero vaccines.

———-“vaccinated”: At least one vaccine.

Adverse outcomes measured: Allergic rhinitis (respiratory allergy), eczema, asthma, and vaccine-preventable diseases (pertussis, measles, mumps, rubella). No neurological or autoimmune outcomes considered.

The KIGGS study is not a vax-unvax study, as defined above. It has several problems that render it useless for measuring the health impact of the full vaccine schedule:

1) Neurological and autoimmune disorders were not measured.

2) Allergic disorders can take years to appear, and some vaccines are given after age 1, so the 1-5 age group should be excluded. The study therefore effectively had only n=50 (age 6-17) zero-vax subjects.

3) The vaccinated group is defined as receiving at least one vaccine. This dilutes the vaccinated group with lightly-vaccinated subjects.

4) The vaccinated group received an unknown number of vaccines. No details are provided about vaccine exposure (e.g. an average number of vaccines received by vaccinated subjects, or percentage that are fully vaccinated).

Low Vaccine Utilization?

The vaccinated group may have had low vaccine utilization. Specifically, from Fig. 1, the percentages of “sufficiently vaccinated” subjects for each disease are:

Pertussis: 10,164/13,359 = 76%

Measles: 10,120/13,359 = 76%

Mumps: 9,789/13,359 = 73%

Rubella: 9,209/13,359 = 69%

These percentages are low compared to vaccination rates in the USA, for example. The low vaccine use in the vaccinated group reduces the sensitivity of the study. The low vaccine use may be due to inclusion of young (e.g. ages 1-3) subjects, since subjects at this age are not fully vaccinated for these diseases.

A Double Standard

Different subject-inclusion criteria were used for the 2 outcome categories: 1) vaccine-preventable illnesses, and 2) allergic disorders. Specifically, for vaccine-preventable diseases, only sufficiently-vaccinated subjects were included. For allergic disorders, all subjects were included, even those that were not sufficiently vaccinated. This is a double-standard. These different inclusion criteria reduce detection of allergic disorders caused by vaccines, and maximize detection of vaccine efficacy. The double-standard suggests the researchers had an agenda to bury evidence of harm and make vaccines look good.

Did Not Have 18,000 Subjects

The thoughtscapism blog erroneously states the KIGGS study had 18,000 subjects, when in fact it had 13,453. The paper states:

“Of the 17,641 individuals in the KIGGS, 14,148 children and adolescents were aged 1–17 years and lived in non-immigrant families. A vaccination card was available for 13 499 of these individuals (95.4%). Of these, 41 were not evaluated because their vaccination card was illegible or seemingly incomplete (follow-up document). Furthermore, five unvaccinated subjects were not evaluated who, according to their parents, had not been vaccinated at the planned date because of frequent illnesses. Evaluable vaccination data were therefore available for 13 453 children and adolescents aged 1–17 years (95.1%).

For 94 of these children and adolescents, 48 girls and 46 boys, no vaccination had been documented at the time of the KiGGS survey.”

So the study compared 13,359 to 94 subjects (13,453 subjects total). The large imbalance in group size means the statistical power is much lower than a comparison of equal group sizes (e.g. 9000 vs 9000 subjects). So describing the study as having 18,000 subjects is misleading to most people. It implies high statistical power, which is not the case.

Possible Documentation Problem

The unvaccinated group was defined as having no documented vaccination. That is not necessarily the same thing as documented affirmation of zero vaccine exposure. Medical records are sometimes lost or misplaced, so children lacking documented vaccination may actually be vaccinated. Only 0.6% of the study subjects were in the unvaccinated group. Accordingly, even rare occurrences of lost records could put significant numbers of vaccinated subjects into the unvaccinated group.

Parents were not asked about vaccine exposure. The paper says that parents were interviewed about their children’s health and possible confounders (e.g. education, income), but not vaccine exposure. It seems strange that parents were not asked about vaccination status of their children.

Conclusion

In view of these flaws, the KIGGS study is essentially meaningless with regard to the safety of the CDC vaccine schedule. The biggest problems are the inadequate number of unvaccinated controls of age 6+ (50), the “at least one vaccine” definition for the vaccinated group, and no investigation of neurological or immune conditions. The KIGGS study therefore cannot be used as evidence of safety for the CDC vaccine schedule.

2) Germany 2013 (Grabenhenrich et al) Full Paper: Early-life determinants of asthma from birth to age 20 years: A German birth cohort study

This study looked at many different risk factors for asthma. Vaccine exposure was one of many exposures considered. Vaccines were not a focus of the study. It had a very long follow-up of 20 years.

Study Characteristics:

Zero-vaccine group size: Study did not have a zero-vaccine group.

Number of subjects: 1,314 at beginning, declining to 941 at 20-year follow-up.

Group Definitions:

——–“unvaccinated”= ?? vaccines total, but no MMR, BCG or tick encephalitis (TE) (none of these 3)

———vaccinated= ?? vaccines total, including MMR, BCG and TE (all 3)

Adverse outcome measured: Asthma only.

This is not a vax-unvax study, as defined above. The study has the following problems that render it useless as evidence for safety of the vaccine schedule:

1) There was no zero-vaccine group.The study completely ignored all vaccines other than MMR, BCG and TE. Since only MMR, BCG and TE vaccines were considered, the “unvaccinated” actually received vaccines. The study states:

“We were not able to examine the effect of other vaccinations in our current analysis because the number of children who were not immunized at all against tetanus, for example, was too small for robust risk estimates.“–Grabenhenrich et al

Accordingly, the “unvaccinated” group definitely received some vaccines. Vaccine exposure (e.g. average number of vaccines) in the “unvaccinated” group was not provided.

2) Neurological and autoimmune outcomes were not measured. Only asthma was considered.

3) Total vaccine exposure was not described. Both vaccinated and “unvaccinated” groups received an unknown number of vaccines (other than MMR, BCG and TE).

Asthma Risk Reduction Is Biologically Plausible

An interesting and perhaps expected finding is that vaccination with BCG, MMR and TE was associated with a 34% reduction in asthma risk. If the vaccines caused the asthma reduction, it may be because the MMR, BCG and TE vaccines induce a Th1-type immune response. This creates a long-term Th1 programming of the immune system, which is known to reduce risk of allergic disorders like asthma.

The immune system can operate in opposite “modes” known as Th1 and Th2. Th1 and Th2 are opposites on a spectrum. Th1 inhibits the Th2 mode, and vice versa. The Th2 mode causes allergic-type immune responses. People with allergic disorders have immune systems programmed to respond in the Th2 mode. The MMR, BCG and TE vaccines induce Th1 and create long-term Th1 immune programming, which can be expected to reduce allergies. So the observed reduction in asthma is not surprising. Note: MMR vaccine induces a Th1 response in about 90%, and a Th2 response in about 10%.

Vaccines with aluminum adjuvant generally induce Th2, and hence cause allergic disorders, including asthma. Vaccines that contain Al adjuvant include Hep B, Hep A, DTaP, HiB, pneumococcal, and meningococcal. I expect that if the study had considered only aluminum-containing vaccines, it would have found a positive association with asthma. However, the TE vaccine apparently contains Al adjuvant, so the fact that it causes Th1 activation is puzzling (citation: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4605778/). Perhaps the TE antigens produce a strong Th1 activation that overwhelms the Th2 stimulation caused by the Al adjuvant (this is speculation). TE definitely seems to induce Th1 despite the Al adjuvant content, and that will tend to reduce asthma risk.

Grabenhenrich et al. is not a vax-unvax study. It provides no evidence supporting the safety of the vaccine schedule.

3) Philippines 2011 (Bloom et al) Full Paper: The effect of vaccination on children’s physical and cognitive development in the Philippines

This study looked at cognitive performance (verbal, math, and language test scores) in 10 year old children, in relation to vaccines received at 0-2 years of age. Subjects were born in 1983-1984, and follow-up cognitive testing was done in 1994. The study was published in an economics journal (nothing wrong with that!), which explains why it did not look at any health/disease outcomes. But of course cognitive performance is generally related to neurological health.

Study Characteristics:

Zero-vaccine group size: 1022

Vaccinated group size: 85

Group Definitions:

———unvaccinated: Zero vaccines

———vaccinated: At least one of each: DPT, polio, measles, and TB (BCG vaccine). Only DPT contains aluminum adjuvant.

Outcomes measured: Cognitive performance (verbal, math, and language test scores). No health outcomes measured (but height and body mass index were measured).

Quote:

“We include in the treatment group children who had at least one vaccination of each of DPT, polio, measles and TB. This gives us 85 fully vaccinated children compared with our control group of 1022 children who received no vaccinations at all.“–Bloom et al

Although this study did compare vaccinated and zero-vaccine subjects, there are several issues that render it useless as evidence of safety for the CDC’s vaccine schedule.

“Fully Vaccinated” = One Dose Of Al-Containing Vaccine

The only Al adjuvant-containing vaccine in this study is DPT. And, according to the treatment-group inclusion criteria, only one dose of DPT is necessary to be considered “fully-vaccinated”. Compare this to the CDC vaccine schedule, which recommends 11 doses of Al-containing vaccines by age 6 months, and 16 doses of Al-containing vaccines by 2 years. Aluminum adjuvant is probably the most dangerous vaccine ingredient.

Another way to look at it is by Al dosage. A single DPT dose contains at most 625 mcg Al adjuvant (Source for this is CHOP and Dr Paul Offit: http://www.chop.edu/centers-programs/vaccine-education-center/vaccine-ingredients/aluminum). By comparison, the CDC vaccine schedule contains up to 3,675 mcg Al in the first 6 months. The low exposure to Al adjuvant in the Bloom study renders it irrelevant to the safety of the CDC vaccine schedule, or Al adjuvant.

Back in 1983-84, the polio vaccine was a live, attenuated virus vaccine. The measles and TB (BCG) vaccines are also live-attenuated and without adjuvant. The live vaccines create an immune response more similar to natural infection than Al-adjuvanted vaccines. They generally produce a Th1 type immune response. This is relevant because early life Th1 stimulation seems to have beneficial effects on brain development. Natural infections (which often stimulate Th1) improve a baby’s brain development. Th2 activation impairs brain development (and causes allergic disorders). New research shows that BCG vaccine (live, stimulates Th1) improves brain development and Hep B vaccine (contains Al adjuvant, stimulates Th2) impairs brain development: http://vaccinepapers.org/two-vaccines-opposite-effects-brain/

So, it is biologically plausible for the polio, measles and TB vaccines to improve cognitive ability. But this is not relevant to the US CDC vaccine schedule, which contains many more Al-adjuvanted vaccines. The CDC schedule does not include TB, live polio or the measles vaccine (by itself; its combined in MMR).

The Bloom study vaccine exposure is very different from the CDC vaccine schedule in that Bloom used fewer Al-adjuvanted vaccines, and more Th1-stimulating vaccines. Th1 stimulation improves brain development and cognitive function. Consequently, it cannot be used as evidence of safety for the (Th2-stimulating) CDC vaccine schedule.

Selection Bias May Explain The Results

The Bloom study reported higher cognitive performance (test scores) among vaccinated children. But correlation is not causation. The study was not randomized. It was observational. Children that receive vaccines are different from children that don’t. This is selection bias and there was a lot of it in the Bloom study.

There were large differences between the vaccinated and unvaccinated groups, including several known to affect cognitive development. For example, the vaccinated children:

1) had mothers with more education,

2) had higher socioeconomic status,

3) lived in larger homes,

4) had more toilet/sanitation access,

5) had fewer siblings,

6) had better-nourished mothers,

7) had more breastfeeding as infants

…than the unvaccinated.

Thats a lot of selection bias! All these differences influence the data in the same direction: boosting the health and cognitive ability of the vaccinated group. How could all these factors possibly be controlled and corrected for? The authors describe intensive efforts to correct for the extreme selection bias. But with only 85 vaccinated subjects, thats almost certainly impossible. Controlling for each factor requires analysis of sub-groups, and with only 85 vaccinated subjects available, the corrections will not be accurate.

The attempt to control for differences in breastfeeding is particularly dubious. The paper states:

“…Anderson et al. (1999) find that breast feeding affects cognitive development in a meta-analysis of studies, while Daniels and Adair (2005) find that breast feeding influences cognitive development in our sample of children. It is therefore important to include breastfeeding as a potential confounding variable…We include birth weight of the child and height at 2 months to control for this effect.“

So they used birth weight and height as a proxy to control for breastfeeding effects. Apparently, they did not have data on breastfeeding. This is not persuasive.

I believe the Bloom study results are explained by selection bias. The vaccinated group had numerous advantages in life, and thats why they had better test scores. The study had far too few subjects, and inadequate data collection to facilitate accurate corrections for the huge amount of selection bias. The association of vaccination with better cognitive function is therefore a mere correlation. Correlation is not causation!

No Health Outcomes Measured

Only body mass index (BMI) and height were measured. No adverse health outcomes were measured. The study cannot be used as evidence of vaccine schedule safety for this additional reason.

85 Is Not Enough

More subjects (e.g. several hundred) would be needed to detect adverse health outcomes having a prevalence of about 5% or less (e.g. autism).

Conclusion

There are no studies of reasonable quality that compare health outcomes of the fully-vaccinated and the never-vaccinated. There are a few studies with zero-vaccine controls, but none are capable of establishing safety. Reasons for this include:

1) number of subjects is too small (e.g. 50-100) to detect adverse outcomes with incidence of a few percent or less (e.g. autism),

2) vaccinated group receives far fewer vaccines than the CDC’s vaccine schedule,

3) vaccinated group is “diluted” with lightly-vaccinated subjects (e.g. that receive only one vaccine),

4) not looking for neurological or immune-related outcomes,

5) severe selection bias (e.g. the vaccinated group had greater education, income etc).

The Mawson 2017 study is the only vax-unvax study ever done. And it shows that full-schedule vaccination is strongly associated with neurological and immune diseases.