Haemophilus influenzae

Hypothesis: conjugate vaccines may predispose children to autism spectrum disorders. 2011, Richmand, Med Hypotheses

For a long time I doubted about the vaccinations from Hib and pneumococcus, because these diseases can really be dangerous.The fact that I personally put the final cross on these vaccinations was the following article published in a rather marginal journal specializing in hypotheses It seems that even for this marginal magazine, the article was too marginal, and accompanied by an editorial article in which they write that, despite , that the theme of the connection between vaccines and autism is already worn to holes and a denial bent, and that although the author of the article is not a scientist at all, his hypothesis is, nevertheless, quite plausible, and it should be checked.

I highly recommend reading this article in full.
Editorial article is also worth reading.
Conjugated vaccines radically change immunological response to carbohydrate antigens In the absence of a conjugated vaccine, carbohydrate antigens usually do not induce an immune response of T cells, but induce a weaker response (T-cell independent). This is due to the fact that B2 cells do not synthesize antibodies without the signal of T-helper cells. In order for this to happen, the B2-cell, and its related T-helper cell, should recognize the same, or similar epitope. But since T cells recognize only protein epitopes, T helper cells are usually able to activate B2 cells in response to protein antigens. In response to bacterial capsular polysaccharides, the immune system forms a response through cells B1 and MZB (Marginal zone B). B1 cells do not begin to react to bacterial carbohydrate antigens until 18-24 months, and their response does not fully mature until about 5 years of age. Therefore, infants and young children are unable to respond effectively to capsular bacteria. Conjugated vaccines use the fact that B2 cells and their related T helper cells do not have to respond to an identical epitope, but rather recognize closely related epitopes. Although the mechanisms by which conjugate vaccines work are not fully understood, it is believed that antigen-presenting cells, treat the combined protein carrier and carbohydrate hapten, which leads to recognition of the protein carrier by T-helper cells, and recognition of carbohydrate antigens by B2 cells. That is, conjugated vaccines change the immunological response to carbohydrate antigens in infants and young children, from a hypo-sensitive to a full T cell response.
Because antibodies against carbohydrate antigens are often autoreactive with their own carbohydrates, the differentiation of B cells to B2 cells can lead to an autoimmune reaction. Therefore, B cells against carbohydrate antigens are carefully regulated by the immune system. Antibodies to native carbohydrates are associated with several autoimmune diseases, such as systemic lupus erythematosus, myocarditis and rheumatic heart disease, Sydenham's chorea, and children's autoimmune neuropsychiatric disorders associated with Streptococcal infections (PANDAS).
Unlike antibodies produced by B2 cells, antibodies produced by B1 and MZB cells are short-lived and low-affinity, and conducted to an autoimmune reaction with
Autism has an increased level of antibodies to nervous structures and an increased level of proinflammatory cytokines in the brain, which indicates that autoimmune and neuroinflammatory processes can play a role in some cases of autism.
Because myelinization (the formation of an insulating nerve fibers) is most intense during the first 9 months of life, and continues in early childhood, neuronal development in infants and young children can be particularly vulnerable to self-reactive antibodies, including those that react with glycoproteins in myelin sheaths.

The first conjugate vaccine (from Hib) appeared in the US in 1988, and was later licensed in most other developed countries, including Denmark in 1993, and Izr ail, where it was licensed in 1992, and introduced into the national vaccination calendar in 1994.
The incidence of autism began to rise dramatically in the US since births in the middle of 1987. In Denmark and Israel, the jump in autism began about 5 years later.
In 1990, the vaccine was licensed to infants from the age of two months, which may explain the further increase in autism.Another explanation for the increase in autism in the mid-90s could be a change in the protein carrier used in the vaccine, which made her more immune gene. If the Hib vaccine is an autism trigger, then an increase in its immunogenicity and a change in the binding site may increase the likelihood of autism.
The licensing of the pneumococcal vaccine in 2000 may partially explain the further increase in autism. Children born in 1995 were the first to be vaccinated against pneumococcus, and this is consistent with CDC data, according to which the level of autism in 1992-1994 did not change, and in 1998 autism was already 57% higher than in 1994, m.
In Denmark, the Hib vaccine was licensed in 1993, but immediately followed by an aggressive vaccination campaign for children, starting in 1988, which coincides with the growth of autism among those born in 1988 and later. > In Israel, the number of children receiving disability benefits due to autism did not change from 1972 to 1995. But from 1996 to 1998, their number increased 5-fold, which is explained by this hypothesis. In 2004, 11% of the beneficiaries were born in 1985-89 (before vaccine licensing), 21.1% were born in 1990-94 (the beginning of vaccination), and 37% were born in 1995-99 (immediately after the vaccination was introduced National calendar). The immune system in response to the carbohydrate membrane of capsular bacteria produces antibodies through B1 and MZB cells in adults, and in children older than 5 years. But children under 5 years of age react poorly to carbohydrate antigens. Conjugated vaccines consist of a protein carrier attached to a carbohydrate antigen, and are able to circumvent this restriction of the immune system to carbohydrate antigens in children. Due to the protein carrier, these vaccines can induce the production of antibodies by B2 cells.
The development of antibodies to carbohydrate antigens via B2 cells is a significant departure from the natural paradigm in which B1 and MZB cells usually produce short-lived antibodies against carbohydrate antigens, and B2 cells produce more long-living against protein antigens. In addition to the fact that the immune system of children under 5 years of age reacts poorly to capsular bacteria, the maternal IgM and IgG2 antibodies do not pass well the placenta, from which it follows that the embryos are probably also not protected from capsular bacteria. From the point of view of evolution, this is quite unexpected. It is possible that this evolutionary flaw is accompanied by a compensatory evolutionary advantage. One possible explanation is that antibodies to carbohydrate antigens can be cross-reactive with neuronal glycoproteins, and a fine balance has been achieved, by evolution, between evolutionary protection against capsular bacteria and the need for development of the nervous system. This is consistent with the fact that myelination begins with infancy, and lasts until early childhood, which coincides with the period during which the immune system is hypo-sensitive to carbohydrate antigens. Moreover, the period during which the immune system is least sensitive to carbohydrate antigens corresponds to the period of the most intense myelination. It is possible that antibodies to carbohydrates not only interfere with the development of the nervous system in infants and young children, but their negative effects are strengthened by a stable a response of the immune system induced by conjugated vaccines, which significantly disturbs the balance achieved by evolution.

Hepatitis B

Hepatitis B vaccination of male neonates and autism diagnosis, NHIS 1997-2002. 2010, Gallagher, J Toxicol Environ Health A

Newborn boys vaccinated against hepatitis had a 3 times higher risk of developing autism spectrum disorder, as compared to unvaccinated, or vaccinated at least one month after birth.


Do the aluminum vaccine adjuvants contribute to the rising prevalence of autism? 2011, Tomljenovic, J Inorg Biochem

The more vaccinations containing aluminum are given in the country, the more children with ASD there are.
The increase in the number of children with ASD in the US correlates with the increase in the number of aluminum adjuvants used. (r = 0.92, p<0.0001)
The authors use Hill’s criteria and conclude that the relationship between aluminum in vaccines and ASD is probably causal. This article is also worth reading in full.


Pilot comparative study on the health of vaccinated and unvaccinated 6- to 12-year old U.S. children. 2017, Mawson, JTS

The study compares homeschooled children in four states of the USA. 405 vaccinated and 261 unvaccinated children.
Acute diseases:
Vaccinated children had chicken pox 4 times less often, whopping cough – 3 times less often and rubella – 10 times less often.
Vaccinated children had otitis media 4 times more often and pneumonia – 6 times more often.
Chronic diseases:
Those vaccinated had allergic rhinitis 30 times more often. They had allergies 4 times more often, ASD – 4 more often, ADHD – 4 times more often, eczema – 3 times more often, learning disabilities – 5 times more often, neurological disorders – 4 times more often. Vaccinated children had any type of chronic illness 2.5 times more often.
Vaccinated children used allergy medicines 21 times more often, antipyretics – 4.5 times more often, ear-drainage tubes – 8 times more often. They went to see a doctor, due to illness, 3 times more often and were hospitalized 1.8 times more often.
Some more interesting results from this study: risk of neurological disorders associated with the use of antibiotics during pregnancy (2.3 times), use of medicine during pregnancy (2.5 times), prematurity (5 times), ultrasound (1.7 times), and ultrasound done more than 3 times during pregnancy – 3.2 times.
The number of neurological disorders in vaccinated children (14.4%) coincides with the CDC studies (15%). The number of learning disabilities also coincides (5.6% of the vaccinated children in this study, and 5% according to available statistics).
However, judging by this study, there is already 3.3% of autistic children among vaccinated, i.e. 1 in 30 children. But, perhaps, it is an overestimation, as it is likely that children with ASD are homeschooled more often. (According to the CDC 2.24% of children are with ASD, i.e. 1 in 45 in 2015 and 1 in 36 in 2017).
Vaccination of a premature baby is associated with a 14 times increase in the risk of neurological disorders.


Neurotoxic effects of thimerosal at vaccine dosages on the encephalon and development in 7 days-old hamsters. 2007, Laurente, Ann Fac Med Lima

Hamsters were given thiomersal injection in doses equivalent to those used for humans. They had lower brain and body mass, low density of neurons in the brain, neuronal death, demyelination and damage to Purkinje cells, which is characteristic of ASD.


Reduced levels of mercury in first baby haircuts of autistic children. 2003, Holmes, Int J Toxicol

The authors measured the amount of mercury in the hair from the first haircut of 94 children with ASD, and found that the concentration of mercury in the hair of children with ASD is significantly lower than in the hair of the control group (0.47 vs. 6.63 ppm).
The mothers of children with ASD had significantly higher levels of mercury exposure (through injections of anti-rhesus immunoglobulin and amalgam fillings) than the mothers in the control group.
Among the children with autism, the more severe symptoms were, the lower was the level of mercury concentration in the hair.
Mercury concentration in the hair of the control group correlated with the number of amalgam fillings in mothers, with fish consumption during pregnancy and with the number of vaccines received. In the ASD group, such correlation was absent.
46% of mother of children with ASD have received injections of anti-rhesus immunoglobulin Rho(D), as compared to 9% of mother in the control group.
Mothers of children with autism also had more amalgam fillings (8.35 vs. 5.5). 37% of mother of children with autism had 10 and more fillings, as compared to 18% of mother in the control group.
The authors conclude that the results support the hypothesis that children with ASD retain mercury in tissues, and are worse at secreting it. The absence of mercury in the hair is probably due to its low level in the blood, which nourishes the hair follicles, and its low level in the blood is due to mercury being retained in the cells, where it causes the greatest biological harm.


A prospective study of thimerosal-containing Rho(D)-immune globulin administration as a risk factor for autistic disorders. 2007, Geier, J Matern Fetal Neonatal Med

There were 2.35 times more mothers with rhesus-conflict in the group of children with ASD. Each of them received anti-rhesus immunoglobulin during pregnancy, which contained thiomersal at the time. Injections of anti-rhesus immunoglobulin started to be given during pregnancy in the late 80s – early 90s. [1]


Associations of prenatal and early childhood mercury exposure with autistic behaviors at 5years of age: The Mothers and Children's Environmental Health (MOCEH) study. 2017, Ryu, Sci Total Environ

Higher levels of mercury in the blood of mothers at late stages of pregnancy and the levels of mercury in umbilical cord are associated with autism at the age of 5 years old.


Blood levels of mercury are related to diagnosis of autism: a reanalysis of an important data set. 2007, Desoto, J Child Neurol

The Ip, 2004 study did not find an association between ASD and the level of mercury in the blood and hair. The authors of this article (Desoto, 2007) drew attention to an error in the statistical calculations, after which (Ip, 2004) corrected the p-value from 0.15 to 0.056, but did not change their conclusion.
However, after the authors of this article conducted their own statistical analysis of the same data, they found a statistically significant correlation between the level of mercury in the blood and autism. They also found that the level of mercury in the hair, as compared to the blood, was lower in children with ASD than in the control group. [1]


The association between mercury levels and autism spectrum disorders: A systematic review and meta-analysis. 2017, Jafari, J Trace Elem Med Biol

A systematic review and meta-analysis of 44 studies. Children with ASD have a significantly higher level of mercury in the blood and brain than healthy children do, while the level of mercury in the hair of children with ASD is significantly lower.


Mercury, lead, and zinc in baby teeth of children with autism versus controls. 2007, Adams, J Toxicol Environ Health A

The level of mercury in baby teeth of children with ASD was 2.1 times higher than that of the control group, while the levels of lead and zinc were the same for both groups. Children with autism also received a significantly higher amount of antibiotics during their first year of life (mainly due to otitis media). It is known that antibiotics almost completely suppress the secretion of mercury in rats, due to changes in intestinal microflora. Thus, an increased use of antibiotics in children with autism might have reduced their ability to secrete mercury, and therefore, might partially explain its higher levels in the teeth. The use of antibiotics in infancy might also partially explain the high incidence of chronic gastrointestinal diseases in children with ASD.
It is reported in another study that the levels of mercury in the cerebellum of children with ASD was 68% higher that that of the control group (but there's no statistical significance).


The value of ecologic studies: mercury concentration in ambient air and the risk of autism. 2011, Blanchard, Rev Environ Health

The higher the state’s concentration of mercury in the air, the higher the risk of autism in it.


Environmental mercury release, special education rates, and autism disorder: an ecological study of Texas. 2006, Palmer, Health Place

Every 1,000 pounds of mercury released into the atmosphere in the school district in Texas, increased the number of children in special education by 43%, and the number of children with ASD by 61%.
The number of children with autism was 437% higher in the cities and 255% higher in the suburbs than in the rural areas.
A different study reports that for every 1,000 pounds of industrial waste released, the number of children with autism increases by 2.6%, and if this waste comes from power plants, than the number of children with ASD increases by 3.7%.
Every 10 miles of distance from industrial sources of mercury or power plants are associated with a decrease in the number of children with ASD by 2% and 1.4% respectively. [1] [2] [3]


A two-phase study evaluating the relationship between Thimerosal-containing vaccine administration and the risk for an autism spectrum disorder diagnosis in the United States. 2013, Geier, Transl Neurodegener

The authors analyzed VAERS database and found that the risk of ASD was 2 times higher in infants who received DTaP vaccine with thiomersal than in those who received a mercury-free vaccine. An analysis of Vaccine Safety Datalink (VSD), a different database, showed that hepatitis B vaccine with thiomersal is associated with an increase in the risk of ASD (OR=3.4).
Infant boys vaccinated against hepatitis B had a 3-times higher risk of developing autism, as compared to unvaccinated boys, or boys vaccinated at least one month after birth.


The risk of neurodevelopmental disorders following Thimerosal-containing Hib vaccine in comparison to Thimerosal-free Hib vaccine administered from 1995 to 1999 in the United States. 2018, Geier, Int J Hyg Environ Health

The Hib vaccine with thiomersal is associated with a 2.75-fold increase in the risk of ADS, 5.4-fold increase for developmental delays, 2.4-fold increase for psychomotor disorders, and 2.7-fold increase for neurological disorders, as compared to those vaccinated with a thiomersal-free vaccine.


Methodological issues and evidence of malfeasance in research purporting to show thimerosal in vaccines is safe. 2014, Hooker, Biomed Res Int

As of today, more than 165 studies have shown the harm of thiomersal, and 16 of them have shown the harm of thiomersal specifically for infants and children who have had outcomes of death, acrodynia, poisoning, allergies, developmental defects, autoimmune responses, developmental delays, and nervous system disorders, including tics, speech and language delays, ADHD and ASD.
Nonetheless, the CDC still insists that there is no link between thiomersal in vaccines and ASD. This is confusing, since the epidemiological study, conducted by the CDC themselves, found a 7.6-times increase in the risk of autism in children, who received vaccines with thiomersal. The same study found that the risk of inorganic sleep disorders was 5 times higher, the risk of speech disorders was 2.1 times higher, and the risk of neurological disorders was 1.8 times higher.
The CDC’s position is based on 6 epidemiological studies, which they funded themselves. All these studies are analyzed in the article:
1) Madsen, 2003. The authors analyzed the data from psychiatric clinics in Denmark from 1971 to 2000, and determined that after the removal of thiomersal from the vaccines (in 1992), the incidence of ASD increased. However:
- The data from 1971 to 1994, only included inpatient diagnoses, while starting in 1995, they also included outpatient diagnoses. Thus, the inclusion criteria expended significantly 2 years after the removal of thiomersal, which created an artificial increase in the autism incidence. There were 4-6 times more outpatients than inpatients. Another study by the same authors analyzing the same data, reported that there were 13.5 times more outpatients. A large Copenhagen clinic, which registered 20% of the ASD patients in Denmark, was only included in the study in 1993, which also artificially inflated the number of autism cases after the removal of thiomersal. The authors do not report it, nor do they correct this anomaly.
- Diagnostic criteria for ASD changed in 1994 (during the transition from ICD-8 to ICD-10). This could cause a 25-fold increase in the number of ASD cases.
- The 2001 data, which showed a decline in the autism rate since 1991, was included in the first version of the article, which was submitted to JAMA. JAMA rejected the article and the authors submitted it to the Pediatrics. One of the reviewers at Pediatrics noticed that the authors do no analyze the decrease in the autism incidence, which could point to the possibility that removal of thiomersal could have played a role in it. In response to this, the authors removed the 2001 data from the article and it got published. If the authors had not removed this data, the results of the study would have been consistent with the results of a more recent study, according to which, the autism incidence in Denmark after 1992 decreased from the peak 1.5% in 1994 to 1% in 2002-4.
2) Stehr-Green, 2003. Conducted in response to a California study, which discovered a correlation between thiomersal and autism. The authors compared the data from 3 countries (Denmark, Sweden and California). Danish data was the same as in the previous study. Swedish data was based only on inpatient cases (that is, on just a small fraction of all ASD cases). Part of the data from California was excluded from the final publication.
3) Hviid, 2003. The authors state that the mean age of autism diagnosis is 4.7 years, but nonetheless, they included 1-year-olds in the analysis. Moreover, rather than counting the number of children, they counted the number of person-years. Thanks to this technique, each group was considered equally, despite the fact that the probability of diagnosis in younger age groups was much lower.
4) Andwers, 2004. A retrospective study in the United Kingdom. It has the same issues, as did the previous study. The authors did not publish the initial data, so it could not be analyzed properly.
5) Verstraeten, 2003. The publication states that there was no association between thiomersal and ASD. However, the first phase of this study, released in an internal presentation, showed that infants who received more than 25 μg of mercury in vaccines and immunoglobulin at the age of one month, had 7.6-fold higher risk of autism, as compared to those who did not receive any mercury. The second phase of the study showed that infants, who received 62.5 μg of mercury before the age of three months, had 2.5-fold higher risk of autism, as compared to those who received less than 37.5 μg. In the third phase, after playing around with statistics, the risk of autism decreased to 1.69. Apparently, the author had been under pressure, since he wrote in an internal CDC correspondence: “I do not wish to be the advocate of the anti-vaccine lobby and sound like being convinced that thimerosal is or was harmful, but at least I feel we should use sound scientific argumentation and not let our standards be dictated by our desire to disprove an unpleasant theory.”
The fourth and fifth phases of the study were based on partial data only and included children at the age of 0-3 years old, even though the average age for autism diagnosis at the time was 4.4 years. Nevertheless, the study found an increased risk for tics and speech delays.
6) Price, 2010. A case-control study in the USA in which the control group received the same vaccines. It is called overmatching, and it is impossible to draw conclusions from this kind of study. Moreover, the initial report discovered that prenatal exposure to thiomersal correlated with an 8-fold increase in the risk of ASD, but for some reason, this data was excluded from the publication.
Five out of the six studies were directly controlled by the CDC, which may indicate a conflict of interest, since vaccine promotion is a central mission of the CDC.


The relationship between mercury and autism: A comprehensive review and discussion. 2016, Kern, J Trace Elem Med Biol

The authors analyzed all studies about the possible relationship between mercury and autism published between 1999 and 2016. They found 91 studies, and 74% of them found a link between mercury and ASD.


The hypothesis described here suggests that sleeping on the back increases the risk of autism, as in five countries (Denmark, the United Kingdom, Australia, Israel and the United States) a sharp increase in autism started immediately after campaigns recommending that infants be placed on their backs. The author writes that the data quality in support of this hypothesis is quite low, but the correlation between sleep in the prone position and SIDS was based on data of similar quality. The author also notes that biologically speaking, sleep in the prone position is more natural and healthy, as almost all mammals (except bats and sloths) sleep that way.

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