AUTISM AND VACCINATION

Autism spectrum disorder (ASD) is a neurodevelopmental illness characterised by restricted

interests, activities, and behaviours that impact social interaction and communication.
Autism is highly familial, implying that genetics might play a significant role in the
development of the disorder. Individuals with Autism spectrum disorder are defined by
persistent deficiencies in social communication and social interaction across many contexts,
as well as confined, repetitive patterns of behaviour, interests, or hobbies, according to the
DSM-5 (APA, Philadelphia, PA, USA, 2013). Autism is now twice as common as it was ten
years ago. 0.5/1000 in the 1960s–1970s to 1/1000 in the 1980s. By the early twenty-first
century, when the DSM-III definition was established in the 1980s, the number had doubled
to 2/1000 1 . The current global prevalence of ASD is estimated to be 1% 2-3 . In 2020's
analysis, the Autism and Developmental Disabilities Monitoring (ADDM) Network of the
Centres for Disease Control and Prevention (CDC) predicted ASD in 8-year-old children to be
1/54 4. It is also recognized as the second most common developmental disability after
mental retardation, among children (Centers for Disease Control and Prevention, 2009) 5.

To date the etiology of Autism Spectrum Disorder is still being debated. Autism is a complex
disorder known to be caused by many environmental factors, genetic mutations, medicines
and complications during pregnancy, etc. Maternal and paternal age, foetal environment
(e.g., sex steroids, maternal infections/immune activation, obesity, diabetes, hypertension,
or ultrasound examinations), perinatal and obstetric events (e.g., hypoxia), medication
(valproate, selective serotonin reuptake inhibitors), smoking and alcohol use, nutrition (e.g.,
short inter-pregnancy intervals, e.g., vitamin D, iron), vaccination and toxic exposure (air
pollution, heavy metals, pesticides) are the biological environmental risk factors for Autism
6
. The importance of advanced parental age as a risk factor for chromosomal abnormalities
is well-known. There is mounting evidence that older parental age has a role in the genesis
of psychiatric and neurodevelopmental diseases, including as bipolar disorder,
schizophrenia, drug use disorders, Attention deficit hyperactivity disorder and autism
spectrum disorder 7. A meta-analysis of 27 observational studies looking at the link between
advanced parental age and the risk of autism recently discovered that the youngest parental
age group was linked to a lower risk of autism in offspring 8 . In the context of autism
pathogenesis, a number of environmental prenatal exposures present within the developing
fetus's immediate surroundings have been investigated, including sex hormone changes,
maternal obesity, diabetes, hypertension, infections and immunological activity, and
ultrasonography exposure. While genetic predisposition may be the source of these
hazards, environmental interactions involving both the mother and the foetus that have the
potential to impair the fetal–maternal–placental system cannot be overlooked. Obesity in
mothers is also thought to affect offspring's brain development and cognitive abilities 9 .
Low-grade neuroinflammation, increased oxidative stress, insulin resistance, glucose, and
leptin signalling, dysregulated serotonergic and dopaminergic signalling, perturbations in
synaptic plasticity, and altered DNA methylation patterns are all possible effects of severe
maternal obesity and a high-fat diet on foetal and offspring neurodevelopment 10-11 . The
involvement of infections and the immune system in the genesis of autism has been
disputed since the discovery of a link between autism and congenital rubella infection. A
growing body of research shows that the immune system and aberrant immunological
function, such as infammation, cytokine dysregulation, and anti-brain autoantibodies,
influence autism trajectories, may even have a role in causing autism in certain
individuals . In instance, maternal influenza is linked to a twofold increase in the incidence
of autism in offspring 12. The importance of maternal infection in the pathophysiology of
autism risk may not lie in the presence of viruses or bacteria per se, but in the
immunological response they elicit, according to studies that found higher inflammatory
markers and antibodies in pregnant women with autistic offspring 13-14 .The analysis of rare
and common genetic variations has revealed that transcriptional dysregulation is one of the
most likely paths to Autism. At least three elements of epigenetic contributions to ASD
should be considered: Firstly the prenatal and postnatal exposure to environmental variable
causing long lasting changes in DNA methylation pattern which can influence gene
expression throughout the individual’s lifespan 15-16, Then the abnormal methylation
patterns which have an impact on many neurodevelopmental genes, that further are known
to contribute to Autism risk 17. Lastly, Hypo- or hypermethylation in gDNA of fathers of
autistic children, particularly around loci related to neurodevelopment 18.

From past many decades there has been a controversy regarding vaccinations contributing
to development of autism. The current recommended immunization schedule for persons
aged 0–6 years in the United States includes six vaccines at 2 months and nine vaccines at
12–15 months (Advisory Committee on Immunization Practices, 2010). At the age of two
months, the immune system is very vulnerable. Although particular immunological
responses mediated by B- and T-lymphocytes are competent in new born (Solomon, 1971),
polymorphonuclear cells in the peripheral blood are less numerous than lymphocytes
(Diem, 1962). A newborn's phagocytic cells and complement system are also impaired. A
high number of immunizations administered when the immune system is weakened may
contribute to the beginning of autism 19. The vaccinations mainly involved in this controversy
are MMR to protect against Measles, rubella and mumps and is given in 2 doses, first dose
at 12-15 months of age and second dose at 15 months to 6 years of age, Hepatitis B vaccine
(HBV) that is protection against Hepatitis B vaccine recommended for all infants at birth and
for children upto 18 years. , DTAP vaccine for Diphtheria, tetanus and acellular pertussis
which is only for the children younger than 7 years of age , Varicella vaccine in two doses for
chickenpox. There are many ongoing investigations going on to bring out association of
autism with any of the vaccinations but no particular result has been proved yet.

Cases of autism reported as an adverse effect following immunisation all over the world is
shown in figure 1. This data has been collected and analysed for WHO’s vigilance services.

MMR VACCINE

The MMR vaccine is a attenuated live virus vaccine included in the recommended paediatric
immunisation schedule in the United States. The first dose should be given at 12–15 months
of age, and the second dose should be given around 4–6 years of age. Combination Measles
(rubeola), mumps, and rubella are all prevented with MMR vaccines, which are live virus
vaccines. MMR vaccinations contain attenuated strains of these three viruses and have been
available in various forms since the 1970s 20. MMR vaccine is highly efficient against measles
and rubella, with a 97 percent or higher vaccine effectiveness after two doses. Many case
control studies, cohort studies conducted in United kingdom , Denmark, united states, Japan
suggest that there is no association between autism and MMR vaccine or there is no
increases risk of autism with MMR vaccine. But according to the 1998 reports , “autism
enterocolitis” can be linked to MMR vaccine and specifically autism regression. Autism has
been linked to elevated levels of measles antibodies. Two laboratories have reported finding
measles virus in three cases of autism, one by conventional reverse transcriptase (RT)-PCR
and the other using real-time TaqMan PCR, the latter in intestinal samples of 75/91
individuals with ASD compared to 5/70 control patients 21. The origin and description of the
measles virus genome fragments revealed in these research have not been proven, and
there have been widespread doubts regarding the scientific procedures used. In two recent
studies, real-time PCR failed to detect the measles virus genome in children with ASD
compared to controls in peripheral blood mononuclear cells (PBMCs) rather than gut
mucosal samples in children with ASD. There was no dose–response relationship between
autism symptoms and antibody concentrations. Measles virus nucleic acid was amplified by
reverse transcriptase-PCR in peripheral blood mononuclear cells from one patient with
autism and two typically developing children 22.

Numerous case–control and cohort studies conducted over the last two decades have found
no link between vaccinations and the incidence of Autism. With the retraction of the Lancet
publication in 2010, the concept that the measles, mumps, and rubella (MMR) vaccination
causes autism through destroying the gut lining was debunked. Yet many studies suggest
othervise.

DTAP vaccine

DTAP is a vaccine containing inactivated toxins protecting against multiple disorders like
Diphtheria, Tetanus, Acellular Pertussis (whopping cough) recommended only for children
younger than 7 year old age. It should be received in 5 doses at different ages, usually at 2
months, 4 months, 6 months, 15-18 months and 4-6 years. DTaP may be given as a stand-
alone vaccine, or as part of a combination vaccine 23. The Institute of Medicine's
Immunization Safety Review Committee examined relation between DTAP or thimerosal and
autism in 2001 and determined that the data is insufficient to accept or reject a causal
association between thimerosal exposure and neurodevelopmental impairment (NDD)
24
.Based on the analysis of the VAERS (Vaccine Adverse Event Reporting System) database,
it was discovered that children who received thimerosal-containing DTaP vaccinations were
more likely to experience reported neurodevelopmental disorder adverse events than
children who received thimerosal-free DTaP vaccines 25. Between the 1980s and the late
1990s, the level of thimerosal in childhood vaccinations based on the recommended vaccine
schedule within the first 6 months of life increased from 75 µgrams of ethyl mercury starting
at 2 months (3 DTP vaccines at 25 µgrams of ethyl mercury each) to approximately 200
µgrams of ethyl mercury starting on the day of birth 26. The current study adds to the
growing body of data linking increased organic-Hg exposure from Thimerosal-containing
childhood immunizations to an increased likelihood of ASD diagnosis. Organic-Hg exposure
from Thimerosal-containing childhood immunizations was found to be related with a future
diagnosis of an ASD using a two-phased, hypothesis-generating and hypothesis-testing,
epidemiological analytical technique in two distinct datasets 27.

HBV (Hepatitis B vaccine)

The hepatitis B vaccination is a subunit vaccine containing outer envelope and inner core
protects from hepatitis B and its significant consequences such as liver cancer and cirrhosis.
Hepatitis B vaccination is given to babies in three doses: First dose at birth, Second dose at
1-2 months of age, Third dose at 6-18 months of age. Anyone under the age of 18 who is not
vaccinated when they were younger should get immunised 19. Adults should receive three
doses of the hepatitis B vaccination, the second four weeks after the first and the third five
months after the second.

The findings of NHIS 1997–2002 confirmed the hypothesis that there is a difference in the
odd ratio for autism diagnosis among boys born before 1999 who were vaccinated with the
hepatitis B vaccine within the first month of life compared to later- or never-vaccinated boys
28-29
. The discovery of an elevated risk of autism diagnosis in male neonates who received
the hepatitis B immunisation is ground breaking.
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