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					                                                Immunization
                                                Table of content
                                          (Last update: 03-25-2008)


Synthesis on immunization ....................................................................................................i
Immunization and its impact on child neurodevelopment
Susan L. Hyman ..................................................................................................................1-5
Autism and immunization
Eric Fombonne....................................................................................................................1-8
Routine immunization in young children recommended vaccine schedule, proven benefits
of vaccines, noted adverse effects of vaccines, best practices for vaccine programs,
vaccine programs for special needs and new vaccines recommended for young children
Noni E. MacDonald ..........................................................................................................1-17
Current immunization practices and their effects on young children’s (birth to five years)
social and emotional development
Scott A. Halperin...............................................................................................................1-10
Childhood immunization
Lance E. Rodewald .............................................................................................................1-6
Immunization: Comments on MacDonald, Halperin, and Rodewald
David M. Salisbury .............................................................................................................1-6
                         Synthesis on immunization

                                (Published online March 25, 2008)



How important is it?

Immunization is a clinical preventive service that is recommended for virtually every
child in the world. After proper administration of a single dose or a series of doses of
vaccine, they generally confer long-lasting immunity upon the recipient. Vaccines
interrupt the circulation of the disease-causing bacteria or virus, which means they
protect not only the child vaccinated, but also potentially individuals who were not
vaccinated.

Historically, infectious diseases have been a significant source of childhood illness, in
many cases leading to disability or death. To this effect, immunization programs for
young children are one of the great public health success stories of the twentieth
century. Through immunization, smallpox and polio have been eradicated from the
western hemisphere, and cases of measles have been reduced by over 99%. In
Canada, immunization programs have reduced the incidence of their target diseases
(diphtheria, tetanus, pertussis, mumps, rubella, etc.) by over 90%.

What do we know?

In the U.S. and Canada, children are now routinely protected against 12 vaccine-
preventable diseases: diphtheria, tetanus, pertussis (whooping cough), poliomyelitis,
hepatitis B, invasive haemophilus influenzae disease (an invasive disease that may
produce any of several clinical syndromes, including meningitis or pneumonia),
invasive pneumococcal disease, measles, mumps, rubella (German measles),
varicella (chicken pox) and influenza.

In general, all of these diseases are serious and may be fatal, while the vaccine
adverse events, if they occur, are usually minor, such as local discomfort and/or
inflammation at the site of the injection and/or mild fever or rash. To reap the
benefit from these vaccines, children must be immunized and immunized on time. In
Canada, the National Advisory Committee on Immunization (NACI) recommends that
all children be immunized at two, four, six and eighteen months of age.

Unfortunately, immunization programs are the victims of their own success. As the
diseases against which the vaccines protect become more rare, they also become
less feared by the population. Vaccine-associated adverse events that are uncommon
become relatively more frequent as the diseases and their manifestations become
rarer. As a result, vaccines that are being used in healthy children become more
feared by parents than diseases that they have never seen.

Among the most controversial allegations at present is whether childhood
immunizations are associated with autism. Two hypotheses have emerged: a link
between MMR (Measles-Mumps-Rubella) vaccine and autism, and exposure of young



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Synthesis on immunization


infants to excessive amounts of thimerosal, a mercury-based chemical used to
stabilize vaccine preparation.

Over the last few years, a number of studies have examined the MMR-autism
hypothesis. To-date, no epidemiological study has found an association between
autism and MMR. Recent reviews of this hypothesis by the Institute of Medicine
concluded that the evidence was in favour of its rejection. Moreover, systematic
reviews of vaccine safety are regularly performed, and there had been no reports of
autism as a possible adverse event following measles vaccine or MMR vaccine.

Children exposed to high doses of methyl mercury were also followed and again, no
increased incidence of autism has ever been documented. (It should be noted that
the thimerosal substance has never been used in the MMR vaccine, and that most
vaccinations now exist in a thimerosal-free format.)

Several epidemiological designs have tested these hypotheses and found that
increased prevalence of autism and related conditions (pervasive developmental
disorders) was due to diagnostic switching, changes in diagnostic criteria, improved
detection of autism in populations and greater awareness about the disorder in both
the professional and lay audience. Since the epidemiologic data to date indicate that
MMR vaccination is not associated with an increase in autism in the population, the
known neurologic and other serious risks of these preventable diseases is considered
to be much greater than the risk of the vaccine.

What can be done?

Education
Parents and immunization providers need to be aware of how important it is to keep
children and patients on track with their immunizations. The very success of
childhood vaccination, however, brings the challenge of communicating to parents
the importance of protecting their children when the diseases prevented through
vaccination are no longer seen. Therefore, immunization programs need to pay more
attention to educating and reassuring parents about diseases and vaccines, by
providing parents with evidence-based information that will enable them to make
informed decisions about their children’s immunization.

Research has shown that a number of factors can enhance vaccine uptake, including
timely reminders, quality parent education materials, after-hours and weekend
clinics, vaccine uptake monitoring, multiple vaccines given during one visit, standing
orders for vaccines, multi-component provider education, and the elimination of
financial barriers to immunization. Evidence-based interventions range from simple
recall and reminder systems to quality improvement activities undertaken by
provider offices. Parents also now have access to informative books and Internet
Web sites devoted to education about vaccines and vaccine-preventable diseases.

In the United Kingdom, routine surveys are conducted to ascertain the attitudes of
parents and health-care professionals, and all immunization promotion materials are
extensively pre-tested and the impacts of such materials evaluated. These forms of
operational immunization research are going to become more important as
immunization programs face increasing pressures, especially with respect to doubts
about the need for immunizations and their safety.




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Improving access
In Canada, health is a provincial responsibility. Each province and territory decides
which vaccines it will fund, which creates confusion and inequities across the
country. Consequently, not all children and infants have access to all NACI-
recommended vaccines, putting them at risk for problems such as acquired deafness
from meningitis due to pneumococal infection. A national immunization program is
therefore needed to improve equity of access to all of the NACI-recommended
vaccines in order to be able to protect all Canadian children from the potential
damage incurred by vaccine-preventable diseases.

Monitoring vaccine safety
To optimize children’s protection, immunization providers need to ensure that the
safest and most effective vaccines are administered to children in as timely and
efficient a manner as feasible. In 1994, Health Canada set up the Advisory
Committee on Causality Assessment (ACCA), an expert committee charged with the
task of monitoring vaccine safety by evaluating reported serious vaccine events in
Canada. Health Canada also funds IMPACT (Immunization Monitoring Program,
ACTive), an active surveillance system for vaccine-associated adverse events. Run by
the Canadian Paediatric Society, this network involves 12 paediatric hospitals across
Canada, which account for over 90% of the tertiary-care paediatric beds in Canada
and serve as the local hospital for 45% of Canada’s paediatric population.

On the international level, the World Health Organization created the Global Advisory
Committee on Vaccine Safety in 1999. Its task is to respond promptly, efficiently and
with scientific rigor to vaccine safety issues of potential global importance.

Policy and infrastructure
The potential for vaccines to prevent suffering and death among children is great and
will continue to increase as new vaccines are developed and traditional vaccines are
improved. Realizing this potential, however, requires carefully developed vaccination
policy recommendations and a delivery infrastructure that is able to conduct the
essential roles of immunization programs: financing the purchase of vaccines,
ensuring that evidence-based strategies are used to raise coverage levels,
monitoring coverage levels and vaccine safety, and conducting surveillance of
vaccine-preventable diseases.




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©2008 Centre of Excellence for Early Childhood Development
    Immunization and Its Impact on Child Neurodevelopment
                                    SUSAN L. HYMAN, PhD
                                University of Rochester, USA
                                  (Published online October 19, 2005)

Topic
Immunization

Introduction
Immunizations have dramatically decreased childhood disability from neurologic
complications of infections such as congenital rubella syndrome, hemophilus influenza
meningitis, measles meningoencephalitis, and the late effect of measles (subacute
sclerosing panencephalitis), among many other examples. With the decreased prevalence
of these infectious diseases, the real and potential neurodevelopmental complications of
the immunizations themselves have become of greater concern to families.1,2 Studies
have linked discrete side effects such as benign febrile seizures with DTP (diphtheria,
tetanus and pertussis) and MMR (measles, mumps and rubella) vaccines.3 Among the
most controversial allegations at present is whether childhood immunizations are
associated with autism.

Subject
It would be a serious public health concern if the prevalence of disabilities in childhood
increased because of the type or number of vaccines being administered. It would be a
similarly serious concern if immunization rates declined and there were a resurgence of
preventable childhood diseases due to concern about potential side effects that have not
been substantiated by scientific data. This summary will describe the controversy linking
immunizations and autism to date.

Problems
The biologic causes of autism are not known, but the evidence indicates a strong genetic
component modified by environmental factors. The questions linking immunizations with
autism spectrum disorders include: 1) Have the prevalence or symptoms of autism
changed with the introduction of new vaccines? 2) Could vaccines given in the second
year of life be associated with the regression in language and social behaviours seen in up
to one-third of children with autism? 3) Do children with autism have more
gastrointestinal symptoms and, if so, is it related to immunization? 4) If not the immune
response to the viral antigen itself, could additives in some vaccines such as thimerosal
produce an immune or toxic response that damages the brain?




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Research Context
Pre-marketing evaluations of vaccines typically examine acute effects emerging over the
two to three months after immunization.4 Clinical data can identify uncommon side
effects once larger numbers of children have been vaccinated. An example is an
intestinal blockage called intussusception associated with the rotavirus vaccine, which
resulted in the vaccine being withdrawn from the market.5 A clinical case series reported
a history of loss of milestones and onset of gastrointestinal symptoms in 12 children with
autism after immunization with measles, mumps and rubella (MMR) vaccine.6 Two lines
of investigation have followed: one looking for evidence of viral infection or
immunologic disorder after immunization in children with autism7,8 and the other looking
for epidemiologic evidence supporting or refuting the association of vaccination
programs and the prevalence of autism on a population level.9,10 A second hypothesis
suggests that mercury exposure, either postnatally11 or prenatally, results in brain damage
leading to autism in susceptible individuals. This represents a separate hypothesis, since
the ethylmercury preservative thimerosal has never been in MMR vaccine.

Research Results
A second case series of 42 children with developmental disabilities (40 with autism
spectrum disorders) evaluated for GI (gastrointestinal) symptoms reported an increased
prevalence of lymphonodular hyperplasia, an enlargement of the regions of the intestine
that produce cells that fight infection.7 This may be a response to non-specific infections
or may indicate specific immunologic abnormalities in the intestine in autism.12 Initial
reports of antibody response to measles virus were based on technology that was not
specific.4,13,14,15 It remains controversial whether measles virus related to the vaccine
strain selectively affects the intestine. Measles virus may persist in multiple body tissues
to maintain the immune response. There is controversy regarding whether the immune
response to concurrently administered antigens such as in the MMR vaccine8 or
sequential natural viral infections16 is associated with intestinal (GI) disease. Biologic
data would suggest that the three vaccines given at once do not alter the immune response
and that current vaccines are less antigenic than those used in the past.17 A GI component
of the autistic disorders may be an independent phenomenon. GE (gastroesophageal)
reflux, increased permeability of the intestine, and increased pancreatic secretions have
all been reported.18 Whether or not GI disease is causally or biologically significant
remains controversial, as does the underlying observation, since children with autism do
not seek medical care for GI complaints any more frequently than children not diagnosed
with autism.19

Epidemiologic data has examined whether the prevalence of autism has increased with
introduction of the MMR in California, Finland and the U.K.2,9,10 No increase in the rates
of autism can be identified relative to the timing of vaccine introduction. No change in
the reports of regression or GI symptoms in cases of children with autism was identified
in the U.K. or France.20,21,22,23 A recent study examining the rates of reported autism in
Denmark among children receiving MMR reported rates comparable to the rate among
children who had not been vaccinated.




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Conclusion
Epidemiologic studies to date have not supported an association between MMR
immunization and autism on a population level. The evidence based on studies examining
viral, histologic and immunologic factors does not support, nor does it refute, the
possibility of rare cases of association.14,15 The Institute of Medicine did not identify
evidence of an association of the preservative thimerosal and autism based on the
currently available data, but noted that mercury is a known neurotoxin and more data
were needed to investigate the potential of this agent to cause neurodevelopmental
symptoms at the doses that were present in vaccines.14,15 Based on the possible potential
for harm and the presence of safe alternatives in terms of vaccine without a preservative,
thimerosal has been removed from vaccinations commonly administered in childhood
while additional research is being completed. No alteration in the currently recommended
immunization schedule has been suggested.

Implications for the Policy and Service Perspectives
Historically, infectious diseases have been a significant source of childhood morbidity
and mortality. To prevent recurrence of these diseases, a high level of immunity is
necessary in the general population. This is why there are rules for immunization at
school entry. Since the epidemiologic data to date indicate that MMR vaccination is not
associated with an increase in autism in the population, the known neurologic and other
serious risks of these preventable diseases is considered to be greater than the risk of the
vaccine. There are no data to suggest that separation of the components of the vaccine
decreases the potential for neurologic side effects. Thimerosal has been removed from
DTaP, H. Flu, and hepatitis B vaccinations. The current initiatives to determine the
prevalence of autism, such as the centres funded by the Center for Disease Control in the
United States, should be able to document whether the rates of diagnosis of autism
spectrum disorders will decrease with the removal of thimerosal from routine
immunizations given in infancy.




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                                          IMMUNIZATION


REFERENCES

1.      Patja A, Davidkin I, Kurki T, Kallio MJT, Valle M, Peltola H. Serious adverse
        events after measles-mumps-rubella vaccination during a fourteen-year
        prospective follow-up. Pediatric Infectious Disease Journal 2000;19(12):1127-
        1134.
2.      Makela A, Nuorti JP, Peltola H. Neurologic disorders after measles-mumps-
        rubella vaccination. Pediatrics 2002;110(5):957-963.
3.      Barlow WE, Davis RL, Glasser JW, Rhodes PH, Thompson RS, Mullooly JP,
        Black SB, Shinefield HR, Ward JI, Marcy SM, DeStefano F, Chen RT, Immanuel
        V, Pearson JA, Vadheim CM, Rebolledo V, Christakis D, Benson PJ, Lewis N.
        The risk of seizures after receipt of whole cell pertussis or measles, mumps, and
        rubella vaccine. New England Journal of Medicine 2001;345(9):656-661.
4.      Halsey NA. The science of evaluation of adverse events associated with
        vaccination. Seminars in Pediatric Infectious Diseases 2002;13(3):205-214.
5.      Peter G, Myers MG. Intussusception, rotavirus, and oral vaccines: Summary of a
        workshop. Pediatrics 2002;110(6):e67.
6.      Wakefield AJ, Murch SH, Anthony A, Linnell J, Casson DM, Malik M,
        Berelowitz M, Dhillon AP, Thomson MA, Harvey P, Valentine A, Davies SE,
        Walker-Smith JA. Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and
        pervasive developmental disorder in children. Lancet 1998;351(9103):637-641.
7.      Wakefield AJ, Anthony A, Murch SH, Thomson M, Montgomery SM, Davies S,
        O'Leary JJ, Berelowitz M, Walker-Smith JA. Enterocolitis in children with
        developmental       disorders.    American      Journal      of    Gastroenterology
        2000;95(9):2285-2295.
8.      Wakefield AJ, Montgomery SM. Measles, mumps, rubella vaccine: through a
        glass, darkly. Adverse Drug Reactions and Toxicological Reviews
        2000;19(4):265-283.
9.      Taylor B, Miller E, Farrington CP, Petropoulos MC, Favot-Mayaud I, Li J,
        Waight PA. Autism and measles, mumps, and rubella vaccine: No
        epidemiological evidence for a causal association. Lancet 1999;353(9169):2026-
        2029.
10.     Dales L, Hammer SJ, Smith NJ. Time trends in autism and in MMR immunization
        coverage in California. JAMA - Journal of the American Medical Association
        2001;285(9):1183-1185.
11.     Bernard S, Enayati A, Redwood L, Roger H, Binstock T. Autism: a novel form of
        mercury poisoning. Medical Hypotheses 2001;56(4):462-471.
12.     Torrente F, Ashwood P, Day R, Machado N, Furlano RI, Anthony A, Davies SE,
        Wakefield AJ, Thomson MA, Walker-Smith JA, Murch SH. Small intestinal
        enteropathy with epithelial IgG complement deposition in children with regressive
        autism. Molecular Psychiatry 2002;7(4):375-382.
13.     Halsey NA, Hyman SL, Conference Writing Panel. Measles-mumps-rubella
        vaccine and autistic spectrum disorder: Report from the new challenges in
        childhood immunization conference convened in Oak Brook, Illinois, June 12-13,
        2000.           Pediatrics          2001;107(5):e84.            Available        at:
        http://pediatrics.aappublications.org/cgi/content/full/107/5/e84. Accessed June 23,
        2005.

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14.     Stratton K, Gable A, Shetty P, McCormick MC, eds. Immunization safety review:
        Measles-mumps-rubella vaccine and autism. Washington, DC: National Academy
        Press; 2001.
15.     Stratton K, Gable A, McCormick MC, eds. Immunization safety review:
        Thimerosal-containing vaccines and neurodevelopmental disorders. Washington,
        DC: National Academy Press; 2001.
16.     Montgomery SM, Morris DL, Pounder RE, Wakefield AJ. Paramyxovirus
        infections in childhood and subsequent inflammatory bowel disease.
        Gastroenterology 1999;116(4):796-803.
17.     Offit PA, Quarles J, Gerber MA, Hackett CJ, Marcuse EK, Kollman TR, Gellin
        BG, Landry S. Addressing parents’ concerns: Do multiple vaccines overwhelm or
        weaken the infant’s immune system? Pediatrics 2002;109(1):124-129.
18.     Quigley EMM, Hurley D. Autism and the gastrointestinal tract. American Journal
        of Gastroenterology 2000;95(9):2154-2156.
19.     Black C, Kaye JA, Jick H. Relation of childhood gastrointestinal disorders to
        autism: nested case-control study using data from the UK General Practice
        Research Database. British Medical Journal 2002;325(7361):419-421.
20.     Taylor B, Miller, E, Lingam R, Andrews N, Simmons A, Stowe J. Measles,
        mumps, and rubella vaccination and bowel problems or developmental regression
        in children with autism: Population study. British Medical Journal
        2002;324(7334):393-396.
21.     Fombonne E, DuMazaubrun C, Cans, C, Granjean H. Autism and associated
        medical disorders in a French epidemiological survey. Journal of the American
        Academy of Child and Adolescent Psychiatry 1997;36(11):1561-1569.
22.     Fombonne E, Chakrabarti S. No evidence for a new variant of measles-mumps-
        rubella-induced autism. Pediatrics 2001;108(4):e58.
23.     Kaye JA, Melero-Montes MD, Jick H. Mumps, measles, and rubella vaccine and
        the incidence of autism recorded by general practitioners: a time trend analysis.
        British Medical Journal 2001;322(7284):460-463.


To cite this document:

Hyman SL. Immunization and its impact on child neurodevelopment. In: Tremblay RE, Barr RG, Peters
RDeV, eds. Encyclopedia on Early Childhood Development [online]. Montreal, Quebec: Centre of
Excellence for Early Childhood Development; 2005:1-5. Available at: http://www.child-
encyclopedia.com/documents/HymanANGxp.pdf. Accessed [insert date].

Copyright © 2005




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                              Autism and Immunization
                             ERIC FOMBONNE, M.D., FRCPsych
     McGill University and The Montreal Children’s Hospital, CANADA
                                  (Published online January 11, 2006)

Topic
Immunization

Introduction
Over the last seven years, a controversy has developed about the possible etiological role
of immunization with respect to autism. The controversy has involved two separate
hypotheses. The first hypothesis posited a link between the Measles-Mumps-Rubella
(MMR) immunization and autism, and more specifically between the measles component
of the MMR vaccine and autism. The second hypothesis involved the exposure of young
children through the immunization schedule to excessive amounts of thimerosal, a
mercury-based chemical used since the 1930s to stabilize vaccine preparation. These two
hypotheses are different, since there is no thimerosal in the MMR vaccine (and never
was). Accordingly, each of these hypotheses has given rise to two separate research
endeavours, which are summarized below.

Recent Research Results
The MMR hypothesis
In 1998, the publication by a prestigious medical journal of a small case series of 12
children presenting in a gastroenterology department in a London hospital raised the
possibility of a new syndrome associating intestinal symptoms, loss of acquired skills and
regression in the course of the development, and autism.1 These children were
presumably normal before the regression, which occurred within 14 days of the MMR
immunization according to retrospective parental reports. However, no attempts were
made to corroborate these retrospective accounts. Neurological investigations showed no
signs of brain inflammation or disorder associated with this clinical picture. Endoscopies
found lymphoid nodular hyperplasia and chronic colitis, both non-specific inflammatory
lesions from the intestine. In the years following this initial report, Wakefield changed his
hypothesis and postulated that atypical patterns of exposure to measles virus were a risk
for chronic intestinal inflammation and for autistic enterocolitis, a presumably new
syndrome. Persistent measles virus infection was thought to increase gut permeability and
allow intake of neurotoxins in the body. In susceptible children, MMR would therefore
increase the risk of intestinal infection and developmental regression.2 Wakefield further
hypothesized that the widespread use of MMR since the 1970s had been responsible for
the epidemic of autism in the world.3 Several of these predictions have been tested, using
a range of different epidemiological designs.


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First, to address the issue of a possible epidemic of autism, several reviews of the existing
literature on this topic indicated that it was not possible to conclude that the incidence of
autism had truly increased over time. Several reports using referral statistics to
educational services were shown to be methodologically flawed4 and inappropriate for
testing the hypothesis of a secular increase in the incidence. Evidence was provided by
several authors5,6,7,8 that a substantial proportion of the increase in prevalence of autism
and related conditions was due to diagnostic switching, changes in diagnostic criteria,
improved detection of autism in populations and increased awareness of the disorder in
the professional and lay audience.

Second, several investigators examined the relationship between changes in
immunization practices and rates of diagnosed autism. If there was an association
between MMR and autism, rates of autism should have increased when MMR
immunization uptake was going up, and conversely. Taylor et al9 investigated this
possibility in a London study where they found no evidence that the massive introduction
of MMR in the U.K. in 1988 was associated with a step-up in the rates of autism, a
finding subsequently replicated in the same country by Chen et al.10 In addition, a case
series analysis conducted by these researchers failed to document a clustering of onset of
autism following MMR immunization. Other ecological studies were conducted by Kaye
et al11 who showed that rates of autism in the U.K. increased between 1988 and 1993, at a
time when there was no change in the uptake of MMR in the population. The same
approach, used by Dales et al12 in California, also indicated that the number of children
diagnosed with autism rose between 1979 and 1995, at a time where MMR coverage in
two-year-old children in that population remained stable. In Sweden, Gillberg and
Heijbel13 compared two birth cohorts born in 1975-1980 and 1980-1984 that had
respectively low and high MMR coverage. In these two cohorts, there were no
differences in the rate of autism and in fact, the rate of autism was slightly lower in the
high MMR coverage cohort.

Third, systematic reviews of adverse events following the introduction of MMR were
carried out in several countries. In Finland, Patja et al14 followed 1.8 million individuals
after the introduction of MMR immunization in that country in 1982. The incidence of
serious events was low (173 serious events; 3.2 per 10,000 vaccine doses), involving a
neurological reaction in 77 children, with no mention of autism ever.

Fourth, since Wakefield had postulated earlier that exposure to the measles virus was also
explaining increasing rates of Crohn’s disease and other inflammatory bowel disorders,
some investigators examined whether or not there was an increase in the rate of
inflammatory bowel disorders in autism. If such an association was found, that could
have given support to Wakefield’s hypothesis. Fombonne15 examined two large series of
1987 subjects with PDD referred in a London hospital and 174 children with autism
included in a large epidemiological survey of educational and psychiatric handicaps in
France. In both datasets, controlled data were available and no cases of Crohn’s disease
or ulcerative colitis were found in any of the autism series, whereas a few cases were
found among the controls, consistent with a low incidence of these disorders in children.
Black et al,16 relying on an electronic database used in general practice in the U.K., also


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failed to document an increased incidence in children with autism compared to controls
of celiac disease, ulcerative colitis, malabsorption, food intolerance and chronic
gastroenteritis.

Fifth, systematic reviews of vaccine safety are regularly performed with monitoring
systems such as the Vaccine Adverse Event Reporting System maintained by the Centers
for Disease Control and Prevention (CDC) in the United States. The CDC also uses the
Vaccine Safety Datalink to perform case control and cohort studies to examine negative
outcomes following exposure to specific vaccines. Before Wakefield’s paper, there had
been no report of autism as a possible adverse event following measles vaccine or MMR
vaccine. Indeed, a systematic review of all the literature performed by the Institute of
Medicine in 1994 reviewed in detail the safety of the triple MMR vaccine, and no
mention of autism can be found in this report.17

Sixth, investigations were performed to validate the new autistic enterocolitis syndrome
postulated by Wakefield. Fombonne and Chakrabarti18 used an epidemiological
representative sample of 96 children with PDD, all but one of whom had received MMR
immunization at the age of 13.5 months. In this epidemiological study, there was no
evidence for an increased incidence of childhood disintegrative disorder, a particular
form of PDD associated with massive regression in development. Compared to another
sample that was not exposed to MMR, no difference was found for the mean age at which
parents first became concerned with their child’s development. In addition, the rates of
regressive autism in exposed and unexposed-to-MMR children were not different,
suggesting that there had been no increase over time in the rates of regressive autism.
Further analyses showed that the children who regressed did not differ from those without
regression for the mean age of parental recognition of symptoms and for their levels of
autistic symptoms. Furthermore, in that study, there was no association between
regression in the developmental course of autistic children and the incidence of
gastrointestinal symptoms. This investigation gave no support for the validation of the so-
called new syndrome of autistic enterocolitis. Another group also showed that regressive
autism had not increased after the introduction of MMR in the U.K.,19 although in this
study, children with regression tended to report more gastrointestinal symptoms. In a
similar vein, DeWilde et al20 used an electronic general practitioner English database and
showed that compared to matched controls, children with PDD were no more likely to
consult their general practitioner in the month following MMR immunization.

Finally, two large epidemiological studies have focused specifically on the role of
individual exposure to MMR and the subsequent onset of autism. In the first study,
Danish children born from 1991 to 1998 were followed from the end of their first year for
several years (n = over 537,000). MMR had been introduced in Denmark in 1987 and
was usually given at the age of 15 months. The study relied on linkages between national
registries to establish diagnostic status and measure exposure. In that large sample, 82%
of children were vaccinated at an average age of 17 months, and 738 children were
diagnosed with autism or PDD at the end of the follow-up period. No association was
found between autism and MMR exposure and between MRR and PDD. The adjusted
risk ratios were below one in a study that was extremely well powered.21 A more recent


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study adopted a case-control design and recruited 1,294 PDD cases matched to 4,469
controls, all selected from the general practitioner research database in the U.K. The
validity of the diagnosis was confirmed on a sub-sample22 and MMR vaccination was not
associated with an increased risk of PDD in that study (adjusted odds ratio .86).23 These
authors also conducted a quantitative analysis of published studies that indicated a
combined odds ratio across studies of 0.87 (95% confidence interval, .76 to 1.001), again
strongly suggestive of no association between MMR exposure and autism. The latter two
studies could not perform separate analyses for the regressive subtype of autism but, as
shown in previous studies attempting to validate the autistic enterocolitis phenotype,
there is little evidence of its distinctiveness. To date, therefore, all epidemiological
studies have failed to document an association between autism and MMR,24 and recent
reviews of this hypothesis by the Institute of Medicine concluded that the evidence was in
favour of rejecting the hypothesis.25

The biological mechanisms that may underlie this association are as yet ill defined.
Uhlmann et al26 have reported an identification of the measles virus genome in the gut of
75 of 91 children with developmental problems, compared to five out of 70 normal
controls. This work has not been replicated in independent laboratories. Concerns have
been raised about the techniques used, the possibility of contamination, and uncertainties
about the identification of the measles virus genome as coming from a vaccine strain.
Even if these findings were replicated, it cannot be inferred that the measles virus is a
cause of autism (rather than a consequence) in a context where all human studies that
have assessed the risk of autism following MMR exposures are negative.

The thimerosal hypothesis
Thimerosal is a form of organic ethyl mercury that has been used since 1930 as a
preservative for stabilization of vaccines. In 1998, the Food and Drug Administration
reviewed the immunization schedule of infants in the U.S. and concluded that exposure to
mercury of infants up to age 18 months exceeded the limits set by various agencies. In
July 1999, a joint statement by the American Academy of Pediatrics and the Public
Health Service called for the removal of thimerosal from all U.S. licensed vaccines. Most
vaccinations now exist in a thimerosal-free format. High-dose exposure to mercury can
produce kidney and neurological damage. Most of the mercury intoxications described in
the literature concern methyl mercury; much less is known about ethyl mercury. Massive
intoxications occurred in industrial disasters, such as in Minamata Bay, Japan, or in Iraq
in the early 1970s. Children exposed to high doses of methyl mercury were followed and
again, no increased incidence of autism has ever been documented. Similarly, two
ongoing cohort studies in the Faroe Islands and the Seychelles are studying the long-term
cognitive and neurological outcomes of prenatal and postnatal exposure to methyl
mercury. In these fish-eating populations, it is well documented that mercury levels are
many times higher than in other populations. The findings from these two cohorts have so
far been inconsistent with subtle psychological deficits (in the areas of attention, memory
and language) reported in the Faroe Islands study,27 whereas the study in the Seychelles28
has failed to replicate these findings.
Following the 1999 thimerosal scare, a controlled observational study was conducted in
Denmark by Hviid et al,29 who compared Danish children who had received thimerosal-


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containing vaccine or thimerosal-free vaccines following a 1992 change in the nationwide
production of pertussis vaccine. The study included over 540,000 children, 407 of whom
were diagnosed with autism and 751 with other PDDs during the study. The adjusted rate
ratios were non-significant both for autism (0.85) and for other PDDs (1.12).
Furthermore, there was no dose-response relationship between increasing levels of
methyl mercury exposure and risk of autism. Another controlled observational study was
conducted in the Vaccine Safety Datalink by Verstratten et al.30 The study was conducted
in two phases and autism was examined as a potential neurodevelopmental outcome
associated with exposure to mercury in the first phase of that study. A sample of 124,000
children were followed in two health maintenance organizations up to the date of an
autism diagnosis or the end of the follow-up period. In the health maintenance
organization where sufficient numbers were detected, 202 children with autism were
identified. Analysis of mercury exposure, treated either as a continuous or a categorical
variable, showed no association with the risk of autism.

Madsen et al31 examined trends in autism rates in Denmark before and after the use of
thimerosal-containing vaccines was discontinued in 1992. Incidence rates were calculated
for the period 1971-2000. The rates remained level up to 1990, when they started to
increase, with a peak in 1999. As autism rates continued to go up after the discontinuation
of thimerosal in the vaccines, the study concluded that there was no support for an
association between thimerosal and autism. A comparable study was conducted in
Denmark by Stehr-Green et al,32 who also showed that rates of autism increased while
thimerosal was progressively eliminated from vaccines in Denmark. The same authors
also included data from Sweden, which showed that the incidence of autism increased in
the mid to late 1980s up to 1993. As for Denmark, rates of autism continued to go up
when thimerosal was practically completely eliminated from the immunization schedule.

Some attempts have been made to reanalyze the CDC data33,34 but methodological flaws
in their analyses have precluded an interpretation of their findings.25 Andrews et al35 have
analyzed the U.K. general practice database between 1988 and 1999. A total of 104
children were diagnosed with autism in this sample of 100,572 children. Hazard ratios for
autism, after receiving increasing doses of thimerosal, were all non-significant.

Conclusion
Thus, there appears to be no epidemiological study that has confirmed a possible increase
in the risk of autism or PDD in children as a function of exposure to the ethyl mercury
used in some vaccine preparations. A review of this hypothesis by the Institute of
Medicine Ad Hoc Committee concluded that the evidence was in favour of rejecting the
hypothesis.25




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REFERENCES

1.      Wakefield AJ, Murch SH, Anthony A, Linnell J, Casson DM, Malik M,
        Berelowitz M, Dhillon AP, Thomson MA, Harvey P, Valentine A, Davies SE,
        Walker-Smith JA. Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and
        pervasive developmental disorder in children. Lancet 1998;351(9103):637-641.
2.      Wakefield AJ, Anthony A, Murch SH, Thomson M, Montgomery SM, Davies S,
        O'Leary JJ, Berelowitz M, Walker-Smith JA. Enterocolitis in children with
        developmental      disorders.    American      Journal   of     Gastroenterology
        2000;95(9):2285-2295.
3.      Wakefield AJ. MMR vaccination and autism. Lancet 1999;354(9182):949-950.
4.      Fombonne E. Is there an epidemic of autism? Pediatrics 2001;107(2):411-413.
5.      Fombonne E. Epidemiological surveys of autism and other pervasive
        developmental disorders: An update. Journal of Autism and Developmental
        Disorders 2003;33(4):365-382.
6.      Gurney JG, Fritz MS, Ness KK, Sievers P, Newschaffer CJ, Shapiro EG. Analysis
        of prevalence trends of autism spectrum disorder in Minnesota [comment].
        Archives of Pediatrics and Adolescent Medicine 2003;157(7):622-627.
7.      Croen LA, Grether JK, Hoogstrate J, Selvin S: The changing prevalence of autism
        in California. Journal of Autism and Developmental Disorders 2002;32(3):207-
        215.
8.      Jick H, Kaye JA. Epidemiology and possible causes of autism. Pharmacotherapy
        2003;23(12):1524-1530.
9.      Taylor B, Miller E, Farrington CP, Petropoulos MC, Favot-Mayaud I, Li J,
        Waight PA. Autism and measles, mumps, and rubella vaccine: no epidemological
        evidence for a causal association. Lancet 1999;353(9169):2026-2029.
10.     Chen W, Landau S, Sham P, Fombonne E. No evidence for links between autism,
        MMR and measles virus. Psychological Medicine 2004;34(3):543-553.
11.     Kaye JA, Melero-Montes MD, Jick H. Mumps, measles, and rubella vaccine and
        the incidence of autism recorded by general practitioners: a time trend analysis.
        BMJ - British Medical Journal 2001;322(7284):460-463.
12.     Dales L, Hammer SJ, Smith NJ. Time trends in autism and MMR immunization
        coverage in California. JAMA - Journal of the American Medical Association
        2001;285(9):1183-1185.
13.     Whiteley P, Rodgers J, Shattock P. MMR and autism. Autism 2000;4(2):207-211.
14.     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. Pediatric Infectious Disease Journal 2000;19(12):1127-
        1134.
15.     Fombonne E. Inflammatory bowel disease and autism. Lancet
        1998;351(9107):955.
16.     Black C, Kaye JA, Jick H. Relation of childhood gastrointestinal disorders to
        autism: nested case-control study using data from the UK General Practice
        Research Database. BMJ - British Medical Journal 2002;325(7361):419-421.




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17.     Institute of Medicine (IOM). Adverse events associated with childhood vaccines:
        Evidence bearing on causality. Washington, DC: National Academies Press;
        1994.
18.     Fombonne E, Chakrabarti S. No evidence for a new variant of measles-mumps-
        rubella-induced autism. Pediatrics 2001;108(4):E58.
19.     Taylor B, Miller E, Lingam R, Andrews N, Simmons A, Stowe J. Measles,
        mumps, and rubella vaccination and bowel problems or developmental regression
        in children with autism: Population study. BMJ - British Medical Journal
        2002;324(7334):393-396.
20.     DeWilde S, Carey IM, Richards N, Hilton SR, Cook DG. Do children who
        become autistic consult more often after MMR vaccination? British Journal of
        General Practice 2001;51(464):226-227.
21.     Madsen KM, Hviid A, Vestergaard M, Schendel D, Wohlfahrt J, Thorsen P,
        Olsen J, Melbye M. A population-based study of measles, mumps, and rubella
        vaccination and autism. New England Journal of Medicine 2002;347(19):1477-
        1482.
22.     Fombonne E, Heavey L, Smeeth L, Rodrigues LC, Cook C, Smith PG, Meng L,
        Hall A. Validation of the diagnosis of autism in general practitioner records. BMC
        Public Health 2004;4:5.
23.     Smeeth L, Cook C, Fombonne E, Heavey L, Rodrigues LC, Smith PG, Hall AJ.
        MMR vaccination and pervasive developmental disorders: a case-control study.
        Lancet 2004;364(9438):963-969.
24.     Fombonne E, Cook EH. MMR and autistic enterocolitis: consistent
        epidemiological failure to find an association. Molecular Psychiatry
        2003;8(2):133-134.
25.     Institute of Medicine (IOM). Immunization safety review: Vaccines and autism.
        Washington, DC: National Academies Press; 2004.
26.     Uhlmann V, Martin CM, Sheils O, Pilkington L, Silva I, Killalea A, Murch SB,
        Walker-Smith J, Thomson M, Wakefield AJ, O'Leary JJ. Potential viral
        pathogenic mechanism for new variant inflammatory bowel disease. Journal of
        Clinical Pathology-Molecular Pathology 2002;55(2):84-90.
27.     Davidson PW, Myers GJ, Cox C, Axtell C, Shamlaye C, Sloane-Reeves J,
        Cernichiari E, Needham L, Choi A, Wang Y, Berlin M, Clarkson TW. Effects of
        prenatal and postnatal methylmercury exposure from fish consumption on
        neurodevelopment: outcomes at 66 months of age in the Seychelles Child
        Development Study. JAMA – Journal of the American Medical Association
        1998;280(8):701-707.
28.     Grandjean P, Weihe P, White RF, Debes F, Araki S, Yokoyama K, Murata K,
        Sorensen N, Dahl R, Jorgensen PJ. Cognitive deficit in 7-year-old children with
        prenatal exposure to methylmercury. Neurotoxicology and Teratology
        1997;19(6):417-428.
29.     Hviid A, Stellfeld M, Wohlfahrt J, Melbye M. Association between thimerosal-
        containing vaccine and autism. JAMA - Journal of the American Medical
        Association 2003;290(13):1763-1766.
30.     Verstraeten T, Davis RL, DeStefano F, Lieu TA, Rhodes PH, Black SB,
        Shinefield H, Chen RT; Vaccine Safety Datalink Team. Safety of thimerosal-


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        containing vaccines: a two-phased study of computerized health maintenance
        organization databases. Pediatrics 2003;112(5):1039-1048.
31.     Madsen KM, Lauritsen MB, Pedersen CB, Thorsen P, Plesner AM, Andersen PH,
        Mortensen PB. Thimerosal and the occurrence of autism: Negative ecological
        evidence from Danish population-based data. Pediatrics 2003;112(3):604-606.
32.     Stehr-Green P, Tull P, Stellfeld M, Mortenson PB, Simpson D. Autism and
        thimerosal-containing vaccines: Lack of consistent evidence for an association.
        American Journal of Preventive Medicine 2003;25(2):101-106.
33.     Geier DA, Geier MR. An assessment of the impact of thimerosal on childhood
        neurodevelopmental disorders. Pediatric Rehabilitation 2003;6(2):97-102.
34.     Geier DA, Geier MR. A comparative evaluation of the effects of MMR
        immunization and mercury doses from thimerosal-containing childhood vaccines
        on the population prevalence of autism. Medical Science Monitor
        2004;10(3):PI33-PI39.
35.     Andrews N, Miller E, Grant A, Stowe J, Osborne V, Taylor B. Thimerosal
        exposure in infants and developmental disorders: a retrospective cohort study in
        the United kingdom does not support a causal association. Pediatrics
        2004;114(3):584-591.


To cite this document:

Fombonne E. Autism and immunization. In: Tremblay RE, Barr RG, Peters RDeV, eds. Encyclopedia on
Early Childhood Development [online]. Montreal, Quebec: Centre of Excellence for Early Childhood
Development;            2006:1-8.            Available            at:           http://www.child-
encyclopedia.com/documents/FombonneANGxp.pdf. Accessed [insert date].

Copyright © 2006




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        Routine Immunization in Young Children
Recommended Vaccine Schedule, Proven Benefits of Vaccines,
Noted Adverse Effects of Vaccines, Best Practices for Vaccine
  Programs, Vaccine Programs for Special Needs and New
       Vaccines Recommended for Young Children
                          NONI E. MACDONALD, MD MSc FRCPc
                              Dalhousie University, CANADA
                                  (Published online August 31, 2004)

Topic
Immunization

Introduction
Our immunization programs for young children are one of the great public health success
stories of the twentieth century. They have changed the face of childhood — literally
saving the lives of thousands of children every year by minimizing or eliminating the
risks of many serious infant and childhood illnesses.1,2 With the exception of safe water,
no other modality, not even antibiotics, has had such a major impact on mortality
reduction and so improved survival.3

Subject
Recommended Immunization Schedule
The National Advisory Committee on Immunization (NACI) provides the federal
government (ie, Health Canada) with ongoing and timely medical, scientific and public
health advice relating to immunization.1 The current NACI-recommended immunization
schedule for children is summarized in Table 1.1,4 Since health is a provincial not federal
responsibility in Canada, each province and territory individually decides which, when
and whether specific vaccines will be included in the vaccine program funded by that
province or territory.5 Unfortunately, this approach has led to an uneven patchwork of
vaccine coverage for children across our land.5,6 For example, as of Dec 2003, the NACI-
recommended newer vaccines (eg, varicella,7 conjugated pneumococcal,8 conjugated
meningococcal,9 and adolescent acellular pertussis10 vaccines [See below.]) that are only
routinely available in some provinces and territories.6 Even though there have been many
calls for a National Immunization Strategy in Canada, as yet we do not have one, in
contrast to the United States, Australia, the United Kingdom and others.5,6,11-14
Benefits of Routine Immunization among Young Children: Lives Saved
Not so many years ago parents and health care workers alike saw first hand the potential
consequences for infants and young children who became infected with the diseases now
prevented by routine immunization programs. In the early 1900s, 5 out of every 1,000


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children born in Canada and the United States died from pertussis (whooping cough)
before they reached their 5th birthday15 and diphtheria (bacteria causing disease that
hinders swallowing and breathing) was one of the most common causes of death in
children from 1 to 5 years of age, killing thousands of children each year.1 Polio (an
infectious viral disease affecting the central nervous system) was a much feared summer
scourge that often killed or crippled.16 Table 2 presents a comparison of the prevalence of
diseases before and after the introduction of routine vaccines.1,2, 8-10,15-18

To reap the benefit from these vaccines, children must be immunized and immunized on
time. These diseases can still kill or maim, even when there is access to modern day
intensive care and antibiotic therapy.19-21 In the mid 1990s, many families living in the
Russian Federation were retaught the lesson of the dangers of diphtheria and the
importance of immunization as diphtheria made a marked resurgence with more than
115,000 cases and 3,000 deaths reported.20 This outbreak occurred in a country where
diphtheria had previously been well controlled. The break up of the former USSR led to
profound social changes that included a dramatic fall off in immunization rates for infants
and children and a failure to give booster doses to adults. Case control studies showed
that those who were immunized were protected; those who were not were in trouble.22
This tragic epidemic was due not to vaccine failure, but to a failure to immunize.

Problems
Adverse Events Less Common with Vaccines than with Disease
Table 3 presents the effects of the disease and the known side effects of the vaccine for
the routine vaccine-preventable diseases for infants and young children.1,8-10,15-17 In
general, all of these diseases are serious and may be fatal, while the vaccine adverse
events, if they occur, are usually minor such as local discomfort and/or inflammation at
the site of the injection and/or mild fever or rash. Research has shown that the local pain
of intramuscular infant immunization with DTaP/IPV/Hib can be diminished by the use
of topical lidocaine-prilocaine without adversely affecting the development of the
protective response from the multicomponent vaccine23 and the pain of multiple infant
injections given during the same visit can be reduced by oral sucrose, oral tactile
stimulation (a bottle or pacifier) and parental holding.24

Serious vaccine adverse events occur with the routine immunizations but are a great deal
rarer than serious events with the diseases.1,2,8-10,15-17 For example, aseptic meningitis (an
infection of the membranes and fluid encasing the brain and spinal cord) occurs in 5% of
those who get mumps (a viral disease which causes swelling of the salivary glands in the
chin and face) and permanent deafness may occur in up to 0.5%.1,2 In contrast, aseptic
meningitis following mumps vaccine with the Jeryl Lynn strain (the type of modified and
weakened mumps viral vaccine strain used in Canada and several other countries) occurs
after less than 1/800,000 doses and maybe as low as 1/3,000,000.2,25 Furthermore, the
vaccine-associated aseptic meningitis is not followed by permanent problems, like
deafness.25

Beyond these known but rare vaccine-associated serious adverse events (Table 3), there
have been periodic allegations that infant vaccines may cause other serious problems
such as SIDS (sudden infant death syndrome),26 and autism.27 However, research has

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shown that these claims are unsubstantiated.28-31 There is no causal relationship between
infant immunization on one hand and SIDS or autism on the other hand. While an event
may have been recognized as happening soon after the receipt of an infant vaccine (ie,
establishing a possible temporal relationship), receipt of the vaccine is not the basis for
the occurrence of an event.32,33

In order to enhance the evaluation of reported serious vaccine events in Canada, the
Advisory Committee on Causality Assessment (ACCA) was set up in 1994 by Health
Canada.33 This expert committee is charged with the task of monitoring signals for
vaccine safety. The committee regularly reviews all reports of serious and unusual
vaccine associated adverse events to determine, through a systematic, standardized
approach whether the association of the event to the receipt of the vaccine is likely
causal, probably causal, possibly causal, unlikely causal, unrelated or unclassifiable.33 On
the international level, the World Health Organization set up the Global Advisory
Committee on Vaccine Safety in 1999 whose task is to respond promptly, efficiently and
with scientific rigor to vaccine safety issues of potential global importance.34

In 1991, to improve the detection of serious vaccine-associated adverse events, vaccine
failures and selected infant and child infectious diseases that are now or are soon to be
vaccine preventable, Health Canada, in collaboration with the Canadian Paediatric
Society and others, piloted a cross-Canada paediatric hospital-based active surveillance
network in 5 centres. The network was then expanded to 11 centres in 1995 and 12
centres in 1999 (IMPACT).35-37 Compiled network data has repeatedly shown that the
routine vaccines for young children are very safe.38 In addition, IMPACT has proven
valuable in detecting rare but unexpected serious events (eg, disseminated Bacille
Calmette-Guerin (BCG) infections in aboriginal infants immunized with BCG39) that
have lead to policy reevaluation.40 IMPACT has also been able to show a sharp decline in
disease following the introduction of a new vaccine41 and a decrease in side effects
following a shift to a new, improved vaccine.42

Research Context
Best Practices for Vaccine Programs
In 1995, NACI initiated a 2-year consultative process to develop guidelines for childhood
immunization practices applicable to both the public and the private systems of vaccine
delivery in Canada. Table 4 provides a brief overview of the guidelines.1 Research has
shown that a number of factors can enhance vaccine uptake, including timely reminders,
quality parent education materials, after-hours and weekend clinics, vaccine uptake
monitoring, multiple vaccines given during one visit, standing orders for vaccines, multi-
component provider education, and the elimination of financial barriers to
immunization.1,5,6,11, 43-47

When it comes to giving consent for immunization, research has shown that what matters
to parents is that they receive the information they need to make an informed
decision,46,48-50 but the mode in which this information is given does not matter.49 Bearing
this in mind, the 2002 edition of the NACI Canadian Immunization Guide was expanded
to include a separate chapter on consent issues and parental concerns regarding
immunization to help health care providers better counsel parents.1 Recognizing that the

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information on vaccines contained in the NACI Canadian Immunization Guide may be
too technical for many parents, the Canadian Paediatric Society supported the
development of a vaccine handbook specifically designed for parents entitled, “Your
Child’s Best Shot,” which was first published in 1997, then updated to include the newer
NACI-recommended vaccines in 2002.2

As noted above, well-informed health care providers are an important factor in enhanced
vaccine uptake, but research has shown that many are not well informed.45,46,50,51 Efforts
to improve on this knowledge deficit include the revamping and upgrading of the NACI
Canadian Immunization Guide, continuing vaccine education events for doctors and
nurses, journal articles, further research, the formation of the Canadian Coalition for
Immunization Awareness and Promotion,52 the formation of the Canadian Association for
Immunization Research and Evaluation53 and the biannual National Immunization
Conference.54

Vaccine Programs for Young Children with Special Needs
While the routine NACI vaccine schedule (Table 1) is appropriate for the majority of
Canadian children there are subgroups with special needs including:
1)   infants and young children born outside of Canada who come as immigrants,
     refugees or foreign adoptees who may not have received all of the vaccines
     recommended in Canada, and/or may not have adequate vaccine documentation.
2)   infants born prematurely
3)   infants and children who are immunocompromised from birth or from disease
4)   infants and children who have bleeding disorders or have a nonfunctional or absent
     spleen
5)   infants and young children who travel to other countries.1 In each of these cases, the
     routine immunization requirements and schedule may need to be adapted.1, 55, 56

Recent Research Results
Newer NACI-recommended Vaccines for Young Children
There are 3 vaccines recently recommended by NACI for infants and young children
which are not yet covered by funded vaccine programs in all of the provinces and
territories.6 These include the varicella vaccine for prevention of chicken pox,7
conjugated pneumococcal vaccine for the prevention of blood infection, pneumonia and
meningitis due to pneumococcal bacteria,8 and conjugated meningococcal vaccine for the
prevention of meningitis and blood infection, again, due to this organism.9 The risks of
these diseases, vaccine benefits and side effects are summarized in Tables 2 and 3. In all
three cases these vaccines have been shown to be safe and effective in preventing serious
diseases in infants and young children, but each is also relatively expensive compared to
the cost of the “regular” infant immunizations.57 The prohibitive costs of these vaccines
has led to delays and disparities in having these vaccines added to the “routine” list
covered by each province and territory.5,6,47 A similar problem exits for the acellular
pertussis vaccine for adolescents and adults. While acellular pertussis vaccine is available
across Canada for infants and young children, despite NACI recommendations, the
acellular vaccine for adolescents and adults is not yet routinely available across the
country. Widespread use of this vaccine in adolescents and adults has the potential to


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decrease pertussis in families and thus decrease exposure of infants who are too young to
be immunized (ie, less than 6 weeks of age), the group at highest risk for fatal disease.58

Conclusions
The NACI-recommended vaccines for young children are a safe and effective means of
eliminating or minimizing the risks of many serious infant and childhood illnesses.
Infants and children who are not immunized continue to be at risk. The NACI Canadian
Guide to Immunization1 is the best detailed source of information on all aspects of
immunization for health care providers and Your Child’s Best Shot2 provides quality
information for parents.

Implications
A National Immunization Program is needed to improve equity of access across this
country to all of the NACI-recommended vaccines for infants and young children in order
to be able to protect all of our children from the potential damage incurred by a vaccine-
preventable disease. Not ensuring equity of access means many infants and children
remain at risk for problems such as acquired deafness from meningitis due to
pneumococal infection, along with its profound developmental implications. Policy
makers at the federal, provincial, and territorial levels must work together to ensure a
National Immunization Program for Canadian infants and children so that all have access
to NACI-recommended vaccines.




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                                       Table 1
              NACI-recommended Immunization Schedule for Infants and Children
                                              (from references 1, 8-10, 15-18)


Age at      DTaP         IPV      Hib     MMR dTapλ             HepB          Vλ   PC*λ   MC**λ Influenza
Vaccination                                   or Td             (3 doses)
Birth                                                           Infancy or                        Before influenza
                                                                pre-                              season in those
                                                                adolescence                       over 6 months, esp.
                                                                                                  in high risk
                                                                                                  categories
 2 months      x         x        x                                                x      x
4 months       x         x        x                                                x      x

6 months       x         x        x                                                x      x
12 months                                 X                                   x    x      x
18 months      x         x        x       x or
4–6 years                                 X
14–16 years                                         x                                     x

              DTaP   Diphtheria, tetanus, pertussis (acellular), infant and young-child-type vaccine
              IPV    Inactivated polio vaccine
              Hib    Heamophilus influenzae type-b conjugate vaccine
              MMR     Measles, mumps, rubella vaccine
              dTap   Tetanus and diphtheria toxoid, (acellular) pertussis, adolescent/adult-type
                     vaccine
              Td     Tetanus and diphtheria toxoid, adult-type vaccine
              HepB Hepatitis B vaccine
              V       Varicella vaccine
              PC      Pneumococcal conjugate vaccine
              MC      Meningococcal conjugate vaccine
              Influenza Influenza virus vaccine

              * Conjugated pneumococcal vaccine: Doses at 2, 4 and 6 months, followed by one dose
              at 12–15 months of age.8
              ** Conjugated meningococcal vaccine: If started at 2 months ― 3 doses; if started at 4 to
              11 months ― 2 doses; if started at >/= 12 months ― 1 dose.9

              λ While all recommended by NACI, acellular pertussis for adolescents, varicella,
              conjugated pneumococcal, and conjugated meningococcal vaccines are not currently
              available in all Canadian provincial and territorial infant and childhood immunization
              programs.



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                                          Table 2
            Serious Illnesses in Infants, Children and Youth in Canada in the
              Pre- and Post-Vaccine Eras (from references 1, 2, 8-10,15-18)

 Disease/          Incidence                                 Incidence After Vaccination
 Organism          Before Vaccination
 Polio             2.5 to 28.3/100,000                       Disease eradicated from Canada and
 3 types of polio  Epidemics: up to 20,000                   from most countries in the world.
 virus             cases of paralysis.
 Diphtheria        In 1924, 9,000 cases                      No cases reported since 1996, and
                   reported. Major cause of                  prior to this only 2–5 per year.
                   death in 1 to 5 year olds.
 Tetanus           60 to 75 cases per year, with             Less than 2 cases per year in past 15
 (lock jaw)        40 to 50 deaths                           years.
 Pertussis         Over 150/100,000 cases per                10/100,000 cases per year with 1 to
 (whooping cough) year with 50 to 100 deaths.                3 deaths in very young infants.
 Heamophilus       Overall 2,000 cases per year              Less than 50 cases per year. Rare
 influenzae type b with 1500 in those <5 years               cause of bacterial meningitis in
                   of age. Leading cause of                  infants.
                   bacterial meningitis in
                   infancy.
 Measles           Cyclic epidemics every 2-3                Now fewer than 400 cases per year.
                   years. 300,000–400,000
                   cases per year.
 Mumps             About 30,000 reported cases               Less than 500 cases per year.
                   per year but many more not
                   reported
 Rubella           About 250,000 cases per                   Less than 100 cases reported per
                   year, with over 200                       year, 1 to 2 congenital rubella
                   congenital rubella syndrome               syndrome (CRS) /year.
                   (CRS)/year
 Influenza               Yearly epidemics with up to         Since influenza virus changes on a
                         20% of the population being         yearly basis, yearly vaccination is
                         infected. Wide variation in         required. Current program is aimed
                         annual incidence. Last              at high risk with limited uptake by
                         major outbreak: 1968 with           others. With well-matched vaccine–
                         50 million cases, 33,000            influenza in community, 70–90% of
                         deaths.                             illness is prevented, if
                                                             immunocompetent. If ill-matched, it
                                                             is only 30–60% protective. Less
                                                             effective if not immunocompetent.




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                                               Table 2
                                               (cont’d)

 Disease/                Incidence                           Incidence After Vaccination
 Organism                Before Vaccination
 Hepatitis B             20,000 new infections per           From 1992 to 2002 in BC after
                         year, 1 in 200 people in            adopting a Grade 6 vaccine program,
                         population is a chronic             overall rate acute infection fell from
                         carrier. BC had a rate of           7 to 2/100,000 and in 12 to 21 year
                         33.7/100,000 in 1992.               olds from 1.7 to 0/100,000.
                         Risk of transmission from
                         an infected mother to her           Immunization of newborn infants
                         newborn infant is 90%.              prevents transmission from mother
                                                             in > 90% of cases.
 Varicella               Infection in 50% of children        Varicella mortality in the US has
 (Chicken pox)           by age 5 and 90% by age             decreased by 76% with national
                         12.                                 program and coverage rates of 80%
                                                             in less than 3 year olds.
 Streptococcus           About 500,000 cases of              Conjugated heptavalent vaccine for
 pneumoniae              pneumococcal diseases per           infants only licensed in Canada in
                         year with over 200,000 in           2001.
                         children under 5 years of
                         age.                                In the US, clinical trials in infants
                         Rate of invasive disease            showed vaccine efficacy of 94% for
                         <5 years 35–64/100,000;             invasive diseases due to strains in
                         < 2 years 59–112/100,000.           vaccine and 89% for invasive
                                                             disease due to any pneumococcal
                                                             strain.
 Neisseria               Endemic in Canada with              Conjugated group C vaccine for
 meningitidis            epidemics every 10 to 15            infants only licensed in Canada in
                         years. 200 to 350 endemic           2001.
                         cases per year. Rates in 3
                         highest age groups:                 In UK, routine infant immunization
                         <1 years 11.3/100,000;              started in 1999 with follow up
                         1–4yr 2.4/100,000;                  campaign for children and
                         15 to19 years 1.5/100,000.          adolescents has decreased disease by
                                                             >90%.
                         Serogroups in 2001:
                         A ― rare;
                         B ―28%;
                         C ― 59%;
                         W 135 ―3%;
                         Y ― 10%.




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                                      Table 3
    Comparison of Effects of Serious Infant and Childhood Diseases and Adverse
              Effects of Vaccines (from references 1, 2, 8-10, 15-17)

Disease/             Effects of Disease                      Side Effects of Vaccine*
Organism

Polio                4–8% have minor illness, 1%             Local discomfort or redness at
                     get severe disease- paralytic           the site of injection in 5%.
                     polio, 1 in 20 hospitalized             Killed vaccine so no risk of
                     patients die and 50% remain             vaccine-associated polio.
                     paralyzed.
Diphtheria           5–10% of cases die even with            DTaP vaccine: Local
                     ICU care, antitoxin and                 discomfort, swelling and /or
                     antibiotics. The toxin may lead         redness at the site of injection
                     to neurological and cardiac             in 20%, fever in 5%. A
                     complications.                          transient nodule may occur at
                                                             the injection site, lasting for a
                                                             few weeks. Up to 70% develop
                                                             redness and swelling at the 4-
                                                             6yr booster.
Tetanus              10% of cases die, even with             See above for DTaP. Local
(lock jaw)           ICU care, antitoxin and                 reactions increase with age,
                     antibiotics. Risk is greatest for       esp. in adults with Td boosters.
                     the very young and the very             Peripheral nerve damage has
                     old.                                    rarely been reported
                                                             (<1/1,000,000).
Pertussis            1/400 infants with pertussis            As above for DTaP.
(whooping            die, 1/400 sustain permanent            Far fewer side effects with the
cough)               brain damage. If under 6                acellular pertussis (aP) vaccine
                     months, 1% of cases die from            than the previous whole-cell
                     pneumonia or fatal oxygen               pertussis vaccine (P).
                     deprivation of the brain.
Heamophilus          5% of cases of meningitis die,          Usually in combination, as
influenzae type b    10–15% have permanent brain             with DTaP/IPV/Hib. See
                     damage and 10–20% have                  above for side effects (same as
                     deafness.                               for DTaP).
Measles              10% have complications such             Usually in combination, as
                     as pneumonia, ear infections.           with MMR. 5–10% have
                     1/1,000 have encephalitis               discomfort or local swelling
                     (infection of the brain) with           and fever, with or without a
                     10% dying and 25% being left            rash.
                     with permanent brain damage,            1/24,000 have low platelets
                     1/25,000 have SSPE (a delayed           <1/1,000,000 have
                     fatal degenerative brain                encephalitis.
                     disease.


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                                               Table 3
                                               (cont’d)

Disease/        Effects of Disease                           Side Effects of Vaccine*
Organism

Mumps           1/20 develop aseptic meningitis              Local discomfort, swelling and
                (viral infection of tissues and fluids       redness or fever in 5–10%.
                around the brain). 1/200 develop             1% develop parotitis (swelling
                encephalitis. 1/200,000 are left             of the largest salivary gland,
                deaf. Inflammation of testicles in           the parotid).
                20–30% of males; inflammation of             1 in 3 million develop aseptic
                ovaries in 5% of post-pubertal               meningitis.
                females.

Rubella         50% have rash, swollen glands,               10% have local discomfort and
                fever; 50% of adolescents and                fever, 5% have swollen glands,
                adults have arthritis and arthralgias;       arthralgias (esp. adults), stiff
                1/6,000 have encephalitis. In the            neck. 1% develop
                first 10 weeks of pregnancy, 85%             noninfectious rash.
                risk of congenital rubella syndrome
                causes death of fetus, deafness,
                blindness and/or heart disease.
Influenza       Highest mortality rate in those over         Local mild reactions at
                65 years and in infants aged                 injection site and/or low fever
                <12 months. Complications:                   for 1 to 2 days in up to 60%.
                pneumonia, febrile seizures,                 Occasional mild
                encephalitis, myocarditis, and               oculorespiratory syndrome.
                myositis, Reye’s syndrome.                   Rare: Guillian-Barre syndrome
                                                             1/1,000,000.
Hepatitis B     Variable: asymptomatic to                    15% experience local
                overwhelming liver disease.                  discomfort and occasionally
                Neonate asymptomatic,                        experience low-grade fever.
                5–15% of 1 to 5 year olds have
                symptoms, 33–50% older children
                egg nausea, jaundice, fever,
                vomiting, big liver, spleen.
                < 1% fulminating fatal liver failure.
                Chronic disease 90% infants,
                25–50% of 1 to 5years, and
                6 to 10% older children. Risk liver
                cancer, liver failure with chronic
                disease.




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                                               Table 3
                                               (cont’d)
Disease/            Effects of Disease                       Side Effects of Vaccine*
Organism

Varicella           Death rate 1–3 /100,000 cases in         15–20% experience mild
(chicken pox)       children. Complications in 5–            swelling, discomfort at
                    10% of previously healthy                injection site and/or fever.
                    children: pneumonia,                     1–5% develop mild rash.
                    encephalitis (1/5,000), cerebellar
                    ataxia (1/4,000), osteomyelitis,
                    hepatitis, septic arthritis. In 50%
                    of children who get flesh-eating
                    disease (necrotizing fascitis),
                    chicken pox precedes it.
                    Shingles in adults. Congenital
                    varicella syndrome.
Streptococcus       Leading cause of invasive                Heptavalent infant/ toddler
pneumoniae          bacterial disease in young               conjugate vaccine well
                    children. Annual cases: 65               tolerated. Mild local reactions
                    meningitis (hearing loss 20–             from 10–15%.
                    30%, brain damage 15–20%),
                    700 cases bacteremia, 2,200
                    cases hospitalized with
                    pneumonia, 9,000 cases non-
                    hospitalized pneumonia. Case
                    fatality rate
                    <6 months 4.3%, 12 years 2%.
                    15 deaths/year in <5 years.
                    Sickle cell disease, HIV more at
                    risk bad disease.
Neisseria           Meningitis 30–50% (MR 5%),               Infant/toddler conjugate C
meningitidis        meningitis + bacteremia 40%,             vaccine: local mild reactions
                    bacteremia alone 7–10% (MR               less common than with
                    20-40%). Other complications:            DTaP/IPV/Hib, severe
                    arthritis, pneumonia, peritonitis.       reactions are very rare.
                    Case fatality rate 10% despite
                    ICU/antibiotics. Highest
                    mortality rate (MR): <1 year
                    1/100,000.

* Anaphylaxis, a potentially life-threatening allergic reaction, occurs rarely (0.11 to 0.31
reports per 100,000 doses of vaccine distributed). It is rarer in infants and young children
and occurs within 30 minutes of receipt of vaccine. Can be treated with an injection of
epinephrine.



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Table 4 National Guidelines for Childhood Immunization Practices: Summary*

1. Immunization services should be readily available.
2. There should be no barriers or unnecessary prerequisites to the receipt of vaccines.
3. Providers should use all clinical encounters to screen for needed vaccines and, when
   indicated, vaccinate children.
4. Providers should educate parents in general terms about immunization.
5.   Providers should inform parents in specific terms about the risks and benefits of the
     vaccines their child is to receive.
6. Providers should recommend deferral or withholding of vaccines for true
    contraindications only.
7. Providers should administer all vaccine doses for which a child is eligible at the time
    of each visit.
8. Providers should ensure that all vaccinations are accurately and completely recorded.
9. Providers should maintain easily retrievable summaries of the vaccination records to
    facilitate age-appropriate vaccination.
10. Providers should report clinically significant adverse events following vaccination
    promptly, accurately, and completely.
11 Providers should report all cases of vaccine-preventable diseases as required under
    provincial and territorial legislation.
12. Providers should adhere to appropriate procedures for vaccine management.
13. Providers should maintain up-to-date, easily retrievable protocols at all locations
    where vaccines are administered.
14. Providers should be properly trained and maintain ongoing education regarding
    current immunization recommendations.
15. Providers should operate a tracking system.
16. Audits should be conducted in all immunization clinics to assess the quality of
    immunization records and assess immunization coverage levels.

*Adapted from the Canadian Immunization Guide, 6th edition.1




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        Dec1-3, 2002. CCDR - Canada Communicable Disease Report 2003;29(S4):1-24.
        Available at: http://www.phac-aspc.gc.ca/publicat/ccdr-rmtc/03pdf/29s4e.pdf .
        Accessed July 26, 2004.
55.     Health Canada. Population and Public Health Branch. Travel Medicine Program.
        Available at: http://www.travelhealth.gc.ca. Accessed July 26, 2004.
56.     Children and youth new to Canada: A health care guide. Ottawa, Ontario:
        Canadian Paediatric Society; 1999.
57.     Tengs TO, Adams ME, Pliskin JS, Safran DG, Siegel JE, Weinstein MC, Graham
        JD. Five-hundred life-saving interventions and their cost-effectiveness. Risk
        Analysis 1995;15(3):369-390.
58.     Mikelova LK, Halperin SA, Scheifele D, Smith B, Ford-Jones E, Vaudry W,
        Jadavji T, Law B, Moore D, members of the Immunization Monitoring Program,
        Active (IMPACT). Predictors of death in infants hospitalized with pertussis: a
        case-control study of 16 pertussis deaths in Canada. Journal of Pediatrics
        2003;143(5):576-581.


To cite this document:

MacDonald NE. Routine immunization in young children recommended vaccine schedule, proven benefits
of vaccines, noted adverse effects of vaccines, best practices for vaccine programs, vaccine programs for
special needs and new vaccines recommended for young children. In: Tremblay RE, Barr RG, Peters
RDeV, eds. Encyclopedia on Early Childhood Development [online]. Montreal, Quebec: Centre of
Excellence for Early Childhood Development; 2004:1-17. Available at: http://www.child-
encyclopedia.com/documents/MacdonaldANGxp.pdf. Accessed [insert date].

Copyright © 2004




Encyclopedia on Early Childhood Development                                                           17
©2004 Centre of Excellence for Early Childhood Development
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               Current Immunization Practices and
      Their Effects on Young Children’s (Birth to Five Years)
                Social and Emotional Development
                                   SCOTT A. HALPERIN, MD
           Dalhousie University and the IWK Health Centre, CANADA
                                  (Published online October 22, 2004)

Topic
Immunization

Introduction
Although it has been over 200 years since the first successful immunization against
smallpox was made by Edward Jenner, only during the last century have vaccines had
their greatest impact. Indeed, immunization has been identified as one of the greatest
public-health achievements of the 20th century.1 Through immunization, smallpox and
polio have been eradicated from the western hemisphere and global eradication may be
achieved within the next five years. Cases of measles have been reduced by over 99% in
the western hemisphere, and tetanus (lockjaw), diphtheria (a serious infection of the
throat that can be fatal), pertussis (whooping cough), invasive disease caused by
Haemophilus influenzae type b, congenital rubella syndrome (infection of the fetus if the
mother gets rubella [German Measles] during pregnancy, which leads to severe birth
defects including mental retardation, cataracts, heart defects and deafness) and mumps
have been reduced by over 90% in jurisdictions using universal immunization.
Vaccination is also one of the most cost-effective medical interventions; in contrast to
most other medical interventions, most immunization programs for young children are
cost-saving.2

Subject
In Canada, the National Advisory Committee on Immunization (NACI)3 recommends
that all children be immunized at two, four, six and 18 months of age against diphtheria,
tetanus, polio, pertussis and H. influenzae type b (meningitis, epiglottitis [infection of the
throat], cellulites [infection just below the skin], septic arthritis [infection of the joints]
and pneumonia [infection of the lung]). In all provinces and territories, this is
accomplished by a single combination vaccine (diphtheria-tetanus-acellular pertussis-
inactivated polio-H. influenzae b [DTaP-IPV-Hib]). A fifth dose of DTaP-IPV (without
the H. influenzae b) is given at four to six years of age, at the time of school entry. Two
doses of a combined measles, mumps (orchitis [infection of the testicles], parotitis
[infection of the salivary gland], meningitis), rubella vaccine (MMR) are given; the first
at 12 months of age and the second either at 18 months of age or at the preschool visit.
Hepatitis B vaccine is given to all Canadian children either as a three-dose infant series

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(variably at birth, one and six months; two, four and 18 months; birth, two and 12
months) or a pre-adolescent two- or three-dose series sometime between nine and 12
years of age. New vaccines recently recommended by NACI include varicella
(chickenpox) vaccine at 12 months of age,4 pneumococcal (meningitis, pneumonia, otitis
media) conjugate vaccine at two, four, six and 12 to 15 months of age,5 meningococcal C
(meningitis, sepsis) conjugate vaccine at two, four and six months of age,6 and a mid-
adolescent dose of an adult formulation of diphtheria-tetanus-acellular pertussis vaccine
(Tdap).7 These last four vaccines have been variably implemented by the provinces and
territories; by autumn 2004, most have implemented the Tdap vaccine, but only half have
implemented the varicella vaccine and fewer still have implemented the meningococcal
or pneumococcal conjugate vaccines.8 The most recent vaccine recommendation from
NACI is for the universal annual influenza immunization of infants between six months
and two years of age for the 2004-2005 flu season.9

Problems
As new vaccines providing protection against additional infectious diseases become
available, NACI will make recommendations on how they should be used.3 However,
implementation of vaccine programs falls under provincial/territorial jurisdiction, which
can lead to regional variability in immunization schedules and inequities in access to
publicly funded vaccine programs. Conversely, despite these enormous accomplishments,
immunization programs are the victims of their own success. As the diseases against
which the vaccines protect become more uncommon, they also become less feared by the
population. Vaccine-associated adverse events that are uncommon become relatively
more frequent as the diseases and their manifestations become more rare. Vaccines that
are being used in healthy children become more feared by parents than diseases that they
have never seen. This makes vaccines easy targets for allegations that suggest they cause
a host of conditions for which there are no other proven explanations. This further erodes
public confidence in vaccination programs, with the risk that vaccine uptake will drop
and the diseases they prevent will return.10

Research Context
Before licensure, vaccines are studied in healthy adults and children to determine their
safety, immunogenicity (ability to elicit protective antibodies or cellular immune
responses) and efficacy (their ability to protect against the target diseases under clinical
trial conditions). Post-licensure, vaccines are evaluated for safety and effectiveness (how
they protect against the target diseases under conditions of normal use). Allegations of
rare adverse events caused by vaccines are investigated through epidemiological and case
control studies. The public is most attuned to these post-licensure studies and
programmatic monitoring that demonstrates ongoing vaccine safety.

Research Questions
Although there are many vaccine-related research questions, the questions of most
importance to parents and vaccinators concern vaccine safety. These can be divided into
three basic questions: 1) Is there any truth to the allegations that vaccines cause rare
unrelated diseases (such as multiple sclerosis, autism or Crohn’s disease)? 2) Is there



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ongoing evidence that current immunization programs are safe? and 3) How do parents
make immunization decisions for their children?

Recent Research Results
1.      Investigating allegations
There is clear evidence that vaccines can be associated with rare adverse events. For
example, live attenuated polio vaccine causes paralytic disease (vaccine associated
paralytic polio) after the first dose in one out of 750,000 doses administered,11 measles
vaccine may cause encephalopathy after one in a million doses,12 and Guillain-Barré
Syndrome has been associated with influenza vaccines containing certain strains (swine
flu, for example).13 However, it has been alleged, and subsequent research has refuted,
that vaccines cause a wide range of problems for which no other pathogenic explanation
is currently known, including pertussis vaccine and sudden infant death syndrome
(SIDS)14 and permanent brain damage;15 measles vaccine and inflammatory bowel
disease;16 hepatitis B vaccine and multiple sclerosis;17 and thimerosal as a vaccine
preservative and autism.18 The most recent vaccine allegation is that the apparent increase
in cases of autism observed over the past two decades is a result of the combined MMR
vaccine, which overwhelms the immune system with three simultaneous viral infections
causing increased gut permeability to neurotoxins, thereby causing irreversible brain
damage leading to autism.19 As a result of these unproven allegations, uptake rates of
MMR vaccine have declined, particularly in the United Kingdom, with a resultant
increase in reported cases of measles.20 Well designed epidemiological studies have
demonstrated that there is no association between the apparent increase in reported cases
of autism and the use of MMR vaccine. In a retrospective cohort study of all births in
Denmark between 1991 and 1998, representing over 530,000 people and 2.1 million
person-years of observation, there was no increased risk of autism associated with receipt
of MMR vaccine.21 In two related studies from the UK, Taylor and colleagues were
unable to detect a correlation between autism and receipt of MMR.22,23 A retrospective
study in Finland examined MMR vaccination records with hospital discharge data in over
500,000 children and found no clustering of hospitalization for autism within three
months of vaccination.24 In the United States, a case-control study of children with
autism in Atlanta showed similar rates of MMR immunization in cases and controls,
suggesting there was no temporal link between autism and MMR immunization.25 A
study in California demonstrated increasing rates of autism between 1980 and 1994 with
steady immunization rates, suggesting no link between MMR immunization and autism.26
Indeed, the increase in cases of autism may be the result of changes in the case definition
and more complete reporting.27 While there does not appear to be evidence that these
allegations have affected immunization rates in Canada, firm data may be lacking.28

2.     Ongoing programmatic monitoring of vaccine safety
In Canada, vaccine-associated adverse event (VAAE) surveillance is the responsibility of
the Immunization and Respiratory Disease Division of the Centre for Infectious Diseases
Prevention and Control of the Population and Public Health Branch of Health Canada,
which uses both active and passive surveillance methodology to monitor vaccine safety.
In the passive system, VAAEs are reported by health-care providers through provincial
public-health authorities to a national database. Severe VAAEs are reviewed by an


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expert advisory committee (Advisory Committee on Causality Assessment) to determine
the relationship of the event to immunization. Health Canada’s active surveillance system
for VAAEs, which is called IMPACT (Immunization Monitoring Program, Active), is
based in 12 pediatric hospitals across Canada that account for over 90% of the tertiary-
care pediatric beds in Canada and serve as the local hospital for 45% of Canada’s
pediatric population.29 IMPACT is a partnership between Health Canada and the
Canadian Paediatric Society. Pediatric infectious disease specialists at each IMPACT site
supervise a nurse monitor who each day surveys all hospital admissions for selected
adverse events ─ potentially related to preceding immunization ─ as well as hospital
admissions and complications of vaccine-preventable diseases. Recent studies from the
IMPACT network have provided some reassuring information about the safety of
vaccines. In one study, IMPACT showed that the number of febrile seizures (fits
associated with high fevers) requiring hospitalization decreased by 79% and the number
of hypotonic-hyporesponsive (rag-doll like) episodes decreased by 60 to 67% after
Canada switched from using the whole-cell pertussis vaccine to the use of acellular
pertussis vaccine in 1997-1998.30 In a second report, IMPACT showed the lack of
encephalopathy or encephalitis (dysfunction or inflammation of the brain) caused by
pertussis containing vaccines during an 11-year period.31 In a third study, IMPACT
described the Canadian experience with the rare association of thrombocytopenia
(decrease in the number of platelets, blood cells that help stop the blood vessels from
leaking) and measles containing vaccines and showed that, in general, there is usually a
good outcome after this complication.32 On the vaccine-preventable disease surveillance
front, IMPACT has recently described the continued severity of pertussis in infants too
young to have completed their three-dose primary immunization series33 and the near
elimination34 and continued control35 of invasive disease caused by H. influenzae type b
after the implementation of universal infant immunization.

3.      What parents want to know about immunization and from whom they want to
        hear it
Recent studies into the knowledge, attitudes, beliefs and behaviours of parents about
immunization have been very informative and must be considered as new vaccine
programs are planned. Parents have many misconceptions about vaccines. They want to
understand the diseases for which their child is being immunized and receive an
explanation of the risks and benefits of each vaccine.36-40 Given the number of vaccines
currently recommended, this       task might appear daunting; however, studies have
demonstrated that parents want information presented in a concise format that can be
accomplished with an increase in contact with the health-care provider of only a few
minutes.41-43 Of utmost importance to parents is the mode of information transfer; while
written information is valued, it must be delivered in conjunction with a face-to-face
discussion with the health-care provider.43,44 Multiple studies have demonstrated that the
most valued factor and critical component in a parent’s decision to immunize is the
recommendation of their doctor or nurse.37,45 Program planners must consider this
observation and be aware that some health-care providers may not always be the best
advocates for immunization, and they themselves may need to be the target of education
programs.46,47



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Conclusions
Immunization programs in Canada have been successful in decreasing the incidence of
their target diseases by over 90%. However, despite these successes, challenges to
vaccine programs exist. Because the diseases have become less common as a result of
immunization, familiarity with and fear of these diseases has diminished and concern
with the vaccines has increased. Vaccines for diseases that are no longer common are
easy targets for unproven allegations about their safety, further jeopardizing gains
achieved through immunization. This has led to the need for equally effective but safer
vaccines and the need to pay more attention to educating and reassuring parents about
diseases and vaccines. At the same time as old vaccine programs need attention to
maintain their relevance in the minds of the public, new vaccines and new vaccine
programs are being introduced. Differences among the provinces and territories in which
vaccines are publicly funded cause confusion and create inequities across the country. It
is hoped that the recent joint federal and provincial/territorial initiative called the
National Immunization Strategy48 will diminish the variability of programs in Canada.

Implications
As Canada moves its national immunization strategy forward, it must take into account
the lessons learned from the past. Immunization programs would benefit from
standardization across Canada. New vaccines, including quadravalent meningococcal
conjugate vaccine (a vaccine against the four most common types of Neisseria
meningitidis, a bacteria that causes meningitis), nasal influenza vaccines, group A
streptococcal vaccine and human papillomavirus vaccine (an infection of the cervix that
predisposes a woman to cervical cancer), are not far from being available. Although
safety, immunogenicity and efficacy data are essential to license a vaccine,
epidemiological and social science research (knowledge, attitudes, beliefs and
behaviours) is needed before programs are implemented. Information from research must
be made available to parents and vaccinators in an easily accessible format. Many good
resources are already available for parents and providers, including books49,50 and Web
sites, some of which contain vaccine information brochures:
     • Canadian Paediatric Society www.cps.ca
     • Canadian Coalition for Immunization Awareness and Promotion
         www.immunize.cpha.ca
     • Division of Immunization and Respiratory Diseases, Health Canada
         http://www.hc-sc.gc.ca/pphb-dgspsp/dird-dimr/
     • It’s Your Health www.hc-sc.gc.ca/english/iyh
     • National Immunization Program of the Centers for Disease Control and
         Prevention (US) www.cdc.gov/nip
     • Immunization Action Coalition (US) www.immunize.org; Vaccine information
         for the public www.vaccineinformation.org
     • National         Network       for     Immunization        Information       (US)
         www.immunizationinfo.org
     • National Partnership for Immunization (US) www.partnersforimmunization.org.




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        professionals' level of confidence in the vaccine and attitudes towards the second
        dose. Communicable Disease & Public Health 2001;4(4):273-277.
48.     F/P/T Advisory Committee on Population Health and Health Security (ACPHHS).
        National immunization srategy: Final report 2003 to the Conference of F/P/T
        Deputy Ministers of Health. Ottawa, Ontario: Minister of Health; 2004. Cat. No.
        H39-4/15-2003. Available at: http://www.phac-aspc.gc.ca/publicat/nis-sni-
        03/pdf/nat_imm_strat_e.pdf. Accessed March 12, 2008.
49.     Gold R. Your child's best shot: A parent's guide to vaccination. 2nd ed. Ottawa,
        Ontario: Canadian Paediatric Society; 2002.
50.     Offit PA, Bell LM. Vaccines: What you should know. 3rd ed. Hoboken, NJ: John
        Wiley; 2003.




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To cite this document:

Halperin SA. Current immunization practices and their effects on young children’s (birth to five years)
social and emotional development. In: Tremblay RE, Barr RG, Peters RDeV, eds. Encyclopedia on Early
Childhood Development [online]. Montreal, Quebec: Centre of Excellence for Early Childhood
Development;              2004:1-10.            Available            at:             http://www.child-
encyclopedia.com/documents/HalperinANGxp.pdf. Accessed [insert date].

Copyright © 2004




Encyclopedia on Early Childhood Development                                                         10
©2006 Centre of Excellence for Early Childhood Development
Halperin SA
                               Childhood Immunization
                                  LANCE E. RODEWALD, MD
       National Immunization Program, Centers for Disease Control and
                              Prevention, USA
                                  (Published online October 19, 2005)

Topic
Immunization

Introduction
Childhood immunization is one of public health’s greatest achievements.1 As a result of
successfully implemented childhood immunization programs, the incidences of vaccine-
preventable diseases are at all-time low levels; measles and polio no longer circulate in
the Americas; and the death of a child from a vaccine-preventable disease is a rare event.

Immunization is a clinical preventive service that is recommended for virtually every
child in the world. Although immunization schedules vary from country to country, every
country implements a basic set of immunizations that help infants survive so that they can
grow and develop into healthy adults.

Subject
In the U.S. and Canada, children are now routinely protected against 12 vaccine-
preventable diseases: diphtheria, tetanus, pertussis (whooping cough), poliomyelitis,
hepatitis B, invasive haemophilus influenzae disease (an invasive disease caused by
Haemophilus influenzae that may produce any of several clinical syndromes, including
meningitis or pneumonia), invasive pneumococcal disease, measles, mumps, rubella
(German measles), varicella (chicken pox) and influenza.

Vaccines generally confer long-lasting immunity upon the recipient after proper
administration of a single dose or a series of doses of vaccine. Vaccines differ from other
clinical preventive services in that they not only protect the child vaccinated, but they
have the ability to protect individuals not vaccinated. This is accomplished by
interrupting the circulation of the disease-causing bacteria or virus — a phenomenon
called “community immunity” or “herd immunity.” Some children cannot be vaccinated
due to a medical contraindication to a vaccine. For example, children with cancer who
are undergoing chemotherapy cannot receive live vaccine viruses. When community
vaccination coverage levels are sufficiently high, the transmission of the prevalent form
of the disease stops, which prevents children who cannot be vaccinated from acquiring
the disease.



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Problems
Childhood immunization programs face many challenges. The number of diseases
preventable through routine vaccination increases as biotechnology brings the fruits of
vaccine science to benefit children. This increase in power and scope comes at the
expense of an increase in the complexity of service delivery and cost of services. To date,
the increased number of vaccinations has not caused a parallel increase in the number of
preventive-care visits to primary-care providers. However, the cost of vaccines and the
burden to families and society to pay for these vaccines have been rising rapidly.2

The very success of childhood vaccination brings the challenge of communicating to
parents the importance of protecting their children when the diseases prevented through
vaccination are no longer seen. A lesson that has been repeatedly observed is that
complacency in the administration of vaccinations can lead to a decline in community-
wide vaccination coverage levels. Once coverage levels decline below the threshold of
community immunity, the disease inevitably returns because the disease-causing bacteria
or viruses continue to circulate in parts of the world.

A particularly important challenge is to maintain high vaccination coverage levels in the
face of vaccine safety concerns. Vaccines routinely used for children have never been
safer than they are today. As new knowledge or technology is developed that can make
vaccines even more safe, immunization recommendations are updated to constantly
provide parents with the safest method of protecting their children from vaccine-
preventable diseases.3 Over the past two decades, some vaccine safety allegations have
led to a loss in confidence and a decline in coverage levels, with a resulting return of
epidemics of disease. Most recently, this phenomenon has been observed in the United
Kingdom’s measles elimination efforts, but well documented cases have occurred in
many countries.4

A basic challenge is to ensure the supply of vaccines routinely recommended for
children. During the past five years, there have been major disruptions in the United
States’ supply of vaccines against nine of the vaccine-preventable diseases of childhood.
The National Vaccine Advisory Committee has made recommendations to address these
disruptions. These remedies include stockpiling vaccines, streamlining regulatory
practices, improving communication among key stakeholders, addressing vaccine
liability concerns and providing financial incentives to vaccine manufacturers to help
them stay in the market.5

Research Context
The overriding objective of childhood immunization research and evaluation is to
optimize children’s protection from vaccine-preventable diseases. This implies having the
safest and most effective vaccines administered to children in as timely and efficient a
manner as feasible.
Immunization research spans most of the health-related research endeavours, including
(1) disease epidemiology (incidence/distribution of disease) to identify target vaccines for
development; (2) immunology (immune systems and responses) to understand and
predict vaccine effects; (3) the science and technology of vaccine invention, development


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and production to provide vaccines for routine use; (4) health services research to
understand effective methods to reach children with vaccines; and (5) evaluation to assess
and improve program effectiveness.6

Research is conducted by academia, private industry and government. Since the scope of
immunization-related research is so broad, this report will concentrate on the downstream
domains of health services research, program evaluation and communications.

Key Research Questions
Once a vaccine is licensed for routine use in children, there are a number of critically
important research and evaluation questions that can be categorized into questions
concerning: (1) technical recommendations; (2) vaccine safety; (3) population-based
uptake; and (4) program evaluation.

Technical recommendations become public health’s population-based “prescription” for
children of the administration schedule for the vaccine, and age groups and other
populations targeted for vaccination. This research domain supports immunization policy
decisions that have important implications for who becomes protected from the specific
diseases prevented by the vaccine. For example, influenza vaccine has been traditionally
targeted toward the frail elderly because their mortality and morbidity from influenza is
so high. However, the epidemiology of influenza suggests that vaccination of children
may be an effective adjunct to this strategy by directly protecting children from the
disease and indirectly protecting vulnerable adults through interruption of disease
transmission. Research questions to support technical recommendations include: (1)
What is the likely impact of a recommendation to vaccinate a certain age group? (2) What
is the cost/benefit ratio for a recommendation? and (3) Will vaccine-induced changes in
disease epidemiology have adverse consequences?

Vaccine safety research is important because the public needs to be confident that the
safest possible vaccines are in routine use. Prior to licensure, each vaccine is extensively
tested for safety and efficacy. However, the initial clinical trials are not powered to
discover rare adverse events. Therefore, continuous monitoring of potential vaccine
adverse events must be in place prior to routine use of a vaccine. The typical research
questions involve whether a vaccine is associated with a specific adverse event and
whether an association is causal or not.7

The best vaccines and the best vaccination recommendations will at best be sub-optimally
effective unless the vaccine achieves a high population-based uptake. There are several
evidence-based interventions to improve vaccination coverage levels among children,
adolescents and adults. The U.S. Task Force on Community Preventive Services
conducted a systematic review of the evidence of effectiveness of many interventions to
improve coverage, and recommended interventions in three categories: (1) increasing
community demand for vaccines; (2) enhancing access to vaccination services; and (3)
provider-based strategies.8
The Task Force’s work to review the evidence has been very useful in focusing the next
generation of research questions. These questions concern how to take evidence-based


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                                          IMMUNIZATION


interventions and implement them broadly and in a cost-effective manner. For example,
reminder/recall systems have over 60 controlled studies supporting their efficacy at
raising coverage in provider offices. However, actual use of recall/reminder systems by
providers remains low in the U.S. Research needs to be directed to identify barriers to
implementation of proven strategies, methods to overcome those barriers, and the
economic cost/benefit ratios for these methods.

Although technically not research, program evaluation is an essential activity that uses
scientific methods to answer specific questions. Critical evaluation questions include: (1)
What are the population-based vaccination coverage levels among age- and geography-
based populations? (2) Are vaccines being handled and administered properly? (3) Are
effective strategies being employed to raise and sustain immunization coverage levels?
and (4) Are the current vaccination recommendations optimal?

The introduction of new vaccines presents additional research questions, most of which
are included in the previous four categories. For the U.S., many of the vaccines that may
be licensed in the next two to three years are likely to be targeted to adolescents. Because
the adolescent immunization platform is not well developed, research will be needed to
identify appropriate venues for vaccination as well as strategies to reach adolescents.

Recent Research Results
Every year, several hundred research studies on childhood immunization are published.
The range of these studies is vast, and includes vaccines in development, disease
epidemiology, effectiveness of vaccination, vaccine safety, communications and program
evaluation.

Conclusions
A most important task for parents and immunization providers is to educate themselves
about the importance of keeping their children and their patients on track with their
immunizations. Every child born into this world arrives unprotected against deadly
vaccine-preventable diseases, and every child born presents an immunization challenge
that must be met if we are to give all children the benefit of vaccination optimally.

Many evidence-based interventions are available to help immunization providers keep
their patients on track for the recommended immunizations. These range from simple
recall and reminder systems to quality improvement activities that offices can undertake.
The U.S. National Vaccine Advisory Committee recently published an updated version of
the Standards for Child and Adolescent Immunization Practices.9 These standards help
immunization providers achieve optimal protection from vaccine-preventable diseases for
their patients.

Parents have access to informative books and Internet Web sites devoted to education
about vaccines and vaccine-preventable diseases. These sources of information can help
answer parents’ questions and concerns about vaccines, vaccine safety and the diseases
that are routinely prevented.



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Implications
The potential for vaccines to prevent suffering and death among children is great and will
continue to increase as new vaccines are developed and traditional vaccines are improved
to make them easier to use. Children will continue to enjoy the benefits of biotechnology
as advances in vaccinology bring more diseases under control.

Realizing this potential, however, requires carefully developed vaccination policy
recommendations and a delivery infrastructure that is able to conduct the essential roles
of immunization programs as outlined by the Institute of Medicine in their report,
“Calling the Shots.” These roles include financing the purchase of vaccines, ensuring that
evidence-based strategies are used to raise coverage levels, monitoring coverage levels
and vaccine safety, and conducting surveillance of vaccine-preventable diseases.10

Recommendations to vaccinate children need to be re-evaluated when new information is
available about vaccine impact, disease epidemiology or vaccine safety, or when a new
vaccine formulation becomes available. Only through science-based immunization
programs will children attain the potential benefit promised by vaccines.




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REFERENCES

1.      Impact of vaccines universally recommended for children--United States, 1990-
        1998. MMWR - Morbidity & Mortality Weekly Report 1999;48(12):243-248.
2.      Hinman AR, Orenstein WA, Rodewald L. Financing immunizations in the United
        States. Clinical Infectious Diseases 2004;38(10):1440-1446.
3.      Pickering LK, Orenstein WA. Development of pediatric vaccine
        recommendations and policies. Seminars in Pediatric Infectious Diseases
        2002;13(3):148-154.
4.      Gangarosa EJ, Galazka AM, Wolfe CR, Phillips LM, Gangarosa RE, Miller E,
        Chen RT. Impact of anti-vaccine movements on pertussis control: the untold
        story. Lancet 1998;351(9099):356-361.
5.      Santoli JM, Peter G, Arvin AM, Davis JP, Decker MD, Fast P, Guerra FA, Helms
        CM, Hinman AR, Katz R, Klein JO, Koslap-Petraco MB, Paradiso PR, Schaffner
        W, Whitley-Williams PN, Williamson DE, Gellin B, National Vaccine Advisory
        Committee. Strengthening the supply of routinely recommended vaccines in the
        United States: recommendations from the National Vaccine Advisory Committee.
        JAMA - Journal of the American Medical Association 2003;290(23):3122-3128.
6.      Peter G, des Vignes-Kendrick M, Eickhoff TC, Fine A, Galvin V, Levine MM,
        Maldonado YA, Marcuse EK, Monath TP, Osborn JE, Plotkin S, Poland GA,
        Quinlisk MP, Smith DR, Sokol M, Soland DB, Whitley-Williams PN, Williamson
        DE, Breiman RF. Lessons learned from a review of the development of selected
        vaccines. National Vaccine Advisory Committee. Pediatrics 1999;104(4 Pt
        1):942-950.
7.      Chen RT, Davis RL, Sheedy KM. Safety of immunizations. In: Plotkin SA,
        Orenstein WA, eds. Vaccines. 4th ed. Philadelphia, Pa: Saunders; 2004:1557-
        1581.
8.      Recommendations regarding interventions to improve vaccination coverage in
        children, adolescents, and adults. Task Force on Community Preventive Services.
        American Journal of Preventive Medicine 2000;18(1 Suppl):92-96.
9.      National Vaccine Advisory Committee. Standards for child and adolescent
        immunization practices. National Vaccine Advisory Committee. Pediatrics
        2003;112(4):958-963.
10.     Committee on Immunization Finance Policies and Practices, Division of Health
        Care Services and Division of Health Promotion and Disease Prevention, Institute
        of Medicine. Calling the shots: immunization finance policies and practices.
        Washington, DC: National Academy Press; 2000. Available at:
        http://www.nap.edu/books/0309070295/html/. Accessed June 28, 2005.

To cite this document:

Rodewald LE. Childhood immunization. In: Tremblay RE, Barr RG, Peters RDeV, eds. Encyclopedia on
Early Childhood Development [online]. Montreal, Quebec: Centre of Excellence for Early Childhood
Development;            2005:1-7.            Available            at:           http://www.child-
encyclopedia.com/documents/RodewaldANGxp.pdf. Accessed [insert date].

Copyright © 2005



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Rodewald LE
                        Immunization:
         Comments on MacDonald, Halperin, and Rodewald
                    DAVID M SALISBURY, CB FRCP FRCPCH FFPH
                Department of Health, London, UNITED KINGDOM
                                  (Published online October 28, 2005)

Topic
Immunization

Introduction
The linked papers from MacDonald, Halperin, and Rodewald provide an overview of
childhood immunization from three authors who have extensive experience in
immunization service provision, policy development and implementation, and vaccine
and vaccination research. The distinction between vaccine and vaccination research is
significant: the introduction of new vaccines requires that they be extensively researched,
especially for their safety and effectiveness; the successful maintenance of immunization
programs requires that the process of vaccination itself be researched. The latter includes
research into the contributions health-care providers make to the process of delivering
and administering vaccines, and the increasingly important interplay of the vaccine
recipients, or their care-provider, in the immunization process.1

In times of high disease prevalence, fears of disease are prevalent. Within today’s
increasingly risk-averse society, once diseases are rare and no longer feared, fears over
vaccine safety become predominant, surpassing the fears of the diseases that the vaccines
are intended to prevent.2 Thus, a perverse situation can arise when parents reject
vaccination, perceiving the dangers of vaccination to be more relevant to their decision-
making than the fears of diseases that could potentially kill or permanently damage their
children.3 Once diseases have become rare, parents can avoid any risks of vaccination,
presuming that their children are safe through the contribution of those who have
vaccinated their children. This option is short-sighted: if enough parents act in this way,
then there will be sufficient susceptible children to sustain transmission of infection,
which in turn may lead to more serious disease if it affects children at older ages.4

Research and Conclusions
MacDonald, Halperin, and Rodewald cover broadly similar topics. MacDonald
concentrates on describing the provision of immunization in Canada; Halperin covers
similar ground, describing immunization arrangements in Canada, but also reviews
research – exclusively into vaccine safety issues; and Rodewald brings a U.S.
perspective, drawing attention to the need for operational research in support of
immunization programs.


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                                          IMMUNIZATION


Each author starts with the statement that immunization is one of the most cost-effective
public health interventions. This is true because the long-established vaccines have
traditionally been cheap and the diseases they prevented plentiful and serious. Under such
circumstances, their use will be cost-effective when compared with other health
interventions. However, as new vaccines are developed, they are coming to market at
increasingly high prices,5 in part reflecting the high costs to industry of their development
and the increasing cost of their manufacture, as regulatory authorities require higher
standards of compliance with good manufacturing practice requirements. In the case of a
vaccine to prevent rotavirus diarrhoea, a condition that affects almost all children but
only mildly in industrialized countries, the greatest contribution towards its cost-
effectiveness will be from the reduction of societal costs (e.g. economic costs as a
consequence of parents taking time from work to care for ill children), not the disease
costs. It should be noted that in developing countries this same disease kills millions of
children annually.6 The vaccine’s availability in such countries will only come about if
low prices there can be offset against high prices in industrialized countries, thereby
possibly undermining their cost-effectiveness. In countries where vaccines are provided
by national authorities, their prospects for introduction will be less promising if they do
not compare well against other possible health interventions that can be obtained at lower
cost. Thus, research on vaccination is increasingly bringing together disciplines of
mathematical modelling to assess the impacts of varying strategies, along with economic
analyses of such differing strategies.7

MacDonald and Halperin both draw attention to the need for consistency in
recommendations on vaccination, noting either varying national level recommendations
or varying degrees of implementation of national recommendations at the local
(provincial/territorial) level. Based on such disparities, MacDonald makes a strong plea
for a national immunization strategy for Canada that would resolve problems of
disparities between federal and local recommendations and provide consistent funding for
all localities. Rodewald specifically draws attention to the adverse impacts that vaccine
shortages have had in the U.S. and the need for a national program to purchase and
stockpile vaccines to minimize fluctuations in their availability.

All three authors draw attention to issues of vaccine safety, emphasizing the adverse
consequences of parental fears over safety concerns, especially when the bases for their
fears may be groundless. Each quotes the putative association between MMR vaccine and
autism, with Halperin reviewing much of the evidence that argues against such an
association. More recent research, notably from Japan,8 pointing to increases in autism —
despite the withdrawal of MMR (mumps, measles and rubella) in that country — adds to
the assurances that the association is false. But some serious adverse events do very
rarely occur after immunization and Halperin describes the process through which such
events can be monitored in Canada. However, the Canadian scheme9 does not allow for
estimates of the vaccine-attributable risk of such events, only the overall risk. There are
techniques for measuring attributable risks,10 and although Halperin refers to results from
such methods, techniques for assessing risks are most important in the current context of
immunization research.



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MacDonald, Halperin, and Rodewald in turn point to the need for policy-makers and
program managers to communicate effectively with parents about immunization in order
to inform parents’ decision-making processes. MacDonald and Halperin both refer to the
experiences in the former Soviet Union with the resurgence of diphtheria to exemplify
this importance, citing the abandonment of routine immunization as the root cause of that
epidemic. However, the causes were more complex than a failure to impress on parents
the importance of routine immunization.11 While Halperin quotes studies that investigate
the contributions that particular health-care professionals can make, and the importance
of specific communication materials,12 MacDonald takes the opposite view, that what
matters is giving information to parents, and that the mode of the message is less
important.13 The Canadian authors also point to the work that has been done in Canada in
producing materials to help parents with decision-making on immunization, but cite no
evidence of how the material has been evaluated, or of its impact. In the United States,
one study that sought to investigate parents’ attitudes to routine immunization14 was
modelled on the routine surveys that are undertaken twice-yearly in the United Kingdom
and are used to inform the communications strategy for that immunization program.15,16
In addition to routine U.K. surveys of parents’ attitudes, similar surveys are done of
health-care professionals,17 and all immunization promotion materials are extensively
pre-tested and the impacts of such materials evaluated. These forms of operational
immunization research are going to become more important as immunization programs
face increasing pressures, especially through doubts over the need for immunizations and
their safety.

Implications
Immunization programs are now highly effective in controlling or even eradicating
communicable diseases. New vaccines are being introduced, but these are proving to be
much more expensive than long-established products, and the previous criteria of cost-
effectiveness may not be so readily demonstrated. In the absence of many of the
historically feared diseases, new fears over vaccine safety are becoming paramount, and
may even threaten the success of long-established programs. Research designed to gain a
better understanding of parents’ and health professionals’ attitudes is becoming
increasingly important.




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REFERENCES

1.      Salisbury DM, Yarwood J. Public perception of immunisation. Lancet
        2004;363(9417):1324.
2.      Salisbury DM. The consumers’ perspective. In: de Quadros CA, ed. Vaccines:
        Preventing disease and protecting health. Washington, DC: Pan American Health
        Organzation; 2004:310-317.
3.      Chen RT, Davis RL, Sheedy KM. Safety of immunizations. In: Plotkin SA,
        Orenstein WA. Vaccines. 4th ed. Philadelphia, Pa: Saunders; 2004:1557-1581.
4.      Anderson RM, May RM. Immunization and herd-immunity. Lancet
        1990;335(8690):641-645.
5.      National Cervical Cancer Coalition. A vaccine every woman should take.
        Available at: http://www.nccc-online.org/view_news.php?nid=24. Accessed
        August 17, 2005.
6.      Widdowson MA, Bresee JS, Gentsch JR, Glass RI. Rotavirus disease and its
        prevention. Current Opinion in Gastroenterology 2005;21(1):26-31.
7.      Melegaro A, Edmunds WJ. Cost-effectiveness analysis of pneumococcal
        conjugate vaccination in England and Wales. Vaccine 2004;22(31-32):4203-4214.
8.      Honda H, Shimizu Y, Rutter M. No effect of MMR withdrawal on the incidence
        of autism: a total population study. Journal of Child Psychology and Psychiatry
        2005;46(6):572-579.
9.      Scheifele DW, Halperin SA, CPS/Health Canada, Immunization Monitoring
        Program, Active (IMPACT). Immunization Monitoring Program, Active: a model
        of active surveillance of vaccine safety. Seminars in Pediatric Infectious Diseases
        2003;14 (3):213-219.
10.     Farrington CP, Nash J, Miller E. Case series analysis of adverse reactions to
        vaccines: A comparative evaluation. American Journal of Epidemiology
        1996;143(11):1165-1173.
11.     Dittmann S, Wharton M, Vitek C, Ciotti M, Galazka A, Guichard S, Hardy I,
        Kartoglu U, Koyama S, Kreysler J, Martin B, Mercer D, Ronne T, Roure C,
        Steinglass R, Strebel P, Sutter R, Trostle M. Successful control of epidemic
        diphtheria in the states of the former Union of Soviet Socialist Republics: Lessons
        learned. Journal of Infectious Diseases 2000;181(Suppl 1):S10-S22.
12.     Ritvo P, Irvine J, Klar N, Wilson K, Brown L, Bremner KE, Rinfret A, Remis R,
        Krahn MD. A Canadian national survey of attitudes and knowledge regarding
        preventative vaccines. Journal of Immune Based Therapies and Vaccines
        2003;1(1):3. Available at: http://www.jibtherapies.com/content/1/1/3. Accessed
        August 17, 2005.
13.     Bjornson GL, Scheifele DW, Gold R. Assessment of parent education methods
        for infant immunization. Canadian Journal of Public Health-Revue Canadienne
        de Santé Publique 1997;88(6):405-408.
14.     Gellin BG, Maibach EW, Marcuse EK. Do parents understand immunizations? A
        national telephone survey. Pediatrics 2000;106(5):1097-1102.
15.     Salisbury DM. Development of immunization policy and its implementation in
        the United Kingdom. Health Affairs 2005;24(3):744-755.



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16.     Yarwood J, Noakes K, Kennedy D, Campbell H, Salisbury DM. Tracking
        mothers’ attitudes to childhood immunisation, 1991 to 2001. Vaccine. In press.
17.     NHS Immunisation Information. Health professionals survey 2004. Available at:
        http://www.immunisation.nhs.uk/newsitem.php?id=49. Accessed August 17,
        2005.


To cite this document:

Salisbury DM. Immunization: Comments on MacDonald, Halperin, and Rodewald. In: Tremblay RE,
Barr RG, Peters RDeV, eds. Encyclopedia on Early Childhood Development [online]. Montreal, Quebec:
Centre of Excellence for Early Childhood Development; 2005:1-5. Available at: http://www.child-
encyclopedia.com/documents/SalisburyANGxp.pdf. Accessed [insert date].

Copyright © 2005




Encyclopedia on Early Childhood Development                                                     5
©2005 Centre of Excellence for Early Childhood Development
Salisbury DM