| Vaccine
Safety > VSD
Vaccine Safety
Datalink (VSD) Project
Completed &
Current Studies
December 2000 - November 2003
While much is known about common vaccine
side effects, there are limitations in our existing knowledge of rare
or unusual adverse events. To help fill these scientific gaps, the
Centers for Disease Control and Prevention (CDC) has formed partnerships
with four large health maintenance organizations to continually evaluate
vaccine safety. This project is known as the Vaccine Safety Datalink
(VSD) and includes data on more than 6 million people. Medical records
of the study population are monitored for potential adverse events
resulting from immunization. The VSD Project allows for planned vaccine
safety studies as well as timely investigations of hypotheses.
The following list is a summary of
significant research projects that have been completed or are currently
underway that examine the safety of vaccines.
- Risk of Hospitalization Because
of Aseptic Meningitis after Measles-Mumps-Rubella Vaccination
in One-to-Two-Year-Old Children
Vaccines containing the Urabe strain
of mumps vaccine have been shown to be associated with an increased
risk of aseptic meningitis. An analysis in VSD, however, showed
that the MMR vaccine used in the United States, containing Jeryl-Lynn
strain of mumps vaccine, is not associated with an increased risk
of aseptic meningitis (Pediatric Infectious Disease Journal 1997;16:500-3).
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- MMR2 at 4-6 Years and
10-11 Years of Age
A comparison of adverse event rates
in the VSD project found that children 10 to 12 years of age were
more likely to have a clinical event after a second MMR vaccination
than were children who received their second MMR at 4 to 6 years
of age. These results favored policy recommendations to give the
second MMR at 4 to 6 years (Pediatrics 1997;100:767-771).
- Risk
of chronic arthropathy among women after rubella vaccination
This study was based on computerized
laboratory data and medical record review comparing women who
had been vaccinated with rubella vaccine and unvaccinated women.
After at least one year of follow-up, there was no evidence of
an increased risk of chronic joint problems associated with vaccination
(JAMA 1997;278:551-6).
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- Thimerosal-containing
vaccines and risk of neurologic disorders
Research is being conducted to
determine associations between exposure to thimerosal-containing
vaccines and a variety of neurologic, developmental, and renal
outcomes. In the preliminary screening phase of this investigation,
CDC and VSD researchers observed no association between exposure
to thimerosal containing vaccines and 12 of the 17 renal and neurological
conditions studied. An inconclusive correlation (i.e., one that
is inadequate to confirm or refute a causal link) was observed
for five of the 17 conditions, including language delays, speech
delays, attention deficit hyperactivity disorder (ADHD), unspecified
developmental delays, and tics. Most recently, CDC investigators
have obtained and examined preliminary data from a third managed
care organization. Analyses of these data using the same methods
and having similar limitations as in the above study, showed no
association for two specific conditions: speech delay, which in
this dataset included language delay, and attention deficit disorder.
The number of events was too small to examine any of the other
associations with tics and the category of unspecified developmental
delays was not defined clearly enough to permit reanalysis. Study
results are being drafted for publication.
- Intussusception following
Rotavirus Vaccine
In Spring 1998, the Vaccine Adverse
Event Reporting System received a number of reports of intussusception
following rhesus rotavirus tetravalent (RRV-TV) vaccination. To
study a potential association, VSD researchers conducted a retrospective
cohort study using data from ten health maintenance organizations
(HMOs). Cases of intussusception were found by search of HMO databases
for a discharge diagnosis of intussusception (ICD-9 code 560.0)
and confirmed by medical chart review in infants 1 – 11 months
of age. The study included data on over 450,000 infants, 56,000
of whom had been vaccinated. The results indicate that RRV-TV
vaccine is associated with an increased incidence of intussusception.
Risk was greatest 3-7 days after vaccination. The study
findings have been submitted for publication.
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- MMR vaccination and
risk of Inflammatory Bowel Disease (IBD)
This VSD project is a population-based,
case-control study, which compared patients diagnosed with IBD
and controls without IBD, and looked at the vaccination history
of MMR vaccine and the timing of vaccinations. The results
of this study indicated no evidence that vaccination with MMR
or other measles-containing vaccines, or the the age of vaccination
early in life, was associated with an increased risk for the development
of IBD. The study findings have been submitted for publication.
- Vaccination and asthma
Researchers on the VSD team evaluated
the safety of influenza vaccination in children with asthma.
Using a retrospective cohort design, they studied the incidence
of hospitalizations and emergency department visits for asthma
following influenza vaccination.
In unadjusted analyses vaccination was associated with
high rates of asthma exacerbations.
However, after controlling for asthma severity, researchers
found that influenza vaccination does not result in acute asthma
exacerbations in children (Archive of Family Medicine; 9: 617-623).
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- Risk
of seizures following vaccination
CDC researchers examined the risk
of seizures following vaccination with whole-cell pertussis and
measles vaccine. The study found increased risks of febrile seizure
within a few days following DTP and during the second week after
MMR vaccination. This research is under review to be submitted
to a peer-reviewed immunization journal.
- Risk of hair loss
following hepatitis B vaccination
The CDC is utilizing the VSD Project
to examine the risk of hair loss after hepatitis B vaccination.
Using a case-control study design, comparisons can be made between
the individuals with the disease (cases) and those without the
disease (controls). If vaccines were causing the hair loss, it
would be expected that more persons with hair loss would have
a history of recent vaccination than persons in the general population.
Preliminary study results found no increased risk of hair loss
in children following hepatitis B vaccination. Results were inconclusive
in adolescents. To further evaluate the preliminary results, the
study is being expanded to examine the adolescent population in
more depth and also to include adults. The research protocol is
currently under revision for additional data collection.
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- Fever and suspected
sepsis after newborn hepatitis B vaccination
To determine if hepatitis B vaccination
increases the risk of fever or sepsis, VSD researchers conducted
a prospective study of healthy newborns at a San Francisco medical
center. A prospective study involves collecting on-going data
in the population of interest to identify events as they occur.
For example, information on these children was collected at birth
and data collection continued throughout the first months of life
to determine what health outcomes, if any, occurred. This study
included 3,302 newborns vaccinated against hepatitis B and 2,353
infants not given the vaccine. The researchers concluded that
there is not a relationship between hepatitis B vaccination and
fever or sepsis in newborns. A manuscript of this study
is being written.
- Hepatitis
B vaccination and risk of multiple sclerosis and other demyelinating
disorders
The VSD is evaluating the risk
of multiple sclerosis and optic neuritis in adults between 18
and 49 years of age. This particular project will include approximately
500 individuals with multiple sclerosis or optic neuritis and
1,000 controls, or individuals without the disease. The study
participants are matched, meaning they possess similar characteristics
(age, gender, etc) with the exception of disease status. Matching
helps control factors that may otherwise confuse the results.
Researchers have reviewed medical records and conducted telephone
interviews to obtain information for data collection and are now
analyzing the data to produce study results.
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- Timing of hepatitis
B vaccination and risk of type 1 (juvenile) diabetes
Researchers in the VSD are looking
at children born between 1988 and 1998 to determine if the timing
of vaccination (at birth versus two months of age or later) against
hepatitis B or if vaccination against Haemophilus influenzae
type b (Hib) increases or decreases the risk of developing diabetes.
Scientists are utilizing a case-control study design involving
about 200 children diagnosed with diabetes and 600 children without
the disease. The medical records of these children are currently
being reviewed and compared by researchers. Data collection has
been completed and researchers are now in the process of analyzing
the data.
- Mortality risk following
vaccination, including
hepatitis B
Research was conducted in the VSD
to examine the risk of death in infants and children (29 days
and 7 years of age) following administration of childhood vaccines,
including hepatitis B. The study includes information from 517
children who died and 1217 healthy children used as controls.
Data was analyzed by comparing vaccination histories for each
vaccine during the week and month prior to the date of death
for each child. The results showed no association between
immunizations and childhood death. A manuscript of study
results has been drafted and has been submitted for publication.
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- Neonatal mortality
risk following vaccination
Utilizing VSD data, researchers
are expanding the study listed above to include information on
newborn deaths (birth to 28 days old) following hepatitis B vaccination.
Data collection is in progress. Clinical reviews of several
hundred deaths will be conducted to determine the cause of of
death and if any deaths could be attributable to Hepatitis B vaccination.
- Ataxia following
vaccination
The CDC is using the VSD Project
to look at the risk of ataxia (inability to control muscle movement)
after childhood vaccination. Researchers are using a case-control
study design involving approximately 400 children with a diagnosis
of ataxia and 1200 children without the disease. Data collection
is complete and investigators are currently analyzing the information.
When completed, the study results will be submitted for publication.
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- Encephalopathy associated
with vaccination
A research project is currently
underway to determine if encephalopathy (general brain disorder)
is related to infant and childhood immunizations, especially whole-cell
pertussis and measles vaccines. A case-control study design is
being used. Data have been collected on approximately 300 children
diagnosed with encephalopathy between 1980 and 1996 and 900 children
without the disease. Data collection has been completed and the
data are being analyzed.
- Wheezing and asthma
associated with vaccinations
To determine what relationship,
if any, exists between wheezing, asthma and vaccines, researchers
are using information contained in the VSD Project. Two cohort
studies are being conducted. Cohort studies involve identifying
a population (such as newborns) and following them through time
to see if the outcome in question (wheezing or asthma) develops.
If vaccines are playing a role in causing these illnesses, it
would be expected that the incidence of wheezing or asthma would
be higher in vaccinated persons versus unvaccinated persons. One
project is analyzing wheezing in infants under 18 months of age
while the other study is looking at the risk of developing asthma
from infant vaccines. Data collection and data analysis in both
studies has been completed. The study results are being
drafted for publication.
- Hepatitis B vaccination
and risk of rheumatoid arthritis
To evaluate the risk of rheumatoid
arthritis in adults receiving hepatitis B vaccine, a case-control
study is being conducted. As part of this research project, a
sub-study will also be conducted to identify potential genetic
markers that put individuals at risk for developing the disease.
A preliminary, or pilot, study has been conducted and the protocol
for an expanded study has also been completed. Currently, data
collection is in progress.
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- Hepatitis B vaccination
and risk of systemic lupus erythematosis and other autoimmune
disorders
This study is currently in the
initial planning phase and will be conducted in an adult population.
A pilot study has been conducted and findings are being reviewed.
- Risk of anaphylaxis
following vaccination
The CDC is using the VSD Project
to better quantify the risk of anaphylaxis (severe allergic reaction)
after vaccination. Data are currently being analyzed.
-
Safety
assessment of 4th and 5th doses of acellularpertussis
vaccine
Utilizing the VSD project, CDC
researchers have begun to conduct post-licensure assessment of
the safety of acellular pertussis vaccine boosters.
This research will examine medical utilization rates and
the occurrence of certain conditions (e.g., fever, limb swelling/cellulitis)
1-14 days compared with 31-60 after receipt of the 4th
and 5th doses of acellular and/or whole cell pertussis
vaccine. Preliminary
findings suggest that there is an elevated risk of fever 1-14
days after dose 4 of whole cell pertussis vaccine and to a lesser
extent also for acelluar vaccine.
No increase in limb swelling has been detected in this
preliminary analysis using automated data, and no major difference
in overall medical utilization rates has been found for different
vaccine schedules. Further
analysis is needed to confirm these preliminary findings.
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-
Link
between use of thimerosal in vaccines and childhood onset neurological
disorders
The
purpose of this Vaccine Safety Datalink database study was to
determine whether there were associations between vaccines that
used thimerosal as a preservative (i.e., an ingredient to prevent
the growth of harmful bacteria and fungi) and a wide range of
neurodevelopmental problems, including autism, attention deficit
disorder, language delays, sleep disorders, emotional disorders,
and tics. Researchers from CDC and participating Health Maintenance
Organizations (HMOs) analyzed the computerized vaccination and
medical records of over 140,000 children from birth up to 9 years
of age.
In one of the first analyses of
the data there was a weak result that found a possible increased
risk for autism among children who received vaccines at the highest
level of thimerosal (> 62.5ug) by the third month of life,
but this result was not statistically significant and was later
found to have been based on incorrect data. These early findings
were not supported by later analyses of additional cases with
more accurate data which showed that children, who received vaccines
containing thimerosal, either by three months of life or by seven
months of life, were not at increased risk for developing autism.
There was no suggestion of an increased risk for autism even among
those children who received vaccines with the highest levels of
thimerosal by seven months of age (i.e., those receiving 162.5
ug, 175 ug, or more than 175 ug thimerosal by 7 months of age).
These results, however, cannot
be considered definitive since the study was not specifically
designed to assess a complex condition such as autism but to guide
the development of follow-up studies at CDC. These studies will
investigate more rigorously possible associations between thimerosal
in vaccines and a number of neurodevelopmental disorders.Further
analysis is needed to confirm these preliminary findings.
For more information about this
study, see Safety
of Thimerosal-Containing Vaccines: A Two-Phased Study of Computerized
Health Maintenance Organization (HMO) Databases (Qs &
As)
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