Safety > Multiple Sclerosis
Sclerosis and the
Hepatitis B Vaccine
a glance: Studies have been completed
which evaluate possible relationships between
hepatitis B vaccination and multiple sclerosis
(MS). The weight of the available scientific
evidence does not support the suggestion
that hepatitis B vaccine causes or worsens
MS or other demyelinating diseases.
is multiple sclerosis (MS)?
Multiple sclerosis (MS) is a disease
of the central nervous system characterized
by the destruction of the myelin sheath
surrounding neurons, resulting in the formation
of "plaques." Because they involve
the destruction of the myelin sheath that
covers nerve tissue, diseases such as MS
are known as "demyelinating"
diseases. MS is a progressive and usually
fluctuating disease with exacerbations
(patients feeling worse) and remissions
(patients feeling better) over many decades.
Eventually, in most patients, remissions
do not reach baseline levels and permanent
disability and sometimes death occurs.
The cause of MS is unknown. The most widely
held hypothesis is that MS occurs in patients
with a genetic susceptibility and is "triggered"
by certain environmental factors. MS is
3 times more common in women than men,
with diagnosis usually made as young adults.
concern that hepatitis B vaccination may
cause MS or exacerbate it derived from case
reports in France in which some individuals
developed MS following hepatitis B vaccination
(Herrolen, 1991). The French media
rapidly picked up on the alleged association
and the issue was also on televised news
reports in the United States. Concerns that
hepatitis B vaccination may cause or precipitate
MS have disrupted immunization programs in
France and elsewhere. Recently, controlled
studies have been completed which evaluate
any possible relationship between hepatitis
B vaccination and MS.
hepatitis B vaccination cause MS?
weight of the available scientific evidence
does not support a causal relationship between
hepatitis B vaccination and MS or other demyelinating
pre-licensure clinical trials did not document
such an effect.
the large number of vaccinations administered
worldwide, it is not surprising that surveillance
systems in the U.S., France, and elsewhere
(Quast, 1991), have received some reports
of MS temporally (coincidentally) associated
with vaccinations. As with all such case
reports, however, they only constitute
signals of possible causal associations.
Further controlled studies are necessary
to establish causation.
of millions of persons worldwide have received
hepatitis B vaccine without developing
MS (or any other autoimmune disease). This
finding provides important negative evidence
as well as an appropriate framework for
assessing this possible association– namely,
that if vaccination causes MS, it does
so extremely rarely.
case-control study was conducted using
CDC’s Vaccine Safety Datalink project to
assess the association between hepatitis
B vaccination and demyelinating diseases
such as MS and optic neuritis among members
of three large managed care organizations
(MCOs) on the West Coast of the US (Verstraeten,
2001). The study included 422 cases
(people with demyelinating disease) and
921 matched controls (people of similar
age, gender, and MCO status who did not
have demyelinating disease). The odds ratio
for ever being vaccinated against hepatitis
B prior to onset of demyelinating symptoms
was 1.09 (95% CI: 0.70-1.70). The researchers
concluded that hepatitis B vaccination
was not associated with demyelinating disease
in the study population.
and colleagues (2001) evaluated the possible
association between hepatitis B vaccination
and MS in a case-control study. The study
included 192 women with MS and 645 controls.
The relative risk associated with hepatitis
B vaccination at any time before onset
of MS and within 2 years of onset was 0.9
and 0.7 respectively. The authors concluded
that there was no association between hepatitis
B vaccination and MS.
case crossover study was conducted in Europe
to evaluate whether MS relapses were associated
with receipt of hepatitis B, tetanus, or
influenza vaccines (Confavreux, 2001).
The study included 643 individuals with
relapsing MS. The relative risk of relapse
during the two-month period following hepatitis
B vaccination was 0.67 and not significantly
different compared with the control period,
which ranged from 2-12 months preceding
the vaccination. The researchers concluded
that there is no evidence of an association
between recent receipt of hepatitis B
vaccine (or tetanus , or
influenza vaccination) and MS relapses.
and Scheifele (2000) investigated
multiple sclerosis in 578,308 adolescents
in British Columbia before and after a
hepatitis B vaccination program was begun.
The authors found no evidence of a link
between hepatitis B vaccination and multiple
sclerosis or other demyelinating disease.
analysis of a U.S. pharmacy benefits management
database did not find a statistically significant
association between claims for hepatitis
B vaccination and subsequent claims for
treatment of CNS demyelinating disorders
European case-control studies (Sturkenboom,
1999; Fourrier, 1999) evaluated vaccination
as a trigger for demyelination. They found
relative risks around 1.5 that were not
statistically significant for onset of
demyelination within 2 months to 1 year
of hepatitis B vaccination.
more is being done to examine the suggested
association between Hepatitis B vaccine
and neurological disorders?
Centers for Disease Control and Prevention
(CDC) and the National Institutes of Health
(NIH) asked the National Academy of Sciences,
Institute of Medicine (IOM) to establish
an independent expert committee to review
hypotheses about existing and emerging
immunization safety concerns. These reviews
involve an assessment of factors such as
the biologic mechanisms of the hypothesis,
competing alternative hypotheses, as well
as the available scientific evidence to
date. The IOM committee recently reviewed
the hypothesized association between Hepatitis
B vaccine and neurological disorders. The
full report with conclusions and recommendations
can be viewed at http://www.nap.edu/books/0309084695/html/index.html
more information on the IOM Immunization
Safety Review Committee go to http://www.iom.edu/imsafety
I delay hepatitis B vaccination until more
Results from studies that have examined the
possible association between hepatitis B
vaccination and MS are reassuring and support
current recommendations for immunizing against
hepatitis B. Concern regarding the alleged
association between hepatitis B vaccination
and MS must be weighed against the vaccine’s
ability to prevent risks associated with
hepatitis B virus infection. For general
information on hepatitis B and hepatitis
B vaccine, go to www.cdc.gov/ncidod/diseases/hepatitis/b/index.htm
research has been conducted to look at the
possible link between vaccines and autoimmune
takes concerns about vaccines and immune
system dysfunction very seriously. Researchers
at CDC and elsewhere have conducted studies
to examine the possible link between vaccines
and autoimmune conditions like multiple
sclerosis (MS), diabetes, and asthma. These
studies have been reassuring, providing
evidence against a link between vaccines
and autoimmune conditions. However, data
has suggested a link between vaccines and
other conditions. For example, recent studies
alopecia (hair loss) may rarely occur
in persons who have received hepatitis
B vaccine. While the mechanisms responsible
for alopecia following vaccination are
not certain, it could be immune-mediated.
Thus, CDC continues to conduct research
to examine the effects vaccines may have
on the immune system. In addition, CDC
and the National Institutes of Health (NIH)
asked the Institute of Medicine (IOM) to
establish an independent expert committee
to review hypotheses about existing immunization
safety concerns. On November 12, 2001 the
Immunization Safety Review Committee held
an open scientific meeting to discuss the
possible association between multiple
immunizations in newborns and infants and
immune system dysfunction.
IOM report and the news release are available
on the Web at:
Zhang SM, Hernan MA, et al. Hepatitis B vaccination
and the risk of multiple sclerosis. N Engl
J Med. 2001;344:327-332.
Suissa S, Saddier P et al. Vaccinations and
the risk of relapse in multiple sclerosis.
N Engl J Med. 2001; 344:319-326.
DeKeyser J, Ebinger G. Central nervous system
demyelination after immunisation with recombinant
hepatitis B vaccine. Lancet 1991; 338:1174-5.
Quast U, Herder
C, Zwisler O. Vaccination of patients with
encephaloymelitis disseminata. Vaccine 1991;9:228-230.
Scheifele DW. School-based hepatitis B vaccination
programme and adolescent multiple sclerosis.
Lancet 2000; 355:549-50.
Touze E, Gout
O, Verdier-Taillefer MH, et al. The first episoce
of central nervous system demyelinization and
hepatitis B vaccination. Rev Neurol 2000; 156:242-6.
T, DeStefano F, Jackson L, Benson P, Okoro
C, Black S, Shinefield H., Mullooly J, Chen
R. & the VSD Team. Risk of demyelinating
disease after hepatitis B vaccination - West
Coast, United States, 1995-1999. Paper presented
at the 50th Annual Epidemic Intelligence
Service Conference, 2001, Atlanta GA.
Zipp F, Weil
JG, Einhaupl KM. No increase in demyelinating
diseases after hepatitis B vaccination. Nat
Touze E, Alperovitch A, Begaud B. Association
between hepatitis B vaccine and multiple sclerosis:
a case-control study. Pharmacoepidemiol Drug
MCJM, Abenhaim L, Wolfson C, Roulet E, Heinzelf
O, Gout O. Vaccinations, demyelination, and
multiple sclerosis study (VDAMS). Pharmacoepidemiol
Drug Safety 1999;8:S170-1.
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