HEPATITIS B VACCINATION
Many new infections with hepatitis B are
sub-clinical or may have a flu-like
illness. Jaundice only
occurs in about 10% of younger children and in 30 to
50%
of adults. Acute infection may
occasionally lead to fulminant hepatic
necrosis, which is often fatal.
The illness usually
starts insidiously – with anorexia and nausea and an ache
in
the right upper abdomen. Fever,
when present, is usually mild. Malaise may
be profound, with disinclination to smoke or to drink
alcohol. As jaundice
develops, there is progressive darkening of
the urine and lightening of the
faeces. In patients who do not develop symptoms suggestive of
hepatitis, the
illness will only be detected by abnormal liver
function tests and/or the
presence of serological markers of hepatitis B
infection (e.g. hepatitis B
surface antigen (HBsAg), antiHBc IgM).
The virus is transmitted by parenteral exposure to infected
blood or body fluids.
Transmission mostly occurs:
●
through vaginal or anal intercourse
●
as a result of
blood-to-blood contact (e.g. sharing of needles and other
equipment
by injecting drug users (IDUs), ‘needlestick’ injuries)
●
through perinatal
transmission from mother to child.
Transmission has also followed bites from
infected persons, although this is
rare. Transfusion-associated infection is now rare in
the UK as blood donations
are screened. Viral inactivation of blood products has
eliminated these as a
source of infection in this country.
The incubation
period ranges from 40 to 160 days, with an average of 60 to 90
days. Current
infection can be detected by the presence of HBsAg in the
serum. Blood and body fluids from these individuals should be
considered to
be infectious. In most individuals, infection will
resolve and HBsAg
disappears from the serum, but the virus persists in
some patients who become
chronically infected with hepatitis B.
Chronic hepatitis B infection is defined as
persistence of HBsAg in the serum
for
six months or longer. Individuals
with chronic infection are sometimes
referred to as chronic carriers. Among those
who are HBsAg positive, those in
whom
hepatitis B e-antigen (HBeAg) is also detected in the serum are the most
infectious. Those who are HBsAg positive and HBeAg negative
(usually
anti-HBe
positive) are infectious but generally of lower infectivity. Recent
evidence
suggests that a proportion of chronically infected people who are
HBeAg negative
will have high HBV DNA levels, and may be more
infectious.
The risk of developing chronic hepatitis B infection
depends on the age at
which infection is acquired. Chronic infection occurs
in 90% of those infected
perinatally but is less frequent in those infected as
children (e.g. 20 to 50% in
children between one and five years of age). About 5%
or less of previously
healthy people, infected as adults, become chronically
infected (Hyams, 1995).
The risk is increased in those whose immunity is
impaired.
Around 20 to 25% of individuals with chronic
HBV infection worldwide have
progressive
liver disease, leading to cirrhosis in some patients. The risk of
progression is related to the level of active viral
replication in the liver.
Individuals with chronic hepatitis B infection – particularly
those with an
active inflammation and/or cirrhosis, where there is
rapid cell turnover – are at
increased risk of developing hepatocellular
carcinoma.
n
Hepatitis B
There are two classes
of products available for immunisation against hepatitis B:
a vaccine that confers active immunity and a
specific immunoglobulin that
provides
passive and temporary immunity while awaiting response to vaccine.
the
hepatitis B vaccine
Hepatitis B vaccine contains HBsAg adsorbed
onto aluminium hydroxide
adjuvant. It is prepared from
yeast cells using recombinant DNA technology.
Fendrix®, for patients with renal insufficiency, is
adjuvanted by monophosophoryl
lipid A, and adsorbed onto aluminium phosphate.
A combined vaccine containing purified inactivated
hepatitis A virus (HAV)
and purified recombinant HBsAg, separately adsorbed
onto aluminium
hydroxide and aluminium phosphate, is also available
where protection against
both hepatitis A and hepatitis B infections is
required.
Thiomersal is not used as a preservative in hepatitis B
vaccines available in the
UK. However, thiomersal is still used in the production
process for Engerix
B®, Twinrix®, Ambirix® and Fendrix® and therefore, residues are present in
the final product.
Hepatitis B-containing vaccines are
inactivated, do not contain live organisms
and
cannot cause the diseases against which they protect.
There are vaccines that are effective in preventing infection
in individuals who
produce specific antibodies to HBsAg (anti-HBs).
However, it is important
that immunisation against hepatitis B does not
encourage relaxation of other
measures designed to prevent exposure to the virus, for
example condom use
and needle exchange. Healthcare workers giving
immunisation should use the
opportunity to provide advice on other preventative
measures or to arrange
referral to appropriate specialist services.
Around 10 to 15% of adults fail to respond to
three doses of vaccine or respond
poorly.
Poor responses are mostly associated with age over 40 years, obesity
and
smoking (Roome et al., 1993).
Lower seroconversion rates have also been
reported
in alcoholics, particularly those with advanced liver disease (Rosman
et al., 1997).
Patients who are immunosuppressed or on renal dialysis may
respond
less well than healthy individuals and may require larger or more
frequent
doses of vaccine.
Hepatitis
B
Hepatitis B vaccine is highly effective at
preventing infection if given shortly
after exposure (see below). Ideally, immunisation
should commence within 48
hours,
although it should still be considered up to a week after exposure.
The vaccine is not effective in patients with
acute hepatitis B, and is not
necessary
for individuals known to have markers of current (HBsAg) or past
(anti-HB)
infection. However, immunisation should not be delayed while
awaiting
any test results.
Hepatitis
B immunoglobulin
Specific hepatitis B immunoglobulin (HBIG)
provides passive immunity and
can give immediate but temporary protection after
accidental inoculation or
contamination with hepatitis B-infected blood. HBIG is given
concurrently
with
hepatitis B vaccine and does not affect the development of active
immunity. If infection has already occurred at the time
of immunisation, virus
multiplication
may not be inhibited completely, but severe illness and, most
importantly,
development of the carrier state may be prevented.
HBIG is used after exposure to give rapid protection
until hepatitis B vaccine,
which should be given at the same time, becomes
effective. The use of HBIG
in
addition to vaccine is recommended only in high-risk situations or in a
known
non-responder to vaccine. Whenever
immediate protection is required,
immunisation with the vaccine should be given. When
appropriate, this
should be combined with simultaneous administration of
HBIG at a different
site. HBIG should
be given as soon as possible, ideally within 48 hours,
although
it should still be considered up to a week after exposure.
HBIG is obtained from the plasma of immunised and
screened human donors.
Because of a theoretical risk of transmission of vCJD
from plasma products,
HBIG used in the UK is now prepared from plasma sourced
from outside the
UK, and supplies are scarce.
All donors are screened for HIV, hepatitis B and
hepatitis C, and all plasma
pools are tested for the presence of RNA from these
viruses. A solventdetergent inactivation step for envelope viruses is included
in the production
process. There is no evidence associating the
administration of HBIG with
acquisition of HIV infection. Not only does the
processing of the plasma from
which it is prepared render it safe, but the screening
of blood donations is
routine practice.
Storage
Vaccines should be stored in the original
packaging at +2˚C to +8˚C and
protected from light. All vaccines are sensitive to
some extent to heat and cold.
Heat speeds up the decline in potency of most vaccines,
thus reducing their
shelf life. Effectiveness cannot be guaranteed for
vaccines unless they have
been stored at the correct temperature. Freezing may
cause increased
reactogenicity and loss of potency for some vaccines.
It can also cause hairline
cracks in the container, leading to contamination of
the contents.
HBIG should be stored in a refrigerator at +2˚C to
+8˚C. These products are
tolerant to ambient temperatures for up to one week.
They can be distributed
in sturdy packaging outside the cold chain if needed.
Presentation
HBIG is a clear, pale yellow fluid or light
brown solution dispensed in vials
containing 200IU or 500IU in approximately 2ml and 4ml
respectively.
|
Vaccine |
Product |
Pharmaceutical |
instructions on |
|
presentation |
handling vaccine |
||
|
Hepatitis B |
Engerix B® |
Suspension for |
Shake the vaccine |
|
white suspension |
|||
|
Combined |
Twinrix Adult® |
Suspensions for |
Shake the vaccine |
|
hepatitis A and |
Twinrix |
injection |
well to obtain a |
|
Ambirix® |
Suspension for |
Shake the vaccine |
|
|
injection in a |
well to obtain a |
||
|
prefilled syringe |
slightly opaque |
||
|
suspension |
Dosage
Currently, licensed vaccines contain
different concentrations of antigen per
millilitre. The appropriate manufacturer’s dosage
should be adhered to.
Different hepatitis B vaccine products can be used to
complete a primary
immunisation course or, where indicated, as a booster
dose in individuals who
have previously received another hepatitis B vaccine
(Bush et al., 1991).
Hepatitis
B
Table 18.1 Dosage of hepatitis B vaccines by age
|
Vaccine product |
ages and group |
Dose |
Volume |
|
Engerix B® |
0–15 years* |
10µg |
0.5ml |
|
Engerix B® |
16 years or over |
20µg |
1.0ml |
|
Fendrix® |
Patients with renal |
20µg |
0.5ml |
|
insufficiency aged |
|||
|
15 years and over |
|||
|
HBvaxPRO Paediatric® |
0–15 years |
5µg |
0.5ml |
|
HBvaxPRO® |
16 years or over |
10µg |
1.0ml |
|
HBvaxPRO40® |
Adult dialysis and |
40µg |
1.0ml |
|
pre-dialysis patients |
* 20µg of Engerix B may be given to children 11–15 of years
age if using the two-dose
schedule (see below)
Table
18.2 Dosage of combined hepatitis A and hepatitis B vaccines by age
|
Vaccine product |
ages |
Dose HaV |
Dose HBV Volume |
|
Twinrix Adult® |
16 years or over 720 ELISA units 20Ìg |
1.0ml |
|
|
Twinrix Paediatric®1–15 years |
360 ELISA units 10Ìg |
||
|
Ambirix® |
1–15 years |
Table 18.3 Dosage of HBIG
|
age group |
Dose |
HBIG is available in 2ml ampoules containing approximately
200IU or
500IU.
Schedule
Follow manufacturer instruction.
There are many different immunisation regimes
for hepatitis B vaccine . Generally the schedule for hepatitis B or combined
hepatitis A and
hepatitis B vaccine consists of three doses, with or
without a fourth booster
dose. One exception involves the use of adult strength
vaccines in children,
where two doses of Ambirix® or adult strength Engerix B® (given at zero and
six to twelve months) are acceptable in those aged 1-15
years and 11-15 years
respectively.
Hepati
administration
Hepatitis B vaccines are routinely
given intramuscularly in the upper arm or
anterolateral
thigh. The buttock must not be used because vaccine efficacy may
be
reduced.
Hepatitis B-containing vaccines can be given at
the same time as other
vaccines such as DTaP/IPV/Hib, hepatitis A, MMR, MenC,
Td/IPV and other
travel vaccines. The vaccines should be given at a
separate site, preferably in a
different limb. If given in the same limb, they should
be given at least 2.5cm
apart (American Academy of Pediatrics, 2003). The site
at which each vaccine
was given should be noted in the individual’s records.
For individuals with a bleeding disorder,
vaccines should be given by deep
subcutaneous
injection to reduce the risk of bleeding.
HBIG can be administered in the upper outer
quadrant of the buttock or
anterolateral
thigh . If more than 3ml is to be
given to young
children and infants, or more than 5ml to older
children and adults, the
immunoglobulin should be divided into smaller amounts
and administered to
different sites. HBIG may be administered, at a
different site, at the same time
as hepatitis B vaccine.
Recommendations for the use of the vaccine
Pre-exposure vaccination
The objective of the immunisation programme
is to provide a minimum of
three doses of hepatitis B vaccine for individuals at
high risk of exposure to the
virus or complications of the disease.
Pre-exposure immunisation is used for individuals who
are at increased risk of
hepatitis B because of their lifestyle, occupation or
other factors. Immediate
post-exposure vaccination is used to prevent infection,
especially in babies
born to infected mothers or following needlestick
injuries (see below).
Where testing for markers of current or past infection
is clinically indicated,
this should be done at the same time as the
administration of the first dose.
Vaccination should not be delayed while waiting for
results of the tests. Further
doses may not be required in those with
clear evidence of past exposure.
Pre-exposure immunisation is recommended for the
following groups.
injecting drug users
IDUs are a group at particular risk of acquiring
hepatitis B infection.
Vaccination is recommended for the following:
●
all current IDUs, as a high priority
● those who
inject intermittently
● those who are
likely to ‘progress’ to injecting, for example those who are
currently
smoking heroin and/or crack cocaine, and heavily dependent
amphetamine
users
● non-injecting
users who are living with current injectors
● sexual
partners of injecting users
● children of
injectors.
individuals who change sexual partners
frequently
Those who change sexual partners frequently,
particularly MSM and male and
female commercial sex workers.
Close family contacts of a case or individual
with chronic
hepatitis B infection
Sexual partners are most at risk, and they
and close household contacts should
be vaccinated. Blood should be taken at the time of the
first dose of vaccine to
determine if they have already been infected. Contacts
shown to be HBsAg,
anti-HBs or anti-HBc positive do not require further
immunisation. Advice
regarding the appropriate use of condoms should be
given; a reasonable level
of protection can be assumed following the second dose,
provided that
completion of the schedule can be assured.
Contacts who have had recent unprotected sex with
individuals who have acute
hepatitis B or who are HBsAg positive require
post-exposure prophylaxis,
including HBIG (see below).
families adopting children from countries
with a high or
intermediate prevalence of hepatitis B
Members of such families may be at risk, as
these children could be chronically
infected (Christenson, 1986; Rudin et al., 1990). When the status
of the child
to be adopted is not known, families adopting children
from any high or
intermediate-prevalence country should be advised as to
the risks and
hepatitis B vaccination recommended. In due course,
testing such children is
advisable because there could be benefits from
referring an infected child for
further management.
foster carers
Some children requiring fostering may have
been at increased risk of acquiring
hepatitis B infection. Emergency placements may be made
within a few hours:
foster carers who accept children as emergency
placements should be made
aware of the risks of undiagnosed infection and how
they can minimise the
risks of transmission of all blood-borne virus
infections. All short-term foster
carers who receive emergency placements, and their
families, should be
offered immunisation against hepatitis B. Permanent
foster carers (and their
families) who accept a child known to be at high risk
of hepatitis B should also
be offered immunisation.
individuals receiving regular blood or blood
products and their
carers
Those individuals receiving regular blood
products, such as people with
haemophilia, should be vaccinated. Those
receiving regular blood transfusions,
for example people with thalassaemia or
other chronic anaemia, should be
vaccinated against hepatitis B. Carers responsible for
the administration of
such products should also be vaccinated.
Patients with chronic renal failure
Patients with renal failure may need
haemodialysis, at which time they may be
at increased risk of hepatitis B. The response to
hepatitis B vaccine among
patients with renal failure is lower than among healthy
adults. Between 45 and
66% of patients with chronic renal failure develop
anti-HBs responses and,
compared with immunocompetent individuals, levels of
anti-HBs decline more
rapidly. However, increased response rates have been
reported in vaccines
formulated for use in patients with chronic renal
failure (Tong et al., 2005).
Immunisation against hepatitis B is recommended for
patients already on
haemodialysis or renal transplantation programmes and
for other patients with
chronic renal failure as soon as it is anticipated that
they may require these
interventions. The vaccines
formulated for use in patients with chronic renal
insufficiency
should be used.
Patients with chronic liver disease
Individuals with chronic liver disease may
be at increased risk of the
consequences of hepatitis B infection. Immunisation
against hepatitis B is
therefore recommended for patients with severe liver
disease, such as
cirrhosis, of whatever cause. Vaccine should also be
offered to individuals with
milder liver disease, particularly those who are
chronically infected with
hepatitis C virus, who may share risk factors that mean
that they are at
increased risk of acquiring hepatitis B infection.
inmates of custodial institutions
Immunisation against hepatitis B is
recommended for all sentenced prisoners
and all new inmates entering prison in the UK.
individuals in residential accommodation for
those with learning
difficulties
A higher prevalence of chronic hepatitis B
infection has been found among
individuals with learning difficulties in residential
accommodation than in the
general population. Close, daily living contact and the
possibility of behavioural
problems may lead to residents being at increased risk
of infection. Vaccination
is therefore recommended.
Similar considerations may apply to children and adults
in day care, schools
and centres for those with severe learning disability.
Decisions on immunisation
should be made on the basis of a local risk assessment.
In settings where the
individual’s behaviour is likely to lead to significant
exposure (e.g. biting or
being bitten) on a regular basis, immunisation should
be offered to individuals
even in the absence of documented hepatitis B
transmission.
People travelling to or going to reside in
areas of high or
intermediate prevalence
Travellers to areas of high or intermediate
prevalence who place themselves at
risk when abroad should be offered immunisation. The
behaviours that place
them at risk will include sexual activity, injecting
drug use, undertaking relief
aid work and/or participating in contact sports.
Travellers are also at risk of
acquiring infection as a result of medical or dental
procedures carried out in
countries where unsafe therapeutic injections (e.g. the
re-use of contaminated
needles and syringes without sterilisation) are a risk
factor for hepatitis B
(Kane et al., 1999; Simonsen et al., 1999). Individuals at high risk of
requiring medical or dental procedures in such
countries should therefore be
immunised, including:
● those who
plan to remain in areas of high or intermediate prevalence for
lengthy
periods
● children and
others who may require medical care while travelling to
visit
families or relatives in high or moderate-endemicity countries
● people with
chronic medical conditions who may require hospitalisation
while
overseas
● those
travelling for medical care.
individuals at occupational risk
Hepatitis B vaccination is recommended for
the following groups who are
considered at increased risk
● healthcare workers in the UK and overseas
(including students and
trainees): all healthcare workers who
may have direct contact with
patients’ blood, blood-stained body fluids or tissues,
require
vaccination. This includes any staff who are at risk of
injury from bloodcontaminated sharp instruments, or of being deliberately
injured or bitten
by patients. Advice should be obtained from the
appropriate
occupational health department.
●
laboratory
staff: any laboratory staff who handle
material that may
contain the virus require vaccination.
●
staff
of residential and other accommodation for those with learning
difficulties: a higher prevalence of
hepatitis B carriage has been found
among certain groups of patients with learning
difficulties in residential
accommodation than in the general population. Close
contact and the
possibility of behavioural problems, including biting
and scratching, may
lead to staff being at increased risk of infection.
Similar considerations may apply to staff in day-care
settings and special
schools for those with severe learning disability.
Decisions on immunisation
should be made on the basis of a local risk assessment.
In settings where
the client’s behaviour is likely to lead to significant
exposures on a
regular basis (e.g. biting), it would be prudent to
offer immunisation to
staff even in the absence of documented hepatitis B
transmission.
●
other occupational risk groups: in some occupational groups, such as
morticians and embalmers, there is an established risk
of hepatitis B, and
immunisation is recommended. Immunisation is also
recommended for
all prison service staff who are in regular contact
with prisoners.
Hepatitis B vaccination may also be considered for
other groups such as the police
and fire and rescue services. In these workers an
assessment of the frequency of
likely exposure should be carried out. For those with
frequent exposure,
pre-exposure immunisation is recommended. For other
groups, post-exposure
immunisation at the time of an incident may be more
appropriate (see below).
Such a selection has to be decided locally by the
occupational health services
or as a result of appropriate medical advice.
Post-exposure
immunisation
Post-exposure prophylaxis is recommended for
the following groups.
Babies born to mothers who are chronically infected with HBV or
to mothers who have had acute hepatitis
B during pregnancy
Hepatitis B infection can be transmitted
from infected mothers to their babies
at or around the time of birth (perinatal
transmission). Babies acquiring
infection at this time have a high risk of becoming
chronically infected with
the virus. The development of the chronic infection
after perinatal transmission
can be prevented in over 90% of cases by appropriate
vaccination, starting at
birth, of all infants born to infected mothers.
UK guidelines (Department of Health, 1998) recommend
that all pregnant
women should be offered screening for hepatitis B
infection during each
pregnancy. Confirmatory testing and testing for
hepatitis B e-markers of those
mothers shown to be infected should follow. Where an
unbooked mother
presents in labour, an urgent HBsAg test should be
performed to ensure that
vaccine can be given to babies born to positive mothers
within 24 hours of birth.
Management of the infant should be based on the results
of these
markers and, if available, HBV viral load testing of
the mother. www.hpa.org.
uk/web/HPAwebFile/HPAweb_C/1223019399138
All babies born to these mothers should receive a
complete course of vaccine
on time. Arrangements should be in place to ensure that
information is shared
with appropriate local agencies to facilitate follow
up.
Babies born to highly infectious mothers should
receive HBIG as well as active
immunisation
(see Table 18.4). HBIG should
preferably be given within 24
hours
of delivery, and should be ordered well in advance of the birth. HBIG
may
be given simultaneously with vaccine but at a different site.
Table
18.4 Vaccination of term babies according to the hepatitis B status of the
mother
|
Hepatitis B status of mother |
Baby should receive |
|
Hepatitis B vaccine |
HBiG |
|
|
Mother is HBsAg positive and HBeAg positive |
Yes |
Yes |
|
Mother is HBsAg positive, HBeAg negative |
||
|
and anti-HBe negative |
Yes |
Yes |
|
Mother is HBsAg positive where e-markers have |
||
|
not been determined |
Yes |
Yes |
|
Mother had acute hepatitis B during pregnancy |
Yes |
Yes |
|
Mother is HBsAg positive and anti-HBe positive |
Yes |
No |
|
A woman who is HBsAg seropositive and known |
||
|
to have an HBV DNA level equal or above |
||
|
1x106IUs/ml in an
antenatal sample* |
Yes |
Yes |
* Where viral load testing has been performed to inform the
management of the mother.
Hepatitis B
Vaccination of pre-term babies
There is evidence that the response to
hepatitis B vaccine is lower in pre-term,
low-birth weight babies (Losonsky et al., 1999). It is,
therefore, important that
premature infants receive the full paediatric dose of
hepatitis B vaccine on
schedule. Babies with a birthweight of 1500g or less,
born to mothers infected
with hepatitis B, should receive HBIG in addition to
the vaccine, regardless of
the e-antigen status of the mother.
It is important that premature infants have their
immunisations at the
appropriate chronological age, according to the
schedule. The occurrence
of apnoea following vaccination is especially increased
in infants who were
born very prematurely.
Very premature infants (born ≤ 28 weeks of gestation) who
are in hospital
should have respiratory monitoring for 48-72 hrs when
given their first
immunisation, particularly those with a previous
history of respiratory
immaturity. If the child has apnoea, bradycardia or
desaturations after
the first immunisation, the second immunisation should
also be given in
hospital, with respiratory monitoring for 48-72 hrs
(Pfister et al., 2004;
Ohlsson et al., 2004; Schulzke et al., 2005; Pourcyrous et al., 2007; Klein
et al., 2008).
As the benefit of vaccination is high in this group of
infants, vaccination
should not be withheld or delayed.
Vaccination schedule and follow-up
For post-exposure prophylaxis in babies born to
mothers infected with hepatitis
B,
the accelerated immunisation schedule is preferred. For these babies this
will
mean an initial dose of vaccine at birth, with further doses at one and two
months
of age and a fourth dose at one year of age.
Testing for HBsAg at one year of age will identify any
babies for whom this
intervention has not been successful and who have
become chronically infected
with hepatitis B, and will allow them to be referred
for assessment and any
further management. This testing can be carried out at
the same time as the
fourth dose is given.
Where immunisation has been delayed beyond the
recommended intervals,
the vaccine course should be completed, but it is more
likely that the child
may become infected. In this instance, testing for
HBsAg above the age of
one year is particularly important.
other groups potentially exposed to hepatitis B
Any individual potentially exposed to
hepatitis B-infected blood
or bodyfluids should be offered protection against
hepatitis B,
depending on their prior vaccination status
and the status of the source www.
hpa.org.uk/cdr/archives/CDRreview/1992/cdrr0992.pdf.
Guidance on postexposure prophylaxis following exposure to hepatitis B has been
issued by the
former PHLS Hepatitis Subcommittee (PHLS Hepatitis
Subcommittee,
1992).A summary of this guidance is given in Table
18.5.
Sexual partners
Any sexual partner of individuals suffering
from acute hepatitis B, and who are
seen
within one week of last contact, should be offered protection with HBIG
and
vaccine. Sexual contacts of an individual with newly diagnosed chronic
hepatitis
B should be offered vaccine; HBIG may be added if unprotected
sexual
contact occurred in the past week.
Persons who are accidentally inoculated or contaminated
This includes those who
contaminate their eyes or mouth, or fresh cuts or
abrasions
of the skin, with blood from a known HBsAg-positive person.
Individuals
who sustain such accidents should wash the affected area well with
soap
and warm water, and seek medical advice. Advice about prophylaxis after
such accidents should be obtained by telephone from the
nearest public health
laboratory or from the local health protection unit
(HPU) or virologist on call.
Advice following accidental exposure may also be
obtained from the
occupational health services, hospital control of
infection officer.
Primary
immunisation
Pre-exposure prophylaxis
For pre-exposure prophylaxis in most adult
and childhood risk groups, an
accelerated schedule should be used, with
vaccine given at zero, one and two
months.
For those who are at continued risk, a fourth dose is recommended
at
12 months. An alternative schedule at zero, one and six months should
only
be used where rapid protection is not required and there is a high
likelihood
of compliance.
Higher completion rates are achieved with the
accelerated schedule (at zero,
one
and two months) in groups where compliance is difficult (e.g. in IDUs and
genito-urinary medicine clinic attenders) (Asboe et
al., 1996). This improved
compliance is likely to offset the slightly reduced
immunogenicity when
compared with the zero-, one- and six-month schedule,
and similar response
rates can be achieved by opportunistic use of a fourth
dose after 12 months.
In addition to the schedules outlined above, for
children under 15 years of
age, a two-dose schedule of a vaccine containing adult
strength hepatitis B,
(Ambirix® for those aged one to 15 years or Engerix B® for those aged 11
to 15 years) at zero and six months provides similar
protection to three doses
of the childhood hepatitis B vaccines (see page 167).
Table 18.5 HBV prophylaxis for reported exposure incidents
Significant exposure Non-significant exposure
Hepatitis B
|
HBV status of |
HBsag positive |
Unknown |
HBsag negative |
Continued risk |
|
Initiate course |
||||
|
> 2 doses HB vaccine |
One dose of |
Finish course |
Finish course |
|
|
Known responder to |
Consider booster Consider booster Consider booster Consider
booster |
|||
|
dose of HB |
dose of HB |
dose of HB |
dose of HB |
|
|
Consider booster Consider booster Consider booster Consider
booster |
||||
|
dose of HB |
dose of HB |
dose of HB |
dose of HB |
|
|
A second dose of A second dose of |
||||
|
HBIG should be |
HBIG should be |
A booster dose may be given at 12 months to those at continuing risk of exposure to HBV.
Source: PHLS Hepatitis Subcommittee (1992).
Hepatitis B
Engerix B® can also be given at a very rapid schedule with three doses given
at zero, seven and 21 days (Bock et al., 1995). When this schedule is used, a
fourth dose is recommended 12 months after the first dose. This schedule is
licensed for use in circumstances where adults over 18 years of age are at
immediate risk and where a more rapid induction of protection is required.
This includes persons travelling to areas of high endemicity, IDUs and
prisoners. In teenagers under 18 years of age, response to vaccine is as good
or better than in older adults (Plotkin and Orenstein, 2004). Although not
licensed for this age group, this schedule can be used in those aged 16 to 18
years where it is important to provide rapid protection and to maximise
compliance (e.g. IDUs and those in prison).
Twinrix Adult® vaccine can also be given at zero, seven and 21 days. This will
provide more rapid protection against hepatitis B than other schedules but full
protection against hepatitis A will be provided later than with
vaccines containing a higher dose of hepatitis A (see Chapter 17). When this
schedule is used, a fourth dose is recommended 12 months after the first dose.
Fendrix® is recommended to be given at zero, one, two and six months.
Post-exposure prophylaxis
For post-exposure prophylaxis, an accelerated schedule of monovalent
hepatitis B vaccine (or a combined vaccine of equivalent strength) should be
used, with vaccine given at zero, one and two months. For those who are at
continued risk, a fourth dose is recommended at 12 months. If HBIG is also
indicated, it should be given as soon as possible, ideally at the same time as
the first dose of vaccine.
Reinforcing immunisation
The full duration of protection afforded by hepatitis B vaccine has yet to be
established (Whittle et al., 2002). Levels of vaccine-induced antibody to
hepatitis B decline over time, but there is evidence that immune memory can
persist in those successfully immunised (Liao et al., 1999). However, recent
evidence suggests that not all individuals may respond in this way (Williams
et al., 2003; Boxall et al., 2004). It is, therefore, recommended that individuals
at continuing risk of infection should be offered a single booster dose of
vaccine, once only, around five years after primary immunisation. Measurement
of anti-HBs levels is not required either before or after this dose. Boosters are
also recommended after exposure to the virus (as above)
Because of the continued presence of infection in other family members, a
single booster dose of hepatitis B vaccine, given with the pre-school booster
for other childhood immunisations, is advised for the children born to hepatitis
B infected-mothers. This will also provide the opportunity to check whether
the child was properly followed up in infancy.
Response to vaccine and the use of additional doses
Except in certain groups (see below), testing for anti-HBs is not recommended.
those at risk of occupational exposure
In those at risk of occupational exposure, particularly healthcare and laboratory
workers, antibody titres should be checked one to four months after the
completion of a primary course of vaccine. Under the Control of Substances
Hazardous to Health (COSHH) Regulations, individual workers have the right
to know whether or not they have been protected. Such information allows
appropriate decisions to be made concerning post-exposure prophylaxis
following known or suspected exposure to the virus (see above).
Antibody responses to hepatitis B vaccine vary widely between individuals. It
is preferable to achieve anti-HBs levels above 100mIU/ml, although levels of
10mIU/ml or more are generally accepted as enough to protect against
infection. Some anti-HBs assays are not particularly specific at the lower
levels, and anti-HBs levels of 100mIU/ml provide greater confidence that a
specific response has been established.
Responders with anti-HBs levels greater than or equal to 100mIU/ml do not
require any further primary doses. In immunocompetent individuals, once a
response has been established further assessment of antibody levels is not
indicated. They should receive the reinforcing dose at five years as
recommended above.
Responders with anti-HBs levels of 10 to 100mIU/ml should receive one
additional dose of vaccine at that time. In immunocompetent individuals,
further assessment of antibody levels is not indicated. They should receive the
reinforcing dose at five years as recommended above.
An antibody level below 10mIU/ml is classified as a non-response to vaccine,
and testing for markers of current or past infection is good clinical practice.
In non-responders, a repeat course of vaccine is recommended, followed by
retesting one to four months after the second course. Those who still have
anti-HBs levels below 10mIU/ml, and who have no markers of current or past
infection, will require HBIG for protection if exposed to the virus (see below).
Patients with renal failure
The role of immunological memory in patients with chronic renal failure on
renal dialysis does not appear to have been studied, and protection may persist
only as long as anti-HBs levels remain above 10mIU/ml. Antibody levels
should, therefore, be monitored annually and if they fall below 10mIU/ml, a
booster dose of vaccine should be given to patients who have previously
responded to the vaccine.
Booster doses should also be offered to any haemodialysis patients who are
intending to visit countries with a high endemicity of hepatitis B and who have
previously responded to the vaccine, particularly if they are to receive
haemodialysis and have not received a booster in the last 12 months.
Contraindications
There are very few individuals who cannot receive hepatitis B-containing
vaccines. When there is doubt, appropriate advice should be sought from a
consultant paediatrician, immunisation co-ordinator or local HPU rather than
withholding vaccine.
The vaccine should not be given to those who have had:
● a confirmed anaphylactic reaction to a previous dose of a hepatitis
B-containing vaccine or
● a confirmed anaphylactic reaction to any component of the vaccine.
Precautions
Minor illnesses without fever or systemic upset are not valid reasons to
postpone immunisation. If an individual is acutely unwell, immunisation may
be postponed until they have fully recovered. This is to avoid confusing the
differential diagnosis of any acute illness by wrongly attributing any signs or
symptoms to the adverse effects of the vaccine.
Pregnancy and breast-feeding
Hepatitis B infection in pregnant women may result in severe disease for the
mother and chronic infection of the newborn. Immunisation should not be
withheld from a pregnant woman if she is in a high-risk category. There is no
evidence of risk from vaccinating pregnant women or those who are breastfeeding with inactivated viral or bacterial vaccines or toxoids (Plotkin and
Orenstein, 2004). Since hepatitis B is an inactivated vaccine, the risks to the
foetus are likely to be negligible, and it should be given where there is a
definite risk of infection.
Premature infants
There is evidence that the response to hepatitis B vaccine is lower in pre-term,
low-birthweight babies (Losonsky et al., 1999). It is, therefore, important that
premature infants receive the full paediatric dose of hepatitis B vaccine on
schedule. Babies with a birthweight of 1500g or less, born to mothers infected
with hepatitis B, should receive HBIG in addition to the vaccine, regardless of
the e-antigen status of the mother.
HiV and immunosuppressed individuals
Hepatitis B vaccine may be given to HIV-infected individuals and should be
offered to those at risk, since infection acquired by immunosuppressed, HIVpositive patients can result in higher rates of chronic infection (Bodsworth et
al., 1991). Response rates are usually lower depending upon the degree of
immunosuppression (Newell and Nelson, 1998; Loke et al., 1990). Increasing
the number of doses may improve the anti-HBs response in HIV-infected
individuals (Rey et al., 2000).
Further guidance is provided by the Royal College of Paediatrics and Child
Health (www.rcpch.ac.uk) the British HIV Association (BHIVA)
immunisation guidelines for HIV-infected adults (BHIVA, 2006) and the
Children’s HIV Association of UK and Ireland (CHIVA) immunisation
guidelines (www.chiva.org.uk).
Precautions for HBiG
When HBIG is being used for prevention of hepatitis B, it must be
remembered that it may interfere with the subsequent development of active
immunity from live virus vaccines. If immunoglobulin has been administered
first, then an interval of three months should be observed before administering
a live virus vaccine. If immunoglobulin has been given within three weeks of
administering a live vaccine, then the vaccine should be repeated three months
later. This does not apply to yellow fever vaccine since HBIG does not contain
significant amounts of antibody to this virus.
adverse reactions
Hepatitis B vaccine is generally well tolerated and the most common adverse
reactions are soreness and redness at the injection site. Other reactions that
have been reported but may not be causally related include fever, rash, malaise
and an influenza-like syndrome, arthritis, arthralgia, myalgia and abnormal
liver function tests.
Serious suspected neurological reactions such as Guillain-Barré syndrome and
demyelinating disease have been reported, although these have been very rare
and a causal relationship with hepatitis B vaccine has not been established
(Shaw et al., 1988; McMahon et al., 1992). The results of recent studies
indicate no association between hepatitis B immunisation and the development
of multiple sclerosis (Ascherio et al., 2001) and that immunisation against
hepatitis B does not increase the short-term risk of a relapse in patients with
multiple sclerosis (Confavreux et al., 2001).
All suspected reactions in children and severe suspected reactions in adults
should be reported to the Commission on Human Medicines using the Yellow
Card scheme.
adverse reactions to HBiG
HBIG is well tolerated. Very rarely, anaphylactoid reactions occur in individuals
with hypogammaglobulinaemia who have IgA antibodies, or those who
have had an atypical reaction to blood transfusion.
No cases of blood-borne infection acquired through immunoglobulin
preparations designed for intramuscular use have been documented in any
country.
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