Pertussis Vaccines
Whoopine-cough Vaccine) is a sterile suspension of inactivat-
ed whole cells of one or more strains of Bordetella pertussis
in saline. The estimated potency is not less than 4 internation-
al units per dose. It may contain a suitable antimicrobial pre-
servative. It should be stored al 2Β° to 8Β°, not be allowed to
freeze, and be protected from light.
Pertussis Vaccine (Adsorbed) (Ph. Eur.) (Per/Vac/Ads; Vac-
cinum Pertussis Adsorbatum) is a sterile suspension of inac-
tivated whole cells of one or more strains of Bordetella
penussis in saline to which hydrated aluminium hydroxide.
aluminium phosphate, or calcium phosphate has been added.
It may contain a suitable antimicrobial preservative. The esti-
mated potency is not less than 4 units per dose. It should be
stored at 2Β° to 8Β°, not be allowed to freeze, and be protected
from light. The BP directs that when Pertussis Vaccine is pre-
scribed or demanded and the form is not stated, either the
plain or the adsorbed vaccine may be dispensed or supplied.
Pertussis Vaccine (Acellular. Component, Adsorbed) (Ph.
Eur.) (Vaccinum Pertussis sine Cellulis ex Elemenlis
Praeparalum Adsorbatum) is a preparation of individually
prepared and purified antigenic components of Bordetella
pertussis adsorbed on a mineral carrier such as aluminium hy-
droxide or hydrated aluminium phosphate. It contains either a
suitably prepared pertussis toxoid or a pertussis toxin-like
protein free from toxic properties produced by expression of
a genetically modified form of the corresponding gene. It may
also contain tilamenious haemagglulinin, pertactin. and other
defined antigens such as fiinbrial-2 and fimbrial-3 antigens.
The final vaccine contains not more than 100 units of bacteri-
al endotoxin per dose. It may contain a suitable antimicrobia]
preservative. It should be stored at 2Β° to 8Β°. not be allowed to
freeze, and be protected from light.
Pertussis Vaccine fUSP 23) is a sterile bacterial fraction or
suspension of killed Bordetella pertussis of a strain or strains
selected for high antigenicity. It contains a preservative. It
contains 12 protective units per immunising dose. It should be
stored at 2Β° to 8Β° and not be allowed to freeze.
Pertussis Vaccine Adsorbed (USP 23) is a sterile bacterial
fraction or suspension of killed Burdetella pertussis of a
strain or strains selected for high antigenicity, precipitated or
adsorbed by the addition of aluminium hydroxide or alumin-
ium phosphate. It contains a preservative. It contains 12 pro-
tective units per immunising dose. It should be stored at 2Β° to
8Β° and not be allowed to freeze.
Adverse Effects
As for vaccines in general.
Local reactions may occur at the site of injection of
pertussis vaccines or pertussis-containing vaccines
and administration may be followed by fever and ir-
ritability. Local reactions and fever occur less fre-
quently following use of the acellular vaccine than
after whole cell vaccine, especially in children over
6 months of age and adults.
Severe reactions which have been reported include
persistent screaming and generalised collapse but
these effects were generally associated with an
earlier type of vaccine and the reactions are stated to
be rarely observed with the currently available vac-
cines.
Rare neurological adverse reactions have included
convulsions and encephalopathy. There has been
much debate, however, on the causal role of pertus-
sis vaccine in such reactions (see below for detailed
discussion). It should be remembered that neurolog-
ical complications occur more frequently as a con-
sequence of pertussis infection than in association
with vaccination.
Asthma. A higher incidence of asthma was reported in 243
children who had received pertussis vaccine than in 203 chil-
dren who had not. However, follow-up of a large Swedish
study showed no difference in the incidence of wheezing or
allergic reactions between children who had received diph-
theria. tetanus, and pertussis vaccines and those who had not.
Effects on the nervous system. There has been continu-
ing debate over several decades concerning the perceived link
between pertussis vaccination and brain damage. Anxiety
among both the public and health care professionals in the
UK in the mid-1970s over the safety of pertussis vaccines led
to a fall in the acceptance rates for infant vaccination and ma-
jor epidemics of pertussis in 1977/79 and 1981/83. Since that
time confidence has been restored, and by 1995 94% of in-
fants were receiving the vaccine before their second birthday.
The consensus of opinion now seems to be that there is a tem-
poral but not necessarily causal relationship between pertus-
sis vaccine and acute neurological illness which may
occasionally lead to long-term dysfunction, and that risks of
not immunising are greater than the potential risks associated
with the vaccine.
The difficulty in ascertaining whether a causal relationship
exists between pertussis vaccine (usually given as diphtheria,
tetanus, and pertussis (DTP) vaccine) and acute neurological
reactions arises partly because primary vaccination is given at
an age when neurological dysfunction with other causes is of-
ten first manifested. The observed temporal relationship may
be entirely coincidental, or may result from indirect factors
such as pyrexia following vaccination, or may represent a di-
rect effect of DTP vaccine. Much of the evidence is based on
large epidemiological studies, in particular the National
Childhood Encephalopathy Study (NCES) from the UK and
its IO-year follow-up. Serious acute neurological illnesses
reported to the NCES7 were found to be more common in in-
fants immunised within 7 days (relative risk 2.4). and espe-
cially within 72 hours of onset, than in unimmunised
children. For previously normal children irrespective of out-
come the risk was estimated as I in 110 (XX) injections. In a
subset of cases diagnosed as infantile spasms, no link with
vaccination was found overall, but there was a small excess of
cases of infantile spasm in previously normal children who
had received either DTP or diphtheria and tetanus (DT) vac-
cines during the previous 7 days (relative risk 2.0-2.5) fol-
lowed by a corresponding deficit during the next 3 weeks,
This suggested that vaccination may trigger the onset of
spasms in a child with an underlying predisposition.
In 1991. the Institute of Medicine (IOM) in the USA reviewed
the available data, including the NCBS results, and concluded
that a causal relationship between DTP vaccine and acute en-
cephalopathy probably existed, with an estimated risk of zero
to 10.5 per million vaccinations. They concurred with the
conclusion that a causal relationship between vaccination and
infantile spasm was unlikely,
The NCES IO-year follow-up found that children who had
had a serious acute neurological illness (excluding infantile
spasms) had an increased risk of death or long-term dysfunc-
tion. but the risk was no greater in children who had received
DTP vaccine in the 7 days before the original acute illness.
The National Vaccines Advisory Committee concluded that
the results were insufficient lo determine whether DTP vac-
cine influenced the development of chronic neurological dys-
function. and this conclusion has been accepted by both the
Advisory Committee on Immunization Practices (ACIP)
and the American Academy of Pediatrics.
Precautions
As for vaccines in general.Because of the
controversy concerning the potential adverse ef-
fects, especially neurotoxicity, of pertussis vaccines
(see under Adverse Effects, above) the precautions
and contra-indications to the use of these vaccines
have sometimes been more stringent than is now
considered necessary. As with other vaccines, im-
munisation should not be carried out in individuals
with a definite history of a severe local or general
reaction to a preceding dose. In children who have a
history of less severe general reactions, immunisa-
tion may be completed omitting the pertussis com-
ponent. or, in the case of local reactions or pyrexia.
substituting an acellular pertussis vaccine.
Whether children with a personal or family history
of convulsions or epilepsy or who have suffered cer-
ebral damage in the neonatal period should receive
pertussis vaccines appears to have been the most dif-
ficult question to resolve in the past. In the UK the
Department of Health now recommends that chil-
dren with a personal or family history of febrile con-
vulsions and children with a close family history of
idiopathic epilepsy should be immunised and chil-
dren whose epilepsy is well controlled may receive
pertussis vaccine; advice on the prevention of fever
should be given at the time of immunisation (see Fe-
ver and Hyperthermia, p. I for comments on the pre-
vention of fever following immunisation),
Immunisation should also be carried out in children
with a history of cerebral damage in the neonatal
period unless there is evidence of an evolving
neurological abnormality. In children with a neuro-
logical problem that is still evolving it is recom-
mended that immunisation should be deferred until
the condition is stable.
A personal or family history of hypersensitivity re-
actions is not generally considered to be a contra-
indication to the use of pertussis vaccines, nor are
stable neurological conditions such as cerebral palsy
or spina bifida.
Although collapse (hypotonic-hyporesponsive episode) after
pertussis vaccination remains a contra-indication to further
doses of the whole cell vaccine in the UK., a follow-up study
of infants who had experienced such an episode in the Neth-
erlands showed a very low incidence of recurrence on second
and subsequent doses.
Interactions
As for vaccines in general.
Poliomyelitis vaccines. A diminished immune response to
pertussis vaccine was reported in infants given inactivated po-
liomyelitis vaccine mixed with diphtheria, tetanus, and per-
tussis vaccine compared with infants given the two vaccines
as separate injections on the same visit.
Uses and Administration
Pertussis vaccines are used for active immunisation
against pertussis (whooping cough).
For primary immunisation combined diphtheria,
tetanus, and whole cell pertussis vaccines
are usually used. For discussion of immunisation
schedules, see below. Acellular pertussis vaccines
are taking the place of whole cell vaccines in several
countries including the USA and are being incorpo-
rated into primary immunisation schedules for in-
fants and children and for reinforcing doses in older
children and adults. In the UK a single-component
acellular vaccine is available only for use when the
pertussis component has been omitted from all or
part of the primary immunisation schedule: if doses
of diphtheria and tetanus remain to be given, diph-
theria, tetanus, and whole cell pertussis vaccine
should be used followed by acellular pertussis at
monthly intervals to complete three doses. A prima-
ry course may also be given with the pre-school tet-
anus and diphtheria booster in a similar way.
Acellular vaccines may also be substituted in indi-
viduals who have a moderate local reaction or py-
rexia following diphtheria, tetanus, and whole cell
pertussis vaccine. Acellular vaccines are given in a
dose of 0.5 mL by deep subcutaneous or intramus-
cular injection.
Acellular vaccine. Vaccination using whole-cell pertussis
vaccines has been effective but adverse reactions are common
(see above). The immunogenicity of the UK whole-cell vac-
cine is estimated at about 90% using the current accelerated
three-dose schedule. Dissatisfaction with whole-cell vac-
cines in the 1970s led to reduced uptake and a resurgence of
pertussis in several countries. In Japan, research into less re-
actogenic pertussis vaccines resulted in the introduction of
acellular vaccines for routine vaccination in the early 1980s.
The antigenic components of acellular pertussis vaccines are
peitussis toxin (PT, also formerly known as lymphocytosis-
promoting factor, LPF) either alone or more usually in com-
bination with filamentous hemagglutinin (FHA). the
69 kilodalton outer membrane protein pertactin, and/or firn-
brial agglutinogens (with 3 major serotypes; also referred to
as firnbrial antigens). Adverse reactions to acellular vaccines
are less frequent and less severe than those associated with
whole-cell vaccines. The acellular vaccines have successful-
ly controlled pertussis infections but formal comparisons of
efficacy with whole-cell vaccines have only been reported
more recently. For studies of primary immunisation pertussis
vaccine is used in combination with diphtheria and tetanus
toxoids (DTP), and diphtheria and tetanus vaccines (DT) are
used in the placebo groups.
As with whole-cell vaccines, acellular vaccines varied in
their efficacy. Multivalent vaccines were generally more ef-
fective than monovalent vaccines. It has been argued that a
monovalent pertussis toxoid. while providing incomplete pro-
tection for the individual, may nevertheless produce adequate
herd immunity lo inhibit disease transmission. However, the
use of multivalent vaccines seems preferable.
In general, acellular vaccines approached the efficacy of and
were better tolerated than whole-cell vaccines. A surpris-
ing result of large studies in Sweden and Italy, in which the
acellular vaccines were considerably more effective than the
whole-cell vaccines, was the low efficacy of the US whole-
cell vaccine (less than 50%). This was attributed to a rapidly
waning effect after 3 doses given at 2,4, and 6 months of age,
suggesting that the booster doses at age 12 to 18 months and
at school entry are essential to the US schedule. The UK
whole-cell vaccine was found to be as effective as a pentava-
lent acellular vaccine and both were more effective than a tri-
valent vaccine in a large study in Sweden.
In the UK. confidence in the whole-cell vaccine has been
largely restored, and uptake of primary immunisation in in-
fants is approximately 90%. Under these circumstances it is
unlikely that there would be any benefit from switching to the
use of the more expensive acellular vaccines. However,
there is some concern over the incidence of pertussis infection
in adults and it is possible that acellular vaccines, which are
better tolerated in older recipients than whole-cell vaccines,
would be more acceptable if booster doses are added at school
entry and in school leavers. In the USA, however, acellular
pertussis vaccines are now recommended for both primary
immunisation in infants and for the booster doses at 12 to 18
months and at, school entry.
Immunization schedule. A review of the epidemiology
and control of pertussis. Pertussis is a common, highly infec-
tious, respiratory disease, predominantly affecting children,
and for which there is no effective treatment. WHO has esti-
mated that 60 million cases of pertussis occur annually and
that the disease is responsible for half a million to one million
deaths each year. The highest incidence of pertussis is ob-
served in developing countries where immunisation is low.
A combined adsorbed diphtheria, tetanus, and pertussis vac-
cine is now used in most countries but both the strength of the
pertussis component and production methods vary, leading to
vaccines of different potencies.
Depending upon the country, the age at which a child is given
the first dose of the combined vaccine varies from 5 weeks to
6 months. In countries with
a high incidence of pertussis WHO recommends that immu-
nisation should start at 6 weeks of age and that the schedule
involve three doses at monthly intervals, A booster dose
should be given one year after the end of the primary series of
3 injections and in some countries a second booster at entry
to school is given. Several reports have described the use of a
two-dose widely-spaced primary immunisation schedule and
this would indeed simplify procedures in developing coun-
tries; however, the limitation of such a schedule is the long
period of risk between doses without adequate protection and
unless the interval can be shortened to 4 weeks, the wide use
of such a schedule is not advisable in endemic areas.