What is DTP ?
Clinical trials into pertussis (whooping cough)
vaccine commenced in 1948 and were completed in 1956. The vaccine used was
given in single doses and not mixed with other vaccines. The trials were
understood to be very comprehensive in that after each injection the child
was visited by a Nurse/Investigator and the child's health was observed
and noted. When the course of injections had been completed the child was
visited for a further two years and the child's progress was monitored.
According to information received from the
Secretary of State for Social Services, Ashley J. (1985), 55 infants from
this period were awarded vaccine damage payments after becoming 80%
disabled in respect of vaccinations with a pertussis element.
The whooping cough vaccination programme
commenced nationally in July 1957 with the pertussis element added to
diphtheria and tetanus toxoids vaccine to form a new triple injection (DTP).This
was used until 1968 when on the advice of the Public Health Laboratory
Service the vaccine was changed from a plain vaccine to an adsorbed
vaccine. The adsorbed vaccine had a mineral adjuvant, aluminium hydroxide,
incorporated. During the period 1957 to 1968 inclusive 310 children were
awarded vaccine damage payments again under the same strict criteria
Ashley J. (1985).
Summary of JABS findings
Since the JABS group was founded in December 1993
families have reported severe health problems in their children after
vaccinations. Table 1 below summarises our findings for DTP vaccinations.
The different categories of vaccination type
reflect how the nature of the DTP vaccine has changed. Since the DTP
vaccine was introduced in 1957 it has often been given at the same time as
others, hence the cases reporting the vaccination combined with polio or
Hib meningitis or both. The DTP vaccinations are also now completed
earlier. The most recent change in national policy from 3, 5, and 10
months to 2, 3, and 4 months was implemented some time between October
1988 and February 1993.
The data shown are based on parental responses to
a questionnaire. It should be remembered that our sample is biased, since
we have data on families who have been affected by the vaccine and we are
reliant on memory recall from respondents. However when analysing effects
such as type of vaccine, batch number , symptoms, problems and time when
symptoms occurred we may be dependent on fewer samples since this
information may not have been supplied.
Graph 1) below summarises those cases where the
vaccination date is clearly known. It would be interesting to check if the
increase and decrease in figures demonstrate an increased tendency for
parents or medical staff to report symptoms following DTP vaccination or
whether these are linked to changes in vaccine content or changes in the
age at which children are vaccinated.
Graph 2) below shows the time sequence reported
to us by parents. The National Childhood Encephalopathy Study. Farrington
et al. (1995) quotes recognised risk periods for DTP vaccines of 0-3, 4-7,
and 8-14 days.We can find similar peaks as well as later ones not
discussed. Since we are dealing with stand alone DTP as well as DTP
combined with other vaccinations, Polio and Hib, it would be interesting
to note if these later reactions are reactions to components of these
other vaccines.
Associations in time (temporal) between events
need not imply that there is a causal association between those events.
However temporal associations should be analysed further. Menkes and
Kinsbourne (1990) comment "in Aicardi's personal series of 20 cases
of seizures or encephalopathy, the onset was within 72 hours, and usually
within 24 hours of pertussis vaccination. 74 % of his cases developed
within 12 hours of the vaccination and 80% within 24 hours, a pattern
often reflected in the literature and not compatible with the notion of a
chance association. "
Graph 3) shows the information from parents who
quoted reactions in hours not days. As can be clearly seen there is a
close temporal association in hours between administration of the vaccine
and parents noticing symptoms. Some of these reactions may be attributable
to types of allergic response to components of the vaccine.
In an attempt to clarify the position with regard
to DTP and other vaccines graphs (Graph 4) to show the time for onset of
symptoms were done for DTP alone, DTP + Polio, DTP+Hib+Polio and DTP+Hib
were plotted. Because of the paucity of data it is difficult to come to
conclusions but there are apparent differences at the 10 day region. Since
DTP vaccine is given in three vaccinations an analysis was attempted to
see if the onset of symptoms differed. Graph 5 below shows that the
reactions to vaccination three apparently clustered around day 3.
What are the problems associated with DTP ?
Table 2 above is from a DTP manufacturer's
information sheet (Connaught DTP Vaccine) outlining the "approximate
rates for adverse events following receipt of DTP vaccine (regardless of
dose number in the series) ". We can compare this with our graphical
representation (Graph 6) below. Notice the high number of fits and
convulsions. Since our survey is based on parents whose children exhibit
symptoms after DTP vaccination we have no way of establishing dose rates.
Graph 7 shows problems, that is long term effects
noticed after the vaccinations. There are large numbers of epilepsy ,brain
damage, development delay and language problems. This in turn may imply
damage to the Central Nervous System. Menkes and Kinsbourne (1990) stated
"It was the consensus of the workshop, and in particular the
participating neurologists, that although the vaccine may possibly
accelerate neurologic signs or symptoms in some children, and a small
proportion of apparent complications may be coincidental, there was no
inherent difficulty in assigning cause and effect to the vaccine and
subsequent neurologic residua." Further they stated " In
implicating pertussis vaccination in the evolution of subsequent
neurologic residua, a careful consideration of the mechanism for vaccine
induced brain damage plays an important supporting role. Pertussis toxin
has been shown to alter cellular signalling. It affects the
catecholaminergic and GABAergic systems in the brain. Although normally a
protein f the size of PT (pertussis toxin) would not be able to cross the
blood-brain barrier, factors known to disrupt the blood brain barrier
include brief hypertensive episodes such as might occur during a coughing
paroxysm,hypoxia, and prolonged seizures, whether or not they are
accompanied by hypoxia. In addition, a direct, endotoxin-mediated attack
on the endothelial cells could create a local effect on the blood brain
barrier. In summary, it was the consensus that there is sufficient
experimental data to implicate both endotoxin and PT in adverse neurologic
reactions to pertussis vaccine."
With the addition of poliomyelitis
vaccine it is interesting to note the number of children reported with
limb problems and paralysis. 10 cases have been reported for all DTP
vaccinations ( Graph 7) and this does not change if we only consider those
vaccinations where DTP and polio were given together. A study undertaken
by the Division of Immunisation, Centers for Disease Control, Atlanta,
Georgia confirmed that injections are an important cause of provocative
poliomyelitis. Sutter R.W. et al. (1992) stated "A significantly
higher proportion of case children had received their last DTP injection
within the 30-day period preceding onset of paralysis. This association
was observed exclusively in children aged 5-11 months, the principal
target group for immunisation in Oman." "The anatomic site of
injection corresponded with the anatomic site of paralysis in all 19 case
patients for whom information was available. In 12 case patients the
injected limb was the only affected limb."
In October 1992 the Hib meningitis
vaccination was introduced into the British immunisation programme.
Children are now given DTP + Hib meningitis + Polio vaccines all at the
same time.
Since the DTP vaccination is given
as a series of 3 injections it is possible for parents to report symptoms
to individual first, second, and third vaccinations or reactions after
more than one vaccination e.g. one and two. These results are shown below
(Graph 8). It would appear most children react after the first dose. What
is interesting is the fact that some children have been given a subsequent
dose after reacting to a previous dose !
Farrington et al., (1995) reported
" an increased incidence of convulsions 0-3 days after DTP
vaccination. The effect was limited to the third dose of vaccine."
Their study appears to have used children admitted and diagnosed with
febrile convulsions.Menkes and Kinsbourne (1990) however state that
"although the majority of seizures following pertussis vaccination
are associated with fever, it was the consensus of the neurologists
attending the workshop, that these do not represent febrile convulsions,
but are non-benign convulsions."
Analysis of our reports shows that
convulsions occur after each vaccination (Graph 9), in fact over twice as
many convulsions were recorded after vaccinations one and two (7 cases)
than after vaccination three (3 cases).
A problem here is that we are
relying on parental description of the term convulsion. We have therefore
shown febrile convulsions and fits as well. It would seem that the first
and second vaccinations show a higher incidence of 'convulsions' than the
third vaccination. In any case it would be interesting to identify the
number of children who have a convulsion but who are not admitted to
hospital as this may indicate under-reporting under the CSM yellow card
system.
A recent Public Health Laboratory
study, Farrington et al. (1995) , emphasised the need for active
surveillance of adverse events and stated that there is an urgent need to
find more reliable methods of adverse event surveillance.This same study
further commented " as more antigens come to be given at the same
time as DTP vaccine, the rate of such adverse events may increase.
Therefore we will repeat the study in cohorts who are given Hib and DTP
simultaneously. Our method will also be used to assess acellular DTP
vaccines if these replace whole-cell vaccines."
Batch numbers
With three doses of DTP a parent
should have 3 batch numbers,if the DTP is coupled with polio and Hib the
situation is further complicated by the need to have these other batch
numbers. In an earlier report it has been stated that parents have had
problems with finding batch numbers. This would appear to be an obvious
precaution in case there are problems with a manufacturer's particular
batch of vaccine. The maximum number of possible different batch numbers
would be 3x119 = 357, our survey has produced only 31, these are shown
below. (Graph 10)
B4475 was found twice from parents
reporting symptoms after the first dose of vaccine, other repeat batch
numbers are caused by adding all the data from batches 1, 2 and 3
together. Farrington et al. (1995) do not mention DTP batch numbers but
states that for MMR information in the U.K., of 966 children, 752 (78%)
had a batch number recorded ! There would seem to be a real need for
improvement in the recording of batch numbers if the situation is similar
for the DTP sample.
Contraindications and DTP vaccine.
The Connaught DTP Vaccine reference
stated "Use of this product is also contraindicated if the child has
a personal or family history of a seizure disorder. However, the ACIP does
not accept family histories of convulsions or other central nervous system
disorders as contraindication to pertussis vaccination."
Parents were asked in the
questionnaire about family histories of epilepsy/fits/convulsions,
antibiotic reactions, asthma, eczema, hayfever as well as reactions to
vaccines. As can be seen from Graph 11 below of 19 respondents 4 had a
parent or sibling with a history of fits/epilepsy/convulsions.
Asthma in the family is figured in
Graph 12. 15 close family members, parents or sibling suffer from asthma
as well as 8 of the children themselves. It is extremely difficult to know
if such information shows up any trends, asthma is common and the close
family members suffering from asthma may be no indication of potential to
react to DTP vaccine.
Graph 13 below shows close family
members who suffer from antibiotic allergies, note that of 36 cases 4
children had an antibiotic allergy. We would be extremely interested if
there are studies which have looked at allergies as contraindications for
vaccination, or whether a familial history of allergies indicates a
potential for adverse reactions.
References
Ashley J., Parliamentary Written
Answers, 22 February 1983, p. 427.
Connaught DTP Vaccine (Diphtheria
and Tetanus Toxoids and Pertussis Vaccine, Adsorbed, USP)
MKTO246 12/88
Farrington P. et al., A new method
for active surveillance of adverse events from diphtheria/tetanus/pertussis
and measles/mumps/rubella vaccines. Lancet, 4 March 1995, Vol 345 pp
567-569
Menkes J. H. & M. Kinsboune,
Workshop on Neurological Complications of Pertussis and Pertussis
Vaccination, Neuropediatrics 21 (1990) pp171-176
Sutter R.W. et al., Attributable
risk of DTP (Diphtheria and Tetanus Toxoids and Pertussis Vaccine)
injection in provoking paralytic poliomyelitis during a large outbreak in
Oman. The Journal of Infectious Diseases 1992;165:pp 444-9
Acknowledgements.
We are extremely grateful to :-
Mr. W. H. Wain B.E.M for his input
on information on the history of DTP.
Ms. K. Lamb and Mr. R. Barr for
bringing pertinent references to our attention.
Parents who submitted the JABS
questionnaire.
31/05/97
