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