Introduction.
Since the first report we have obviously had more questionnaires returned and more personal communications, both have again been used as data sources. The sources of information in terms of reported cases for MMR to date (Nov. 1994) are :-
156 cases used as a data source
116 cases with date of vaccination known
115 cases with type of vaccine known
106 cases with type and batch number known
this gives us a fair sample size. However when analysing effects such as symptoms, problems, and time when symptoms occurred we may be dependent on fewer samples since this information may not have been supplied.
How frequent are MMR vaccine problems ?
Ehrengut1 (1989) gives 27 examples of neurological reaction using data from 1979 to 1989. this would seem to indicate low risk. Studies in Canada2 indicate 1 in 62000 cases of meningitis with vaccines based on the Urabe strain of mumps. In a letter dealing with the recent withdrawal of PLUSERIX and IMMRAVAX types of MMR the Chief Medical Officer3 quotes that these types with the Urabe strain of mumps vaccine may carry a risk of meningitis in 1 in 11,000 cases.
Other side effects occur but the central argument seems to have concerned only meningitis. The information we received can hardly be attributed to a blaze of publicity although we have had a lot more media attention. We have used those reports where the date of vaccination and type is known accurately. The results are shown in graphs for all MMR vaccinations 1(a) and then separately where the type of vaccine is known 1(b) IMMRAVAX, 1(c) MMR2 , 1(d) PLUSERIX .
In an earlier report we stated that since the withdrawal of the above two vaccines it would be interesting to see how the number of cases with problems following MMR2 1(c) vaccination alters . This has risen from 14 to 20 cases . IMMRAVAX has risen from 22 to 16 cases and PLUSERIX from 42 to 58. A major problem for parents (and therefore our group ) has been obtaining the brand and or batch number to identify the type of vaccine used.
Information prior to vaccination.
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.
What has become apparent as we accumulate data is that the vaccination is not being explained in detail (84% No) as graph 2(a) shows above. In graph 2(b) any explanation of possible side effects no matter how short was scored as a yes, which gives the 40% above, 59% of respondents stated that the no side effects had been explained to them. It is arguable that if parents feel there are no side effects because they were not told of them any changes to the child after vaccination may be missed or delayed in reporting until the changes are very major. Since one of the group's aims is the ability to make informed decisions on vaccination by parents being given information graph 3 shows us the major sources of information. As expected Health Visitors and GPs/Doctors predominate, with very low ratings on media influences.
Symptoms.
The time taken for symptoms to appear following MMR vaccination is shown above in Graph 4(a). For comparison we have included data from Ehrengut's study 4(b). Notice we have the same peak around the 10 day mark but many more earlier reactions. When a parent notices a change in a child's condition they will try to think of an event which caused it. There will thus be a temptation to associate two closely linked events as cause and effect. Stewart & Prabhu (1993)8 state ' doctors are asked to report all suspected reactions for both new and established vaccines. A proved causal relationship is not required before reporting' . A report in Canada2 asked for reporting of ' CNS reactions within 60 days of administration of measles, mumps and rubella vaccines ' . We have used this time limit for the present graphs. On the point of causation some parents quoted symptoms within hours these are shown below in graph 5. Although not establishing a link itself close proximity of two events can be a good indication of causality.
Separate graphs for the three MMR vaccines are shown below in Graph 6. It would appear that there are differences between the vaccines. For example PLUSERIX 6(e) appears to cause many more earlier symptoms than IMMRAVAX 6(b) or MMR2 6(d) and it would appear a statistical analysis to see if significant differences exist is called for. Nationally however vaccines were used in different proportions until their withdrawal. PLUSERIX and IMMRAVAX accounted for 85 % of the MMR vaccines distributed , (Stewart & Prabhu (1993)8 , which leaves 15% for MMR2 until the withdrawal. We have 115 cases where vaccine types are known, theoretically this give us 95 predicted cases for PLUSERIX and IMMRAVAX with 20 predicted cases for MMR2. Comparing predicted and observed cases using a chi-squared test we obtain a value of 0.623, 0.3 > p < 0.5. There is therefore no significant difference between the proportions of vaccine types in our sample and those in the vaccine programme. Provided further information of the breakdown of the two Urabe type vaccines in the 85% can be obtained a proportionate statistical analysis is possible to see if one vaccine may have caused more problems independent of the fact that it may be commonest vaccine.
As mentioned earlier, (page 1), the Urabe strain of mumps vaccine appears to cause higher numbers of meningitis. Ehrengut's data was reworked, splitting his results into Urabe strains Graph 6(a) and Jeryl Lynn strains Graph 6(c) with the intention of comparing his and our results on a strain for strain basis. Unfortunately from his data only 2 cases are available for Urabe type vaccinations 6(a) to compare with the relevant Pluserix 6(e) and Immravax 6(b) (Urabe vaccines in the U.K.). His work gives 25 cases for Jeryl Lynn 6(c) vaccines with the relevant MMR2 6(d) (Jeryl Lynn vaccine in U.K.) . Exact comparisons are therefore difficult to make.
The graph for PLUSERIX 6(e) shows separate clusters of symptoms appearing at discrete intervals. It would be interesting to know if these groups identify with the body reacting to different components of the vaccine (Measles, Mumps and Rubella antigens ) or merely represent a range of different symptoms. Do the earliest reactions represent allergic responses ? Since the incubation period for measles is 8-15, usually 12 days does this clustering on the graph represent reactions to the measles component ?
Families have reported a wide range of symptoms following MMR vaccinations. These symptoms are shown above 7(a) along with graphs for separate types of MMR vaccine, IMMRAVAX 7(b), MMR2 7(c), PLUSERIX 7(d).
It is tempting to think that our results show that some vaccines are more likely to cause certain symptoms to appear, for example our examples of meningitis show 2 for Immravax, 3 for Pluserix and none for MMR2.
To do this a statistical analysis is necessary where we would need to take into account the frequency of use of the vaccine type as described above. Obviously the vaccine with most usage may show the most symptoms, and need not be the most dangerous. When we can obtain this information a calculation to show whether there are significant differences could in theory be undertaken.
It is interesting to note that on the basis of information dissemination on symptoms following MMR vaccination the original Health Education Authority booklet 'Immunisation'4 listed mild fevers, a rash, swollen faces and a mild form of mumps, convulsion with fever or encephalitis are stated to be 'extremely rare'. This wording had not changed in the 6/934 edition. However another booklet (12/93)5 now has a separate section 'What are the side-effects of MMR immunisation ?' 'one child in 1000 may have a convulsion ( a fever fit)..... Encephalitis affects less than one in 1,000,000 children.'
The latest MR leaflet for the present campaign lists mild fever, a rash, sore or aching joints, or feel a bit 'off colour'. Thus a limited trend for more information appears to have gone into reverse !
No mention is made of the wide spectrum of symptoms we have found, which are supported by a publication6 from New Zealand.
Problems.
Parents reporting lasting problems have provided us with the information shown below in Graph 8, once again all MMR problems 8(a) and then problems with separate MMR vaccine types 8(b), (c) and (d) are shown.
The above remarks concerning frequency of use again apply but an interesting fact emerging is the number of auto-immune problems e.g. auto-immune Urticaria. Guillain-Barré syndrome, juvenile diabetes and juvenile arthritis may fall into this category where the presence of foreign antigens triggers the body into producing antibodies which attack not just the foreign antigens (the vaccine) but also some of the body's own cells. For some auto-immune diseases there is a familial pattern, inheriting the genes which produce certain antigens (markers) on your own cells means you have a high risk of developing the disease, screening is available for some diseases, for example the B27 antigen with ankylosing spondylitis. Is a familial history a contra-indication to vaccination ? We have contacted some other organisations to look at this point further. Recent and current research7 on possible links of MMR with Guillain-Barré syndrome is being carried out. It is proposed to utilise links with other groups to examine and conduct further research for example on Autism.
Immune deficiencies with resultant or concurrent epilepsy also appear where problems with frequent infections occur. Deafness following MMR vaccination has been reported in Urabe8 strains of vaccine.
The most obvious problems are epilepsy and speech/language/communication problems. Obviously this then causes learning problems as indicated. In the first report we stated that "If we can depend on a degree of goodwill in terms of our respondents it may be useful to ask particular questions on familial patterns of allergies, epilepsy, asthma etc., to try to establish if children in these families are at higher risk ; it needs to be pointed out however that a statistical analysis would be very difficult. "
To begin with the group only had raw data and as one member put it at the second meeting " no denominator ". That is we have no way of assessing what proportion of the total vaccinated population we represent. However if we compare two groups both of whom suffered problems after vaccination, we can get the results shown in graph 9 below to look at the asthma factor. Although the groups are not equal in size the graph implies that the group with asthma in the immediate family 9(a) and experiencing problems following vaccination experienced them earlier. Is this difference significant ? Very careful examination of the comparison groups will be required before deciding whether a statistical analysis can be done.
Graph 10 below shows the problems reported in groups with 10(a) and without asthma 10(b) in the immediate family. The large differences in group sizes make conclusions somewhat premature. However 31 out of 128 cases (24%) reported asthma in the immediate family, does this mean that our sample has a higher proportion of asthma families and if so what does this fact mean ? Similarly 13/128 (10%) reported an antibiotic allergy in the family, and 18/128 (14%) reported fits in the family. If respondents continue to return questionnaires we can address these problems and see if familial patterns have consequences with vaccination problems.
Batch numbers.
As stated previously we have 78 cases where the batch numbers are known and these are reproduced in graph 11. Another aspect of vaccination is that the vaccine itself may not normally cause a problem but that a particular production batch of the vaccine may have a problem. We now have several families with the same batch number. With some batch numbers similarities of time for symptoms to appear are emerging, similarities of symptoms, for example meningitis, high temperatures and also similarities of problems such as speech,language and communication problems.
Conclusions.
We are aware that parents have also contacted us with reports of D.T.P., Pertussis, Polio, Measles, B.C.G. and Rubella problems, many of these before the present combination vaccines. When time allows we will analyse their bodies of information.
Our questionnaires were done in haste and need more refinement, we do not want to elicit responses on the basis of leading questions. Currently we are circulating a second questionnaire to look at familial problems, this also addresses a question of post vaccination problems being under reported because of judgements that the vaccines are safe and could not be the cause of the problem. To achieve this we are asking respondents if their case has been reported under the yellow card system.
In terms of information with regard to relevant studies/articles we would be grateful if members in the know would point out such material to JABS. We could then look more closely at our findings.
References.
1. Ehrengut W. Mumps Vaccine and Meningitis. Lancet, Sept. 23rd. 1989; p 751.
2. Vaccine-related Mumps Meningitis.Canada Diseases Weekly Report. Vol. 16- 50,15th. Dec. 1990, pp 253-4.
3. Chief Medical Officer Letter, 14th September 1992.
4. 'Childhood diseases haven't died. Children have.', Health Education Authority, 500m 1/91 ISBN 1 85448 0197 and 450m 6/93 ISBN 185448 0197.
5). 'A guide to childhood immunisations' , Health Education Authority, 450m 12/ 93 ISBN 1 85448 994 1
6). 'Immunisation' The Immunisation Awareness Society, Box 56-048, Dominion Rd., Auckland, New Zealand.
7). Rees J., Hughes R. Guillain-Barré syndrome after measles, mumps, and rubella vaccine. Lancet, 1994, Vol. 343, p. 733
8). Stewart, B.A. J. ,Umesh Prabhu P. 'Reports of sensorineural deafness after measles, mumps, and rubella immunisation' Archives of Diseases in Childhood 1993; Vol. 69 ; pp 153-4