Incidence of adverse reactions after administration of high dose diphtheria with tetanus vaccine to school leavers: retrospective questionnaire study

BMJ 1996;313:533-534 (31 August)

Papers

Incidence of adverse reactions after administration of high dose diphtheria with tetanus vaccine to school leavers: retrospective questionnaire study

P D Sidebotham, S W Lenton

School of Medicine, University of Southampton, Southampton SO16 6YD Peter D Sidebotham, lecturer, community child health. Department of Child Health, Bath and West Community NHS Trust, Bath BA1 3QE Simon W Lenton, consultant paediatrician. Correspondence to: Dr Lenton.

In October 1994, after an increased incidence of diphtheriain eastern Europe, the Department of Health recommended thatall children aged 15-18 years should receive a combined tetanusand low dose diphtheria vaccine in place of tetanus vaccinealone.¹ Low dose vaccine is recommended for adults and olderchildren because of the possibility of serious reactions inthose who are immune. In March 1995, 220 children aged between14 years 4 months and 16 years 1 month were inadvertently givenhigh dose diphtheria with tetanus vaccine. When this error wasdiscovered the immunisation sessions were halted and stocksof the high dose vaccine were withdrawn from schools.

Subjects, methods, and results

Following an official inquiry into the incident, the parentsof all children involved were sent a questionnaire about theincidence, severity, and duration of side effects experiencedby the children after being given the high dose vaccine. Threepossible local reactions and five systemic reactions were listed,together with an indication of severity (see appendix).

A total of 153 (70%) questionnaires were returned. One childhad received only polio vaccine, and two forms were returnednot completed. These three were therefore excluded.

Twenty six children (17%) reported consulting a doctor afterthe vaccination. Forty eight children (32%) missed 1-15 (mean3.5) days of school. The commonest reasons given were flu-likesymptoms (15 children), fever (10), and headache (10).

A total of 141 (94%) children reported one or more reactionsto the vaccine (table 1). Most reactions (93% local and 85%systemic) were classified as mild or moderate and lasted lessthan a week. However, 47 children (31%) reported at least onesevere local or systemic reaction.

Table 1--Numbers of reported reactions to high dose diphtheria with tetanus vaccine in 141 children aged 14-16 years
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                                         Mild              Moderate                Severe             Total (%)
Reaction                               (n = 380)            (n = 311)             (n = 87)            (n = 778)
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Redness at injection site                 45                   64                     15               124 (83)
Swelling at injection site                30                   82                      8               120 (80)
Itching or pain                           52                   65                      1               118 (79)
Fever                                     68                    8                     12                88 (59)
Tiredness; feeling generally unwell       67                   24                     22               113 (75)
Headache                                  34                   50                      8                92 (60)
Joint or muscle aches                     56                   18                      4                78 (52)
Rash                                      21                   --                     13                34 (23)
Wheeze                                     7                   --                      4                11 (7)

Appendix
Gradings of severity of reactions to high dose diphtheria-tetanus vaccine that were used in questionnaire
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Reaction                                 Mild                                   Moderate                                Severe
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Redness at the injection site            Covering less than size of 50p coin    Over part of upper arm                  Involving whole upper arm*
Swelling at the injection site           Lump smaller than 50p coin             Over part of upper arm                  Swelling of whole upper arm*
Itching or pain                          At injection site only                 Whole upper arm                         Affecting armpit
Fever                                    Felt feverish or hot but temperature   Temperature raised but less             Temperature more than 38.5°C
                                           not measured                           than 38.5°C
Tiredness, feeling generally unwell      Feeling unwell but able to carry on    Not able to carry on with               Had to stay in bed
                                           with normal activities                 normal activities
Headache                                 Mild headache, able to carry on with   Moderate pain requiring pain            Severe or persistent pain,
                                           normal activities                      killers                                 had to stay in bed
Joint or muscle aches                    Mild aches affecting arms or legs      Pain with limited movement of           Severe pains with limited
                                                                                  arms or legs                            movement of arms or legs
Allergic symptoms such as rash or        Mild wheeze; mild or faint rash                                                Severe, itchy or painful rash;
  wheeze                                                                                                                  severe wheeze with difficulty
                                                                                                                          breathing
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*Specified to conform as far as possible to grading as given in Immunisation against infectious disease (Department of Health, 1992).

Comment

Before the 1940s the use of high dose (25 Lf) diphtheria vaccinein adults led to unacceptably high reaction rates. Studies atthis time showed a lower dose (5 Lf) vaccine to be equally immunogenic,with lower reaction rates.² Reported reaction rates to the dosescurrently used (1.5 Lf) are similarly low, being in the regionof 1.4-5.6% for systemic and 12.1-19% for local reactions.³⁴ One study, however, found an overall rate of 57.8%.⁵

The responses to our questionnaire indicate that a much higherproportion of children had adverse effects from the high dosediphtheria-tetanus vaccine. Our sample was fortunately small;this, together with a relatively high non-response rate, placeslimitations on the interpretation of the data. In addition,a delay in waiting for the results of the inquiry meant thatour study relied on parents reporting retrospectively and sometime after the incident. This has drawbacks in that the responsesare subjective, depended on the parents' recall, and may havebeen subject to bias. This is particularly important as manyof the parents were understandably angry that the wrong dosehad been given. The fact that 32% of respondents suffered reactionssevere enough to miss school provides a more objective measure,particularly as these children were in the first year of GCSEwork and consequently reluctant to miss school.

In showing such a high morbidity, our results reinforce recommendationson the use of low dose diphtheria for older children and adults.We emphasise the importance of specifying the dose on orderforms and always checking the dose of vaccine on the vial beforegiving the vaccine.

Funding: NHS. Conflict of interest: None.