Adverse events after vaccination with dTap in high school students who have previously been vaccinated with d2T5

Canada Communicable Disease Report

1er February 2006

Volume 32

Number 03

Background

The goal of pertussis control in Canada is to reduce the morbidity and mortality of pertussis across the entire lifespan(1). In 2003, the National Advisory Committee on Immunization (NACI) recommended administering a single dose of the adolescent/adult formulation of acellular pertussis vaccine to preadolescents and adolescents who have not received a dose of acellular vaccine(2).

In 2004, the Quebec Department of Health and Social Services (MSSS) introduced the combined diphtheria-tetanus-acellular pertussis (dTap) vaccine to replace the diphtheria-tetanus vaccine ( d2T5) given as a booster to adolescents. The Canadian Immunization Guide recommends that d2T5 not be administered < 5 years after the last dose of the same vaccine, because the occurrence of adverse events is higher when repeated doses are given at close intervals. There was reason to anticipate the same phenomenon when dTap was administered < 5 years after a previous vaccinations with d2T5.

When cases of pertussis occurred in Montreal area high schools, it was decided that the benefit of protection against pertussis was greater than the risk of adverse events following the second vaccination. The dTap vaccine manufactured by Sanofi Pasteur (Adacel) was offered to 1,367 students at two Montreal high schools, whether they had previously received d2T5 or not. The school nurses at the CSLC St-Henri, which services the two schools, vaccinated 839 students, or 61% of the total. Follow-up to these vaccinations made it possible to compare the occurrence of vaccine adverse events in relation to the time that had elapsed since the last dose of d2T5 vaccine.

Methodology

The retrospective cohort study included 839 students vaccinated in May 2004. The frequency rate of adverse events following dTap vaccination was compared in relation to the time that had elapsed since the last dose of d2T5. A short, self-administered questionnaire was distributed to students during the final exam period in June 2004, about a month after they were vaccinated.

All the vaccinated students were supposed to answer the questionnaire, whether or not they had experienced any adverse events. They were supposed to drop off the questionnaires themselves at the school nurse's office. A questionnaire was considered valid for the purposes of the study if it was partially or fully completed by a student who had been vaccinated in May 2004.

The variables were as follows: name, date of birth, sex, vaccination history and the presence or absence of vaccine adverse events (time to first symptoms, type of symptoms, duration, severity, any doctor's visit, hospitalization). For the purposes of evaluating the severity of the vaccine adverse events, the questionnaire asked whether the symptoms were mild (easy to tolerate), moderate (interfered with activities) or severe (prevented activities). The questionnaire also asked whether a doctor had been consulted or whether hospitalization had taken place.

Immunization status for dTap and previous doses of d2T5, as reported in responses to the questionnaire, were validated from the CLSC immunization records if the adolescent had been vaccinated there, or from information on the previous dose on the vaccination authorization form kept on file at the CLSC. The inclusion period for our analysis was 7 days.

Results and discussion

In all, 465 validated questionnaires were collected, which represents a response rate of 55% of the 839 vaccinated adolescents. The percentage of girls and boys who responded was similar for all grades. Of the 465 vaccinated students, 178 (38%) had received a dose of d2T5 within the past 5 years. In all, 41% (190) of respondents reported one or more vaccine adverse events, a percentage which remained unchanged whether the individuals had received a dose of d2T5 in the past 5 years or not (Table 1).

Table 1. Relative risk of certain adverse events and d T vaccination in the past 5 years

Adverse events Total Vaccination with d2T5 in the past 5 years p*
(N = 465) Yes (N = 178) No (N = 287)
Adverse events: Yes 190 (41%) 73 (41%) 117 (41%) 0.96
Adverse events: No 275 (59%) 105 (59%) 170 (59%)
Specific adverse events** :
Local reaction
Pain 103 (22%) 36 (20%) 67 (23%) 0.43
Bump 65 (14%) 22 (12%) 43 (15%) 0.43
Fever 27 (5.8%) 12 (6.7%) 15 (5.2%) 0.50
Vomiting 8 (1.7%) 4 (2.2%) 4 (1.3%) 0.49
Allergy 3 (0.6%) 2 (1.1%) 1 (0.3%) 0.31
Rash 6 (1.3%) 4 (2.2%) 2 (0.7%) 0.15
Joint pain 46 (9.9%) 21 (12%) 25 (8.7%) 0.29
Other 21 (4.5%) 9 (5.1%) 12 (4.2%) 0.66

* Comparison with subjects who have not received d2T5 in the past 5 years.

** The column totals are higher than the totals indicated because some students reported more than one vaccine adverse event.

Local reactions were the most common adverse reaction. Pain was reported by 103 respondents, while 65 others reported bumps at the injection site. There was no statistically significant difference between the sexes with respect to adverse reactions except for bumps, which were more frequent in girls (20%, 48/245) than in boys (8%, 17/219 [p = 0.0002]). The frequency of adverse reactions did not increase when the last dose of d2T5 was more recent (Table 2).

Table 2. Previous vaccination with d2T5 and post-dTap adverse events

Vaccination with d 2T5 over the past 5 years

N out of 465

Presence of vaccine adverse events*

p**

N

%

No

287 117
41

Yes

< 2 years

33 11 35 0.57

2 years

53 23 43 0.72

From 3 to 5 years

44 20 45 0.56

Time unknown

48 19 40 0.89

* Five records did not contain any responses to this question; they are considered to indicate an absence of vaccine adverse events.

** Comparison with the subjects who have not received d2T5 in the past 5 years.

Subjects considered 7.4% (14) of vaccine adverse events to be severe; the percentage was 1.7% (3/178) among those who had received d2T5 within the past five years and 3.8% (11/287) among the others. Six individuals saw a doctor (1.7% and 1.0% respectively), but no one was hospitalized. The adverse events occurred on average 14 hours after vaccination and lasted on average 68 hours.

Of the 143 students who reported having received a dose of d2T5 in the past 5 years and who answered the question on adverse events following this dose, 25 said they had had vaccine adverse events. Of these, 23 (92%) had again presented with the same type of symptoms as after their dTap vaccination. Nine said the symptoms were less severe this time, 12 said the severity was the same and 3 (12%) said it was worse. The latter had local reactions and fever. The previous vaccinations were not recent.

Discussion

These data on a total of 465 individuals suggest that previous vaccination with d2T5 does not increase the risk of local reaction at the injection site following vaccination with dTap. These results are consistent with recent results from the Yukon(3) and Prince Edward Island (SA Halperin, personal communication, June 2005). The reported adverse events and their severity are consistent with those described as common in the Protocole d'immunisation du Québec (PIQ) in cases where the vaccine is administered after an interval of > 5 years.

The number of respondents corresponds to about half the vaccinated students, which could cast doubt on the validity of the results if those who experienced adverse events were less likely to respond, but this does not seem to be a likely hypothesis. Validating the previous vaccinations may be a problem. However, we have determined that the results do not change if previous vaccinations not performed at the CLSC are excluded.

Conclusion

The data in this study do not suggest any increase in vaccine adverse events when dTap is administered to an adolescent who has recently been vaccinated with d2T5.

References

  1. Health Canada. National Consensus Conference on Pertussis. CCDR 2003;29S3:1-36.

  2. NACI. Prevention of pertussis in adolescents and adults. CCDR 2003;29(ACS-5,6):1-9.

  3. David ST, Hemsley IA et al. Enhanced surveillance for vaccine- associated adverse events: dTap catch-up of high school students in Yukon. CCDR 2005;31(11):117-26.

Source: M Tremblay, MD, MSc, Direction de la santé publique de Montréal; J-L Grenier, MD, MSc, Direction de la santé publique des Laurentides; G De Serres, MD, PhD, Institut national de santé publique du Québec, Université Laval, Direction de la santé publique de Québec; S Ménard, MD, Direction de la santé publique de l'Estrie; E Toth, MSc, Institut national de santé publique du Québec; R Roussel, MD, Direction de la santé publique du Bas St-Laurent; H Favron, MD, Direction de la santé publique de la Montérégie, M Landry, MD, LLCM, Institut national de santé publique du Québec, Ministère de la santé et des services sociaux du Québec; D Thiffault, chef de programme jeunesse-adulte, CSSS du Sud Ouest-Verdun (site CLSC St. Henri); H Godin, school nurse, CSSS du Sud Ouest-Verdun (site CLSC St. Henri), Quebec.

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