THE JOURNAL OF THE CANADIAN PAEDIATRIC SOCIETY

FEATURE ISSUES

1998 National Report (interim) on Immunization
Vaccine Safety Issues And Surveillance

REPORTED ADVERSE EVENTS TEMPORALLY ASSOCIATED WITH VACCINE ADMINISTRATION IN CANADA: 1993 to 1997 SUMMARY TABLES

The monitoring of vaccine safety is both a vital and a complex task. In Canada, several activities are aimed at ensuring that vaccines administered to children and adults are safe and effective. Activities include both passive and active surveillance, as well as the availability of national expertise to review issues of concern. Descriptions of these activities can be found in the 1996 National Report on Immunization, or the web site of the Division of Immunization <www.hc-sc.gc.ca/hpb/lcdc/bid/di>.

The passive Vaccine Associated Adverse Events (VAAE) Surveillance System aggregates case reports of suspected adverse events submitted to provincial public health authorities by health care providers. Reporters include physicians and public health nurses.

Data provided in this summary represent case reports received involving vaccinations given from 1993 to 1997. It is important to note that an established causal relationship is not required, and, in some cases, the vaccine may not have been responsible for the reaction. In fact, for cases with events that may be considered serious, only about 25% are felt causally related, and the majority of the cases turn out to be reactions explainable by the biological properties of the vaccine. However, it is by monitoring all cases reported that important signals of concern can be uncovered. At the same time, it is well recognized that there are varying degrees of under-reporting from all passive monitoring programs. It has also been recognized that the degree of under-reporting varies with the nature of the adverse event. Reactions considered minor are the least likely to be reported, for obvious reasons in that they may be anticipated and already well documented. On the other hand, the most serious reactions are also the ones most likely to get reported and, thus, the least likely to be missed. In reviewing serious cases, temporal inclusion criteria are applied because some events have maximum time frames beyond which it is unlikely that the vaccine could be causally related to an event and that an intervening event is more likely to have been responsible. Table 10 lists the adverse event definitions used; temporal criteria that may be applied are given in Appendix 1. Of note, temporal criteria are not applied to any unusual or unexpected reactions, and the temporal criteria can be changed upon more careful review of the case.

This section presents a series of tables providing an overview of reported adverse event cases from 1993 to 1997. The cases have all undergone triage and evaluation for new signals, and have already been available for use and have been used to address any vaccine safety concerns that have arisen to this point. In addition, the Advisory Committee on Causality Assessment has reviewed all serious case reports. Provincial public health authorities are provided the opportunity to request ad hoc queries of their data and receive summaries as requested. On a population and product basis, Canada’s vaccine adverse event monitoring program has one of the highest reporting rates of any drug monitoring program. This is a credit to the diligence of public heath nurses and practitioners in the provinces and territories who are well aware of the importance of vaccination to the public’s health and the importance of watching over their safety.

Figures 7 and 8 show the number and rate per 100,000 population of adverse event reports submitted by each province or territory from 1993 to 1997. Provincial variations exist for several reasons, unrelated to the actual safety of vaccines in use (and bearing in mind that a proven causal relationship is not always required for a report to be accepted). These variations include vaccination delivery whether by public health or private physician (public health delivered programs have a much higher reporting rate); whether provinces or territories have made efforts to stimulate reporting by routinely providing copies of reporting forms and instructions reminding health care providers of the importance of submitting cases of concern; and whether special vaccination programs have taken place, which increase the number of vaccine doses distributed.

Figure 7) Vaccine associated adverse events. Number of reports by province and territory, Canada, 1993 to 1997. BC British Columbia; Alta Alberta; Sask Saskatchewan; Man Manitoba; Ont Ontario; Que Quebec; NB New Brunswick; NS Nova Scotia; PEI Prince Edward Island; Nfld Newfoundland; NWT Northwest Territories

Figure 8) Vaccine associated adverse events. Reports by 100,000 population by province and territory, Canada, 1993 to 1997. BC British Columbia; Alta Alberta; Sask Saskatchewan; Man Manitoba; Ont Ontario; Que Quebec; NB New Brunswick; NS Nova Scotia; PEI Prince Edward Island; Nfld Newfoundland; NWT Northwest Territories

Table 11 shows the distribution of reported cases by selected age group from 1993 to 1997. Just over one-third of cases involve vaccine recipients under one year of age. This reflects, not simply the fact that a high proportion of vaccine is administered to that age group, but also the fact that many reports of a mild or moderate nature in fact do not get reported until the infant or child is ready for the next dose. Doses given close together in the first year of life are more likely to have any adverse events mentioned at the subsequent dose administered shortly afterwards.

Table 12 shows the distribution of vaccines involved in case reports from 1993 to 1997. Because many vaccines are given in combination, the column totals add up to more than the total number of case reports received. Variations from year to year reveal the patterns of vaccine use. For example, measles mass immunization campaigns in 1996 are reflected in the greater distribution of case reports for measles-containing vaccines in that year. The arrival of acellular pertussis vaccines only began in 1997, and this, along with the less reactogenic nature of the vaccine, is reflected in the low number of case reports involving that vaccine.

Table 10 illustrates the adverse reactions coded on case reports by year from 1993 to 1997. As noted, the most common reactions, accounting for 48%, are fever and local reactions. These are considered minor and expected side effects of vaccination. Monitoring such reactions permits some degree of assurance over time that vaccines are not becoming more reactogenic. Less than 5% of all reported reactions are considered serious, and other work reviewing these, as indicated in the introduction to this section, has demonstrated that only about 25% may be deemed causally related to the vaccine, with the majority of these, expected on the basis of what is known about the vaccine.

Table 13 highlights the distribution of reports by time to onset of the adverse event. If more than one interval is given for cases with more than one reaction, the shortest interval is displayed. Most reactions tend to begin in the first 24 h after vaccination, with few reactions noticed after two weeks.

VACCINE ASSOCIATED ADVERSE EVENT (VAAE) SURVEILLANCE SYSTEM: A FIVE-YEAR REVIEW

From January 1, 1993 to December 31, 1998, the total number of vaccine associated adverse event reports received at the Laboratory Centre for Disease Control (LCDC) were 26,903. Of these, 23,335 (87%) fit the inclusion criteria published in the Canada Communicable Disease Report (1) and, of these, 22,252 were selected, based on a vaccine administration date from 1993 to 1997, for the following five-year review.

The distribution of VAAE reports by province and territory indicates that over the past two years, British Columbia submitted the largest number of reports (Figure 7), with Alberta following close behind. However, when rates (per 100,000 population) are calculated, it can be seen that, for 1997, the reverse is true (Figure 8). Also noteworthy is that, on average, even though Quebec and Ontario have submitted the next highest number of reports (801 and 504, respectively), this situation changes when provincial and territorial populations are taken into account. The reporting rates from Saskatchewan, Newfoundland and Prince Edward Island as well as the two territories (Nunavit not yet reporting) are, on average, higher than the two most populous provinces.

Table 11 provides a yearly breakdown of the VAAE reports, by selected age groups (chosen to correspond with provincial and territorial childhood immunization schedules), over the five years ending in 1997. Of the 22,252 reports analyzed, 8155 (37%) indicated that the vaccine recipient was under one year of age at the time of vaccination. In 1996, the five to 19-year-old age group accounted for 38% of the VAAE reports; most likely, this is a reflection of Canada-wide measles mass vaccination campaigns that were intended as catch-up programs. As well, new provincial and territorial two-dose measles schedules resulted in more measles vaccine (M, MR, MMR) being distributed and administered and, therefore, more potential adverse events. This is further supported by the results in Table 10 [12b] which shows that, in 1996, 2333 VAAE reports (39%) were submitted in which measles vaccine (M, MR, MMR) was administered (along with possibly other vaccines) and at least one adverse reaction was reported.

TABLE 11: Vaccine Associated Adverse Event Surveillance System: Reports by age group, Canada, 1993 to 1997. Reports received at the Laboratory Centre for Disease Control as of December 31, 1998
Age group	1993	1994	1995	1996	1997	Total
Unknown	31	33	35	42	58	199
0 to 1 month	61	76	94	87	77	395
2 to 3 months	411	574	713	617	477	2792
4 to 5 months	403	542	728	625	446	2744
6 to 7 months	281	330	403	375	262	1651
8 to 9 months	62	79	100	68	55	364
10 to 11 months	39	40	43	43	44	209
12 to 23 months	624	723	830	864	721	3762
2 to 4 years	449	415	423	599	334	2220
5 to 9 years	502	569	585	1063	462	3181
10 to 19 years	327	257	273	1205	433	2495
20 to 29 years	80	77	58	80	137	432
30 to 39 years	98	89	93	84	157	521
40 to 49 years	75	81	107	77	134	474
50 to 59 years	52	53	64	60	104	333
60+ years	78	78	78	103	143	480
Total	3573	4016	4627	5992	4044	22,252

Table 12 provides a breakdown of the number of VAAE reports by adverse event for each year from 1993 to 1997. The two most commonly reported adverse reactions, namely, fever and local reactions (severe pain and/or swelling), accounted for 48% of all reactions over the five-year review period while the more serious reactions such as encephalopathy, paralysis, meningitis/encephalitis and thrombocytopenia acounted for less than 1% of all reactions.

Table 13 provides a breakdown of the number of VAAE reports by time of onset of symptoms (at time of reporting) which essentially summarizes imprecise estimates made by the parents and guardians of young vaccinated children (often younger than one year of age). To complicate matters further, over the five-year review period, two reporting formats were used; the earliest of which only allowed for one interval for the first reaction to be reported. As a result, many reactions were reported without rigorous attention to detail and many intervals were not reported. In 1997, 598 incidents (14.8%) were reported in which the initial advere reaction occurred within 24 h of vaccination while only one occurred at least a month later.

TABLE 13: Vaccine associated adverse events reports by time of onset of symptoms and year, Canada, 1993 to 1997
Time of onset	1993	1994	1995	1996	1997
Unknown	464	1141	2107	3984	3131
0 to less than 1 h	219	228	165	284	68
1 to 8 h	1680	1572	1442	610	417
9 to 16 h	302	269	240	132	75
17 to 23 h	104	111	88	73	38
1 to 7 days	675	580	469	686	258
8 to 14 days	88	78	83	187	43
15 to 21 days	17	13	19	26	8
22 to 30 days	9	10	8	8	1
One month or more	15	14	6	2	5
Total	3573	4016	4627	5992	4044
If more than one interval is given for cases with more than one reaction, the shortest interval is displayed

REFERENCE

1. Adverse Events Temporally Associated with Vaccines – 1992 Report. Can Commun Dis Rep 1995;21:127-8.

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