Adverse Events Following Immunization (AEFI) Bi-annual Report from January 1 to June 30, 2019

Safety assessment summary for January 1 to June 30, 2019

Background

Vaccines are closely monitored in Canada at all phases of the vaccine product 'life cycle' from discovery through market authorization (pre-market) and beyond, as people begin using them (post-market). Many stakeholders are involved in vaccine safety surveillance, including the federal government, provincial, territorial and local public health authorities, health care providers, vaccine industry and the public. Provincial and territorial vaccination programs monitor AEFIs and report them to the Public Health Agency of Canada (PHAC). PHAC conducts post-market safety surveillance through the Canadian Adverse Events Following Immunization Surveillance System (CAEFISS). CAEFISS is managed by PHAC and is unique in that it includes both passive (spontaneous reports from federal, provincial and territorial (FPT) public health authorities) and active surveillance. Active surveillance is conducted by Immunization Monitoring Program ACTive (IMPACT), a network of 12 pediatric hospitals across Canada that screens hospital admissions for specific AEFIs. Vaccine safety concerns are monitored and addressed through the Vaccine Vigilance Working Group (VVWG).

An Adverse Event Following Immunization (AEFI) is defined as any untoward medical occurrence which follows immunization and which does not necessarily have a causal relationship with the usage of the vaccine. The adverse event may be any unfavourable or unintended sign, abnormal laboratory finding, symptom or disease. Serious AEFIs are those which are life-threatening, result in hospitalization or a prolongation of hospitalization, result in persistent or significant disability, or where the outcome is a birth defect or death, as defined by the World Health Organization (WHO) (PDF). AEFIs not meeting the definition of a serious event are classified as non-serious.

WHO defines a vaccine safety signal as information (from one or multiple sources) that indicates a new and potentially causal association, or a new aspect of a known association, between a vaccine and an event previously unknown or incompletely documented that could affect health. Epidemiological studies are usually needed to assess the causal relationship between the vaccine and the signal. The primary purpose of vaccine post-market surveillance is to detect safety concerns. These concerns include a possible increase in the severity or frequency of expected AEFIs, or occurrence of one or more unexpected events (i.e., an event that is not consistent with Canadian product information or labelling). This allows vaccination providers and public health vaccination program providers to take public health action at the level of the:

• individual (such as further investigations to confirm a diagnosis and determine possible causes, consultation to rule out allergy to one or more vaccine components, or evaluate whether or not to give subsequent doses of a vaccine), and/or
• vaccination program (such as investigation of a cluster of adverse events, review of procedures to ensure that vaccine storage requirements have been strictly followed, or consideration of a change in policy to adopt a less reactogenic vaccine)

PHAC also shares AEFI data with Health Canada's Health Products and Food Branch, the national regulatory authority for vaccines in Canada. This enables formal action related to vaccines marketed in Canada to take place if needed. These actions may include issuing communications to vaccination providers or the public regarding the safety concern or requiring additional information or investigation by the vaccine distributor, or changes to the product labelling.

Vaccine safety surveillance reports summarizing CAEFISS data are released by PHAC on a routine basis. The bi-annual reports, similar to the previous quarterly reports, summarize all AEFI reports received by PHAC from January to June and July to December, regardless of the date the vaccine was administered.

In this report, the data for January to June 2019 as well as the 4-year averages for the same time period are shown. However, because these data reflect the date the reports were received and not the date the vaccine was given, the ability to compare and interpret patterns is limited. The report does provide a data snapshot that highlights serious and non-serious AEFI reports received for descriptive purposes.

Results highlighted for January 1 to June 30, 2019

Data presented in this Bi-annual Report include AEFI reports routinely received from January 1 to June 30, 2019 and comparisons are made to the average number of reports received in the same time period over the previous 4 calendar years (2015-2018). The data analysed were extracted from the CAEFISS database on July 24, 2019 by PHAC.

It is important to note that in previous reports one jurisdiction was excluded due to data transmission technical issues. As of January 2018, the issues have been resolved and all jurisdictions are now reporting in full. This is reflected by the increase of the total number of reports and in the results of the analysis for this reporting period.

All reports are processed and coded using MedDRA, a standardized medical terminology that supports data entry, retrieval, evaluation and presentation of clinical information and further coded with a main reason for reporting through a detailed review of individual case safety reports. Therefore, if more than one event is described, the one that is determined to have led to reporting is coded as the primary AEFI. In addition, all reports describing a serious event were reviewed and unless highlighted in this report, found either to be expected (based on known vaccine-related adverse reactions), to have alternate explanations not related to vaccination, or are currently being monitored or investigated further.

Number of AEFI and serious AEFI reports

A total of 1,757 AEFI reports were submitted to PHAC from January to June of 2019. During the same time period of 2015, 2016, 2017 and 2018 PHAC received an average of 1,473 (range: 1,229-1,747) [Figure 1].

A total of 115 AEFI reports received by PHAC between January and June of 2019 were classified as serious (7% of all AEFI reports). During the same time period for 2015, 2016, 2017 and 2018, PHAC received an average of 121 (range: 91-175) serious AEFI reports (7% to 11% of all AEFI reports). As noted above, all technical issues have been resolved and all jurisdictions are now reporting as of January 2018, which led to a slight increase in the number of AEFI reports received during this period. The proportion of serious reports was similar to previous periods.

Figure 1 - Text description

Total AEFI reports received, by bi-annual calendar year (serious and non-serious) for 2019

Half year	Year	Number of AEFI reports
		Non-serious	Serious
July-Dec	2017	1,284	115
Jan-Jun	2018	1,637	110
July-Dec	2018	1,257	111
Jan-Jun	2019	1,642	115

Total AEFI reports received, by bi-annual calendar year (serious and non-serious) for the average of the previous 4 years

Half year	Year	Average number of AEFI reports
		Non-serious	Serious
July-Dec	2013-2016	1,073	107
Jan-Jun	2014-2017	1,220	119
July-Dec	2014-2017	1,150	116
Jan-Jun	2015-2018	1,352	121

Frequency of serious and non-serious AEFI reports by age group

Table 1 shows the number of serious and non-serious AEFI reports by age group from January to June 2019 and comparison with the 2015-2018 average for the same time period. The majority of serious adverse events (SAEs) were in those less than 18 years of age (85%, n=98) with approximately two-thirds (65%, n=75) of total serious reports being reported in children under the age of 2. Possible reasons for the greater proportion of SAEs in the less than 18 age group may be due to the IMPACT surveillance system, which actively searches for specific surveillance targets in children admitted to pediatric tertiary care hospitals. Also, the number of vaccines received by children less than 2 years of age creates more opportunities for adverse events temporarily associated with immunization and to report to a health care provider. As noted above, all technical issues have been resolved and all jurisdictions are now reporting as of January 2018, which led to a slight increase in the number of reports received during this period. The proportion of serious reports was similar to previous periods.  

Table 1: Total AEFI reports received (proportion of total reports), by age group (serious and non-serious), January-June of 2019 and 2015-18 average for the same time period

Age group	Serious reports		Non-serious reports
	2019	Average 2015-18	2019	Average 2015-18
0 to <1 year	36 (31%)	36 (30%)	237 (14%)	177 (13%)
1 to <2 years	39 (34%)	39 (32%)	258 (16%)	191 (14%)
2 to <7 years	12 (10%)	13 (10%)	170 (10%)	124 (9%)
7 to <18 years	11 (10%)	13 (10%)	224 (14%)	242 (18%)
18 to <65 years	13 (11%)	15 (12%)	513 (31%)	442 (33%)
65 years and over	3 (3%)	6 (5%)	231 (14%)	162 (12%)
Unknown	1 (1%)	1 (1%)	9 (1%)	14 (1%)
Total	115	121	1,642	1,352

AEFI reports received by reporter type

Figure 2 presents the originating reporter of the AEFI reports (both serious and non-serious) received during January to June 2019. The majority of reports received were reported by registered nurses (RN) (69%), followed by medical doctors (MD) (13%) and consumers (8%).

Figure 2 - Text description

Reports received by reporter type, January-June 2019

AEFI reports received by type of originating reporter	Percentage of total AEFI reports
ConsumerFootnote 1	8%
IMPACT	3%
MD	13%
OtherFootnote 2	4%
Other healthcare professional	1%
Pharmacist	2%
RNFootnote 3	69%
Footnote 1 Consumer includes family members. Return to footnote 1 referrer Footnote 2 Other includes First Nations and Inuit Heath Branch, labs, medical group. Return to footnote 2 referrer Footnote 3 RN (registered nurse) includes nurse practitioners and infection control professionals. Return to footnote 3 referrer

AEFIs by major classification

Figure 3 presents the main types of AEFIs (both serious and non-serious) reported during January to June of 2019. Excluding the "Other events" category, the majority of the AEFIs reported were vaccination site reactions, followed by allergic or allergic-like events.

Figure 3 - Text description

Primary reason for AEFI reporting, January - June of 2019 (serious and non-serious)

Main reason for reporting an adverse event following immunization	Percentage of total AEFI reports
Reaction at or near the vaccination site	37%
Allergic or allergic-like event	18%
Other eventsFootnote 1	20%
Rash	10%
Systemic event	7%
Neurologic event	8%
Vaccination anxiety	1%
Footnote * Other events include: gastro-intestinal reaction, para/anesthesia, thrombocytopenia, hypotonic-hyporesponsive episode (HHE), persistent crying, intussusception, arthritis, arthralgia, parotitis, and undefined – other Return to footnote 1 referrer

The main types of AEFI by level of seriousness reported between January-June of 2019 compared to the 2015-2018 average for the same time period are shown in Table 2. Between January and June of 2019 as well as in the past 4 years, excluding the "Other events" category, reactions at or near the vaccination site, allergic or allergic-like events, and rash were the main AEFIs reported for non-serious cases. Excluding the "Other events" category, neurologic events (which are most often seizures triggered by fever), systemic events (i.e., events involving many body systems often accompanied by fever) and vaccination site reaction were the most frequent AEFIs reported for the serious cases between January and June of 2019 as well as in the past 4 years.

Table 2: Total AEFI reports received (proportion of total reports), by primary AEFI reported (serious and non-serious), January to June of 2019, compared to 2015-18 average for the same time period

Primary AEFI reported	Serious reports		Non-serious reports
	2019	Average	2019	Average
		2015-18		2015-18
Reaction at or near the vaccination site	13 (11%)	11 (9%)	676 (41%)	602 (45%)
Allergic or allergic-like event	6 (5%)	8 (7%)	260 (16%)	217 (16%)
Rash	1 (1%)	1 (0%)	224 (14%)	194 (14%)
Systemic event	20 (17%)	29 (24%)	76 (5%)	94 (7%)
Neurologic event	39 (34%)	41 (34%)	73 (4%)	49 (4%)
Vaccination anxiety	1 (1%)	0 (0%)	16 (1%)	17 (1%)
Vaccination error	0 (0%)	0 (0%)	0 (0%)	1 (0%)
Other eventsFootnote 1	35 (30%)	31 (26%)	317 (19%)	179 (13%)
Total	115	121	1,642	1,352
Footnote 1 Other events include: gastro-intestinal reaction, para/anesthesia, thrombocytopenia, hypotonic-hyporesponsive episode (HHE), persistent crying, intussusception, arthritis, arthralgia, parotitis, and undefined – other Return to footnote 1 referrer

Vaccines administered in AEFI reports

Table 3 lists the most commonly administered vaccines among AEFI reports between January-June of 2019. Pneumococcal vaccines had the most AEFI reports (in both serious and non-serious reports) followed by measles, mumps, rubella, varicella (MMRV and MMR + V), and Diphtheria, Tetanus and acellular Pertussis (DTaP) infant series vaccines in serious reports. For non-serious reports, influenza and MMRV and MMR + V vaccines had the most AEFI reports following Pneumococcal vaccines. As seen in previous years, the highest proportion of serious reports were MMRV and MMR + V and DTaP infant series vaccines following pneumococcal vaccine. An increase in the number of reports received for some vaccines was noted during the reporting period, including zoster and pneumococcal vaccines. This could be explained by increases in vaccine uptake and changes to the jurisdictional immunization programs (e.g.: integration of pneumococcal vaccine to most jurisdictional programs). As noted above, all technical issues have been resolved and all jurisdictions are now reporting as of January 2018, which led to a slight increase in the number of reports received during this period. The proportion of serious reports was similar to previous periods.

Table 3: Total AEFI reports received, by vaccine administered (serious and non-serious), January-June of 2019, compared to 2015-18 average for the same time period^{Footnote * Footnote a}

Vaccines administered	Serious reports		Non-serious reports
	2019	Average	2019	Average
		2015-18		2015-18
1.       DTaP booster	0 (0%)	2 (1%)	5 (0%)	18 (1%)
2.       DTaP infant series	45 (16%)	44 (17%)	342 (12%)	251 (12%)
3.       Hepatitis B	5 (2%)	5 (2%)	93 (3%)	98 (4%)
4.       Human papillomavirus (HPV)	6 (2%)	4 (2%)	109 (4%)	110 (5%)
5.       Influenza	19 (7%)	32 (12%)	419 (15%)	392 (18%)
6.       Measles, mumps, rubella, varicella (MMRV and MMR + V)	54 (20%)	45 (17%)	411 (14%)	280 (13%)
7.       Meningococcal	44 (16%)	39 (15%)	290 (10%)	221 (10%)
8.       Other vaccines	1 (0%)	1 (0%)	30 (1%)	15 (1%)
9.       Pneumococcal	59 (22%)	54 (21%)	461 (16%)	341 (16%)
10.     Rotavirus	25 (9%)	22 (8%)	171 (6%)	95 (4%)
11.     Tdap booster	7 (3%)	6 (2%)	279 (10%)	199 (9%)
12.     Travel vaccines	6 (2%)	5 (2%)	102 (4%)	82 (4%)
13.     Zoster virus	2 (1%)	1 (0%)	140 (5%)	80 (4%)
Total	273	261	2,852	2,182
Footnote a Excludes 8 reports due to missing vaccine trade name. Return to footnote a referrer Footnote * Totals add up to more than the total number of AEFI reports as one AEFI report may involve more than one vaccine. Including 1) DTaP-IPV, DTaP; 2) DTaP-IPV-Hib, DTaP-HB-IPV-Hib, DTaP-Hib, DTaP-HB-IPV; 3) HB, HB-dial; 4) HPV-2, HPV-4, HPV-9; 5) Inf,  H1N1-09; 6) MMR, MMRV, Var; 7) Men-C-ACYW-135, Men-C-C, Men-B, Men-P, Men-P-ACYW-135; 8) Rab, Hib, IPV,; 9) Pneu-C-10, Pneu-C-13, Pneu-C-7,  Pneu-P-23; 10) Rot-1, Rot-5, Rota; 11) Tdap, Tdap-IPV, Td-IPV, T, Td; 12) Chol-Ecol-O, HA, HA-Typh-I, HAHB, Typh-I, Typh-O, YF, JE; 13) Zos, RVZ. For list of current vaccines, please refer to the Reporting AEFI in Canada: User guide to completion and submission of the AEFI reports. HB-dial – Hepatitis B-Dialysis HPV-9 – Human papillomavirus 9-valent vaccine, recombinant H1N1-09 – H1N1 adjuvanted Men-B – Multicomponent meningococcal B vaccine (recombinant, adsorbed) Rot-1 - Rotavirus Rot-5 - Rotavirus T – Tetanus Toxoid Adsorbed Return to footnote * referrer

Summary

This bi-annual report for 2019 is based on reports of adverse events received at PHAC from FPT public health authorities and active, pediatric hospital based surveillance. Detailed evaluation of the reports and reporting patterns in collaboration with provincial/territorial vaccine safety focal points of the VVWG and Health Canada have not identified any vaccine safety signals of concern. The tables and figures in this report provide a snapshot of the data provided to, and reviewed by, PHAC.