Research Article: Demonstration of background rates of three conditions of interest for vaccine safety surveillance

Date Published: January 15, 2019

Publisher: Public Library of Science

Author(s): Anne E. Wormsbecker, Caitlin Johnson, Laura Bourns, Tara Harris, Natasha S. Crowcroft, Shelley L. Deeks, Mark Simonds Riddle.


Adverse events following immunization (AEFIs) are unwanted or unexpected health outcomes following vaccination, which may or may not be causally-linked to vaccines. AEFI reporting is important to post-marketing vaccine safety surveillance and has the potential to identify new or rare AEFIs, show increases in known AEFIs, and help to maintain public confidence in vaccine programs. Knowledge of the expected incidence (i.e. background rate) of a possible AEFI is essential to the investigation of vaccine safety signals. We selected three rarely reported AEFIs representing the spectrum of causal association with vaccines, from proven (immune thrombocytopenia [ITP]) to questioned (Kawasaki disease [KD]) to unsubstantiated (multiple sclerosis [MS]) and determined their background rates.

We extracted data on hospitalizations (CIHI Discharge Abstract Database) for ITP, KD, and MS among Ontario children for the period 2005 to 2014 from IntelliHEALTH. As ITP can be managed without hospitalization, we also extracted emergency department (ED) visits from the CIHI National Ambulatory Care Reporting System. For all conditions, we only counted the first visit and if the same child had both an ED visit and a hospitalization for ITP, only the hospitalization was included. We calculated rates by year, age group and sex using population estimates from 2005–2014, focusing on age groups within the Ontario immunization schedule around vaccine(s) of interest.

Per 100,000 population, annual age-specific incidence of ITP in children age 1 to 7 years ranged from 8.9 to 12.2 and annual incidence of KD in children less than 5 years ranged from 19.1 to 32.1. Average annualized incidence of adolescent (11–17 years) MS across the study period was 0.8 per 100,000.

Despite limitations, including lack of clinical validation, this study provides an example of how health administrative data can be used to determine background rates which may assist with interpretation of passive vaccine safety surveillance.

Partial Text

Monitoring for potential adverse events following immunization (AEFI), whether they are in relation to new vaccines, immunization schedule changes, or existing vaccines, is the core of post-marketing vaccine safety surveillance. In the Canadian province of Ontario, AEFI reporting by designated health care providers is mandatory under the Health Promotion and Protection Act 1990; however, vaccine recipients or their caregivers can also voluntarily report AEFI. With the exception of active surveillance at two children’s hospitals, most vaccine safety monitoring is through passive surveillance. A full description of AEFI surveillance in Ontario has been published elsewhere [1]. We undertook the present analysis in the context of Ontario’s broader efforts, including revised case definitions and the publication of an annual report [1], to strengthen its vaccine safety surveillance.

Ontario is Canada’s largest province (population ~14 million, 2016 [25]) and has a single-payer, publicly-funded health care system. Provincial health care administrative data are collected by the Canadian Institute for Health Information (CIHI) and provided to the Ministry of Health and Long-Term Care (MOHLTC). CIHI data are included in the MOHLTC’s IntelliHEALTH knowledge repository, which contains de-identified data collected from various sectors of Ontario’s health care system. Public health, health care and government analysts, epidemiologists, planners, policy and decision makers, and researchers have secure online access to IntelliHEALTH. This access is provided through the MOHLTC’s information access policies, based on the Personal Health Information Protection Act. Of note, although IntelliHEALTH is readily available to local public health agencies, it does not contain immunization information.

Age-specific counts and incidences of health care utilization for ITP, KD and MS (also sex-specific) are shown for the age groups of interest in Table 1 for the study period overall.

The background rates we have estimated for ITP and KD are consistent with rates obtained through different methods in the same or similar settings, but we were not able to draw this conclusion regarding MS. With the caveat that caution should be used when comparing rates across literature and data sources, methods of analysis, health care systems and populations, other studies report similar incidence of childhood ITP to ours. We were unable to find comparable Ontario or Canadian data on the incidence of ITP in children, but a United Kingdom study using administrative data from 1990 to 2005 reported a rate of ITP of 6.8 per 100,000 person years in children <2 years and 7.2 per 100,000 person years in those aged 2–5 years [27]. A systematic review of ITP incidence among a broader age group of children in several European countries reported the incidence of ITP to be between 1.9–6.4 cases per 100,000 children < 16 years of age [28]. The single year prevalence of ITP (>2 ITP insurance claims separated by at least 30 days) in 2002 in the American state of Maryland was 9.3 per 100,000 children aged 1–5 years [29]. Although the setting, methods, and age groups were different, this finding is similar to the incidence we found (10.5 per 100,000 among children 1–7 years) for this acute condition. The sex distribution of pediatric ITP we observed was also similar in other studies, with the majority of cases being male, especially in the younger age groups [27,29–30].




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