Measles Outbreak with Unique Virus Genotyping, Ontario, Canada, 2015.

The province of Ontario continues to experience measles virus transmissions despite the elimination of measles in Canada. We describe an unusual outbreak of measles in Ontario, Canada, in early 2015 that involved cases with a unique strain of virus and no known association among primary case-patients. A total of 18 cases of measles were reported from 4 public health units during the outbreak period (January 25-March 23, 2015); none of these cases occurred in persons who had recently traveled. Despite enhancements to case-patient interview methods and epidemiologic analyses, a source patient was not identified. However, the molecular epidemiologic analysis, which included extended sequencing, strongly suggested that all cases derived from a single importation of measles virus genotype D4. The use of timely genotype sequencing, rigorous epidemiologic investigation, and a better understanding of the gaps in surveillance are needed to maintain Ontario's measles elimination status.

Assessment of sex-specific differences in adverse events following immunization reporting in Ontario, 2012-15.

We assessed sex-specific trends within passive vaccine safety surveillance in Ontario, Canada. AEFIs reported following vaccines administered between 2012 and 2015 were included. There were 2466 AEFI reports; 66.2% were female. Annualized reporting rates were 5.9 and 3.1 per 100,000 population, for females and males respectively. The female:male reporting rate ratio (RRR) was 1.9. Sex-specific differences by age group were greatest in adults 18-64years (RRR 6.3); whereas there were no differences in children <10years. Vaccine-specific RRRs were highest for vaccines recommended for routine use in adults or high risk populations. All event categories were female-predominant. The highest event-specific RRRs were for oculorespiratory syndrome (5.1), anaesthesia/paraesthesia (4.6) and anaphylaxis (3.0). Serious AEFIs (n=113) were more evenly distributed (57.5% female, RRR 1.3) than non-serious (66.6% female, RRR 1.9). AEFI reporting among females was consistently elevated within the passive surveillance system in Ontario. Further study of the relationship between sex/gender and AEFI reporting is needed.

The epidemiology of invasive pneumococcal disease in older adults from 2007 to 2014 in Ontario, Canada: a population-based study.

BACKGROUND: In Ontario, pneumococcal conjugate vaccines (PCVs) have been sequentially introduced into the publicly funded childhood vaccination program since 2005. A 23-valent polysaccharide pneumococcal vaccine (PPV23) has been routinely recommended for adults aged 65 years and older since 1996. To determine the effect of herd immunity, we examined the epidemiology of invasive pneumococcal disease in adults aged 65 years and older. METHODS: Invasive pneumococcal disease is a provincially reportable disease. We were therefore able to conduct a descriptive epidemiologic analysis that included assessing time trends for patients aged 65 years and older using surveillance data from 2007 to 2014. Using serotype information within the surveillance data, cases were grouped into categories according to vaccine type and periods and then compared using Poisson regression. RESULTS: A total of 3825 cases of invasive pneumococcal disease were reported among adults aged 65 years and older, for an overall annualized incidence of 25.4 cases per 100 000 population. There was a decrease in incidence due to serotypes included in 7-valent PCV (3.0 to 0.7 cases per 100 000 population) (p < 0.001). For 13-valent PCV serotypes, there was a decrease in incidence between 2011 and 2014 (9.8 to 5.3 cases per 100 000 population (p < 0.001)). Serotypes unique to PPV23 and those not included in a vaccine increased from 2.3 to 5.8 and from 2.4 to 7.2 cases per 100 000 population, respectively (p < 0.001). INTERPRETATION: In older adults, among serotypes contained in PCVs, we have shown a decrease in incidence of invasive pneumococcal disease. This is likely due to herd immunity from the childhood program. A burden of illness due to unique PPV23 serotypes and those that are not covered by a vaccine exists and has increased over time.

The Epidemiology of Invasive Haemophilus influenzae Non-Serotype B Disease in Ontario, Canada from 2004 to 2013.

BACKGROUND: Since the widespread use of Haemophilus influenzae (Hi) type b (Hib) vaccines among children aged <5 years, an increase in invasive non-Hib disease incidence has been reported internationally. We sought to describe the epidemiology of invasive non-Hib disease in Ontario, Canada (population ~13.5 million). METHODS: Confirmed invasive non-Hib cases (non-typeable [NTHi] and serotypes a, c, d, e, and f) were obtained from the provincial laboratory data system from 2004-2013. Data were deterministically linked to the provincial reportable disease system to provide further case information. Antibiotic resistance data were analysed separately from 2010-2014. Descriptive analyses included incidence rates, age group, serotype, site of specimen collection and resistance patterns; ethnicity data were not available. Temporal trends were evaluated by Poisson regression and p-values <0.05 were considered significant. RESULTS: A total of 1307 cases of invasive non-Hib disease were included, increasing from 0.67 cases to 1.60 cases /100,000 from 2004 to 2013. Significant increases in the incidence of NTHi (0.50 to 1.28 cases/100 000 population), Hia (0.02 to 0.08 cases/100, 000) and Hif (0.13 to 0.18 cases/100, 000 population) were seen. Among persons aged 40-64 years, 3 Hi strains significantly increased over time; NTHi (0.22 to 0.99 cases/100, 000), Hia (0.00 to 0.06 cases/100, 000) and Hif (0.05 to 0.21 cases/100, 000). Among persons aged 65-84 years, there was a significant increase of NTHi (1.62 to 3.14 cases/100, 000) and Hia (0.00 to 0.34 cases/100, 000). Among persons aged 85+ years, only NTHi significantly increased from 4.89 to 10.28 cases/100, 000). Antimicrobial resistance (AMR) to ampicillin and clarithromycin was seen in greater than 25% of isolates but AMR did not increase over the duration of this study. CONCLUSIONS: The incidence of invasive non-Hib disease has increased over time; NTHi, Hif and Hia are emerging pathogens, and should be monitored.

Trends in medical and nonmedical immunization exemptions to measles-containing vaccine in Ontario: an annual cross-sectional assessment of students from school years 2002/03 to 2012/13.

BACKGROUND: Under Ontario legislation, for select vaccine-preventable diseases nonimmunized or under-immunized students must undergo vaccination or provide a statement of exemption, or risk suspension from school. At the time of this assessment, these diseases included measles, mumps, rubella, diphtheria, tetanus and polio. METHODS: Exemptions data for the school years 2002/03 to 2012/13 were obtained from the Immunization Records Information System used in Ontario. Temporal trends were expressed for 7- and 17-year-old students by exemption classification (medical, prior immunity, religious or conscientious belief, total) at the provincial level, by school year and by birth cohort. Regional analysis was conducted for the 2012/13 school year. A temporal trend analysis of exemptions for measles-containing vaccines was performed by using a Poisson distribution with a 2-sided test (α = 5%). RESULTS: For both 7- and 17-year-old students, religious or conscientious exemptions for measles-containing vaccines significantly increased over the study period (p < 0.001 in both age groups), whereas medical exemptions decreased (p < 0.001 in both age groups). The trends were reproduced when examined by birth cohort. The percentage of Ontario students with any exemption classification (total exemptions) remained low (< 2.5%) during the study period, although considerable geographic variation was noted. INTERPRETATION: Ontario data suggest that nonmedical exemptions have increased during the last 11 years, consistent with trends reported elsewhere. The trend toward increasing religious or conscientious exemptions coupled with declining medical exemptions explains why total exemptions have remained stable or decreased at the provincial level. The prominent geographic variability in exemptions suggests that targeted interventions may be suitable for consideration.

Vaccine safety implications of Ontario, Canada's switch from DTaP-IPV to Tdap-IPV for the pre-school booster.

Ontario, Canada, replaced the 4-6 year old diphtheria (D, d), tetanus (T), acellular pertussis (aP, ap) and polio (IPV) booster from DTaP-IPV to Tdap-IPV in May 2012. We assessed the impact of this replacement on the rate and types of reported adverse events following immunization (AEFIs). We used AEFIs reported among 4-6 years olds, through the provincial surveillance system, following administration of DTaP-IPV or Tdap-IPV from 2009 to 2013. Reporting rates per 100,000 doses distributed were calculated using publicly funded doses distributed as the denominator. A total of 204 AEFIs were reported (DTaP-IPV, n=182; Tdap-IPV, n=22). AEFI reporting rates were 33.1 and 6.3 per 100,000 doses distributed for DTaP-IPV and Tdap-IPV, respectively. Injection site reaction rate was lower for Tdap-IPV compared with DTaP-IPV (1.7 vs 20.6 per 100,000 doses). The replacement resulted in a decline in the number of reports and AEFI reporting rates, most notably a substantial decrease in injection site reactions.

Adverse events following immunization in Ontario's female school-based HPV program.

BACKGROUND: In September 2007, a school-based human papillomavirus (HPV) vaccination program targeting grade 8 girls (approximately 13 years old) and delivered by public health was implemented in Ontario, Canada. We assessed reports of adverse events following immunization (AEFI) from the school-based program as part of quadrivalent HPV (HPV4) vaccine safety surveillance and to contribute to a comprehensive HPV vaccine program evaluation. METHODS: AEFIs following HPV4 vaccine (Gardasil(®)) administered between September 1, 2007 and December 31, 2011 were extracted from the province's reportable disease system. Confirmed AEFI reports among females 12-15 years old (i.e. assumed to have received vaccine through the program) were included. Events were grouped according to provincial AEFI case definitions. Rates were calculated using doses distributed as the denominator. RESULTS: Between 2007 and 2011, 133 confirmed AEFIs were reported while 691,994 HPV4 vaccine doses were distributed in the school-based program. The overall reporting rate was 19.2 HPV4 AEFI per 100,000 doses distributed. Annual reporting rates decreased from 30.0 to 18.3 per 100,000 doses distributed. Frequently reported events included 'allergic reaction-dermatologic/mucosa' (25%), 'rash' (22%), and 'local/injection site reaction' (20%); 26% of reports had a non-specific event of 'other severe/unusual events' selected. Ten serious AEFIs were reported (7.5% of reports) including 2 anaphylaxis, 2 seizures, 1 thrombocytopenia and 1 death. Further review found that the reports of anaphylaxis did not meet the Brighton anaphylaxis definition and the death was attributed to a preexisting cardiac condition. CONCLUSIONS: Overall these findings are consistent with the safety profile of HPV4 vaccine from pre-licensure clinical trials and post-marketing surveillance reports and importantly, no new safety signals were identified, especially no reports of VTE in this younger female population. Continued assessment of HPV4 AEFI surveillance data may be important to detect and investigate safety signals.

Coverage from Ontario, Canada's school-based HPV vaccine program: the first three years.

BACKGROUND: In 2007, Ontario implemented a school-based human papillomavirus (HPV) vaccination program targeting grade 8 girls. Girls may complete the series in grade 9 (extended eligibility). Limitations in the existing provincial data sources for assessing HPV vaccine coverage in Ontario prompted the use of two surveys of Health Units (HUs) to calculate provincial vaccine coverage for the first three years of the vaccination program. METHODS: We surveyed Ontario's 36 HUs in March and November 2011 to obtain vaccine coverage information, including source of denominator data, and use of local information systems. The second survey was necessary in order to assess coverage including extended eligibility for the third year. HU-reported HPV vaccine coverage was compared to coverage estimates obtained from two provincial systems: the Immunization Records Information System (IRIS) and the HPV reimbursement database, a system used to remunerate HUs for HPV vaccine doses administered. RESULTS: 100% of HUs participated in the two surveys. The provincial coverage estimates using HU-reported data were: 51% (2007-2008), 58% (2008-2009), and 59% (2009-2010) with large variation by HU. Coverage increased significantly over time. The number of HUs that were able to report on doses given as part of extended eligibility also increased over time (47% in 2007-2008 to 89% in 2009-2010; p=0.0008). Comparisons across the three data sources (survey, IRIS and reimbursement database) revealed significantly different coverage estimates. Class or school lists were the most common source of denominator data used by HUs (27/36, 75%), however independent schools were not included by all. CONCLUSIONS: As not all HUs were able to report on HPV vaccine coverage including extended eligibility doses these findings likely underestimate the true coverage attained by Ontario's program. Although coverage is below the Canadian Immunization Committee benchmark of 80% within two years of program implementation, the upward trend in coverage is encouraging.