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Heterogeneity in the number of lifetime/recent partners among women participating in PISCES

Background: Papanicolaou smear screening has significantly reduced cervical cancer morbidity and mortality. However, inequalities still persist across different socioeconomic status (SES) groups. These inequalities have been associated with differential participation in screening. However, even with equal participation to screening, some women may still have greater risk of cervical cancer because of sexual behavior. We aim to identify the sociodemographic characteristics of women who reported greater sexual activity and/or screening underuse.Methods: We used data from (i) the Canadian Community Health Survey—2005, a population-based survey of 130,000 Canadians, and (ii) a multicenter study including 952 women screened for cervical cancer.Results: Aboriginals and women with lower SES reported greater sexual activity and lower screening participation, which may produce synergetic effects toward higher cervical cancer risk. Women who did not complete high school and aboriginals were, respectively, 3.6 and 2.5 times more likely to report sexual debut before 15 years old compared with women with university degree and Caucasians. Women who did not complete high school were 2.2 times more likely to have never been screened compared with women with university degree. East and South Asian women were, respectively, 4.3 and 3.1 times more likely to have never been screened than Canadian-born women but reported lower levels of sexual activity and were adherent to screening guidelines when screened at least once.Conclusions: The success of human papillomavirus vaccination at reducing cervical cancer and inequalities will depend on achieving high coverage among high-risk subpopulations.Impact: These groups must be monitored closely, and if need be, targeted for additional interventions. Cancer Epidemiol Biomarkers Prev; 22(4); 641–52. ©2013 AACR.

Socio-demographic characteristics associated with sexual activity of women aged 25 to 44 recruited in PISCES (n=496)

Background Real-world evidence of human papillomavirus (HPV) vaccine effectiveness (VE) against longitudinal outcomes is lacking among gay, bisexual, and other men who have sex with men (GBM). We compared 12-month incidence and persistence of anal HPV infection between vaccinated and unvaccinated GBM. Methods We recruited GBM aged 16–30 years in Montreal, Toronto, and Vancouver, Canada, from 2017 to 2019. Participants were followed over a median of 12 months (interquartile range, 12–13 months). Participants self-reported HPV vaccination and self-collected anal specimens for HPV DNA testing. We calculated prevalence ratios (PR) for 12-month cumulative incidence and persistence with ≥1 quadrivalent vaccine type (HPV 6/11/16/18) between vaccinated (≥1 dose at baseline) and unvaccinated participants using a propensity score-weighted, modified Poisson regression. Results Among 248 participants, 109 (44.0%) were vaccinated at baseline, of whom 62.6% received 3 doses. PRs for HPV 6/11/16/18 were 0.56 (95% confidence interval [CI], .24–1.31) for cumulative incidence and 0.53 (95% CI, .25–1.14) for persistence. PRs were 0.23 (95% CI, .05–1.03) and 0.08 (95% CI, .01–.59) for incidence and persistence, respectively, among participants who received their first dose at age ≤23 years and 0.15 (95% CI, .03–.68) and 0.12 (95% CI, .03–.54) among participants who were sexually active for ≤5 years before vaccination. Conclusions Findings support national recommendations for HPV vaccination at younger ages or soon after sexual debut.

Using observational data, human papillomavirus vaccination was associated with a lower anal prevalence of vaccine-preventable types among young, sexually active gay and bisexual men soon after implementation of publicly funded vaccination programs. Supplemental digital content is available in the text., Background Starting in 2015, human papillomavirus (HPV) vaccine has been publicly funded for gay, bisexual, and other men who have sex with men (GBM) 26 years or younger in Canada. Methods Self-identified GBM who reported having sex with another man within the past 6 months were enrolled using respondent-driven sampling (RDS) between February 2017 and August 2019 in Montreal, Toronto, and Vancouver, Canada. Men aged 16 to 30 years self-collected anal specimens for HPV-DNA testing. Prevalence was estimated using RDS-II weights. We compared the prevalence of quadrivalent (HPV-6/11/16/18) and 9-valent (HPV-6/11/16/18/31/33/45/52/58) vaccine types between GBM who self-reported HPV vaccination (≥1 dose) and those reporting no vaccination using a modified Poisson regression for binary outcomes. Results Among 645 GBM who provided a valid anal specimen (median age, 26 years; 5.9% HIV positive), 40.3% reported receiving ≥1 dose of HPV vaccine, of whom 61.8% received 3 doses. One-quarter were infected with ≥1 quadrivalent type (crude, 25.7%; RDS weighted, 24.4%). After adjustment for potential confounders, vaccinated GBM had a 27% lower anal prevalence of quadrivalent types compared with unvaccinated GBM (adjusted prevalence ratio [aPR], 0.73; 95% confidence interval [CI], 0.54–1.00). Lower prevalence ratios were found among vaccinated participants who were vaccinated >2 years before enrollment (aPR, 0.47; 95% CI, 0.25–0.86) or received their first vaccine dose at age ≤23 years (aPR, 0.64; 95% CI, 0.42–0.99). Point estimates were similar for ≥2 or 3 doses and 9-valent types. Conclusions Human papillomavirus vaccination was associated with a lower anal prevalence of vaccine-preventable HPV types among young, sexually active GBM. Findings will help inform shared decision making around HPV vaccination for GBM and their healthcare providers.

On March 3, 2021, faced with ongoing morbidity and mortality from coronavirus disease 2019 (COVID-19) and insufficient supplies of authorized, available vaccines against COVID-19 in Canada, the National Advisory Committee on Immunization (NACI) issued a strong recommendation to allow for an extended interval between vaccine doses to maximize the number of people protected as quickly as possible. NACI's recommendation was released in the form of a rapid response because of the urgency of the situation and was based on a review of the evidence; principles of immunology; historical experience with vaccines; modelling studies; and consideration of ethics, equity, feasibility, and acceptability. Since then, many questions and concerns have been raised. This article aims to provide further explanation of the rationale for the decision and prepare health care providers with information they need as they support their patients in the vaccination rollout.Le 3 mars 2021, devant la morbidité et la mortalité continues causées par la maladie à coronavirus 2019 (COVID-19) et l’offre insuffisante de vaccins autorisés et disponibles contre la COVID-19 au Canada, le Comité consultatif national de l’immunisation a publié une forte recommandation préconisant un intervalle prolongé entre les doses des vaccins, afin d’optimiser le nombre de personnes protégées le plus rapidement possible. La recommandation du comité, qui a pris la forme d’une réponse rapide en raison de l’urgence de la situation, repose sur l’examen des données probantes, les principes immunologiques, l’expérience des vaccins, les études de modélisation et les principes d’éthique, d’équité, de faisabilité et d’acceptabilité. De nombreuses questions et inquiétudes ont été soulevées depuis. Le présent article vise à mieux expliquer les motifs de cette recommandation et à fournir aux dispensateurs de soins l’information dont ils ont besoin pour soutenir leurs patients pendant le déploiement de la vaccination.

Le 3 mars 2021, devant la morbidité et la mortalité continues causées par la maladie à coronavirus 2019 (COVID-19) et l’offre insuffisante de vaccins autorisés et disponibles contre la COVID-19 au Canada, le Comité consultatif national de l’immunisation a publié une forte recommandation préconisant un intervalle prolongé entre les doses des vaccins, afin d’optimiser le nombre de personnes protégées le plus rapidement possible. La recommandation du comité, qui a pris la forme d’une réponse rapide en raison de l’urgence de la situation, repose sur l’examen des données probantes, les principes immunologiques, l’expérience des vaccins, les études de modélisation et les principes d’éthique, d’équité, de faisabilité et d’acceptabilité. De nombreuses questions et inquiétudes ont été soulevées depuis. Le présent article vise à mieux expliquer les motifs de cette recommandation et à fournir aux dispensateurs de soins l’information dont ils ont besoin pour soutenir leurs patients pendant le déploiement de la vaccination.

Introduction In 2015/2016, Canada’s largest provinces implemented publicly-funded human papillomavirus (HPV) vaccination programs for gay, bisexual, and other men who have sex with men (GBM) ≤ 26 years old. We sought to describe HPV vaccine uptake among GBM and determine barriers and facilitators to vaccine initiation with a focus on healthcare access and utilization. Methods Engage is a cohort study among GBM aged 16 + years in three Canadian cities recruited from 2017 to 2019 via respondent driven sampling (RDS). Men completed a comprehensive questionnaire at baseline. By publicly-funded vaccine eligibility (≤26 years old = eligible for vaccination, ≥27 years old = ineligible), we described HPV vaccine uptake (initiation = 1 + dose, completion = 3 doses) and explored factors associated with vaccine initiation using Poisson regression. All analyses were weighted with the RDS-II Volz-Heckathorn estimator. Results Across the three cities, 26–35% and 14–21% of men ≤ 26 years and 7–26% and 2–9% of men ≥ 27 years initiated and completed HPV vaccination, respectively. Vaccine initiation was significantly associated with STI/HIV testing or visiting a HIV care specialist in the past six months (≤26: prevalence ratio[PR] = 2.15, 95% confidence interval[CI] 1.06–4.36; ≥27: PR = 2.73, 95%CI 1.14–6.51) and past hepatitis A or B vaccination (≤26: PR = 2.88, 95%CI 1.64–5.05; ≥27: PR = 2.03, 95%CI 1.07–3.86). Among men ≥ 27 years old, vaccine initiation was also positively associated with accessing PrEP, living in Vancouver or Toronto, but negatively associated with identifying as Latin American and increasing age. Vaccine initiation was twice as likely among men ≥ 27 years with private insurance versus no insurance. Conclusions Sixty-five to 74% of men eligible for publicly-funded vaccine across the three cities remained unvaccinated against HPV by 2019. High vaccine cost may partly explain even lower uptake among men ≥ 27 years old. Men seeking sexual health care were more likely to initiate vaccination; bundling vaccination with these services may help improve HPV vaccine uptake.

Background In Ontario, Canada, little is currently known about the extent to which un-immunized children may cluster geographically. Our objectives were to: describe the geographic distribution of fully un-immunized children; identify geographic clusters (hotspots) of un-immunized children; and to characterize the contribution of spatial effects and covariates on hotspots, where found. Methods Our analytic cohort consisted of Ontario students aged 7–17 years in the 2016–2017 school year. We defined students as un-immunized if they had zero doses of any vaccine and a non-medical exemption recorded in Ontario’s registry. We calculated unadjusted proportions of un-immunized students by Census Subdivision (CSD) and then used a sequential approach to identify hotspots starting first with hotspot identification at the CSD level and then probed identified hotspots further by Dissemination Area (DA) and including covariates. Hotspots were identified using the Besag-York-Mollie Bayesian spatial model and were defined as areas with >95% probability of having two times the proportion of un-immunized students, relative to the province overall. Results We identified 15,208 (0.94%) un-immunized children within our cohort consisting of more than 1.61 million students. Unadjusted proportions of un-immunized students varied greatly by geography, ranging from 0% to 21.5% by CSD. We identified 16 hotspot CSDs which clustered in five distinct areas, all of which were located in southern Ontario. The contribution of covariates and spatial effects on the risk of having un-immunized students varied greatly across hotspot areas. Conclusions Although the provincial proportion (0.94%) of un-immunized students is small, geographical clustering of such students is evident in Ontario and in some areas presents an important risk for future outbreaks. Further qualitative work within these hotspot areas would be a helpful next step to better characterize the factors associated with vaccine refusal in these communities.

Starting in 2015/16, most Canadian provinces introduced publicly-funded human papillomavirus (HPV) vaccination programs for gay, bisexual, and other men who have sex with men (GBM) aged ≤ 26 years. We estimated 12-month changes in HPV vaccine coverage among community-recruited GBM from 2017 to 2021 and identified baseline factors associated with vaccine initiation (≥1 dose) or series completion (3 doses) among participants who were unvaccinated or partially vaccinated at baseline.We recruited sexually-active GBM aged ≥ 16 years in Montreal, Toronto, and Vancouver, Canada, from 02/2017 to 08/2019 and followed them over a median of 12 months (interquartile range = 12-13 months). We calculated the proportion who initiated vaccination (≥1 dose) or completed the series (3 doses) by 12-month follow-up. Analyses were stratified by city and age-eligibility for the publicly-funded programs at baseline (≤26 years or 26 years). We used multivariable logistic regression to identify baseline factors associated with self-reported incident vaccine initiation or series completion.Among 165 unvaccinated participants aged ≤ 26 years at baseline, incident vaccine initiation (≥1 dose) during follow-up was 24.1% in Montreal, 33.3% in Toronto, and 38.9% in Vancouver. Among 1,059 unvaccinated participants aged 26 years, incident vaccine initiation was 3.4%, 8.9%, and 10.9%, respectively. Higher education and trying to access pre-exposure prophylaxis for HIV were associated with incident vaccination among those aged ≤ 26 years, while younger age, residing in Vancouver (vs. Montreal), being diagnosed with anogenital warts, having both government and private extended medical insurance, and being vaccinated against influenza were associated with incident vaccination among those aged 26 years.We observed substantial gains in HPV vaccine coverage among young GBM within 5 + years of targeted program implementation, but gaps remain, particularly among older men who are ineligible for publicly-funded programs. Findings suggest the need for expanded public funding or insurance coverage for HPV vaccines.

Objectives Describe Ontario's school-based human papillomavirus (HPV) vaccination program from the perspective of local public health units (PHUs). Methods In 2018, Vaccine Preventable Diseases (VPD) managers at each of Ontario's 35 PHUs were invited to participate in an online survey regarding the organization and delivery of their HPV vaccination program. Questions were asked on the school-based program, training and support of vaccine providers, communication and promotion, assessing coverage rates and perceptions of the program's strengths and challenges. Descriptive statistics were generated for close-ended items. A thematic content analysis was performed for open-ended items. Results Eighteen PHUs (54%, n = 19/35) responded. All responding PHUs provided the HPV vaccine in publicly funded schools but only 6 reported being permitted to provide HPV vaccine in private schools. Fact sheets, Q&As or other written information locally developed by the PHUs were the main tools used to communicate with parents (n = 17), students (n = 13), school personnel (n = 13) and school board officials (n = 9). The most frequently reported barriers were: limited program resources, negative perceptions held by parents and/or school staff regarding the HPV vaccine, logistical issues (e.g., getting the consents forms returned, collaboration with schools for vaccine delivery) and the fact that HPV vaccination is not mandatory under Ontario legislation. Conclusion Local public health units that implement HPV vaccine programs in schools identified logistical barriers, public perceptions about the HPV vaccine and the voluntary nature of the program as the main barriers.

Introduction In Ontario, Canada, parents have the responsibility to report their child’s routine infant and childhood vaccines to the provincial immunization registry (the Digital Health Immunization Repository; DHIR) without healthcare provider validation. Despite its use in routine immunization coverage monitoring, no study has previously examined the completeness of immunization data within the DHIR. Methods We assessed the completeness of DHIR immunizations, as compared to immunizations within the Electronic Medical Records—Primary Care (EMRPC) database, also known as EMRALD, a network of family physician electronic medical records (EMRs). We linked client records from the DHIR and EMRPC to a centralized population file. To create the study cohort, we examined children born during 2005–2008 and further defined the cohort based on those rostered to an EMRPC physician, visit criteria to ensure ongoing care by an EMRPC provider, and school attendance in Ontario at age 7. We calculated up-to-date (UTD) immunization coverage at age 7 for individual vaccines and overall using data from the DHIR and EMRPC separately, and compared the estimates. Results The analytic cohort to assess DHIR data completeness included 2,657 children. Overall UTD coverage (all vaccines assessed) was 82.0% in the DHIR and 67.6% in EMRPC. UTD coverage was higher in the DHIR for all vaccines assessed individually, with the exception of meningococcal C conjugate vaccine (difference = 0.3%). After excluding two EMRPC sites with irregularities in immunization data, the difference in overall UTD coverage between systems decreased from 14.4% to 6.6% Interpretation These results validate the use of DHIR for coverage assessment but also suggest that bidirectional exchange of immunization information has the potential to increase immunization data completeness in both systems.

Background In children with epilepsy, fever and illness are known triggers for seizure; therefore, clinicians and parents could be concerned that immunization-induced inflammation and fever could also trigger seizures. We sought to estimate the risk of emergency department (ED) visit or hospitalization for epilepsy/seizure and all causes after immunization in children younger than 7 years of age with epilepsy. Methods We conducted a self-controlled case series of children diagnosed with epilepsy before their 7th birthday and immunized from 2005 to 2015 in Ontario (population 14.2 million) and Manitoba (population 1.3 million), Canada, using administrative healthcare data. We estimated the age- and season-adjusted relative incidence (aRI) of epilepsy/seizure-related and all-cause ED visits/hospitalizations during various risk periods 0-28 days after inactivated and live immunizations versus a control period 35-83 days postimmunization. Estimates from each province were analyzed separately and then combined in a random-effects meta-analysis. Results The combined risk of epilepsy/seizure-related hospitalization/ED visit was increased 0-2 days after inactivated vaccines (aRI = 1.5, 95% confidence interval: 1.1-1.9) and 7-10 days after live vaccines (aRI = 1.9, 1.4-2.7). For all-cause ED visit/hospitalization, the combined aRI estimate was 0.9 (0.8-1.2) 0-2 days after inactivated vaccines and 1.3 (1.1-1.5) 7-10 days after live vaccines. Conclusions The risk of epilepsy/seizure-related ED visit/hospitalization was modestly increased among children with epilepsy during peak periods of fever and inflammation following inactivated and live vaccines. These risks must be balanced against the risk of complications from vaccine-preventable diseases.

Background Serosurveys for SARS-CoV-2 aim to estimate the proportion of the population that has been infected. Aim This observational study assesses the seroprevalence of SARS-CoV-2 antibodies in Ontario, Canada during the first pandemic wave. Methods Using an orthogonal approach, we tested 8,902 residual specimens from the Public Health Ontario laboratory over three time periods during March–June 2020 and stratified results by age group, sex and region. We adjusted for antibody test sensitivity/specificity and compared with reported PCR-confirmed COVID-19 cases. Results Adjusted seroprevalence was 0.5% (95% confidence interval (CI): 0.1–1.5) from 27 March–30 April, 1.5% (95% CI: 0.7–2.2) from 26–31 May, and 1.1% (95% CI: 0.8–1.3) from 5–30 June 2020. Adjusted estimates were highest in individuals aged ≥ 60 years in March–April (1.3%; 95% CI: 0.2–4.6), in those aged 20–59 years in May (2.1%; 95% CI: 0.8–3.4) and in those aged ≥ 60 years in June (1.6%; 95% CI: 1.1–2.1). Regional seroprevalence varied, and was highest for Toronto in March–April (0.9%; 95% CI: 0.1–3.1), for Toronto in May (3.2%; 95% CI: 1.0–5.3) and for Toronto (1.5%; 95% CI: 0.9–2.1) and Central East in June (1.5%; 95% CI: 1.0–2.0). We estimate that COVID-19 cases detected by PCR in Ontario underestimated SARS-CoV-2 infections by a factor of 4.9. Conclusions Our results indicate low population seroprevalence in Ontario, suggesting that public health measures were effective at limiting the spread of SARS-CoV-2 during the first pandemic wave.

Between 18-Dec-2017 and 27-Jun-2018, a mumps outbreak occurred in two Canadian Indigenous communities. An outbreak dose of mumps-containing vaccine was offered as part of control measures. We conducted a cohort study and survival analysis to describe the outbreak and evaluate the outbreak dose, extracting immunization information on all community members (n=3,135) from immunization records. There were 70 mumps cases; 56% had received two pre-outbreak vaccine doses. Those who received a pre-outbreak dose more distantly had higher rates of mumps compared to those with more recent doses (adjusted hazard ratio = 3.4 (95%CI: 0.7–20.6) for receipt >20 years before vs. receipt ≤3 years). During the outbreak, 33% (1,010/3,080) of eligible individuals received an outbreak dose. The adjusted hazard ratio for no outbreak dose receipt was 2.7 (95%CI: 1.0–10.1). Our results suggest that an outbreak dose of mumps-containing vaccine may be an effective public health intervention, but further study is warranted.

In 2017 Ontario experienced the largest mumps outbreak in the province in 8 years, at a time when multiple outbreaks were occurring across North America. Of 259 reported cases, 143 occurred in Toronto, primarily among young adults. Routine genotyping of the small hydrophobic gene indicated that the outbreak was due to mumps virus genotype G. We performed a retrospective study of whole genome sequencing of 26 mumps virus isolates from early in the outbreak, using a tiling amplicon method. Results indicated that two of the cases were genetically divergent, with the remaining 24 cases belonging to two major clades and one minor clade. Phylogeographic analysis confirmed circulation of virus from each clade between Toronto and other regions in Ontario. Comparison with other genotype G strains from North America suggested that the presence of co-circulating major clades may have been due to separate importation events from outbreaks in the United States. A transmission network analysis performed with the software program TransPhylo was compared with previously collected epidemiological data. The transmission tree correlated with known epidemiological links between nine patients and identified new potential clusters with no known epidemiological links.

Canada eliminated measles in 1998. We conducted a sero-epidemiology study to estimate population immunity to measles in the province of Ontario, Canada and to identify groups at higher risk of outbreaks. We used a previously developed modified enzyme immunoassay to test 1,199 residual sera from patients aged 1–39 years. We re-tested negative and equivocal sera using a plaque reduction neutralization assay. We interpreted our results in the context of Ontario’s immunization program and vaccine coverage data. Of 1,199 sera, 1035 (86.3%, 95% confidence interval (CI) 84.4, 88.2) were above the measles threshold for protection, 70 (5.8%, 95% CI 4.5, 7.2) were equivocal and 94 (7.8%, 95% CI 6.3, 9.4) were negative. The proportion of positive sera was highest for those 1–5 years, with 180/199 (90.5%, 95% CI 86.4, 94.5) positive sera, and lowest for those age 12–19 years, at 158/199 (79.4%, 95% CI 73.8, 85.0). Adjusted for age, females were more likely than males to have antibody titers above the threshold of protection (odds ratio = 1.60, 95% CI 1.14, 2.24). Most of the study cohort were eligible for two measles vaccine doses, and vaccine uptake in Ontario is >90% for school-aged cohorts. We observed a higher than expected proportion of sera with antibody levels below the threshold of protection, suggesting that immunity in some Ontario age-groups may be waning, despite high vaccine coverage. Alternatively, the traditional measles correlates of protection may not be an appropriate measure of population protection in measles-eliminated settings.

Background The combined measles, mumps, rubella (MMR) and measles, mumps, rubella, and varicella (MMRV) vaccines are part of Ontario’s routine immunization schedule. Objective To assess adverse events following immunization (AEFIs) reported in Ontario following administration of MMR and MMRV vaccines between 2012 and 2016. Methods Reports of AEFIs were extracted from the provincial surveillance database on May 9, 2017. Events were grouped by provincial surveillance definitions. Reporting rates were calculated using provincial population estimates or net doses distributed as the denominator. A serious AEFI is defined as an AEFI that resulted in an in-patient hospitalization or death. Results Overall, 289 AEFIs were reported following administration of MMR (n=246) or MMRV (n=43) vaccines, for annualized reporting rates of 16.6 and 8.8 reports per 100,000 distributed doses, respectively. The highest age-specific reporting rate was in children aged 1 to 3 years for MMR (7.7 per 100,000 population) and children aged 4 to 9 years for MMRV (0.8 per 100,000 population). Systemic reactions were the most frequently reported event category, while rash was the most frequently reported event for both vaccines. There were 22 serious AEFIs, 19 following MMR and 3 following MMRV (1.3 and 0.6 per 100,000 doses distributed, respectively). Conclusions Our assessment found a low reporting rate of adverse events following MMR and MMRV vaccines in Ontario. No safety concerns were identified. Our findings are consistent with the safety profiles of these vaccines. Continued monitoring of vaccine safety is necessary to maintain timely detection of unusual postvaccine events and public confidence in vaccine safety.

Older adults are at increased risk of herpes zoster (HZ) and post-herpetic neuralgia (PHN) and HZ vaccines are available to help prevent infection. The objective of our study was to provide updated data on incidence of HZ and PHN related to clinical and demographic factors in older adults to inform immunization practices. We conducted a population-based, retrospective cohort study and included all cases of HZ seen in outpatient, emergency department, and hospital settings for adults aged 65 years and over between April 1, 2002 to August 31, 2016 in Ontario, Canada. We calculated the incidence of HZ and PHN, and estimated the proportion within each subgroup that developed PHN. We also assessed incidence by neighbourhood-level income quintile before and after the availability of vaccine for private purchase. The average annual incidence of HZ in any setting was 59.0 per 10,000 older adults, with higher incidence in outpatient as opposed to hospital settings. Incidence was higher in the oldest age groups, females, and those classified as immunocompromised or frail. Relative to the pre-vaccine era, the disparities in incidence of HZ by neighbourhood-level income increased, with higher rates of HZ and PHN seen in those residing in lower income quintiles. Additional prevention efforts should be targeted toward adults who are immunocompromised, frail, and those living in lower socioeconomic quintiles. Future work should assess the impact of the zoster vaccine program with a particular focus on equity in the publicly-funded era.

BACKGROUND Pertussis remains poorly controlled relative to other diseases targeted by childhood vaccination programs. We combined estimates from four population-based studies of pertussis vaccine effectiveness (VE) in three Canadian provinces using a meta-analytic approach to improve precision and explore regional variation in VE and durability of protection. METHODS Studies were conducted in Alberta, Manitoba, and Ontario over periods ranging from 1996 to 2015. Adjusted log odds ratios (OR; VE = 100*[1-OR]) of the effect of vaccination on pertussis risk were estimated by time since last vaccination in each study and pooled using DerSimonian and Laird random-effects models. We used the I2 statistic to estimate between-study heterogeneity and assessed methodological and clinical heterogeneity through subgroup analyses of study design and age. RESULTS Data on 3,270 pertussis cases and 23,863 controls were available. Pertussis VE declined from 86% (95% CI 79%-90%, I2 = 81.5%) at

POINTS CLES Le 11 mars 2020[1][1], les taux alarmants de propagation du coronavirus du syndrome respiratoire aigu severe 2 (SRAS-CoV-2) ont pousse l’Organisation mondiale de la sante (OMS) a declarer l’etat de pandemie concernant la nouvelle maladie a coronavirus 2019 (COVID-19). La

KEY POINTS Alarming levels of spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) triggered the World Health Organization (WHO) to declare novel coronavirus disease 2019 (COVID-19) a pandemic on Mar. 11, 2020.[1][1] The pandemic is ongoing and has caused substantial morbidity and

Objectives Children with epilepsy are at increased risk of complications from vaccine-preventable infections, yet information on vaccine coverage in these children is scarce. We aimed to compare vaccine coverage among children with epilepsy to children without epilepsy. Study design We conducted a retrospective cohort study including all 2005–2013 births in Manitoba and Ontario, Canada, creating two cohorts: 2-year-olds and 7-year-olds (followed to age 2 and 7 years). We split each cohort into epilepsy and non-epilepsy subcohorts. We assessed vaccination coverage based on provincial schedules and determined timeliness of MMR (measles, mumps, rubella) dose 1 (recommended at 12 months) and DTaP (diphtheria, tetanus, pertussis) dose 4 (recommended at 18 months). We used logistic regression to calculate adjusted odds ratios (aORs) of the association between epilepsy and vaccination, combining both provincial estimates using random effects meta-analysis. Results We included 16,558 2-year-olds (Manitoba, 653; Ontario, 15,905) and 13,004 7-year-olds (Manitoba, 483; Ontario, 12,521) with epilepsy. At age 2 years, the aOR for up-to-date vaccination among children with versus without epilepsy was 0.9 (95% confidence interval 0.8–1.1); at age 7 years it was 1.0 (0.9–1.1). Infants diagnosed with epilepsy before age 6 months were less likely to be up-to-date at age 2 years (0.9; 0.8–0.9), although this difference disappeared by age 7 years. Vaccine timeliness was similar between children with and without epilepsy for MMR dose 1 and DTaP dose 4. Conclusions Overall, this study suggests that children with epilepsy are not significantly under-vaccinated compared to their peers without epilepsy. As children with epilepsy are at a higher risk of complications from vaccine-preventable diseases, vaccination in children with epilepsy should be optimized, especially early in life, as these children may not be able to rely on herd protection.

Introduction: Invasive pneumococcal disease (IPD) is a disease of public health significance in Ontario, Canada, where publicly funded pneumococcal vaccination programs target children, older adults, and people at high risk of disease. Since the implementation of pneumococcal conjugate vaccines (PCV), serotype replacement has been documented, where non-PCV serotypes replace the niche created by the reduction in vaccine-preventable serotypes. Our objective was to determine whether there has been serotype replacement or a change in IPD severity in Ontario since implementation of the childhood 13-valent (PCV13) program by assessing IPD burden over a 12-year period (2007-2018). Methods: We included all confirmed IPD cases reported in Ontario’s integrated Public Health Information System (iPHIS) and defined the pre-PCV13 era (January 2007-December 2010) and post-PCV13 era (January 2011-December 2018). We grouped IPD serotypes according to associated vaccine type: PCV13; 23-valent polysaccharide vaccine (unique PPV23); and non-vaccine-preventable (NVP). We used population data to calculate incidence and hospitalization rates (per 100,000 population) by age group, vaccine type, and era. Results: In the post-PCV13 era, PCV13-specific incidence and hospitalization rates decreased, while the incidence and hospitalizations due to unique PPV23 and NVP serotypes increased; this was consistent across all age groups. The greatest decrease in incidence (RR=0.4) and hospitalizations (RR=0.4) was observed in children

Background and objectives Ontario introduced a universal publicly-funded group A rotavirus (RVA) immunization program in August 2011, using monovalent vaccine. RVA immunization programs have decreased the incidence of RVA acute gastroenteritis in many countries but it is unclear if it will contribute to the emergence of certain genotypes. We monitored RVA trends and genotypes in Ontario before and after implementation of the publicly-funded immunization program. Methods RVA detection was conducted at Public Health Ontario Laboratories from January 2009 to December 2011 (pre-program period) and January 2012 to October 2015 (publicly-funded RVA immunization program period) and number of RVA-positive specimens and percent positivity were analysed. A convenience sample of RVA-positive stool specimens, from September 2010 to December 2011 (pre-program period) and January 2012 to June 2013 (program period), were genotyped using heminested PCR. A literature review on the burden of illness from emergent genotype was performed. Results Stool specimens showed a significant decrease in RVA percent positivity from the 36 month pre-program period (14.4%; 1537/10700) to the 46 month program period (6.1%; 548/9019). An increase in the proportion of RVA G10 among genotyped specimens, associated with five different P genotypes, from the pre-program (6.3%; 13/205) to the program (31.5%; 40/127) period was observed. Our literature review identified approximately 200 G10-positive human stool specimens from 16 different countries. Conclusions This study documented a decrease in the number of RVA-positive specimens and percent positivity after implementation of the immunization program. An unexpected increase in the proportion of RVA G10 was detected following program introduction. Ongoing RVA surveillance is important in evaluating both the long-term impact of immunization and emergence of RVA genotypes.

Introduction Most infants are born with immunity to measles through maternal antibodies transferred in pregnancy, which decay over time. However, in measles elimination settings, where measles does not circulate endemically and most immunity is from immunization rather than infection, maternal antibody levels are lower. This results in infant immunity that wanes earlier, and a wider susceptibility gap between maternal antibody decay and infant immunization than in non-eliminated settings. We aimed to systematically quantify the extent and duration of protection from measles in infants in settings that have sustained measles elimination. Methods We conducted a systematic review of studies of measles maternal antibody waning in infants in measles elimination settings. We searched MEDLINE, Embase, CINAHL, Scopus, BIOSIS Previews, and Global Health databases for relevant studies. Studies were included if they were set in countries that had eliminated measles for ≥3 years, and if the study cohort included healthy, full-term, unvaccinated infants ≤12 months, born to healthy mothers, and reported a relevant measure of measles maternal antibody in infants. We assessed study quality using the MetaQAT tool. Results We identified 4692 unique citations, eight of which met inclusion criteria. One study reported anti-measles antibody in cord blood, six reported antibody in infant sera, and one reported both. Two studies reported that 80 and 100% of infants were protected from measles at birth. One study reported no protection amongst 3–7 month old infants, and another reported limited protection in infants >4 months. The remaining studies reported the proportion of infants with detected antibody, but not the proportion immune. Conclusion Although limited, these data suggest that in settings that have sustained measles elimination, some infants are susceptible to measles well before the age of routine measles immunization. Setting-specific seroprevalence and vaccine effectiveness studies are required to evaluate this in different jurisdictions.

OBJECTIVE: To explore the utility of laboratory data and determine the validity of healthcare administrative data for describing the frequency of measles in Ontario. METHODS: We linked Ontario healthcare utilization administrative data to Public Health Ontario (PHO) laboratory data from 01 January 2006 to 30 November 2012. RESULTS: The sensitivity of the administrative data was 54% and the positive predictive value was 1% when compared with 50 cases identified in laboratory data as a gold standard. CONCLUSIONS: As measles is no longer endemic in Ontario, the high number of measles-coded healthcare visits found in Ontario health administration data exceeds the true number of cases. Great caution should be taken in using administrative data to calculate the incidence of measles in areas where it has been eliminated.

Background There is mounting evidence that the recent resurgence of pertussis in many countries is in part related to the acellular vaccine, which has been administered in Canada since 1997. This vaccine elicits a different cell-mediated immune response than the previously used whole-cell vaccine, and its effectiveness wanes over time. The aim of this study is to understand the immunological, demographic and clinical factors that mediate protection from pertussis on exposure. Methods This is a household case-control study protocol. Following notification of an index case in a household, a study team will conduct a home visit to collect data and biological specimens. The study team will return to the household 8 weeks from the onset of illness in the index case. The Th1, Th2 and Th17 responses, cytokine expression, IgG subclass, blood cell counts and presence of Bordetella pertussis will be determined. We will use laboratory and statistical analyses to determine immunological differences between contacts who are infected with B. pertussis and contacts who remain healthy, and to determine which clinical and demographic covariates are associated with a reduced risk of infection. Interpretation The results of this study will be essential for understanding the immune response required for protection from infection with B. pertussis and will contribute to our understanding of the shortcomings of the current vaccine.

Summary The basic reproduction number, R nought (R 0 ), is defined as the average number of secondary cases of an infectious disease arising from a typical case in a totally susceptible population, and can be estimated in populations if pre-existing immunity can be accounted for in the calculation. R 0 determines the herd immunity threshold and therefore the immunisation coverage required to achieve elimination of an infectious disease. As R 0 increases, higher immunisation coverage is required to achieve herd immunity. In July, 2010, a panel of experts convened by WHO concluded that measles can and should be eradicated. Despite the existence of an effective vaccine, regions have had varying success in measles control, in part because measles is one of the most contagious infections. For measles, R 0 is often cited to be 12–18, which means that each person with measles would, on average, infect 12–18 other people in a totally susceptible population. We did a systematic review to find studies reporting rigorous estimates and determinants of measles R 0 . Studies were included if they were a primary source of R 0 , addressed pre-existing immunity, and accounted for pre-existing immunity in their calculation of R 0 . A search of key databases was done in January, 2015, and repeated in November, 2016, and yielded 10 883 unique citations. After screening for relevancy and quality, 18 studies met inclusion criteria, providing 58 R 0 estimates. We calculated median measles R 0 values stratified by key covariates. We found that R 0 estimates vary more than the often cited range of 12–18. Our results highlight the importance of countries calculating R 0 using locally derived data or, if this is not possible, using parameter estimates from similar settings. Additional data and agreed review methods are needed to strengthen the evidence base for measles elimination modelling.

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.

Bordetella pertussis is a Gram-negative bacterium that causes respiratory infections in humans. Ongoing molecular surveillance of B. pertussis acellular vaccine (aP) antigens is critical for understanding the interaction between evolutionary pressures, disease pathogenesis, and vaccine effectiveness. Methods currently used to characterize aP components are relatively labor-intensive and low throughput. To address this challenge, we sought to derive aP antigen genotypes from minimally processed short-read whole-genome sequencing data generated from 40 clinical B. pertussis isolates and analyzed using the SRST2 bioinformatic package. SRST2 was able to identify aP antigen genotypes for all antigens with the exception of pertactin, possibly due to low read coverage in GC-rich low-complexity regions of variation. Two main genotypes were observed in addition to a singular third genotype that contained an 84-bp deletion that was identified by SRST2 despite the issues in allele calling. This method has the potential to generate large pools of B. pertussis molecular data that can be linked to clinical and epidemiological information to facilitate research of vaccine effectiveness and disease severity in the context of emerging vaccine antigen-deficient strains.

Background Vaccine effectiveness (VE) studies provide essential evidence on waning vaccine-derived immunity, a major threat to pertussis control. We evaluated how study design affects estimates by comparing 2 case-control studies conducted in Ontario, Canada. Methods We compared results from a test-negative design (TND) with a frequency-matched design (FMD) case-control study using pertussis cases from 2005–2015. In the first study, we identified test-negative controls from the public health laboratory that diagnosed cases and, in the second, randomly selected controls from patients attending the same physicians that reported cases, frequency matched on age and year. We compared characteristics of cases and controls using standardized differences. Results In both designs, VE estimates for the early years postimmunization were consistent with clinical trials (TND, 84%; FMD, 89% at 1–3 years postvaccination) but diverged as time since last vaccination increased (TND, 41%; FMD, 74% by 8 years postvaccination). Overall, we observed lower VE and faster waning in the TND than the FMD. In the TND but not FMD, controls differed from cases in important confounders, being younger, having more comorbidities, and higher healthcare use. Differences between the controls of each design were greater than differences between cases. TND controls were more likely to be unvaccinated or incompletely vaccinated than FMD controls (P Conclusions The FMD adjusted better for healthcare-seeking behavior than the TND. Duration of protection from pertussis vaccines is unclear because estimates vary by study design. Caution should be exercised by experts, researchers, and decision makers when evaluating evidence on optimal timing of boosters.

Background Internationally, Canada was one of the first countries to offer free HPV vaccination to young gbMSM. The provinces of British Columbia (BC), Ontario (ON) and Quebec (QC) implemented HPV vaccination programs in 2015–2016 for gbMSM aged 9–26. We explored HPV vaccine initiation and among unvaccinated men, potential barriers to uptake. Methods Engage is a sexual health study among gbMSM aged 16+ in Vancouver BC, Toronto ON, and Montreal QC, the largest urban centres in each province. Men are recruited via respondent driven sampling (RDS). We estimated the proportion that had initiated HPV vaccination and among unvaccinated men, compared proportions to responses on HPV vaccine knowledge and willingness, healthcare access and sexual orientation disclosure by age (eligible for free vaccination: ≤26 and ineligible for free vaccination: ≥26 years old). Proportions were RDS unadjusted. Results From 01/2017 to 31/12/2018, 2099 men enrolled (542 Vancouver, 378 Toronto, 1179 Montreal). Their median age was 33 years (IQR 27–46). In Vancouver, Toronto, and Montreal, 48.6%, 44.1% and 44.2% of men aged ≤26 and 24.9%, 30.3% and 7.1% of men aged ≥26 had 1+ dose of the HPV vaccine, respectively. Among unvaccinated men, more men aged ≥26 versus ≤26 accessed healthcare (family doctor/sexual health/HIV care) (87.2% vs 78.9%, p=0.0008) and disclosed their sexual orientation to their family doctor (86.2% vs 64.4%, p Conclusion Preliminary analyses indicate that HPV vaccine initiation in this population remains suboptimal. Among unvaccinated gbMSM ≤26, accessing healthcare, not disclosing sexual orientation and willingness to get vaccinated may be barriers to vaccine uptake. Disclosure No significant relationships.

Background Canada was one of the first countries to offer publicly funded programs providing HPV vaccine free of charge to gbMSM. In 2015–2016, the provinces of British Columbia (BC), Ontario (ON), and Quebec (QC) implemented programs for gbMSM aged 9–26 years. We sought to explore where men received the HPV vaccine and the influence of healthcare engagement on vaccination. Methods Engage is a sexual health study among gbMSM aged 16+ in the largest urban centres in each province: Vancouver, BC; Toronto, ON; and Montreal, QC. Men are recruited via respondent driven sampling (RDS). We compared proportions (non-RDS adjusted) to questionnaire responses on healthcare engagement among vaccinated (1+ doses) versus unvaccinated in the subset of men aged ≤26 years old at enrolment. Results From 01/2017 to 31/12/2018, 477 men aged ≤26 enrolled (144 Vancouver, 84 Toronto, 249 Montreal). Their median age was 24 years (IQR 22–25). In Vancouver, Toronto and Montreal, respectively, 48.6%, 44.1%, 44.2% had initiated HPV vaccination with 58.6%, 56.8% and 48.2% of vaccinated men having received all 3 doses. Popular venues for vaccination included a: sexual health clinic (50.7%), medical clinic not specializing in sexual health (14.8%), community health centre (10.6%), and doctor’s office (7.4%). Compared to unvaccinated men, more vaccinated men had a family doctor (65.9% vs 52.3%, p=0.0047), had a different provider/clinic for sexual health care or had a HIV care provider (66.8% vs 51.8%, p=0.0022), had a STI/HIV test in the past year (90.8% vs 68.6%, p Conclusion Compared to unvaccinated men, vaccinated men were more engaged in healthcare. It is unknown whether men requested the vaccine or providers offered it. Nevertheless, our findings suggest opportunistic HPV vaccination when men receive other services, particularly those related to sexual health. Disclosure No significant relationships.

Background Immunocompromised adults are at .increased risk of herpes zoster (HZ) infection and related complications. We aimed to assess the incidence of hospital-attended HZ (ie, seen in hospital or emergency department) in immunocompromised populations and compare it to immunocompetent populations. Methods We calculated incidence rates (IRs) of hospital-attended HZ in Ontario, Canada, between 1 April 2002 and 31 August 2016 in adults ≥18 years of age categorized as immunocompromised or immunocompetent. We repeated these analyses by type of immunocompromising condition and provided incidence rate ratios (IRRs) comparing to immunocompetent adults. We also calculated IRs and IRRs of HZ complications by immunocompromised status. Results There were 135 206 incident cases of hospital-attended HZ during the study period. Immunocompromised adults accounted for 13% of these cases despite representing 3% of the population. The risk of hospital-attended HZ was higher for immunocompromised adults compared with immunocompetent adults (IRR, 2.9 [95% confidence interval {CI}, 2.9–3.0]) and ranged across type of immunocompromising conditions, from 2.6 (95% CI, 2.6–2.7) in those with a solid tumor malignancy to 12.3 (95% CI, 11.3–13.2) in those who had undergone hematopoietic stem cell transplant. The risk of any HZ complication was higher in immunocompromised adults (IRR, 3.6 [95% CI, 3.5–3.7]) and highest for disseminated zoster (IRR, 32.8 [95% CI, 27.8–38.6]). Conclusions The risk of hospital-attended HZ and related complications was higher in immunocompromised populations compared with immunocompetent populations. Our findings underscore the high-risk nature of this population and the potential benefits that may be realized through HZ vaccination.

Background Given that measles is eliminated in Canada and measles immunisation coverage in Ontario is high, it has been questioned whether Ontario’s measles outbreak response is worthwhile. Aim Our objective was to determine cost-effectiveness of measles containment protocols in Ontario from the healthcare payer perspective. Methods We developed a decision-analysis model comparing Ontario’s measles containment strategy (based on actual 2015 outbreak data) with a hypothetical ‘modified response’. The modified scenario assumed 10% response costs with reduced case and contact tracing and no outbreak-associated vaccinations; it was based on local and provincial administrative and laboratory data and parameters from peer-reviewed literature. Short- and long-term health outcomes, quality-adjusted life years (QALYs) and costs discounted at 1.5%, were estimated. We conducted one- and two-way sensitivity analyses. Results The 2015 outbreak in Ontario comprised 16 measles cases and an estimated 3,369 contacts. Predictive modelling suggested that the outbreak response prevented 16 outbreak-associated cases at a cost of CAD 1,213,491 (EUR 861,579). The incremental cost-effectiveness ratio was CAD 739,063 (EUR 524,735) per QALY gained for the outbreak response vs modified response. To meet the commonly accepted cost-effectiveness threshold of CAD 50,000 (EUR 35,500) per QALY gained, the outbreak response would have to prevent 94 measles cases. In sensitivity analyses, the findings were robust. Conclusions Ontario’s measles outbreak response exceeds generally accepted cost-effectiveness thresholds and may not be the most efficient use of public health resources from a healthcare payer perspective. These findings should be balanced against benefits of increased vaccine coverage and maintaining elimination status.