Prevalence of Oral Human Papillomavirus Infection Among Urban Gay, Bisexual, and Other Men Who Have Sex With Men in Canada, 2017-2019.

BACKGROUND: Oral human papillomavirus (HPV) infections are a leading cause of oropharyngeal cancers. In 2015 and 2016, HPV vaccines became publicly funded for gay, bisexual, and other men who have sex with men (GBM) under 27 years of age in most Canadian provinces. METHODS: Between 2017 and 2019, sexually-active GBM in Montreal, Toronto, and Vancouver were recruited through respondent-driven sampling. Participants aged 16 to 30 years were invited to self-collect oral rinse specimens for HPV testing. We estimated HPV prevalence in the oral tract overall and compared these by vaccination status. RESULTS: Among the 838 GBM with a valid oral specimen, 36.9% reported receiving ≥1 dose of HPV vaccine. Overall, oral HPV prevalence was 2.6% (95% confidence interval, CI: 1.5, 3.7%) for at least one HPV type and 1.2% (95% CI: 0.5, 1.9%) for any high-risk type. We detected quadrivalent (HPV 6/11/16/18) vaccine-preventable types in 0.3% (95% CI: 0.0, 1.0%) of vaccinated individuals and 1.1% (95% CI: 0.1, 2.0%) in unvaccinated individuals. CONCLUSIONS: Oral HPV prevalence was low in a population of young urban GBM in Canada of whom 37% were vaccinated. Findings serve as a benchmark for monitoring of vaccination impacts on oral HPV infection within this priority population.

BNT162b2 Effectiveness Against Delta and Omicron Variants of Severe Acute Respiratory Syndrome Coronavirus 2 in Adolescents Aged 12-17 Years, by Dosing Interval and Duration.

BACKGROUND: Two- and 3-dose BNT162b2 vaccine effectiveness (VE) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, including Delta and Omicron variants, was assessed among adolescents in Canada, where first and second doses were spaced longer than the manufacturer-specified 3-week interval. METHODS: Test-negative design estimated VE against laboratory-confirmed SARS-CoV-2 infection ≥14 days after vaccination among 12-17-year-olds in Quebec and British Columbia, Canada, between 5 September 2021 and 30 April 2022 (epidemiological weeks 36-17). VE was explored by the interval between first and second doses, time since the second dose, and with a third dose. RESULTS: The VE against Delta was ≥90% until at least 5 months after the second dose. The VE against Omicron decreased from about 65%-75% at 2-3 weeks to ≤50% by the third month after vaccination, restored to approximately 65% by a third dose. Although confidence intervals overlapped, VE against Omicron was about 5%-7% higher (absolute) when first and second doses were spaced ≥8 versus 3-4 weeks apart. CONCLUSIONS: In adolescents, 2 BNT162b2 doses provided strong and sustained protection against Delta but reduced and rapidly waning VE against Omicron. A longer interval between first and second doses and a third dose marginally improved Omicron protection.

Vaccine Effectiveness Against 12-Month Incident and Persistent Anal Human Papillomavirus Infection Among Gay, Bisexual, and Other Men Who Have Sex With Men.

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.

Self-reported Human Papillomavirus Vaccination and Vaccine Effectiveness Among Men Who Have Sex with Men: A Quantitative Bias Analysis.

BACKGROUND: Self-report of human papillomavirus (HPV) vaccination has ~80-90% sensitivity and ~75-85% specificity. We measured the effect of nondifferential exposure misclassification associated with self-reported vaccination on vaccine effectiveness (VE) estimates. METHODS: Between 2017-2019, we recruited sexually active gay, bisexual, and other men who have sex with men aged 16-30 years in Canada. VE was derived as 1-prevalence ratio × 100% for prevalent anal HPV infection comparing vaccinated (≥1 dose) to unvaccinated men using a multivariable modified Poisson regression. We conducted a multidimensional and probabilistic quantitative bias analysis to correct VE estimates. RESULTS: Bias-corrected VE estimates were relatively stable across sensitivity values but differed from the uncorrected estimate at lower values of specificity. The median adjusted VE was 27% (2.5-97.5th simulation interval = -5-49%) in the uncorrected analysis, increasing to 39% (2.5-97.5th simulation interval = 2-65%) in the bias-corrected analysis. CONCLUSION: A large proportion of participants erroneously reporting HPV vaccination would be required to meaningfully change VE estimates.

Single-Dose Messenger RNA Vaccine Effectiveness Against Severe Acute Respiratory Syndrome Coronavirus 2 in Healthcare Workers Extending 16 Weeks Postvaccination: A Test-Negative Design From Québec, Canada.

BACKGROUND: In Canada, first and second doses of messenger RNA (mRNA) vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were uniquely spaced 16 weeks apart. We estimated 1- and 2-dose mRNA vaccine effectiveness (VE) among healthcare workers (HCWs) in Québec, Canada, including protection against varying outcome severity, variants of concern (VOCs), and the stability of single-dose protection up to 16 weeks postvaccination. METHODS: A test-negative design compared vaccination among SARS-CoV-2 test-positive and weekly matched (10:1), randomly sampled, test-negative HCWs using linked surveillance and immunization databases. Vaccine status was defined by 1 dose ≥14 days or 2 doses ≥7 days before illness onset or specimen collection. Adjusted VE was estimated by conditional logistic regression. RESULTS: Primary analysis included 5316 cases and 53 160 controls. Single-dose VE was 70% (95% confidence interval [CI], 68%-73%) against SARS-CoV-2 infection; 73% (95% CI, 71%-75%) against illness; and 97% (95% CI, 92%-99%) against hospitalization. Two-dose VE was 86% (95% CI, 81%-90%) and 93% (95% CI, 89%-95%), respectively, with no hospitalizations. VE was higher for non-VOCs than VOCs (73% Alpha) among single-dose recipients but not 2-dose recipients. Across 16 weeks, no decline in single-dose VE was observed, with appropriate stratification based upon prioritized vaccination determined by higher vs lower likelihood of direct patient contact. CONCLUSIONS: One mRNA vaccine dose provided substantial and sustained protection to HCWs extending at least 4 months postvaccination. In circumstances of vaccine shortage, delaying the second dose may be a pertinent public health strategy.

Two-Dose Severe Acute Respiratory Syndrome Coronavirus 2 Vaccine Effectiveness With Mixed Schedules and Extended Dosing Intervals: Test-Negative Design Studies From British Columbia and Quebec, Canada.

BACKGROUND: The Canadian coronavirus disease 2019 (COVID-19) immunization strategy deferred second doses and allowed mixed schedules. We compared 2-dose vaccine effectiveness (VE) by vaccine type (mRNA and/or ChAdOx1), interval between doses, and time since second dose in 2 of Canada's larger provinces. METHODS: Two-dose VE against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or hospitalization among adults ≥18 years, including due to Alpha, Gamma, and Delta variants of concern (VOCs), was assessed ≥14 days postvaccination by test-negative design studies separately conducted in British Columbia and Quebec, Canada, between 30 May and 27 November (epi-weeks 22-47) 2021. RESULTS: In both provinces, all homologous or heterologous mRNA and/or ChAdOx1 2-dose schedules were associated with ≥90% reduction in SARS-CoV-2 hospitalization risk for ≥7 months. With slight decline from a peak of >90%, VE against infection was ≥80% for ≥6 months following homologous mRNA vaccination, lower by ∼10% when both doses were ChAdOx1 but comparably high following heterologous ChAdOx1 + mRNA receipt. Findings were similar by age group, sex, and VOC. VE was significantly higher with longer 7-8-week versus manufacturer-specified 3-4-week intervals between mRNA doses. CONCLUSIONS: Two doses of any mRNA and/or ChAdOx1 combination gave substantial and sustained protection against SARS-CoV-2 hospitalization, spanning Delta-dominant circulation. ChAdOx1 VE against infection was improved by heterologous mRNA series completion. A 7-8-week interval between first and second doses improved mRNA VE and may be the optimal schedule outside periods of intense epidemic surge. Findings support interchangeability and extended intervals between SARS-CoV-2 vaccine doses, with potential global implications for low-coverage areas and, going forward, for children.

Time trends in social contacts of individuals according to comorbidity and vaccination status, before and during the COVID-19 pandemic.

BACKGROUND: As we are confronted with more transmissible/severe variants with immune escape and the waning of vaccine efficacy, it is particularly relevant to understand how the social contacts of individuals at greater risk of COVID-19 complications evolved over time. We described time trends in social contacts of individuals according to comorbidity and vaccination status before and during the first three waves of the COVID-19 pandemic in Quebec, Canada. METHODS: We used data from CONNECT, a repeated cross-sectional population-based survey of social contacts conducted before (2018/2019) and during the pandemic (April 2020 to July 2021). We recruited non-institutionalized adults from Quebec, Canada, by random digit dialling. We used a self-administered web-based questionnaire to measure the number of social contacts of participants (two-way conversation at a distance ≤2 m or a physical contact, irrespective of masking). We compared the mean number of contacts/day according to the comorbidity status of participants (pre-existing medical conditions with symptoms/medication in the past 12 months) and 1-dose vaccination status during the third wave. All analyses were performed using weighted generalized linear models with a Poisson distribution and robust variance. RESULTS: A total of 1441 and 5185 participants with and without comorbidities, respectively, were included in the analyses. Contacts significantly decreased from a mean of 6.1 (95%CI 4.9-7.3) before the pandemic to 3.2 (95%CI 2.5-3.9) during the first wave among individuals with comorbidities and from 8.1 (95%CI 7.3-9.0) to 2.7 (95%CI 2.2-3.2) among individuals without comorbidities. Individuals with comorbidities maintained fewer contacts than those without comorbidities in the second wave, with a significant difference before the Christmas 2020/2021 holidays (2.9 (95%CI 2.5-3.2) vs 3.9 (95%CI 3.5-4.3); P<0.001). During the third wave, contacts were similar for individuals with (4.1, 95%CI 3.4-4.7) and without comorbidities (4.5, 95%CI 4.1-4.9; P=0.27). This could be partly explained by individuals with comorbidities vaccinated with their first dose who increased their contacts to the level of those without comorbidities. CONCLUSIONS: It will be important to closely monitor COVID-19-related outcomes and social contacts by comorbidity and vaccination status to inform targeted or population-based interventions (e.g., booster doses of the vaccine).

Time trends in social contacts before and during the COVID-19 pandemic: the CONNECT study.

BACKGROUND: Since the beginning of the COVID-19 pandemic, many countries, including Canada, have adopted unprecedented physical distancing measures such as closure of schools and non-essential businesses, and restrictions on gatherings and household visits. We described time trends in social contacts for the pre-pandemic and pandemic periods in Quebec, Canada. METHODS: CONNECT is a population-based study of social contacts conducted shortly before (2018/2019) and during the COVID-19 pandemic (April 2020 - February 2021), using the same methodology for both periods. We recruited participants by random digit dialing and collected data by self-administered web-based questionnaires. Questionnaires documented socio-demographic characteristics and social contacts for two assigned days. A contact was defined as a two-way conversation at a distance ≤ 2 m or as a physical contact, irrespective of masking. We used weighted generalized linear models with a Poisson distribution and robust variance (taking possible overdispersion into account) to compare the mean number of social contacts over time and by socio-demographic characteristics. RESULTS: A total of 1291 and 5516 Quebecers completed the study before and during the pandemic, respectively. Contacts significantly decreased from a mean of 8 contacts/day prior to the pandemic to 3 contacts/day during the spring 2020 lockdown. Contacts remained lower than the pre-COVID period thereafter (lowest = 3 contacts/day during the Christmas 2020/2021 holidays, highest = 5 in September 2020). Contacts at work, during leisure activities/in other locations, and at home with visitors showed the greatest decreases since the beginning of the pandemic. All sociodemographic subgroups showed significant decreases of contacts since the beginning of the pandemic. The mixing matrices illustrated the impact of public health measures (e.g. school closure, gathering restrictions) with fewer contacts between children/teenagers and fewer contacts outside of the three main diagonals of contacts between same-age partners/siblings and between children and their parents. CONCLUSION: Physical distancing measures in Quebec significantly decreased social contacts, which most likely mitigated the spread of COVID-19.

Immunogenicity of 2 and 3 Doses of the Quadrivalent Human Papillomavirus Vaccine up to 120 Months Postvaccination: Follow-up of a Randomized Clinical Trial.

BACKGROUND: Several countries have implemented a 2-dose (2D) human papillomavirus (HPV) vaccination schedule for adolescents based on immunobridging studies. We compared immunogenicity of 2D vs 3-dose (3D) schedules of the quadrivalent vaccine (4vHPV) up to 10 years after the first dose. METHODS: Girls aged 9-13 years were randomized to receive 2D or 3D and were compared with women aged 16-26 receiving 3D at day 1 and months 7, 24, and 120 after the first dose. Antibody levels for HPV6/11/16/18 were evaluated using the competitive Luminex immunoassay (cLIA) and total immunoglobulin G assay. Geometric mean titers (GMTs) and seropositivity rates were compared between the different groups at different time points. Noninferiority of GMT ratios was defined as the lower bound of the 2-sided 95% confidence interval (CI) being greater than 0.5. Kinetics of antibody titers over time among study groups were examined. RESULTS: At 120 months, data from 35 2D girls, 38 3D girls, and 30 3D women were used for analyses. cLIA seropositivity rates were above 95% for all HPV vaccine types and all schedules, except HPV18, with the lowest seropositivity observed among 3D women (60.0%; 95% CI, 40.6%-77.3%). GMT ratios (cLIA) for both 2D and 3D girls were noninferior to 3 doses in women for HPV6/11/16/18. Trends were comparable between assays. CONCLUSIONS: GMTs for HPV6/11/16/18 after 2D or 3D of 4vHPV in girls were noninferior to 3D in adult women up to 120 months postvaccination. This study demonstrates long-term immunogenicity of the 2D HPV vaccine schedule.

Effectiveness and cost-effectiveness of vaccination against herpes zoster in Canada: a modelling study.

BACKGROUND: Two vaccines against herpes zoster are currently authorized for use in Canada: the recombinant subunit zoster vaccine and live attenuated zoster vaccine. We compared the effectiveness and cost-effectiveness of these 2 vaccines. METHODS: We used a decision analytic static cohort model parametrized with Canadian epidemiologic and economic data. We performed the economic analysis from the health care system perspective, using a lifetime horizon and a 3% discount rate for costs and benefits. The primary outcome was the incremental cost per quality-adjusted life-year (QALY) gained, relative to no vaccination. We ran 30 000 simulations varying all model parameters, including vaccine costs, efficacy and waning. RESULTS: The number needed to vaccinate (NNV) was higher for the live attenuated zoster vaccine than for the recombinant subunit zoster vaccine for all herpes zoster-related events at all ages. For example, in persons exactly 65 years old, for herpes zoster, median NNV was 21 (90% uncertainty interval [UI] 13-31) versus 8 (90% UI 6-18), and for postherpetic neuralgia, NNV was 64 (90% UI 33-93) versus 31 (90% UI 23-73). For the recombinant vaccine, the median cost-effectiveness ratios varied between cost-saving and $25 881 per QALY gained for adults aged 50 years or older. For the live vaccine, the cost-effectiveness ratios varied between cost-saving and $130 587 per QALY gained and were less than $45 000 per QALY gained only for those 65 to 75 years old. Given its higher efficacy, we estimated that the cost for the complete series of the recombinant vaccine could be $150 to $200 more than the cost of the live vaccine and still be considered cost-effective. INTERPRETATION: Our model predicted that the recombinant subunit zoster vaccine is likely cost-effective in Canada for adults 60 years or older, and is likely more cost-effective than live attenuated zoster vaccine. These results have informed updated national and provincial recommendations on herpes zoster vaccination.

Promoting vaccination in the province of Québec: the PromoVaQ randomized controlled trial protocol.

BACKGROUND: Vaccination has a huge public health impact. Maintaining vaccine coverage is key to avoid the devastating consequences of resurgence. In the Province of Québec, vaccine coverage in young children are sub-optimal, mostly due to ambivalence toward vaccine safety and efficacy. We previously conducted a regional study in the Québec's Eastern Townships region, the PromoVac Study, to test a new educational intervention, based on motivational interviewing techniques, aimed at promoting infant vaccination. This first study evidenced that the intervention led to a marked increase in mothers' intention to vaccinate, and vaccine coverage in their infants. The current study protocol aims at scaling up these results at a provincial level using a randomized controlled trial design. METHODS: This pragmatic, randomized, controlled, parallel-group clinical trial will compare the effectiveness of the motivational interviewing to an educational intervention, including the distribution of an information flyer as standard of care on vaccination coverage in four maternity wards across the Province of Québec (PromovaQ). Adult mothers of children born in participating maternity wards were recruited between March 2014 and February 2015. Vaccination coverage will be assessed at 3-years of age, thus the trial is expected to be completed in March 2019. Statistical analyses will be conducted under the intention-to-treat principle. Vaccine coverage will be analyzed using Chi-squared distribution testing and logistic regression to identify determinant factors. Secondary outcomes will include vaccine hesitation and intention scores, mother's knowledge, attitudes and beliefs about immunization, and psychosocial determinants of intention to vaccinate. DISCUSSION: In the case results of this Provincial RCT be confirmed, serious consideration should then be given by Ministry of Health authorities to the possible implementation of MI-based strategies across provincial maternity wards. To ensure adequate input and secure implementation, study design and results will be reviewed with relevant stakeholders, including the children's families, and provincial and regional decision-makers. Results will be adapted and shared with all stakeholders. TRIAL REGISTRATION: ClinicalTrials.gov NCT02666872 (Retrospectively registered as January 28, 2016).

Promoting vaccination in maternity wards ─ motivational interview technique reduces hesitancy and enhances intention to vaccinate, results from a multicentre non-controlled pre- and post-intervention RCT-nested study, Quebec, March 2014 to February 2015.

BackgroundMany countries are grappling with growing numbers of parents who delay or refuse recommended vaccinations for their children. This has created a need for strategies to address vaccine hesitancy (VH) and better support parental decision-making regarding vaccination.AimTo assess vaccination intention (VI) and VH among parents who received an individual motivational-interview (MI) based intervention on infant immunisation during post-partum stay at a maternity ward between March 2014 and February 2015.MethodsThis non-controlled pre-/post-intervention study was conducted using the results from parents enrolled in the intervention arm of the PromoVaQ randomised control trial (RCT), which was conducted in four maternity wards across the Province of Quebec. Participants (n = 1,223) completed pre- and post-intervention questionnaires on VI and VH using Opel's score. Pre-/post-intervention measures were compared using McNemar's test for categorical variables and Wilcoxon signed-rank test for continuous variables.ResultsPre-intervention: overall VI was 78% and significantly differed across maternity wards (74%, 77%, 84%, 79%, p = 0.02). Post-intervention: VI rose significantly across maternity wards (89%, 85%, 95%, 93%) and the overall increase in VI was 12% (78% vs 90%, p < 0.0001). VH corroborated these observations, pre- vs post-intervention, for each maternity ward (28% vs 16%, 29% vs 21%, 27% vs 17%, 24% vs 13%). Overall, VH was curbed post-intervention by 40% (27% vs 16%; p < 0.0001).ConclusionsCompared with pre-intervention status, participants who received the MI-based intervention on immunisation displayed lower hesitancy and greater intention to vaccinate their infant at 2 months of age.

Impact of vaccine delays at the 2, 4, 6 and 12 month visits on incomplete vaccination status by 24 months of age in Quebec, Canada.

BACKGROUND: Timeliness in the administration of recommended vaccines is often evaluated using vaccine delays and provides more information regarding the susceptibility of children to vaccine-preventable diseases compared with vaccine coverage at a given age. The importance of on-time administration of vaccines scheduled at the first visit is well documented, but data are scarce about the impact of vaccine delays at other visits on vaccination status by 24 months of age. Using vaccine delays for the first three doses of DTaP-containing vaccines and for the first dose of measles-containing vaccines as markers of timeliness at the 2, 4, 6 and 12 month visits, we estimated the proportion of incomplete vaccination status by 24 months of age attributable to a vaccine delay at each of these visits. METHODS: We used the data from six cross-sectional coverage surveys conducted in the Province of Quebec from 2006 to 2016 which included 7183 children randomly selected from the universal health insurance database. A vaccine dose was considered delayed if received 30 days or more after the recommended age. The impact of new vaccine delays at each visit on incomplete vaccination status by 24 months of age was estimated with the attributable risk in the population. RESULTS: The proportion of children with vaccine delay was 5.4% at 2 months, 13.3% at 4 months, 23.1% at 6 months and 23.6% at 12 months. Overall, 72.5% of all 2-year-old children with an incomplete status by 24 months were attributable with a vaccine delay, of which 16.1% were attributable with a first vaccine delay at 2 months, 10.6% at 4 months, 14.0% at 6 months and 31.8% at 12 months. CONCLUSIONS: While great emphasis has been put on vaccine delays at the first vaccination visit, the prevalence of vaccine delays was greater with later visits and most children with an incomplete vaccination status by 24 months had a vaccine delay occurring during these later visits. Interventions to improve timeliness should address vaccine delays at each visit and not only focus on the first visit.

Herpes Zoster Burden in Canadian Provinces: A Narrative Review and Comparison with Quebec Provincial Data.

BACKGROUND: The main aim of this review was to assess incidence rates and trends of medically attended and death cases of herpes zoster in Canada. METHODS: The search was conducted in five databases (PubMed, Cochrane, Embase, PsycNET, and Web of Science). Data on herpes zoster-related consultations and hospitalisations and deaths were also extracted from three Quebec provincial administrative databases (RAMQ, MED-ECHO, and ISQ). RESULTS: The electronic search yielded 587 publications. Seventeen publications satisfied inclusion criteria. These publications reported data from eleven studies. Ten studies used provincial databases, and one study used the Canadian Primary Care Sentinel Surveillance Network electronic database. Seven studies evaluated overall rates of medically attended cases (consultations and hospitalisations). Four of these studies reported an increase in rates of medically attended cases during the study period; one study reported stable rates, and two studies reported only an average rate. The rates varied from 316 to 450/100,000 p.y. The Quebec analysis shows similar rates with a slight decreasing trend (from 369 to 350/100,000 p.y.). Incidence rates of consultations were reported separately in three studies. Two studies reported an increase in rates (from 258 to 348/100,000 p.y. and from 324 to 366/100,000 p.y.), and the third study reported a decrease (from 525 to 479/100,000 p.y.). Hospitalization rates were reported separately in two studies, both reporting a decrease (from 12 to 8 cases/100,000 p.y. and from 9 to 4 cases/100,000 p.y.). Quebec data also showed a decrease, from 9 to 6 cases/100,000 p.y. One study reported herpes zoster-related deaths. In this study, the reported death rate was 0.7/1,000,000 p.y. in the overall population and 5.5/1,000,000 p.y. in those aged ≥65 years. Quebec analysis showed a death rate of 1.2/1,000,000 p.y. in the overall population and 8.6/1,000,000 p.y. in those aged ≥65 years. CONCLUSIONS: The results of the reviewed studies and our analysis of Quebec provincial data indicate important variations in the reported overall incidence rates of medically attended herpes zoster cases in Canada. The trends in time are heterogeneous in studies in which hospitalisations and medical consultations were pooled together. We observed a decrease in hospitalization rates and a slight increase in consultation rates in studies reporting hospitalisations and consultations separately. These results consolidate the understanding of the herpes zoster burden in Canada and might be used as a tool in decision-making regarding future preventive interventions.

"Nature Does Things Well, Why Should We Interfere?": Vaccine Hesitancy Among Mothers.

Parents' decision to use vaccination services is complex and multi-factorial. Of particular interest are "vaccine-hesitant" parents who are in the middle of the continuum between vaccine acceptance and refusal. The objective of this qualitative longitudinal study was to better understand why mothers choose to vaccinate-or not-their newborns. Fifty-six pregnant mothers living in different areas of Quebec (Canada) were interviewed. These interviews gathered information on mothers' views about health and vaccination. Almost half of the mothers were categorized as vaccine-hesitant. A second interview was conducted with these mothers 3 to 11 months after birth to look at their actual decision and behavior concerning vaccination. Our results show the heterogeneity of factors influencing vaccine decision making. Although the majority of vaccine-hesitant mothers finally chose to follow the recommended vaccine schedule for their child, they were still ambivalent and they continued to question their decision.

Impact of interventions to improve HPV vaccination acceptance and uptake in school-based programs: Findings of a pilot project in Quebec.

CONTEXT: Vaccination coverage against human papillomavirus (HPV) in school-based programs in Quebec, Canada, is suboptimal despite more than a decade of introduction. Three interventions to improve HPV vaccine acceptability and coverage in school-based programs were developed, implemented as part of a multicomponent strategy and evaluated. METHOD: Sixty-four (64) schools were recruited, of which 32 received the interventions (pilot schools), and 32 received usual vaccination activities (control schools). Two approaches were used to assess the impact of the interventions. Pre-post questionnaires were completed by parents in both pilot and control schools. Quantitative analyses of vaccination coverage using the Quebec immunization registry were conducted. RESULTS: Participating parents (n = 989 in the pre-intervention survey and n = 772 in the post-intervention one) were generally aware of HPV and HPV vaccination. Most parents were confident about vaccination, had little or no hesitation and had decided to have their child vaccinated. Parents in the pilot schools were less concerned about vaccine safety than those in the control schools after the interventions. Parents in the pilot schools were also more likely to have decided to have their child vaccinated. A statistically significant difference of 7.4 % in HPV vaccine coverage between pilot and control schools was observed (82.9 % vs 75.5 %, p <0.0001). CONCLUSION: Although school-based programs offer equitable access to vaccination and minimize access barriers, it remains crucial to identify effective interventions to improve vaccine uptake further and reach the WHO cervical cancer elimination goal. Our multicomponent strategy appears to have positively impacted HPV vaccine acceptability and coverage and could be adapted to other contexts where vaccination is delivered in school-based programs.

Development of Promising Interventions to Improve Human Papillomavirus Vaccination in a School-Based Program in Quebec, Canada: Results From a Formative Evaluation Using a Mixed Methods Design.

BACKGROUND: Despite the availability of school-based human papillomavirus (HPV) vaccination programs, disparities in vaccine coverage persist. Barriers to HPV vaccine acceptance and uptake include parental attitudes, knowledge, beliefs, and system-level barriers. A total of 3 interventions were developed to address these barriers: an in-person presentation by school nurses, an email reminder with a web-based information and decision aid tool, and a telephone reminder using motivational interviewing (MI) techniques. OBJECTIVE: Here we report on the development and formative evaluation of interventions to improve HPV vaccine acceptance and uptake among grade 4 students' parents in Quebec, Canada. METHODS: In the summer of 2019, we conducted a formative evaluation of the interventions to assess the interventions' relevance, content, and format and to identify any unmet needs. We conducted 3 focus group discussions with parents of grade 3 students and nurses. Interviews were recorded, transcribed, and analyzed for thematic content using NVivo software (Lumivero). Nurses received training on MI techniques and we evaluated the effect on nurses' knowledge and skills using a pre-post questionnaire. Descriptive quantitative analyses were carried out on data from questionnaires relating to the training. Comparisons were made using the proportions of the results. Finally, we developed a patient decision aid using an iterative, user-centered design process. The iterative refinement process involved feedback from parents, nurses, and experts to ensure the tool's relevance and effectiveness. The evaluation protocol and data collection tools were approved by the CHU (Centre Hospitalier Universitaire) de Québec Research Ethics Committee (MP-20-2019-4655, May 16, 2019). RESULTS: The data collection was conducted from April 2019 to March 2021. Following feedback (n=28) from the 3 focus group discussions in June 2019, several changes were made to the in-person presentation intervention. Experts (n=27) and school nurses (n=29) recruited for the project appreciated the visual and simplified information on vaccination in it. The results of the MI training for school nurses conducted in August 2019 demonstrated an increase in the skills and knowledge of nurses (n=29). School nurses who took the web-based course (n=24) filled out a pretest and posttest questionnaire to evaluate their learning. The rating increased by 19% between the pretest and posttest questionnaires. Several changes were made between the first draft of the web-based decision-aid tool and the final version during the summer of 2019 after an expert consultation of experts (n=3), focus group participants (n=28), and parents in the iterative process (n=5). More information about HPV and vaccines was added, and users could click if more detail is desired. CONCLUSIONS: We developed and pilot-tested 3 interventions using an iterative process. The interventions were perceived as potentially effective to increase parents' knowledge and positive attitudes toward HPV vaccination, and ultimately, vaccine acceptance. Future research will assess the effectiveness of these interventions on a larger scale.

Effectiveness of BNT162b2 Vaccine Against Omicron-SARS-CoV-2 Subvariants in Children 5-11 Years of Age in Quebec, Canada, January 2022 to January 2023.

BACKGROUND: In premarketing clinical trials conducted before Omicron emergence, BNT162b2 vaccine efficacy against COVID-19 was 90% in children. We conducted postmarketing evaluation of 1- and 2-dose vaccine effectiveness (VE) against Omicron BA.1, BA.2 and BA.4/5 subvariants in 5- to 11-year olds. METHODS: We estimated VE against SARS-CoV-2 infection using a test-negative design. Specimens collected between January 9, 2022, and January 7, 2023, from children 5-11 years old in Quebec, Canada, and tested by nucleic acid amplification test were eligible. We estimated VE by time since last vaccine dose, interval between doses and by period of Omicron subvariant predominance. RESULTS: A total of 48,826 NAATs were included in overall analysis. From 14-55 to 56-385 days postvaccination, 2-dose VE against symptomatic infection decreased from 68% (95% CI, 62-74) to 25% (95% CI, 11-36). Two-dose VE with restriction to specimens collected from acute care hospitals (emergency rooms or wards) did not decline but was stable at ~40%. VE against symptomatic infection remained comparable at any interval between doses but increased with longer interval among children tested in acute care settings, from 18% (95% CI, -17 to 44) with 21- to 55-day interval to 69% (95% CI, 43-86) with ≥84-day interval. Two-dose VE against symptomatic infection dropped from 70% (95% CI, 63-76) during BA.1, to 32% (95% CI, 13-47) with BA.2 and to nonprotective during BA.4/5 dominance. CONCLUSIONS: In children 5-11 years of age, VE against symptomatic infection was stable at any interval between doses but decreased with time since the last dose and against more divergent omicron subvariants.

School-based vaccination program against HPV and Hepatitis B: A longitudinal analysis of vaccine coverage between 2015 and 2021 in Quebec.

BACKGROUND: HPV vaccination prevents cancers, including 90% of cervical cancer. Since 2008, a school-based HPV vaccination program has been implemented in Quebec, but vaccine coverage is suboptimal. The COVID-19 pandemic disrupted school-based vaccination programs. This study aimed to assess variation in HPV vaccination coverage in the school-based program between 2015 and 2022 in Quebec and to identify sociodemographic characteristics associated with non-vaccination. METHODS: HPV vaccine coverage data were extracted from the Quebec Immunization Registry for students in Grade 4 and matched to the 2016 Canadian census sociodemographic data. Descriptive analysis was conducted to explore individual-level vaccine coverage according to sociodemographic data. A Generalized Estimating Equations model assessed the independent association between non-vaccination and students' sociodemographic characteristics. RESULTS: HPV vaccine coverage (at least one dose) was 84% in 2018-2019 and 85% in 2019-2020. A decrease was observed during the pandemic. In 2020-2021, the HPV vaccine coverage (at least one dose) was 52% (at the end of the school year) and rose to 84% with intense catch-up activities. In 2021-2022, the coverage was slightly lower than before the pandemic (81%). Factors in the dissemination area were statistically significantly associated with non-vaccination: material (p-value = 0.0001) and social deprivation index (p-value = 0.0048), the proportion of immigration (p-value < 0.0001), and the language spoken at home (English (p-value = 0.0318), other than French or English (p-value = 0.0001). CONCLUSION: School-based vaccination programs offer equitable access to vaccination, and our analysis showed that some groups have consistently lower vaccine acceptance and uptake. Strategies to improve HPV vaccine coverage should target children living in areas with a higher proportion of immigrants, non-French speakers, and people from underprivileged backgrounds. Although it is too early to assess the full impact of COVID-19 on school-based programs in Quebec, it remains important to ensure that catch-up strategies are implemented for missed doses.

Immunogenicity of 2 doses of HPV vaccine in younger adolescents vs 3 doses in young women: a randomized clinical trial.

IMPORTANCE: Global use of human papillomavirus (HPV) vaccines to prevent cervical cancer is impeded by cost. A 2-dose schedule for girls may be possible. OBJECTIVE: To determine whether mean antibody levels to HPV-16 and HPV-18 among girls receiving 2 doses was noninferior to women receiving 3 doses. DESIGN, SETTING, AND PATIENTS: Randomized, phase 3, postlicensure, multicenter, age-stratified, noninferiority immunogenicity study of 830 Canadian females from August 2007 through February 2011. Follow-up blood samples were provided by 675 participants (81%). INTERVENTION: Girls (9-13 years) were randomized 1:1 to receive 3 doses of quadrivalent HPV vaccine at 0, 2, and 6 months (n = 261) or 2 doses at 0 and 6 months (n = 259). Young women (16-26 years) received 3 doses at 0, 2, and 6 months (n = 310). Antibody levels were measured at 0, 7, 18, 24, and 36 months. MAIN OUTCOMES AND MEASURES: Primary outcome was noninferiority (95% CI, lower bound >0.5) of geometric mean titer (GMT) ratios for HPV-16 and HPV-18 for girls (2 doses) compared with young women (3 doses) 1 month after last dose. Secondary outcomes were noninferiority of GMT ratios of girls receiving 2 vs 3 doses of vaccine; and durability of noninferiority to 36 months. RESULTS: The GMT ratios were noninferior for girls (2 doses) to women (3 doses): 2.07 (95% CI, 1.62-2.65) for HPV-16 and 1.76 (95% CI, 1.41-2.19) for HPV-18. Girls (3 doses) had GMT responses 1 month after last vaccination for HPV-16 of 7736 milli-Merck units per mL (mMU/mL) (95% CI, 6651-8999) and HPV-18 of 1730 mMU/mL (95% CI, 1512-1980). The GMT ratios were noninferior for girls (2 doses) to girls (3 doses): 0.95 (95% CI, 0.73-1.23) for HPV-16 and 0.68 (95% CI, 0.54-0.85) for HPV-18. The GMT ratios for girls (2 doses) to women (3 doses) remained noninferior for all genotypes to 36 months. Antibody responses in girls were noninferior after 2 doses vs 3 doses for all 4 vaccine genotypes at month 7, but not for HPV-18 by month 24 or HPV-6 by month 36. CONCLUSIONS AND RELEVANCE: Among girls who received 2 doses of HPV vaccine 6 months apart, responses to HPV-16 and HPV-18 one month after the last dose were noninferior to those among young women who received 3 doses of the vaccine within 6 months. Because of the loss of noninferiority to some genotypes at 24 to 36 months in girls given 2 doses vs 3 doses, more data on the duration of protection are needed before reduced-dose schedules can be recommended. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00501137.