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.

Effectiveness of 13-Valent Pneumococcal Conjugate Vaccine Against Invasive Disease Caused by Serotype 3 in Children: A Systematic Review and Meta-analysis of Observational Studies.

The 13-valent pneumococcal conjugate vaccine (PCV13) is the only licensed PCV with serotype 3 polysaccharide in its formulation. Postlicensure PCV13 effectiveness studies against serotype 3 invasive pneumococcal disease (IPD) in children have shown inconsistent results.  We performed a systematic review and meta-analysis of observational studies to assess PCV13 vaccine effectiveness (VE) for serotype 3 IPD in children. We systematically searched PubMed, Embase, and the Cochrane library for studies published before 14 August 2017. We identified 4 published studies and 2 conference posters that provided PCV13 VE estimates stratified by serotype. The pooled PCV13 VE against serotype 3 IPD from the random-effects meta-analysis was 63.5% (95% confidence interval [CI], 37.3%-89.7%). A sensitivity analysis including conference posters gave a pooled VE estimate of 72.4% (95% CI, 56.7%-88.0%). The pooled data from case-control studies with similar methodologies and high quality support direct PCV13 protection against serotype 3 IPD in children.

A DELPHI study on aspects of study design to overcome knowledge gaps on the burden of disease caused by serogroup B invasive meningococcal disease.

BACKGROUND: Value assessment of vaccination programs against serogroup B invasive meningococcal disease (IMD) is on the agenda of public health authorities. Current evidence on the burden due to IMD is unfit for pinning down the nature and magnitude of the full social and economic costs of IMD for two reasons. First, the concepts and components that need to be studied are not agreed, and second, measures of the concepts that have been studied are weak and inconsistent. Thus, the economic evaluation of the available serogroup B meningococcal (MenB) vaccines is difficult. The aims of this DELPHI study are to: (1) agree on the concepts and components determining the burden of MenB diseases that need to be studied; and (2) seek consensus on appropriate methods and study designs to measure quality of life (QoL) associated with MenB induced long-term sequelae in future studies. METHODS: We designed a DELPHI questionnaire based on the findings of a recent systematic review on the QoL associated with IMD-induced long-term sequelae, and iteratively interviewed a panel of international experts, including physicians, health economists, and patient representatives. Experts were provided with a controlled feedback based on the results of the previous round. RESULTS: Experts reached consensus on all questions after two DELPHI rounds. Major gaps in the literature relate (i) to the classification of sequelae, which allows differentiation of severity levels, (ii) to the choice of QoL measures, and (iii) to appropriate data sources to examine long-term changes and deficits in patients' QoL. CONCLUSIONS: Better conceptualisation of the structure of IMD-specific sequelae and of how their diverse forms of severity might impact the QoL of survivors of IMD as well as their family network and care-providers is needed to generate relevant, reliable and generalisable data on QoL in the future. The results of this DELPHI panel provide useful guidance on how to choose the study design, target population and appropriate QoL measures for future research and hence, help promote the appropriateness and consistency in study methodology and sample characteristics.

Pattern and correlates of public support for public health interventions to reduce the consumption of sugar-sweetened beverages.

OBJECTIVE: To examine the pattern and correlates of public support for twelve public health interventions aimed at reducing sugar-sweetened beverage (SSB) consumption. DESIGN: Cross-sectional population-based survey. Respondents were recruited using a random digit dialling procedure (landline telephone) and a random selection of telephone numbers (mobile telephone). Sampling quotas were applied for age, and the sample was stratified according to administrative regions. SETTING: The province of Québec, Canada. SUBJECTS: One thousand adults aged between 18 and 64 years and able to answer the survey questionnaire in French or English. RESULTS: Support was observed for a number of public health interventions, but the more intrusive approaches were less supported. Support for taxation as well as for sale and access restriction was positively associated with the perceived relevance of the government intervention, perceived effectiveness, and perceived associations between SSB consumption and chronic diseases. Believing that SSB consumption is a personal choice and daily consumption were generally negatively associated with strong support and positively associated with strong opposition. Sparse associations between sociodemographic and socio-economic characteristics were observed, with the exception of sex and age: women were generally more likely to support the examined public health strategies, while younger respondents were less likely to express support. CONCLUSIONS: Increasing perceived effectiveness and government responsibility for addressing the issue of SSB consumption could lead to increased support for SSB interventions. Increasing the belief that SSB consumption could be associated with chronic diseases would increase support, but SSB consumers and younger individuals are expected to be resistant.

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.

Epidemiology and Control of Meningococcal Disease in Canada: A Long, Complex, and Unfinished Story.

The epidemiology of meningococcal disease in Canada has been punctuated by outbreaks caused by serogroup A strains in the 1940s, virulent serogroup C clones from 1985 to 2001, a serogroup B clone in Quebec from 2003 to 2014, and more recently a W clone in British Columbia. Region- and province-wide immunization campaigns have been implemented to control these outbreaks using meningococcal C polysaccharide and conjugate vaccines, a quadrivalent ACWY conjugate vaccine, and a serogroup B protein-based vaccine. Meningococcal C conjugate vaccines have been included in routine immunization programs for children, and ACWY conjugate vaccines have been included in school-based programs for adolescents in most jurisdictions. In contrast, serogroup B protein-based vaccines were only recommended and used for high-risk individuals and to control outbreaks. Currently, the immunization schedules adopted in provinces and territories are not uniform. This is not explained by notable epidemiologic differences. Publicly funded immunization programs are the result of a complex decision-making process. Political factors including public opinion, media attention, interest groups' advocacy campaigns, decision-makers' priorities and budgetary constraints have played important roles in shaping meningococcal programs in Canada, and this should be recognized. As the recent occurrence of outbreaks caused by virulent W clones shows, continued investments in epidemiological surveillance at both the provincial and national levels are necessary, so there can be early warning and informed decisions can be made.

A postpartum vaccination promotion intervention using motivational interviewing techniques improves short-term vaccine coverage: PromoVac study.

BACKGROUND: Due to the increasing number of vaccine-hesitant parents, new effective immunization promotion strategies need to be developed to improve the vaccine coverage (VC) of infants. This study aimed to assess the impact of an educational strategy of vaccination promotion based on motivational interviewing (MI) techniques targeting parents and delivered at the maternity ward, for the VC of infants at 3, 5, and 7 months of age. METHODS: An individual educational information session, administered using MI techniques, regarding immunization of infants aged 2, 4, and 6 months was (experimental group) or was not (control group) proposed to parents during the postpartum stay at the maternity ward. Immunization data were obtained through the Eastern Townships Public Health registry for infants at 3, 5, and 7 months of age. Absolute VC increases at 3, 5, and 7 months in the experimental group were calculated and the relative risks with the respective 95% confidence intervals were computed using univariate logistic regression with the generalized estimating equations (GEE) procedure. Multivariate regression using GEE was used to adjust for confounding variables. RESULTS: In the experimental and control groups, 1140 and 1249 newborns were included, respectively. A significant increase in VC of 3.2, 4.9, and 7.3% was observed at 3, 5, and 7 months of age (P < 0.05), respectively. The adjusted relative risk of the intervention's impact on vaccination status at 7 months of age was 1.08 (95% confidence interval: 1.03-1.14) (P = 0.002). CONCLUSIONS: An educational strategy using MI techniques delivered at the maternity ward may be effective in increasing VC of infants at ages 3, 5, and 7 months. MI could be an effective tool to overcome vaccine hesitancy.

Impact of an Immunization Campaign to Control an Increased Incidence of Serogroup B Meningococcal Disease in One Region of Quebec, Canada.

Background: Invasive meningococcal disease (IMD) incidence increased in Quebec, starting in 2003, and was caused by a serogroup B sequence type 269 clone. The Saguenay-Lac-Saint-Jean (SLSJ) region was particularly affected with a rate of 3.4 per 100000 person-years in 2006-2013. In May 2014, an immunization campaign was launched in SLSJ, using the 4-component protein-based meningococcal vaccine (MenB-4C). We aimed to evaluate the impact of the campaign 2 years after its initiation. Methods: Immunization registry data and serogroup B invasive meningococcal disease (B-IMD) cases notified to public health authorities and confirmed by culture or polymerase chain reaction from July 1996 to December 2016 were analyzed, including a multivariate Poisson regression model of incidence rates. Results: By the end of the campaign, 82% of the 59000 targeted SLSJ residents between 2 months and 20 years of age had been immunized. Following the initiation of the campaign, no B-IMD case occurred among vaccinees, whereas 2 cases were reported among unvaccinated adult SLSJ residents, and a third case in an unvaccinated child who had stayed in the region during the week prior to disease onset, in 2015. B-IMD incidence decreased in all other regions in the years 2015-2016 but sporadic cases continued to occur. A multivariate analysis showed a significant effect of the campaign in the SLSJ region (relative B-IMD risk: 0.22; P = .04). Conclusions: Results suggest a high level of protection provided by MenB-4C following mass vaccination at regional level. This, along with reassuring safety data, supports the current recommendations for MenB-4C use for controlling outbreaks caused by clones covered by the vaccine.

Comparison of Phenotypic and Genotypic Approaches to Capsule Typing of Neisseria meningitidis by Use of Invasive and Carriage Isolate Collections.

Neisseria meningitidis serogroup B (MnB) is a leading cause of bacterial meningitis; however, MnB is most commonly associated with asymptomatic carriage in the nasopharyngeal cavity, as opposed to the disease state. Two vaccines are now licensed for the prevention of MnB disease; a possible additional benefit of these vaccines could be to protect against disease indirectly by disrupting nasopharyngeal carriage (e.g., herd protection). To investigate this possibility, accurate diagnostic approaches to characterize MnB carriage isolates are required. In contrast to invasive meningococcal disease (IMD) isolates, which can be readily serogrouped, carriage isolates often lack capsule expression, making standard phenotypic assays unsuitable for strain characterization. Several antibody-based methods were evaluated for their abilities to serogroup isolates and were compared with two genotyping methods (real-time PCR [rt-PCR] and whole-genome sequencing [WGS]) to identify which approach would most accurately ascertain the polysaccharide groups associated with carriage isolates. WGS and rt-PCR were in agreement for 99% of IMD isolates, including those with coding sequences for MnB, MnC, MnW, and MnY, and the phenotypic methods correctly identified serogroups for 69 to 98% of IMD isolates. In contrast, only 47% of carriage isolates were groupable by genotypic methods, due to mutations within the capsule operon; of the isolates identified by genotypic methods, ≤43% were serogroupable with any of the phenotypic methods tested. These observations highlight the difficulties in the serogrouping and capsular genogrouping of meningococcal carriage isolates. Based on our findings, WGS is the most suitable approach for the characterization of meningococcal carriage isolates.

Characterization of invasive Neisseria meningitidis strains from Québec, Canada, during a period of increased serogroup B disease, 2009-2013: phenotyping and genotyping with special emphasis on the non-carbohydrate protein vaccine targets.

BACKGROUND: The epidemiology of invasive meningococcal disease (IMD) in Québec, Canada, has been dominated in the past decade by a clone of serogroup B (MenB) Neisseria meningitidis defined by multi-locus sequence typing (MLST) as sequence type (ST)-269. With the licensure of a new MenB vaccine Bexsero (4CMenB) in Canada, this study characterized invasive N. meningitidis recovered in Québec from 2009 to 2013, with an objective to examine the diversity of the 4CMenB vaccine antigens. Isolates were serogrouped by antisera and genogrouped by PCR, and further typed by whole cell ELISA for serotype and serosubtype antigens. Clonal analysis was done by MLST. Isolates were genotyped by analysis of their 4CMenB vaccine antigen genes of PorA, factor H binding protein (fHbp), Neisserial Heparin Binding Antigen (NHBA), and Neisseria Adhesin A (NadA). RESULTS: Of the 263 IMD isolates analysed, 229, 16, 10, 7, and 1 belonged to MenB, MenY, MenW, MenC, and MenX, respectively. Of the 229 MenB, 159 (69.4 %) were typed as ST-269 clonal complex (CC); and they possessed a restricted number of three fHbp and five nhba gene alleles. Nine N. meningitidis isolates (eight MenB and one MenY) were found to possess at least one gene that encoded for an antigen that matched exactly with protein variants in the 4CMenB vaccine. Two MenB expressed PorA antigen P1.4 and possessed the nhba gene for peptide 2; four other MenB were predicted to have NHBA peptide 2; another two MenB were predicted to encode fHbp peptide 1.1; and a single MenY was found to have nadA gene for NadA peptide 8. In addition, another 172 isolates were found to possess genes for variant 1 fHbp peptides other than peptide 1.1 or NadA variant 1-2/3 peptides other than peptide 8; and therefore, may potentially be covered by 4CMenB. CONCLUSION: The most prevalent clone of N. meningitidis in Quebec was ST-269 CC; and 96 % of the isolates in this CC were predicted to be covered by 4CMenB vaccine. Extensive genetic diversity was found in the other IMD isolates in Québec which might suggest a lower coverage by the vaccine when compared to the ST-269 MenB.

PCV13, PCV15 or PCV20: Which vaccine is best for children in terms of immunogenicity?

Background: The new 15- and 20-valent pneumococcal conjugate vaccines (PCV15 and PCV20) have been marketed on the basis of immunogenicity criteria, one of them being a non-inferior response as compared with the 13-valent vaccine (PCV13). In the past, PCV13 was also authorized on the basis of the same criteria, using the 7-valent vaccine (PCV7) as a reference. Methods: Our aim was to compare the immunogenicity of these three vaccines in toddlers. Functional opsonophagocytic activity (OPA) titre ratios measured in the same and different randomized trials were computed to assess the respective immunogenicity of these four products. Results: Results suggest that both PCV15 and PCV20 are less immunogenic than PCV13 for most common serotypes and that the two new vaccines induce a broadly similar response. The PCV7 vaccine was already slightly more immunogenic than PCV13 meaning that PCV15 and PCV20 compare poorly with PCV7. Results also point towards a reduced immunogenicity of the 2+1 dose schedule compared to the 3+1 dose schedule for PCV13, PCV15 and PCV20. Conclusion: Post-marketing studies will have to be conducted to assess the effectiveness of PCV15 and PCV20 and their real-life benefit over PCV13.

Temporal variations in the serogroup distribution of invasive meningococcal disease in Quebec, Canada, due to emerging unique clade of serogroup Y strain belonging to the Sequence Type-23 clonal complex.

OBJECTIVE: To identify recent trends in invasive meningococcal diseases (IMD) in Quebec, Canada, with a focus on MenY cases and MenY strains. METHODS: IMD cases and MenY strains from January 1, 2015 to August 11, 2023 were analyzed for clonal analysis and prediction of susceptibility to MenB vaccines. MenY strains of ST-23 CC from Quebec were analyzed with global MenY strains by core-genomic multi-locus sequence typing (cg-MLST). RESULTS: Since 2015 the serogroup distribution of IMD in Quebec has shifted from predominantly MenB to mainly MenY, with most (80.9 %) of the latter belonging to ST-23 CC. The median age of MenY cases due to ST-23 CC were statistically younger than MenY cases due to non-ST-23 CC. MenY of ST-23 CC showed genetic diversity and the major genetic cluster were similar to the Swedish Y1 strain. The increase in invasive MenY disease in Quebec was due to a sub-clade of Lineage 23.1 which caused an elevated proportion of severe disease in young adults. CONCLUSION: The increase in invasive MenY disease in Quebec, Canada was driven by the expansion of a sub-clade of Lineage 23.1 in young adults. Currently available quadrivalent A,C,W,Y-conjugate meningococcal vaccines were predicted to provide protection against these strains.

Respiratory infection and otitis media visits in relation to pneumococcal conjugate vaccine use in Saskatchewan.

BACKGROUND: In Saskatchewan, pneumococcal conjugate vaccination (PCV) was offered to high-risk children in 2002 and to all infants in 2005. OBJECTIVE: To describe trends in the frequency of medical visits for lower respiratory tract infection (LRI) and otitis media (OM) in relation to PCV use during the period 1990 to 2008. METHODS: Statistics regarding the number of children covered by the health insurance plan, PCV administration, and medical visits with a diagnostic code associated with LRI and OM were provided by Saskatchewan Health. Monthly rates were analyzed using dynamic state space models. RESULTS: In all series, there was a marked seasonal cycle and some higher-than-expected winter peak values, possibly associated with epidemics of specific respiratory viruses. Three abrupt decreases in baseline rate were observed for LRI and the final one, in February 2007, could be related to the increased proportion of children vaccinated with PCV. There was no statistical correlation between PCV use and OM visit frequency. CONCLUSION: Many environmental, biological and administrative factors may influence health services use, and an effect of low magnitude of a particular vaccine pertaining to nonspecific outcomes could be obscured in time-series analyses.

HISTORIQUE: En Saskatchewan, le vaccin conjugué contre le pneumocoque (VCP) est offert aux enfants très vulnérables depuis 2002, et à tous les nourrissons depuis 2005. OBJECTIF: Décrire les tendances en matière de fréquence de rendezvous chez le médecin pour des infections des voies respiratoires inférieures (IVRI) ou une otite moyenne (OM) par rapport à l'utilisation du VCP entre 1990 et 2008. MÉTHODOLOGIE: Santé Saskatchewan a fourni les statistiques relatives au nombre d'enfants couverts par le régime d'assurance-maladie, à l'administration du VCP et aux rendez-vous médicaux dont le code médical s'associait à une IVRI ou à une OM. Les chercheurs ont analysé les taux mensuels au moyen de modèles dynamiques à espace d'état. RÉSULTATS: Dans toutes les séries, les chercheurs ont constaté un cycle saisonnier marqué et certaines valeurs hivernales de pointe plus élevées que prévu, qui s'associaient peut-être à des épidémies de virus respiratoires particuliers. Ils ont observé trois diminutions abruptes des taux de départ pour ce qui est des IVRI. La dernière, en février 2007, pourrait être liée à l'augmentation de la proportion d'enfants ayant reçu le VCP. Ils n'ont remarqué aucune corrélation statistique entre l'utilisation du VCP et la fréquence des rendez-vous liés à l'OM. CONCLUSION: De nombreux facteurs environnementaux, biologiques et administratifs peuvent influer sur l'utilisation des services de santé, et l'effet marginal d'un certain vaccin sur des issues non spécifiques peut être masqué dans des analyses de séries chronologiques.

Burden of rotavirus disease: A population-based study in Eastern Townships, Quebec.

BACKGROUND: Since July 2010, the National Advisory Committee on Immunization of Canada has recommended rotavirus vaccination for all healthy infants. However, before implementing this vaccine in routine health programs, Canadian provinces need to establish current epidemiological data on rotavirus-associated acute gastroenteritis (AGE). METHODS: A retrospective cohort study of children <5 years of age with AGE from 2002 to 2008 was performed in Eastern Townships, Quebec (population in 2006: 298,780). Data were collected on visits to outpatient clinics, emergency department (ED) visits, hospitalizations (standard and short-stay units) and nosocomial AGE. The winter residual estimation and Brandt methods were used to estimate the proportion of AGE attributable to rotaviruses. RESULTS: During the six-year study period, a total of 1435 hospitalizations, 3631 ED visits and 6220 ambulatory care visits were attributed to AGE. The specific rotavirus burden was estimated to be 449 to 666 for hospitalizations, 1050 to 1361 for ED visits and 1633 to 1687 for outpatient visits. The epidemic curve showed a periodicity with higher incidence in March and April. Short-stay unit hospitalizations represented 58% of all hospitalizations. The annual incidence rate of rotaviruses was estimated to be 50 to 74 per 10,000 children for hospitalizations, 117 to 152 per 10,000 children for ED visits and 182 to 188 per 10,000 children for outpatient visits. CONCLUSION: Most available retrospective studies probably underestimate rotavirus-associated hospitalizations because they do not take into account short-stay unit hospitalizations. Furthermore, these data on emergency and outpatient visits provide an exhaustive appraisal of the rotavirus burden, which serves as crucial information for the evaluation of immunization programs.

HISTORIQUE: Depuis juillet 2010, le Comité consultatif national de l'immunisation recommande de vacciner tous les nourrissons en santé contre le rotavirus. Cependant, avant d'ajouter ce vaccin aux programmes de vaccination systématique, les provinces canadiennes doivent obtenir des données épidémiologiques à jour sur la gastro-entérite aiguë (GEA) associée au rotavirus. MÉTHODOLOGIE: Les chercheurs ont effectué une étude de cohorte rétrospective auprès d'enfants de moins de cinq ans ayant eu une GEA entre 2002 et 2008 en Estrie, au Québec (population de 298 780 habitants en 2006). Ils ont colligé les données aux consultations externes, au département d'urgence (DU), chez les patients hospitalisés (unités standard et de courte durée) et relatives aux cas de GEA nosocomiales. Ils ont utilisé l'estimation hivernale résiduelle et les méthodologies de Brandt pour évaluer la proportion de GEA attribuables aux rotavirus. RÉSULTATS: Pendant la période d'étude de six ans, 1 435 hospitalisations, 3 631 consultations au DU et 6 220 consultations externes étaient attribuables à la GEA. On estimait que le fardeau propre à la GEA se situait entre 449 et 666 pour les hospitalisations, entre 1 050 et 1 361 pour les consultations au DU et entre 1 633 et 1 687 pour les consultations externes. La courbe épidémique a révélé une périodicité à l'incidence plus élevée en mars et avril. Les hospitalisations de courte durée représentaient 58 % de toutes les hospitalisations. On estime que le taux d'incidence annuel des rotavirus oscille entre 50 et 74 cas sur 10 000 enfants sur le plan des hospitalisations, entre 117 et 152 cas sur 10 000 enfants sur le plan des consultations au DU et entre 182 et 188 cas sur 10 000 enfants sur le plan des consultations externes. CONCLUSION: Selon toute probabilité, la plupart des études rétrospectives disponibles sous-estiment le nombre d'hospitalisations associées au rotavirus parce qu'elles ne tiennent pas compte des hospitalisations dans les unités de courte durée. De plus, ces données sur les consultations externes et à l'urgence fournissent une évaluation détaillée du fardeau du rotavirus, qui contient de l'information capitale pour évaluer les programmes de vaccination.

Influenza vaccines may protect against cardiovascular diseases: The evidence is mounting and should be known by the Canadian public health community.

Evidence on the protective effect of influenza vaccines to prevent cardiovascular disease (CVD) is mounting. We identified 28 systematic reviews/meta-analyses on the effect of influenza vaccines on CVD using different research questions, data sources, selection criteria and outcomes. Most results leaned towards a protective effect. Results of recently published experimental and observational studies not included in these reviews were going in the same direction. The evidence is very robust for cardiovascular deaths and nonfatal myocardial infarction in high-risk individuals, but lower for heart failure, arrhythmia, and stroke and also for all outcomes in low-risk adults. There is also limited evidence for pneumococcal polysaccharide vaccines and evidence has to be collected from ongoing trials on respiratory syncytial virus vaccines. Up to now, this effect has not been considered in economic evaluations of influenza vaccines and its inclusion may change CVD results markedly. This effect is not mentioned in the Canadian Immunization Guide and not known by a majority of vaccinators. The objective of this short commentary is to alert the Canadian public health community and to provide information that could be used at the field level to promote the usefulness of influenza vaccines.

Increase of invasive pneumococcal disease in children temporally associated with RSV outbreak in Quebec: a time-series analysis.

Background: Respiratory viruses have been previously suspected to trigger invasive pneumococcal disease (IPD). After progressive non-pharmaceutical interventions (NPI) lifting, an unusual RSV outbreak has been observed in the Fall 2021, raising concerns about the possible consequences on IPD. We aimed to analyse the evolution of IPD incidence across age-groups since NPI lifting, and its temporal association with respiratory viral infections. Methods: We conducted a time-series analysis using 1) population-based IPD surveillance data and 2) statistics from the laboratory surveillance network of respiratory viruses in the province of Quebec, Canada, from January 2013 to January 2022. The monthly IPD incidence was analysed by quasi-Poisson regression models across age-groups. The fraction of IPD incidence change potentially attributable to different viruses in 2021-2022 was estimated. Findings: A total of 7712 IPD cases were included. After a major decrease in IPD incidence from April 2020, IPD rate started to increase in <5-year-old children in October 2021, exceeding the pre-NPI trend (+62%). This was temporally associated with an unusual surge in RSV cases (+53% versus pre-NPI trend). During this 2021-22 surge, the fraction of IPD attributable to RSV dynamics in children was 77% (95% CI [33-100]). By contrast, the IPD incidence in older age-groups remained low, and was temporally associated with influenza dynamics. Interpretation: These results provide new evidence on the role of respiratory viruses in driving IPD dynamics, with possible differences between children and adults. In the coming future, the potential benefit of interventions targeting RSV, such as vaccines, for IPD prevention should be considered. Funding: The study was supported by a grant from the Quebec Ministry of Health and Social Services ('ministère de la Santé et des Services sociaux du Québec'). Publication was supported by a grant from "Fondation de l'Assistance Publique - Hôpitaux de Paris et de l'Alliance « Tous Unis contre le Virus ¼ (Fondation de France/Institut Pasteur/APHP)". N.O. was supported by the ESPID (European Society of Pediatric Infectious Diseases) 2021-2023 Fellowship Award and the 2022 ISPPD (International Symposium on Pneumococci and Pneumococcal Diseases) Robert Austrian Research award.

Effectiveness of thirteen-valent pneumococcal conjugate vaccine to prevent serotype 3 invasive pneumococcal disease in Quebec in children, Canada.

In the province of Quebec, Canada, a 2 + 1 dose pneumococcal conjugate vaccine (PCV) program for children was implemented in 2004. PCV7 was replaced by PCV10 in 2009, by PCV13 in 2011 and by PCV10 in 2018, without catch-up in all instances. The objective was to estimate PCV13 effectiveness to prevent serotype 3 invasive pneumococcal disease in children aged less than 5 years, using 2010-2018 mandatory notification and laboratory surveillance data, an indirect cohort design and multivariate logistic regression models. A total of 29 cases of serotype 3 and 290 non-vaccine serotype cases as controls were analysed. Overall vaccine effectiveness (≥1 dose) was estimated at 59% [-39% to 88%]. During the first year after the last dose effectivness was 88% [47% to 97%] whereas no protection was observed thereafter. There was no trend towards increased effectiveness with the number of doses. PCV13 protection against serotype 3 IPD seems to be short-lived.

Clonal diversity of Streptococcus pneumoniae serotype 19A collected from children < 5 years old in Québec, Canada, 2016-2021.

Streptococcus pneumoniae serotype 19A is a highly diverse, often antimicrobial-resistant Gram-positive bacterium which can cause invasive pneumococcal disease (IPD). In 2021, public health authorities in the Canadian province of Québec observed an increase of serotype 19A IPD in children <5 years. The purpose of this study was to determine the clonal composition of serotype 19A isolates collected from this age group in Québec, from 2016 to 2021. Forty-one and 37 IPD isolates from children <5 years from Québec and the remainder of Canada, respectively, were sequenced using the Illumina NextSeq platform. Phylogenetic analysis using SNVPhyl identified three clusters, corresponding to three common clones of serotype 19A: CC199, CC320 and ST695. CC199, predominantly represented by ST416, accounted for similar proportions of serotype 19A isolates collected from children in Québec (19.5 %) and other Canadian jurisdictions (OCJs, 21.6 %), with significant presence of ermB (62.5 % and 60 % of ST416 isolates, respectively). CC320 was more commonly identified from OCJs in comparison to Québec (18.9 % vs. 7.3 %, respectively), but were highly antimicrobial-resistant regardless of region. ST695 was the most common clone of serotype 19A collected in Québec from children <5 years, representing 65.9 % of isolates collected over the study period (40.5 % of isolates collected in OCJs). Phylogenetic analysis identified geographical differences in ST695 across Canada; including a large clade specific to Québec (with both susceptible and macrolide-resistant [ermB] subclades), and a separate macrolide-resistant (mefA) clade associated with OCJs. The Québec-specific ermB-ST695 clone represented 48.1 % of ST695 collected from the province. Continued genomic surveillance of S. pneumoniae serotype 19A is required to: i) track the prevalence and clonal composition of serotype 19A in Québec in future years; ii) characterize the clonal distribution of serotype 19A in adult populations; and iii) monitor whether the currently geographically restricted ermB-ST695 clone observed in Québec expands to OCJs.