Single-dose Effectiveness of Mpox Vaccine in Quebec, Canada: Test-negative Design With and Without Adjustment for Self-reported Exposure Risk.

INTRODUCTION: During the 2022 mpox outbreak, the province of Quebec, Canada, prioritized first doses for pre-exposure vaccination of people at high mpox risk, delaying second doses due to limited supply. We estimated single-dose mpox vaccine effectiveness (VE) adjusting for virus exposure risk based only on surrogate indicators available within administrative databases (eg, clinical record of sexually transmitted infections) or supplemented by self-reported risk factor information (eg, sexual contacts). METHODS: We conducted a test-negative case-control study between 19 June and 24 September 2022. Information from administrative databases was supplemented by questionnaire collection of self-reported risk factors specific to the 3-week period before testing. Two study populations were assessed: all within the administrative databases (All-Admin) and the subset completing the questionnaire (Sub-Quest). Logistic regression models adjusted for age, calendar-time and exposure-risk, the latter based on administrative indicators only (All-Admin and Sub-Quest) or with questionnaire supplementation (Sub-Quest). RESULTS: There were 532 All-Admin participants, of which 199 (37%) belonged to Sub-Quest. With exposure-risk adjustment based only on administrative indicators, single-dose VE estimates were similar among All-Admin and Sub-Quest populations at 35% (95% confidence interval [CI]:-2 to 59) and 30% (95% CI:-38 to 64), respectively. With adjustment supplemented by questionnaire information, the Sub-Quest VE estimate increased to 65% (95% CI:1-87), with overlapping confidence intervals. CONCLUSIONS: Using only administrative data, we estimate one vaccine dose reduced the mpox risk by about one-third; whereas, additionally adjusting for self-reported risk factor information revealed greater vaccine benefit, with one dose instead estimated to reduce the mpox risk by about two-thirds. Inadequate exposure-risk adjustment may substantially under-estimate mpox VE.

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.

Do intentions lead to action? Results of a longitudinal study assessing determinants of Tdap vaccine uptake during pregnancy in Quebec, Canada.

BACKGROUND: In Canada, vaccination against pertussis (Tdap) during pregnancy has been recommended since 2018, with suboptimal uptake. We aimed to assess the determinants of intention and uptake of Tdap vaccine among pregnant women in Quebec. METHODS: Participants (< 21 weeks of pregnancy) were recruited in four Quebec regions. Two online surveys were administered during pregnancy (< 21 weeks and > 35 weeks). One measured vaccination intention and the other assessed the actual decision. Questionnaires were informed by the Theory of Planned Behaviour (TPB). We used logistic multivariate analysis to identify determinants of Tdap vaccination uptake during pregnancy using responses to both questionnaires. RESULTS: A total of 741 women answered the first survey and 568 (76.7%), the second survey. In the first survey most participants intended to receive the Tdap vaccine during their pregnancy (76.3%) and in the second survey, 82.4% reported having been vaccinated against Tdap during their pregnancy. In multivariate analysis, the main determinants of vaccine uptake were: a recommendation from a healthcare provider (OR = 7.6), vaccine intention (OR = 6.12), social norms (or thinking that most pregnant women will be vaccinated (OR = 3.81), recruitment site (OR = 3.61 for General Family Medicine unit) perceived behavioral control (or low perceived barriers to access vaccination services, (OR = 2.32) and anticipated feeling of guilt if not vaccinated (OR = 2.13). Safety concerns were the main reason for not intending or not receiving the vaccine during pregnancy. CONCLUSION: We observed high vaccine acceptance and uptake of pertussis vaccine in pregnancy. The core components of the TPB (intention, social norms and perceived behavioral control) were all predictors of vaccine uptake, but our multivariate analysis also showed that other determinants were influential: being sufficiently informed about Tdap vaccination, not having vaccine safety concerns, and anticipated regret if unvaccinated. To ensure high vaccine acceptance and uptake in pregnancy, strong recommendations by trusted healthcare providers and ease of access to vaccination services remain instrumental.

SARS-CoV-2 seroprevalence in health care workers from 10 hospitals in Quebec, Canada: a cross-sectional study.

BACKGROUND: The COVID-19 pandemic has disproportionately affected health care workers. We sought to estimate SARS-CoV-2 seroprevalence among hospital health care workers in Quebec, Canada, after the first wave of the pandemic and to explore factors associated with SARS-CoV-2 seropositivity. METHODS: Between July 6 and Sept. 24, 2020, we enrolled health care workers from 10 hospitals, including 8 from a region with a high incidence of COVID-19 (the Montréal area) and 2 from low-incidence regions of Quebec. Eligible health care workers were physicians, nurses, orderlies and cleaning staff working in 4 types of care units (emergency department, intensive care unit, COVID-19 inpatient unit and non-COVID-19 inpatient unit). Participants completed a questionnaire and underwent SARS-CoV-2 serology testing. We identified factors independently associated with higher seroprevalence. RESULTS: Among 2056 enrolled health care workers, 241 (11.7%) had positive SARS-CoV-2 serology. Of these, 171 (71.0%) had been previously diagnosed with COVID-19. Seroprevalence varied among hospitals, from 2.4% to 3.7% in low-incidence regions to 17.9% to 32.0% in hospitals with outbreaks involving 5 or more health care workers. Higher seroprevalence was associated with working in a hospital where outbreaks occurred (adjusted prevalence ratio 4.16, 95% confidence interval [CI] 2.63-6.57), being a nurse or nursing assistant (adjusted prevalence ratio 1.34, 95% CI 1.03-1.74) or an orderly (adjusted prevalence ratio 1.49, 95% CI 1.12-1.97), and Black or Hispanic ethnicity (adjusted prevalence ratio 1.41, 95% CI 1.13-1.76). Lower seroprevalence was associated with working in the intensive care unit (adjusted prevalence ratio 0.47, 95% CI 0.30-0.71) or the emergency department (adjusted prevalence ratio 0.61, 95% CI 0.39-0.98). INTERPRETATION: Health care workers in Quebec hospitals were at high risk of SARS-CoV-2 infection, particularly in outbreak settings. More work is needed to better understand SARS-CoV-2 transmission dynamics in health care settings.

Vaccination Against Influenza in Pregnancy: A Survey of Canadian Maternity Care Providers.

OBJECTIVE: Influenza vaccine uptake among Canadian pregnant individuals is suboptimal. Failure to incorporate vaccination into routine prenatal care and a lack of recommendations from healthcare providers are recognized as barriers to vaccination. The aim of this study was to assess Canadian maternity care providers' knowledge, attitudes, and practices regarding influenza vaccination in pregnancy. METHODS: A cross-sectional Web-based questionnaire was sent during July and August 2017 to family physicians, obstetricians-gynaecologists, midwives, pharmacists, and nurses who care for pregnant individuals. A multivariable logistic regression model was used to determine variables independently associated with providers' recommendation of the influenza vaccine in pregnancy. RESULTS: The analysis included 1061 providers. Most participants (85%) reported being vaccinated against influenza themselves, and 72% reported recommending the influenza vaccine to all of their pregnant patients during the previous influenza season. Participants' attitudes regarding influenza vaccination during pregnancy were generally positive: 64% strongly agreed that pregnant individuals are at an increased risk of complications from influenza, and 69% strongly agreed that it is safe to vaccinate pregnant individuals against influenza. The main determinants of participants' recommendations for influenza vaccination to all pregnant patients were following official recommendations on influenza vaccination, discussing vaccines with most or all pregnant individuals seen in their practice, and being vaccinated themselves during the previous influenza season. CONCLUSION: Enhancing influenza vaccine uptake in pregnancy is largely dependent on maternity care providers' recommendations. This study provides valuable insight on providers' knowledge, attitudes, and practices.

Antigenic and genetic characterization of Bordetella pertussis recovered from Quebec, Canada, 2002-2014: detection of a genetic shift.

Despite vaccination, cyclical peaks of Bordetella pertussis incidence rates are still observed in Canada and other developed countries, making pertussis one of the most prevalent vaccine preventable bacterial diseases. In the postacellular vaccine era, evolution of bacterial strains has resulted in strains with altered vaccine antigens. Previous Canadian studies have focused on isolates mainly from the provinces of Ontario and Alberta, with only small numbers of isolates from other provinces. Therefore, in this study, we examined a larger sample (n = 52) of isolates from Quebec, Canada, between 2002 and 2014. Isolates were characterized by serotype, sequence type, and prevalence of pertactin deficiency. The Quebec isolates shared characteristics similar to other Canadian isolates and to isolates circulating globally. Although pertactin-deficient isolates were not present, a significant shift in sequence type was observed in more recent years. This study highlights the importance of continually monitoring disease-causing isolates to track evolutionary trends and gain a better understanding of the molecular epidemiology of pertussis in Canada.

Antibody concentrations against the infecting serotype in vaccinated and unvaccinated children with invasive pneumococcal disease in the United Kingdom, 2006-2013.

BACKGROUND: This study aimed to estimate, following invasive pneumococcal disease (IPD), the proportion of children with protective immunoglobulin G (IgG) concentrations against the infecting serotype compared with other vaccine serotypes, and to assess risk of recurrent IPD. METHODS: Pneumococcal antibody concentrations were available for 413 children with vaccine-type IPD diagnosed during 2006-2013. We compared serotype-specific IgG concentrations against the infecting vs other vaccine serotypes, after adjusting for confounders such as age using multilevel analyses. RESULTS: After IPD, a higher proportion of vaccine-naive children had IgG concentrations ≥0.35 µg/mL against their infecting serotype than other vaccine serotypes (51% vs 36%; P < .001). In contrast, among children immunized with pneumococcal conjugate vaccine (PCV) both before and after IPD, the proportion with IgG concentrations ≥0.35 µg/mL against the infecting serotype was lower compared with other vaccine serotypes (71% vs 98%; P < .001). These children also had lower IgG geometric mean concentrations (GMCs) against the infecting serotype (2.22 µg/mL) vs other vaccine serotypes (15.64 µg/mL) in multilevel models (IgG GMC ratio, 0.24; 95% confidence interval, .18-.32), although their IgG GMC was higher compared with vaccine-naive children. Vaccinated children with IgG concentrations <0.35 µg/mL against their infecting serotype generally remained unresponsive despite further vaccine doses. However, recurrent IPD with the same infecting serotype was rare (7/3030 children [0.2%]) and not associated with unresponsiveness. CONCLUSIONS: Vaccination with PCV before and/or after IPD was associated with lower IgG concentrations against the infecting serotype compared with other vaccine serotypes, but recurrent IPD was rare. Further studies are needed to understand this phenomenon in immunized children.

Antenatal tetanus, diphtheria, and acellular pertussis (Tdap) immunization and risk of serogroup 19 IPD in children: An indirect cohort study.

The tetanus-diphtheria-acellular pertussis (Tdap) vaccine has been indicated for pregnant women in Quebec, Canada since 2018. Recent literature suggests maternal Tdap interferes with the pneumococcal vaccine response in children exposed in utero because of maternally transferred anti-diphtheria antibodies, a phenomenon known as blunting. Using an indirect cohort study, we investigated whether maternal Tdap vaccination could alter the protection of PCV vaccines against serotype 19A/F IPD (conjugated to diphtheria toxoid in PCV10). Thirty-seven immunized IPD cases (serotype 19A/F) and 90 immunized IPD controls (non-vaccine serotypes) were analyzed using multivariate logistic regression. Our analyses did not identify antenatal Tdap exposure as a risk factor for IPD in vaccinated children, with and odds ratio close to the null (odds ratio = 0.82, 95%CI = 0.32-2.07). As this study is the first to assess the impact of maternal immunization on pneumococcal disease risk, future investigations involving a larger number of cases should be conducted to confirm or infirm our findings.

Neighborhood-level vaccine impact on COVID-19 infection and hospital admission in Quebec, Canada, during the Delta and early Omicron periods.

OBJECTIVE: To assess the impact of COVID-19 vaccination on COVID-19 infection and hospitalisation at the population-level, and to assess the indirect effects of vaccination in the province of Quebec, Canada. METHODS: We performed a time-stratified, neighborhood-level ecologic study. The exposure was neighborhood-level vaccination (primary series) coverage; outcomes were COVID-19 infection and hospitalisation rates. We used robust Poisson regression to estimate weekly relative rates of infection and hospitalisation versus vaccination. RESULTS: Higher vaccination coverage was associated with lower COVID-19 infection rates from July 18-December 4 for the year 2021 (Delta period) (RR≈0.46 [0.39; 0.54] - 0.94 [0.83; 1.05], 85-100% vs. 60-74% coverage). From December 5-December 25, this association reversed (RR≈1.28 [1.16; 1.41] - 1.41 [1.31; 1.52]), possibly due to the Omicron variant, social behaviors and accumulation of susceptibles in more vaccinated neighborhoods. Vaccine impact against hospitalisation was maintained throughout (RR≈0.43 [0.29; 0.65] - 0.88 [0.64; 1.22]). Vaccination provided substantial indirect protection (RR≈0.43 [0.34; 0.54] - 0.81 [0.65; 1.03]). CONCLUSIONS: This study confirmed the protective impact of vaccination against severe disease regardless of variant, at the population level. Ecological analyses are a valuable strategy to evaluate vaccination programs. Population-level effects can have substantial effects and should be accounted for in public health and vaccination program planning.

Burden of disease of respiratory syncytial virus in infants, young children and pregnant women and people.

Background: Passive immunization products for infants and pregnant women and people have sparked interest in understanding Canada's respiratory syncytial virus (RSV) burden. This rapid review examines RSV burden of disease in infants, young children and pregnant women and people. Methods: Electronic databases were searched to identify studies and systematic reviews reporting data on outpatient visits, hospitalizations, intensive care unit admissions, deaths and preterm labour associated with RSV. We also contacted Canadian respiratory virus surveillance experts for additional data. Results: Overall, 17 studies on infants and young children and 10 studies on pregnant women and people were included, in addition to primary surveillance data from one Canadian territory (Yukon). There were higher rates of medical utilization for infants than older children. Hospitalization rates were highest in infants under six months (more than 1% annually), with 5% needing intensive care unit admission, but mortality was low. Severe outcomes often occurred in healthy full-term infants and burden was higher than influenza. Respiratory syncytial virus attack rate was 10%-13% among pregnant women and people. Only one study found a higher hospitalization rate in pregnant women and people compared to non-pregnant women and people. Limited evidence was found on intensive care unit admission, death and preterm birth for pregnant women and people. Conclusion: While risk of severe outcomes is larger in high-risk infants and children, healthcare burden is greatest in healthy term infants. The RSV severity for pregnant women and people appears to be similar to that for non-pregnant women and people.

Vaccination during pregnancy and modulation of IgG response to pertussis vaccines in infants: The impact of different vaccine formulations.

The IgG response following infant diphtheria-tetanus-acellular pertussis (DTaP) immunization is influenced by the formulation of the infant and/or the adult vaccine (Tdap) given during pregnancy. DTaP vaccines containing either 3 (DTaP3) or 5 (DTaP5) pertussis antigens are commonly used. By conducting a secondary analysis of a large randomized controlled trial, we compared IgG levels against pertussis vaccine antigens in children of Td- and Tdap5-vaccinated mothers, after stratifying by infant vaccine formulation. After immunization with a primary series of DTaP5, but not DTaP3, IgG GMCs against pertussis antigens were significantly lower in infants of Tdap-immunized mothers compared with infants of Td-vaccinated mothers (pertussis toxin: GMC = 52.3[Tdap5] vs 83.5[Td], p < 0.001). Before and after the DTaP booster dose, IgG GMCs were similar in infants of Tdap- and Td-immunized mothers specifically when infants received the DTaP3 vaccine. The combination of the TdaP5 vaccine for mothers and the DTaP3 vaccine for children could attenuate Tdap-associated immunomodulation.

Live virus neutralizing antibodies against pre and post Omicron strains in food and retail workers in Québec, Canada.

Background: Measuring the ability of SARS-CoV-2 antibodies to neutralize live viruses remains an effective approach to quantify the level of protection of individuals. We assessed the neutralization activity against the ancestral SARS-CoV-2, Delta, Omicron BA.1, BA.2, BA.2.12.1, BA.4 and BA.5 strains, in 280 vaccinated restaurant/bar, grocery and hardware store workers in Québec, Canada. Methods: Participants were recruited during the emergence of Omicron BA.1 variant. The neutralizing activity of participant sera was assessed by microneutralization assay. Results: Serum neutralizing antibody (NtAb) titers of all participants against the ancestral SARS-CoV-2 strain were comparable with those against Delta variant (ranges of titers 10-2032 and 10-2560, respectively), however, their response was significantly reduced against Omicron BA.1, BA2, BA.2.12.1, BA.4 and BA.5 (10-1016, 10-1016, 10-320, 10-80 and 10-254, respectively). Individuals who received 2 doses of vaccine had significantly reduced NtAb titers against all SARS-CoV-2 strains compared to those infected and then vaccinated (≥1 dose), vaccinated (≥2 doses) and then infected, or those who received 3 doses of vaccine. Participants vaccinated with 2 or 3 doses of vaccine and then infected had the highest NtAb titers against all SARS-CoV-2 strains tested. Conclusion: We assessed for the first time the NtAb response in food and retail workers. We found that vaccination prior to the emergence of Omicron BA.1 was associated with higher neutralizing activity against pre-Omicron variants, suggesting the importance of updating vaccines to increase antibody response against new SARS-CoV-2 variants. Vaccination followed by infection was associated with higher neutralizing activity against all SARS-CoV-2 strains tested.

The safety of seasonal influenza vaccination among adults prescribed immune checkpoint inhibitors: A self-controlled case series study using administrative data.

BACKGROUND: Immune checkpoint inhibitor (ICI) therapy for patients undergoing cancer treatment carries a risk of severe immune-related adverse events (IRAEs). Questions remain about whether seasonal influenza vaccination might increase the risk of developing IRAEs among these patients given that vaccines are immunomodulatory. Previous vaccine safety studies on patients with cancer prescribed ICI therapy have demonstrated conflicting results. METHODS: Using health administrative data from Ontario, Canada among adults diagnosed with cancer who had been prescribed ICI therapy and who had received an influenza vaccine from 2012 to 2019, we conducted a self-controlled case series study. The pre-vaccination control period started 42-days post-ICI initiation until 14-days prior to vaccination, the risk period was 1-42 days post-vaccination, and the post-vaccination control period was after the risk period until ICI discontinuation or a maximum period of two years. Emergency department (ED) visit(s) and/or hospitalization for any cause after ICI initiation was used to identify severe IRAEs. We fitted a fixed-effects Poisson regression model accounting for seasonality and calendar time to estimate relative incidence of IRAEs between risk and control periods. RESULTS: We identified 1133 records of cancer patients who received influenza vaccination while prescribed ICI therapy. Most were aged ≥ 66 years (73 %), were male (63 %), had lung cancer (54 %), and had received ICI therapy with a programmed cell death protein 1(PD-1) inhibitor (91 %). A quarter (26 %) experienced an ED visit and/or hospitalization during the observation period. Rates of ED visits and/or hospitalizations in the risk vs. control periods were similar, with an incidence rate ratio of 1.04 (95 % CI: 0.75-1.45). Subgroup and sensitivity analyses yielded similar results. CONCLUSION: Seasonal influenza vaccination was not associated with an increased incidence of ED visit or hospitalization among adults with cancer treated with ICI therapy and our results support further evidence of vaccine safety.

Contamination of public whirlpool spas: factors associated with the presence of Legionella spp., Pseudomonas aeruginosa and Escherichia coli.

This work explores the factors associated with contamination of public spas by Legionella spp., Pseudomonas aeruginosa and Escherichia coli. Physicochemical and microbiological parameters were measured in water samples from 95 spas inQuébec, Canada. Spa maintenance was documented by a questionnaire. Legionella spp. were detected in 23% of spas, P. aeruginosa in 41% and E. coli in 2%. Bacteria were found in concerning concentrations (Legionella spp. ≥ 500 CFU/l, P. aeruginosa ≥ 51 CFU/100 ml or E. coli ≥ 1 CFU/100 ml) in 26% ofspas. Observed physicochemical parameters frequently differed from recommended guidelines. The following factors decreased the prevalence of concerning microbial contamination: a free chlorine concentration ≥ 2 mg/l or total bromine ≥ 3 mg/l (p = 0.001), an oxidation-reduction potential (ORP) > 650 mV (p = 0.001), emptying and cleaning the spa at least monthly (p = 0.019) and a turbidity ≤ 1 NTU (p = 0.013). Proper regulations and training of spa operators are critical for better maintenance of these increasingly popular facilities.

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.

Tdap vaccine in pregnancy and immunogenicity of pertussis and pneumococcal vaccines in children: What is the impact of different immunization schedules?

BACKGROUND: In 2019, the 3 + 1 schedule for children's vaccination (2-4-6-18 months old) was changed for a reduced 2 + 1 schedule (2-4-12 months old) in Quebec, Canada. We compared the post-booster anti-pertussis and anti-pneumococcus IgG antibody concentrations among children of Tdap-vaccinated and unvaccinated mothers for different vaccine schedules and vaccine formulations. METHODS: We conducted an observational cohort study. An invitation letter to potential participants was provided during a routine vaccination visit. Children's blood samples were analyzed post-booster at 13 (2 + 1 schedule) or 19 (3 + 1 schedule) months of age for antibodies against pertussis antigens (pertussis toxin (PT), filamentous hemagglutinin (FHA) and pertactin (PRN)) and pneumococcal antigens (serotypes 4, 18C, 19A, and 19F). IgG concentrations among children of Tdap-vaccinated and unvaccinated mothers for each vaccination schedule were compared using geometric mean concentrations (GMCs) and GMC ratios (GMRs), adjusting for potentially immune-response-influencing factors (aGMR). Serotype-specific pneumococcal seroprotection rates were also compared. RESULTS: A total of 360 children were included for pertussis analysis and 248 for pneumococcal analysis. For the 2 + 1 schedule, 13-month-old children of Tdap-vaccinated mothers had lower GMCs against PT, FHA, and PRN, with aGMR (95 %CI) of 0.77 (0.65-0.90), 0.66 (0.55-0.79), 0.72 (0.52-0.99), respectively. For the 3 + 1 schedule, at 19 months old, the interference appeared to be attenuated (higher aGMR values). GMCs against PT were slightly higher in the 3 + 1 than the 2 + 1 schedule: 126.5 IU/ml vs 91.6 IU/ml; aGMR = 1.27. GMCs against PT, FHA and PRN were slightly higher among children who received Infanrix hexa® compared to those who received Pediacel® at 12 months old. For pneumococcal antibodies, at 13 months old, there was no strong evidence of immune interference in children of Tdap-vaccinated mothers. CONCLUSION: Infant vaccination schedule may influence immune interference associated with maternal Tdap vaccination. More studies are needed to assess the clinical impact of this interference on children's protection.

Effectiveness of previous infection-induced and vaccine-induced protection against hospitalisation due to omicron BA subvariants in older adults: a test-negative, case-control study in Quebec, Canada.

BACKGROUND: Older adults (aged ≥60 years) were prioritised for COVID-19 booster vaccination due to severe outcome risk, but the risk for this group is also affected by previous SARS-CoV-2 infection and vaccination. We estimated vaccine effectiveness against omicron-associated hospitalisation in older adults by previously documented infection, time since last immunological event, and age group. METHODS: This was a population-based test-negative case-control study done in Quebec, Canada, during BA.1 dominant (December, 2021, to March, 2022), BA.2 dominant (April to June, 2022), and BA.4/5 dominant (July to November, 2022) periods using provincial laboratory, immunisation, hospitalisation, and chronic disease surveillance databases. We included older adults (aged ≥60 years) with symptoms associated with COVID-19 who were tested for SARS-CoV-2 in acute-care hospitals. Cases were defined as patients who were hospitalised for COVID-19 within 14 days after testing positive; controls were patients who tested negative. Analyses spanned 3-14 months after last vaccine dose or previous infection. Logistic regression models compared COVID-19 hospitalisation risk by mRNA vaccine dose and previous infection versus unvaccinated and infection-naive participants. FINDINGS: Between Dec 26, 2021, and Nov 5, 2022, we included 174 819 specimens (82 870 [47·4%] from men and 91 949 [52·6%] from women; from 8455 cases and 166 364 controls), taken from 2951 cases and 48 724 controls in the BA.1 period; 1897 cases and 41 702 controls in the BA.2 period; and 3607 cases and 75 938 controls in the BA.4/5 period. In participants who were infection naive, vaccine effectiveness against hospitalisation improved with dose number, consistent with a shorter median time since last dose, but decreased with more recent omicron subvariants. Four-dose vaccine effectiveness was 96% (95% CI 93-98) during the BA.1 period, 84% (81-87) during the BA.2 period, and 68% (63-72) during the BA.4/5 period. Regardless of dose number (two to five doses) or timing since previous infection, hybrid protection was more than 90%, persisted for at least 6-8 months, and did not decline with age. INTERPRETATION: Older adults with both previous SARS-CoV-2 infection and two or more vaccine doses appear to be well protected for a prolonged period against hospitalisation due to omicron subvariants, including BA.4/5. Ensuring that older adults who are infection naive remain up to date with vaccination might reduce COVID-19 hospitalisations most efficiently. FUNDING: Ministère de la Santé et des Services Sociaux du Québec. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.