The Changing Landscape of Respiratory Viruses Contributing to Hospitalizations in Quebec, Canada: Results From an Active Hospital-Based Surveillance Study.

BACKGROUND: A comprehensive description of the combined effect of SARS-CoV-2 and respiratory viruses other than SARS-CoV-2 (ORVs) on acute respiratory infection (ARI) hospitalizations is lacking. OBJECTIVE: This study aimed to compare the viral etiology of ARI hospitalizations before the pandemic (8 prepandemic influenza seasons, 2012-13 to 2019-20) and during 3 pandemic years (periods of increased SARS-CoV-2 and ORV circulation in 2020-21, 2021-22, and 2022-23) from an active hospital-based surveillance network in Quebec, Canada. METHODS: We compared the detection of ORVs and SARS-CoV-2 during 3 pandemic years to that in 8 prepandemic influenza seasons among patients hospitalized with ARI who were tested systematically by the same multiplex polymerase chain reaction (PCR) assay during periods of intense respiratory virus (RV) circulation. The proportions of infections between prepandemic and pandemic years were compared by using appropriate statistical tests. RESULTS: During prepandemic influenza seasons, overall RV detection was 92.7% (1384/1493) (respiratory syncytial virus [RSV]: 721/1493, 48.3%; coinfections: 456/1493, 30.5%) in children (<18 years) and 62.8% (2723/4339) (influenza: 1742/4339, 40.1%; coinfections: 264/4339, 6.1%) in adults. Overall RV detection in children was lower during pandemic years but increased from 58.6% (17/29) in 2020-21 (all ORVs; coinfections: 7/29, 24.1%) to 90.3% (308/341) in 2021-22 (ORVs: 278/341, 82%; SARS-CoV-2: 30/341, 8.8%; coinfections: 110/341, 32.3%) and 88.9% (361/406) in 2022-23 (ORVs: 339/406, 84%; SARS-CoV-2: 22/406, 5.4%; coinfections: 128/406, 31.5%). In adults, overall RV detection was also lower during pandemic years but increased from 43.7% (333/762) in 2020-21 (ORVs: 26/762, 3.4%; SARS-CoV-2: 307/762, 40.3%; coinfections: 7/762, 0.9%) to 57.8% (731/1265) in 2021-22 (ORVs: 179/1265, 14.2%; SARS-CoV-2: 552/1265, 43.6%; coinfections: 42/1265, 3.3%) and 50.1% (746/1488) in 2022-23 (ORVs: 409/1488, 27.5%; SARS-CoV-2: 337/1488, 22.6%; coinfections: 36/1488, 2.4%). No influenza or RSV was detected in 2020-21; however, their detection increased in the 2 subsequent years but did not reach prepandemic levels. Compared to the prepandemic period, the peaks of RSV hospitalization shifted in 2021-22 (16 weeks earlier) and 2022-23 (15 weeks earlier). Moreover, the peaks of influenza hospitalization shifted in 2021-22 (17 weeks later) and 2022-23 (4 weeks earlier). Age distribution was different compared to the prepandemic period, especially during the first pandemic year. CONCLUSIONS: Significant shifts in viral etiology, seasonality, and age distribution of ARI hospitalizations occurred during the 3 pandemic years. Changes in age distribution observed in our study may reflect modifications in the landscape of circulating RVs and their contribution to ARI hospitalizations. During the pandemic period, SARS-CoV-2 had a low contribution to pediatric ARI hospitalizations, while it was the main contributor to adult ARI hospitalizations during the first 2 seasons and dropped below ORVs during the third pandemic season. Evolving RVs epidemiology underscores the need for increased scrutiny of ARI hospitalization etiology to inform tailored public health recommendations.

Influenza Hospitalization Burden by Subtype, Age, Comorbidity, and Vaccination Status: 2012-2013 to 2018-2019 Seasons, Quebec, Canada.

BACKGROUND: Influenza immunization programs aim to reduce the risk and burden of severe outcomes. To inform optimal program strategies, we monitored influenza hospitalizations over 7 seasons, stratified by age, comorbidity, and vaccination status. METHODS: We assembled data from 4 hospitals involved in an active surveillance network with systematic collection of nasal samples and polymerase chain reaction testing for influenza virus in all patients admitted through the emergency department with acute respiratory infection during the 2012-2013 to 2018-2019 influenza seasons in Quebec, Canada. We estimated seasonal, population-based incidence of influenza-associated hospitalizations by subtype predominance, age, comorbidity, and vaccine status, and derived the number needed to vaccinate to prevent 1 hospitalization per stratum. RESULTS: The average seasonal incidence of influenza-associated hospitalization was 89/100 000 (95% confidence interval, 86-93), lower during A(H1N1) (49-82/100 000) than A(H3N2) seasons (73-143/100 000). Overall risk followed a J-shaped age pattern, highest among infants 0-5 months and adults ≥75 years old. Hospitalization risks were highest for children <5 years old during A(H1N1) but for highest adults aged ≥75 years during A(H3N2) seasons. Age-adjusted hospitalization risks were 7-fold higher among individuals with versus without comorbid conditions (214 vs 30/100 000, respectively). The number needed to vaccinate to prevent hospitalization was 82-fold lower for ≥75-years-olds with comorbid conditions (n = 1995), who comprised 39% of all hospitalizations, than for healthy 18-64-year-olds (n = 163 488), who comprised just 6% of all hospitalizations. CONCLUSIONS: In the context of broad-based influenza immunization programs (targeted or universal), severe outcome risks should be simultaneously examined by subtype, age, comorbidity, and vaccine status. Policymakers require such detail to prioritize promotional efforts and expenditures toward the greatest and most efficient program impact.

Relative Severity of Common Human Coronaviruses and Influenza in Patients Hospitalized With Acute Respiratory Infection: Results From 8-Year Hospital-Based Surveillance in Quebec, Canada.

BACKGROUND: Few data exist concerning the role of common human coronaviruses (HCoVs) in patients hospitalized for acute respiratory infection (ARI) and the severity of these infections compared with influenza. METHODS: Prospective data on the viral etiology of ARI hospitalizations during the peaks of 8 influenza seasons (from 2011-2012 to 2018-2019) in Quebec, Canada, were used to compare patients with HCoV and those with influenza infections; generalized estimation equations models were used for multivariate analyses. RESULTS: We identified 340 HCoV infections, which affected 11.6% of children (n = 136) and 5.2% of adults (n = 204) hospitalized with ARI. The majority of children (75%) with HCoV infections were also coinfected with other respiratory viruses, compared with 24% of the adults (P < .001). No deaths were recorded in children; 5.8% of adults with HCoV monoinfection died, compared with 4.2% of those with influenza monoinfection (P = .23). The risk of pneumonia was nonsignificantly lower in children with HCoV than in those with influenza, but these risks were similarly high in adults. Markers of severity (length of stay, intensive care unit admissions, and case-fatality ratio) were comparable between these infections in multivariate analyses, in both children and adults. CONCLUSIONS: In children and adults hospitalized with ARI, HCoV infections were less frequent than influenza infections, but were as severe as influenza monoinfections.

A systematic literature review of the recombinant subunit herpes zoster vaccine use in immunocompromised 18-49 year old patients.

BACKGROUND: The adjuvanted recombinant zoster vaccine (RZV) is indicated for prevention of herpes zoster (HZ) in adults aged ≥50 years. Questions regarding the use of RZV in immunocompromised patients < 50-year-old, who are at increased risk for HZ, were raised. OBJECTIVES: The objective of this systematic review was to consolidate existing evidences on safety, immunogenicity and efficacy of RZV in immunocompromised adults aged 18-49 years. METHODS: Four databases were searched. Preferred Reporting Items for Systematic review and Meta-Analysis Protocols (PRISMA-P) guidelines were followed. Screening and classification of search items was performed using the web-based platform DistillerSR. RESULTS: The search identified 1389 potentially relevant records. Six studies fulfilled inclusion criteria. The proportion of patients aged 18-49 varied between 23 and 62%. Pain at injection site (98.6%) and fatigue (75.3%) were the most common adverse events. The proportion of patients reporting serious adverse events (SAEs) ranged between 8.1 and 30.8% in RZV and between 4.1 and 36.5% in placebo groups. SAEs deemed related to vaccination were reported in < 1% of patients in both RZV and placebo groups. The proportion of patients that experienced clinically significant underlying disease-related events ranged between 0.0 and 20.0% in RZV and 0.0 and 26.7% in placebo groups. The humoral and cell-mediated immune response rate ranged between 65.4 and 96.2% and 50.0-93.0%, respectively. Vaccine efficacy in hematopoietic stem cell transplant patients was 72% (95%CI, 39-88%) in 18-49-year-olds and 67% (95%CI, 53-78%) in ≥ 50-year-olds (median follow-up 21 months). Vaccine efficacy in ≥ 18-year-old patients with hematologic malignancies was estimated at 87.2% (95%CI, 44.3-98.6%) up to 13 months post-vaccination. CONCLUSIONS: Results suggest that RZV has an acceptable safety profile and induces immunity in an important proportion of ≥ 18-year-old immunocompromised patients. Longer follow-up studies are warranted to assess the duration of RZV induced immunity in immunocompromised patients.

Impact of the adolescent pertussis booster dose on the incidence of pertussis in British Columbia and Quebec, Canada.

Impact of an adolescent tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine program was assessed in the provinces of British Columbia and Quebec, Canada. In both provinces, the Tdap booster has been in place since 2004, targeting Grade 9 students (14-15-years-of-age). Incidence rate ratios (IRRs) standardizing notification rates among teens 15-19-years-old to infants <1-year-old decreased following introduction of the Tdap program and were significantly halved during the 2009-2012 post-Tdap versus 2000-2003 pre-Tdap period. This program impact, however, is tempered by the observation that pertussis incidence among 15-19-year-olds was already lower than any other pediatric age group, following gradual decline from pre-teen rates even before the Tdap program. The risk of hospitalization among adolescents 15-19-years-old was also low throughout at <1/100,000. Furthermore, IRRs increased in 2013-2017 when an increasing proportion of 15-19-year-olds were primed with acellular pertussis vaccine only, suggesting short-lived Tdap booster-dose effectiveness that warrants further monitoring.

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.

Respiratory syncytial virus contributes to more severe respiratory morbidity than influenza in children < 2 years during seasonal influenza peaks.

PURPOSE: To compare the frequency and the severity of influenza and respiratory syncytial viruses (RSV) infections among children < 24 months hospitalized with respiratory symptoms. METHODS: Data from a prospective study conducted during the peak of five influenza seasons in the Province of Quebec, Canada were used. RESULTS: We detected higher frequency of RSV compared to influenza viruses (55.3% vs. 16.3%). Radiologically confirmed pneumonia was significantly more frequent in children with RSV (39%) than those with influenza (18%) and the clinical course was more severe in RSV than influenza-infected children, especially among infants < 3 months. CONCLUSION: Even during peak weeks of influenza season, we found a higher burden and severity of RSV compared with influenza virus disease in hospitalized children < 24 months.

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.

Mid-Season Estimates of Influenza Vaccine Effectiveness against Influenza A(H3N2) Hospitalization in the Elderly in Quebec, Canada, January 2015.

BACKGROUND: The 2014/15 influenza season in Canada was characterized by an early epidemic due to vaccine-mismatched influenza A(H3N2) viruses, disproportionately affecting elderly individuals ≥65-years-old. We assessed vaccine effectiveness (VE) against A(H3N2) hospitalization among elderly individuals during the peak weeks of the 2014/15 epidemic in Quebec, Canada. METHODS: Nasal specimens and clinical/epidemiological data were collected within 7 days of illness onset from elderly patients admitted with respiratory symptoms to one of four participating hospitals between November 30, 2014 and January 13, 2015. Cases tested RT-PCR positive for influenza A(H3N2) and controls tested negative for any influenza. VE was assessed by test-negative case-control design. RESULTS: There were 314 participants including 186 cases (62% vaccinated) and 128 controls (59% vaccinated) included in primary VE analysis. Median age was 81.5 years, two-thirds were admitted from the community and 91% had underlying comorbidity. Crude VE against A(H3N2) hospitalization was -17% (95%CI: -86% to 26%), decreasing to -23% (95%CI: -99 to 23%) with adjustment for age and comorbidity, and to -39% (95%CI: -142 to 20%) with additional adjustment for specimen collection interval, calendar time, type of residence and hospital. In sensitivity analyses, VE estimates were improved toward the null with restriction to participants admitted from the community (-2%; 95%CI: -105 to 49%) or with specimen collection ≤4 days since illness onset (- 8%; 95%CI: -104 to 43%) but further from the null with restriction to participants with comorbidity (-51%; 95%CI: -169 to 15%). CONCLUSION: The 2014/15 mismatched influenza vaccine provided elderly patients with no cross-protection against hospitalization with the A(H3N2) epidemic strain, reinforcing the need for adjunct protective measures among high-risk individuals and improved vaccine options.

Other respiratory viruses are important contributors to adult respiratory hospitalizations and mortality even during peak weeks of the influenza season.

BACKGROUND: During peak weeks of seasonal influenza epidemics, severe respiratory infections without laboratory confirmation are typically attributed to influenza. METHODS: In this prospective study, specimens and demographic and clinical data were collected from adults admitted with respiratory symptoms to 4 hospitals during the 8-10 peak weeks of 2 influenza seasons. Specimens were systematically tested for influenza and 13 other respiratory viruses (ORVs) by using the Luminex RVP FAST assay. RESULTS: At least 1 respiratory virus was identified in 46% (21% influenza, 25% noninfluenza; 2% coinfection) of the 286 enrolled patients in 2011-2012 and in 62% (46% influenza, 16% noninfluenza; 3% coinfection) of the 396 enrolled patients in 2012-2013. Among patients aged ≥75 years, twice as many ORVs (32%) as influenza viruses (14%) were detected in 2011-2012. During both seasons, the most frequently detected ORVs were enteroviruses/rhinoviruses (7%), respiratory syncytial virus (6%), human metapneumovirus (5%), coronaviruses (4%), and parainfluenza viruses (2%). Disease severity was similar for influenza and ORVs during both seasons. CONCLUSIONS: Although ORV contribution relative to influenza varies by age and season, during the peak weeks of certain influenza seasons, ORVs may be a more frequent cause of elderly hospitalization than influenza.

Evaluating trauma center process performance in an integrated trauma system with registry data.

BACKGROUND: The evaluation of trauma center performance implies the use of indicators that evaluate clinical processes. Despite the availability of routinely collected clinical data in most trauma systems, quality improvement efforts are often limited to hospital-based audit of adverse patient outcomes. OBJECTIVE: To identify and evaluate a series of process performance indicators (PPI) that can be calculated using routinely collected trauma registry data. MATERIALS AND METHODS: PPI were identified using a review of published literature, trauma system documentation, and expert consensus. Data from the 59 trauma centers of the Quebec trauma system (1999, 2006; N = 99,444) were used to calculate estimates of conformity to each PPI for each trauma center. Outliers were identified by comparing each center to the global mean. PPI were evaluated in terms of discrimination (between-center variance), construct validity (correlation with designation level and patient volume), and forecasting (correlation over time). RESULTS: Fifteen PPI were retained. Global proportions of conformity ranged between 6% for reduction of a major dislocation within 1 h and 97% for therapeutic laparotomy. Between-center variance was statistically significant for 13 PPI. Five PPI were significantly associated with designation level, 7 were associated with volume, and 11 were correlated over time. CONCLUSION: In our trauma system, results suggest that a series of 15 PPI supported by literature review or expert opinion can be calculated using routinely collected trauma registry data. We have provided evidence of their discrimination, construct validity, and forecasting properties. The between-center variance observed in this study highlights the importance of evaluating process performance in integrated trauma systems.

The changing epidemiology of meningococcal disease in Quebec, Canada, 1991-2011: potential implications of emergence of new strains.

BACKGROUND: In order to inform meningococcal disease prevention strategies, we analysed the epidemiology of invasive meningococcal disease (IMD) in the province of Quebec, Canada, 10 years before and 10 years after the introduction of serogroup C conjugate vaccination. METHODOLOGY: IMD cases reported to the provincial notifiable disease registry in 1991-2011 and isolates submitted for laboratory surveillance in 1997-2011 were analysed. Serogrouping, PCR testing and assignment of isolates to sequence types (ST) by using multilocus sequence typing (MLST) were performed. RESULTS: Yearly overall IMD incidence rates ranged from 2.2-2.3/100,000 in 1991-1992 to 0.49/100,000 in 1999-2000, increasing to 1.04/100,000 in 2011. Among the 945 IMD cases identified by laboratory surveillance in 1997-2011, 68%, 20%, 8%, and 3% were due to serogroups B, C, Y, and W135, respectively. Serogroup C IMD almost disappeared following the implementation of universal childhood immunization with monovalent C conjugate vaccines in 2002. Serogroup B has been responsible for 88% of all IMD cases and 61% of all IMD deaths over the last 3 years. The number and proportion of ST-269 clonal complex has been steadily increasing among the identified clonal complexes of serogroup B IMD since its first identification in 2003, representing 65% of serogroup B IMD in 2011. This clonal complex was first introduced in adolescent and young adults, then spread to other age groups. CONCLUSION: Important changes in the epidemiology of IMD have been observed in Quebec during the last two decades. Serogroup C has been virtually eliminated. In recent years, most cases have been caused by the serogroup B ST-269 clonal complex. Although overall burden of IMD is low, the use of a vaccine with potential broad-spectrum coverage could further reduce the burden of disease. Acceptability, feasibility and cost-effectiveness studies coupled with ongoing clinical and molecular surveillance are necessary in guiding public policy decisions.

Pediatric trauma mortality by type of designated hospital in a mature inclusive trauma system.

BACKGROUND: Previous studies have shown divergent results regarding the survival of injured children treated at pediatric trauma centers (PTC) and adult trauma centers (ATC). AIMS: (1) To document, in a regionalized inclusive trauma system, at which level of trauma centers were the injured children treated and (2) to compare the in-hospital mortality over five levels of trauma care, ranging from pediatric level I trauma centers (PTC) to designated local trauma hospitals (level IV) for the whole study sample and for subgroups of severely injured children and head trauma. MATERIALS AND METHODS: A retrospective analysis included data on 11,053 injured children (age ≤16 years) treated between April 1998 and March 2005 in 58 designated trauma hospitals in the province of Quebec, Canada. Multiple imputation was used to handle missing physiological data and multivariate logistic regression was used to compare mortality over levels of care. RESULTS: PTC treated 52.2% of the children. Children treated at PTC were more often transferred from another hospital (73%) and were more severely injured. ATC level I, II, III and IV centers treated, respectively, 3.0%, 16.2%, 24.3% and 4.3% of children. Compared with children treated at a PTC, the risk of mortality was higher for children treated at each other ATC, i.e. level I (adjusted odds ratio [OR] = 3.1; 95% confidence interval [CI]: 1.3-7.5), level II (OR = 2.5; 95% CI: 1.3-5.0), level III (OR = 5.2; 95% CI: 2.1-13.1) and level IV (OR = 9.9; 95% CI: 2.4-41.3). Similar findings were observed among the subsamples of children who were more severely injured (Injury Severity Score >15) and who sustained head injuries. CONCLUSIONS: In our trauma system, PTC cared for more than half of the injured children and patients treated there have better survival than those treated at all other levels of ATC.