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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.
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Subtipo H1N1 del Virus de la Influenza A , Vacunas contra la Influenza , Gripe Humana , Adulto , Lactante , Niño , Humanos , Preescolar , Gripe Humana/epidemiología , Gripe Humana/prevención & control , Estaciones del Año , Quebec/epidemiología , Subtipo H3N2 del Virus de la Influenza A , Hospitalización , Comorbilidad , VacunaciónRESUMEN
BACKGROUND: There is a need to understand the duration of infectivity of primary and recurrent coronavirus disease 2019 (COVID-19) and identify predictors of loss of infectivity. METHODS: Prospective observational cohort study with serial viral culture, rapid antigen detection test (RADT) and reverse transcription polymerase chain reaction (RT-PCR) on nasopharyngeal specimens of healthcare workers with COVID-19. The primary outcome was viral culture positivity as indicative of infectivity. Predictors of loss of infectivity were determined using multivariate regression model. The performance of the US Centers for Disease Control and Prevention (CDC) criteria (fever resolution, symptom improvement, and negative RADT) to predict loss of infectivity was also investigated. RESULTS: In total, 121 participants (91 female [79.3%]; average age, 40 years) were enrolled. Most (n = 107, 88.4%) had received ≥3 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine doses, and 20 (16.5%) had COVID-19 previously. Viral culture positivity decreased from 71.9% (87/121) on day 5 of infection to 18.2% (22/121) on day 10. Participants with recurrent COVID-19 had a lower likelihood of infectivity than those with primary COVID-19 at each follow-up (day 5 odds ratio [OR], 0.14; P < .001]; day 7 OR, 0.04; P = .003]) and were all non-infective by day 10 (P = .02). Independent predictors of infectivity included prior COVID-19 (adjusted OR [aOR] on day 5, 0.005; P = .003), an RT-PCR cycle threshold [Ct] value <23 (aOR on day 5, 22.75; P < .001) but not symptom improvement or RADT result.The CDC criteria would identify 36% (24/67) of all non-infectious individuals on day 7. However, 17% (5/29) of those meeting all the criteria had a positive viral culture. CONCLUSIONS: Infectivity of recurrent COVID-19 is shorter than primary infections. Loss of infectivity algorithms could be optimized.
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COVID-19 , Adulto , Femenino , Humanos , COVID-19/diagnóstico , Prueba de COVID-19 , Personal de Salud , Estudios Prospectivos , SARS-CoV-2 , MasculinoRESUMEN
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.
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Mpox , Vacuna contra Viruela , Humanos , Quebec/epidemiología , Autoinforme , Estudios de Casos y ControlesRESUMEN
BACKGROUND: Monkeypox, a viral zoonotic disease, is causing a global outbreak outside of endemic areas. OBJECTIVE: To characterize the outbreak of monkeypox in Montréal, the first large outbreak in North America. DESIGN: Epidemiologic and laboratory surveillance data and a phylogenomic analysis were used to describe and place the outbreak in a global context. SETTING: Montréal, Canada. PATIENTS: Probable or confirmed cases of monkeypox. MEASUREMENTS: Epidemiologic, clinical, and demographic data were aggregated. Whole-genome sequencing and phylogenetic analysis were performed for a set of outbreak sequences. The public health response and its evolution are described. RESULTS: Up to 18 October 2022, a total of 402 cases of monkeypox were reported mostly among men who have sex with men (MSM), most of which were suspected to be acquired through sexual contact. All monkeypox genomes nested within the B.1 lineage. Montréal Public Health worked closely with the affected communities to control the outbreak, becoming the first jurisdiction to offer 1 dose of the Modified Vaccinia Ankara-Bavarian Nordic vaccine as preexposure prophylaxis (PrEP) to those at risk in early June 2022. Two peaks of cases were seen in early June and July (43 and 44 cases per week, respectively) followed by a decline toward near resolution of the outbreak in October. Reasons for the biphasic peak are not fully elucidated but may represent the tempo of vaccination and/or several factors related to transmission dynamics and case ascertainment. LIMITATIONS: Clinical data are self-reported. Limited divergence among sequences limited genomic epidemiologic conclusions. CONCLUSION: A large outbreak of monkeypox occurred in Montréal, primarily among MSM. Successful control of the outbreak rested on early and sustained engagement with the affected communities and rapid offer of PrEP vaccination to at-risk persons. PRIMARY FUNDING SOURCE: None.
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Mpox , Minorías Sexuales y de Género , Masculino , Humanos , Filogenia , Homosexualidad Masculina , Mpox/epidemiología , Brotes de Enfermedades , América del Norte/epidemiología , AutoinformeRESUMEN
The Canadian Sentinel Practitioner Surveillance Network reports mid-season 2023/24 influenza vaccine effectiveness (VE) of 63% (95%â¯CI: 51-72) against influenza A(H1N1)pdm09, lower for clade 5a.2a.1 (56%; 95%â¯CI: 33-71) than clade 5a.2a (67%; 95%â¯CI: 48-80), and lowest against influenza A(H3N2) (40%; 95%â¯CI: 5-61). The Omicron XBB.1.5 vaccine protected comparably well, with VE of 47% (95%â¯CI: 21-65) against medically attended COVID-19, higher among people reporting a prior confirmed SARS-CoV-2 infection at 67% (95%â¯CI: 28-85).
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COVID-19 , Subtipo H1N1 del Virus de la Influenza A , Vacunas contra la Influenza , Gripe Humana , Humanos , Gripe Humana/epidemiología , Gripe Humana/prevención & control , Estaciones del Año , Subtipo H3N2 del Virus de la Influenza A/genética , Eficacia de las Vacunas , Canadá/epidemiología , Vigilancia de Guardia , Vacunación , Estudios de Casos y ControlesRESUMEN
The Canadian Sentinel Practitioner Surveillance Network estimated vaccine effectiveness (VE) during the unusually early 2022/23 influenza A(H3N2) epidemic. Like vaccine, circulating viruses were clade 3C.2a1b.2a.2, but with genetic diversity affecting haemagglutinin positions 135 and 156, and reassortment such that H156 viruses acquired neuraminidase from clade 3C.2a1b.1a. Vaccine provided substantial protection with A(H3N2) VE of 54% (95% CI: 38 to 66) overall. VE was similar against H156 and vaccine-like S156 viruses, but with potential variation based on diversity at position 135.
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Vacunas contra la Influenza , Gripe Humana , Humanos , Gripe Humana/epidemiología , Gripe Humana/prevención & control , Subtipo H3N2 del Virus de la Influenza A , Estaciones del Año , Eficacia de las Vacunas , Canadá/epidemiología , Variación GenéticaRESUMEN
BACKGROUND: The influenza A(H3N2) vaccine was updated from clade 3C.3a in 2015-2016 to 3C.2a for 2016-2017 and 2017-2018. Circulating 3C.2a viruses showed considerable hemagglutinin glycoprotein diversification and the egg-adapted vaccine also bore mutations. METHODS: Vaccine effectiveness (VE) in 2016-2017 and 2017-2018 was assessed by test-negative design, explored by A(H3N2) phylogenetic subcluster and prior season's vaccination history. RESULTS: In 2016-2017, A(H3N2) VE was 36% (95% confidence interval [CI], 18%-50%), comparable with (43%; 95% CI, 24%-58%) or without (33%; 95% CI, -21% to 62%) prior season's vaccination. In 2017-2018, VE was 14% (95% CI, -8% to 31%), lower with (9%; 95% CI, -18% to 30%) versus without (45%; 95% CI, -7% to 71%) prior season's vaccination. In 2016-2017, VE against predominant clade 3C.2a1 viruses was 33% (95% CI, 11%-50%): 18% (95% CI, -40% to 52%) for 3C.2a1a defined by a pivotal T135K loss of glycosylation; 60% (95% CI, 19%-81%) for 3C.2a1b (without T135K); and 31% (95% CI, 2%-51%) for other 3C.2a1 variants (with/without T135K). VE against 3C.2a2 viruses was 45% (95% CI, 2%-70%) in 2016-2017 but 15% (95% CI, -7% to 33%) in 2017-2018 when 3C.2a2 predominated. VE against 3C.2a1b in 2017-2018 was 37% (95% CI, -57% to 75%), lower at 12% (95% CI, -129% to 67%) for a new 3C.2a1b subcluster (n = 28) also bearing T135K. CONCLUSIONS: Exploring VE by phylogenetic subcluster and prior vaccination history reveals informative heterogeneity. Pivotal mutations affecting glycosylation sites, and repeat vaccination using unchanged antigen, may reduce VE.
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Epidemias , Vacunas contra la Influenza , Gripe Humana , Humanos , Gripe Humana/epidemiología , Gripe Humana/prevención & control , Subtipo H3N2 del Virus de la Influenza A , Filogenia , Eficacia de las Vacunas , Vacunación , Canadá/epidemiología , Estaciones del AñoRESUMEN
The seasonal nature of outbreaks of respiratory viral infections with increased transmission during low temperatures has been well established. Accordingly, temperature has been suggested to play a role on the viability and transmissibility of SARS-CoV-2, the virus responsible for the COVID-19 pandemic. The receptor-binding domain (RBD) of the Spike glycoprotein is known to bind to its host receptor angiotensin-converting enzyme 2 (ACE2) to initiate viral fusion. Using biochemical, biophysical, and functional assays to dissect the effect of temperature on the receptor-Spike interaction, we observed a significant and stepwise increase in RBD-ACE2 affinity at low temperatures, resulting in slower dissociation kinetics. This translated into enhanced interaction of the full Spike glycoprotein with the ACE2 receptor and higher viral attachment at low temperatures. Interestingly, the RBD N501Y mutation, present in emerging variants of concern (VOCs) that are fueling the pandemic worldwide (including the B.1.1.7 (α) lineage), bypassed this requirement. This data suggests that the acquisition of N501Y reflects an adaptation to warmer climates, a hypothesis that remains to be tested.
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Enzima Convertidora de Angiotensina 2/metabolismo , SARS-CoV-2/metabolismo , Glicoproteína de la Espiga del Coronavirus/metabolismo , Enzima Convertidora de Angiotensina 2/química , COVID-19/patología , COVID-19/virología , Calorimetría , Humanos , Interferometría , Polimorfismo de Nucleótido Simple , Unión Proteica , Estructura Cuaternaria de Proteína , SARS-CoV-2/aislamiento & purificación , Glicoproteína de la Espiga del Coronavirus/química , Temperatura , TermodinámicaRESUMEN
The objective of this study was to validate the use of spring water gargle (SWG) as an alternative to oral and nasopharyngeal swab (ONPS) for SARS-CoV-2 detection with a laboratory-developed test. Healthcare workers and adults from the general population, presenting to one of two COVID-19 screening clinics in Montréal and Québec City, were prospectively recruited to provide a gargle sample in addition to the standard ONPS. The paired specimens were analyzed using thermal lysis followed by a laboratory-developed nucleic acid amplification test (LD-NAAT) to detect SARS-CoV-2, and comparative performance analysis was performed. An individual was considered infected if a positive result was obtained on either sample. A total of 1297 adult participants were recruited. Invalid results (n = 18) were excluded from the analysis. SARS-CoV-2 was detected in 144/1279 (11.3%) participants: 126 from both samples, 15 only from ONPS, and 3 only from SWG. Overall, the sensitivity was 97.9% (95% CI: 93.7-99.3) for ONPS and 89.6% (95% CI: 83.4-93.6; p = 0.005) for SWG. The mean ONPS cycle threshold (Ct ) value was significantly lower for the concordant paired samples as compared to discordant ones (22.9 vs. 32.1; p < 0.001). In conclusion, using an LD-NAAT with thermal lysis, SWG is a less sensitive sampling method than the ONPS. However, the higher acceptability of SWG might enable a higher rate of detection from a population-based perspective. Nonetheless, in patients with a high clinical suspicion of COVID-19, a repeated analysis with ONPS should be considered. The sensitivity of SWG using NAAT preceded by chemical extraction should be evaluated.
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COVID-19 , Manantiales Naturales , Adulto , COVID-19/diagnóstico , Humanos , Antisépticos Bucales , Nasofaringe , SARS-CoV-2/genética , Saliva , Manejo de Especímenes/métodos , AguaRESUMEN
Influenza virus circulation virtually ceased in Canada during the COVID-19 pandemic, re-emerging with the relaxation of restrictions in spring 2022. Using a test-negative design, the Canadian Sentinel Practitioner Surveillance Network reports 2021/22 vaccine effectiveness of 36% (95%â¯CI: -38 to 71) against late-season illness due to influenza A(H3N2) clade 3C.2a1b.2a.2 viruses, considered antigenically distinct from the 3C.2a1b.2a.1 vaccine strain. Findings reinforce the World Health Organization's decision to update the 2022/23 northern hemisphere vaccine to a more representative A(H3N2) clade 3C.2a1b.2a.2 strain.
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COVID-19 , Vacunas contra la Influenza , Gripe Humana , Canadá/epidemiología , Humanos , Subtipo H3N2 del Virus de la Influenza A , Gripe Humana/epidemiología , Gripe Humana/prevención & control , Pandemias/prevención & control , Eficacia de las VacunasRESUMEN
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 (nâ =â 136) and 5.2% of adults (nâ =â 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 (Pâ <â .001). No deaths were recorded in children; 5.8% of adults with HCoV monoinfection died, compared with 4.2% of those with influenza monoinfection (Pâ =â .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.
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Infecciones por Coronavirus , Gripe Humana , Infecciones del Sistema Respiratorio , Adulto , Niño , Infecciones por Coronavirus/epidemiología , Hospitalización , Hospitales , Humanos , Gripe Humana/epidemiología , Estudios Prospectivos , Quebec/epidemiología , Infecciones del Sistema Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/virología , Estaciones del AñoRESUMEN
Influenza vaccine effectiveness against influenza and noninfluenza respiratory viruses (NIRVs) was assessed by test-negative design using historic datasets of the community-based Canadian Sentinel Practitioner Surveillance Network, spanning 2010-2011 to 2016-2017. Vaccine significantly reduced the risk of influenza illness by >40% with no effect on coronaviruses or other NIRV risk.
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Infecciones por Coronavirus/epidemiología , Vacunas contra la Influenza/inmunología , Gripe Humana/prevención & control , Infecciones del Sistema Respiratorio/virología , Adolescente , Adulto , Anciano , Canadá/epidemiología , Estudios de Casos y Controles , Niño , Preescolar , Infecciones por Coronavirus/etiología , Femenino , Humanos , Inmunogenicidad Vacunal , Lactante , Vacunas contra la Influenza/administración & dosificación , Gripe Humana/epidemiología , Masculino , Persona de Mediana Edad , Infecciones del Sistema Respiratorio/prevención & control , Estudios Retrospectivos , Factores de Riesgo , Estaciones del Año , Vigilancia de Guardia , Adulto JovenRESUMEN
Interim results from Canada's Sentinel Practitioner Surveillance Network show that during a season characterised by early co-circulation of influenza A and B viruses, the 2019/20 influenza vaccine has provided substantial protection against medically-attended influenza illness. Adjusted VE overall was 58% (95% confidence interval (CI): 47 to 66): 44% (95% CI: 26 to 58) for A(H1N1)pdm09, 62% (95% CI: 37 to 77) for A(H3N2) and 69% (95% CI: 57 to 77) for influenza B viruses, predominantly B/Victoria lineage.
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Subtipo H1N1 del Virus de la Influenza A/aislamiento & purificación , Subtipo H3N2 del Virus de la Influenza A/aislamiento & purificación , Virus de la Influenza B/aislamiento & purificación , Vacunas contra la Influenza/administración & dosificación , Gripe Humana/epidemiología , Gripe Humana/prevención & control , Adolescente , Adulto , Anciano , Antígenos Virales/análisis , Canadá/epidemiología , Niño , Preescolar , Femenino , Genotipo , Pruebas de Inhibición de Hemaglutinación , Humanos , Lactante , Subtipo H1N1 del Virus de la Influenza A/genética , Subtipo H1N1 del Virus de la Influenza A/inmunología , Subtipo H3N2 del Virus de la Influenza A/genética , Subtipo H3N2 del Virus de la Influenza A/inmunología , Virus de la Influenza B/genética , Virus de la Influenza B/inmunología , Vacunas contra la Influenza/inmunología , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Nasofaringe/virología , Nariz/virología , Reacción en Cadena en Tiempo Real de la Polimerasa , Estaciones del Año , Vigilancia de Guardia , Análisis de Secuencia de ADN , Adulto JovenRESUMEN
Vaccine effectiveness (VE) against influenza B was derived separately for Victoria and Yamagata lineages across 8 seasons (2010-2011 to 2017-2018) in Canada when trivalent influenza vaccine was predominantly used. VE was ≥50% regardless of lineage match to circulating viruses, except when the vaccine strain was unchanged from the prior season.
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Protección Cruzada/inmunología , Virus de la Influenza B/clasificación , Vacunas contra la Influenza/inmunología , Gripe Humana/prevención & control , Estaciones del Año , Potencia de la Vacuna , Adolescente , Adulto , Anciano , Canadá , Niño , Preescolar , Bases de Datos Factuales , Monitoreo Epidemiológico , Femenino , Humanos , Inmunogenicidad Vacunal , Lactante , Vacunas contra la Influenza/normas , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
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.
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Monitoreo Epidemiológico , Gripe Humana/epidemiología , Vigilancia de la Población , Infecciones por Virus Sincitial Respiratorio/epidemiología , Femenino , Humanos , Lactante , Recién Nacido , Gripe Humana/virología , Masculino , Estudios Prospectivos , Quebec/epidemiología , Infecciones por Virus Sincitial Respiratorio/virología , Virus Sincitial Respiratorio Humano , Estaciones del AñoRESUMEN
IntroductionFindings from the community-based Canadian Sentinel Practitioner Surveillance Network (SPSN) suggest children were more affected by the 2018/19 influenza A(H1N1)pdm09 epidemic.AimTo compare the age distribution of A(H1N1)pdm09 cases in 2018/19 to prior seasonal influenza epidemics in Canada.MethodsThe age distribution of unvaccinated influenza A(H1N1)pdm09 cases and test-negative controls were compared across A(H1N1)pdm09-dominant epidemics in 2018/19, 2015/16 and 2013/14 and with the general population of SPSN provinces. Similar comparisons were undertaken for influenza A(H3N2)-dominant epidemics.ResultsIn 2018/19, more influenza A(H1N1)pdm09 cases were under 10 years old than controls (29% vs 16%; p < 0.001). In particular, children aged 5-9 years comprised 14% of cases, greater than their contribution to controls (4%) or the general population (5%) and at least twice their contribution in 2015/16 (7%; p < 0.001) or 2013/14 (5%; p < 0.001). Conversely, children aged 10-19 years (11% of the population) were under-represented among A(H1N1)pdm09 cases versus controls in 2018/19 (7% vs 12%; p < 0.001), 2015/16 (7% vs 13%; p < 0.001) and 2013/14 (9% vs 12%; p = 0.12).ConclusionChildren under 10 years old contributed more to outpatient A(H1N1)pdm09 medical visits in 2018/19 than prior seasonal epidemics in Canada. In 2018/19, all children under 10 years old were born after the 2009 A(H1N1)pdm09 pandemic and therefore lacked pandemic-induced immunity. In addition, more than half those born after 2009 now attend school (i.e. 5-9-year-olds), a socio-behavioural context that may enhance transmission and did not apply during prior A(H1N1)pdm09 epidemics.
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Subtipo H1N1 del Virus de la Influenza A/aislamiento & purificación , Gripe Humana/epidemiología , Gripe Humana/virología , Adolescente , Adulto , Distribución por Edad , Anciano , Canadá/epidemiología , Niño , Preescolar , Efecto de Cohortes , Epidemias , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estaciones del Año , Vigilancia de Guardia , Adulto JovenRESUMEN
Using a test-negative design, the Canadian Sentinel Practitioner Surveillance Network assessed interim 2018/19 vaccine effectiveness (VE) against predominant influenza A(H1N1)pdm09 viruses. Adjusted VE was 72% (95% confidence interval: 60 to 81) against medically attended, laboratory-confirmed influenza A(H1N1)pdm09 illness. This substantial vaccine protection was observed in all age groups, notably young children who appeared to be disproportionately affected. Sequence analysis identified heterogeneity in emerging clade 6B.1 viruses but no dominant drift variant.
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Subtipo H1N1 del Virus de la Influenza A/aislamiento & purificación , Vacunas contra la Influenza/administración & dosificación , Gripe Humana/prevención & control , Vacunación/estadística & datos numéricos , Potencia de la Vacuna , Adolescente , Adulto , Anciano , Canadá/epidemiología , Estudios de Casos y Controles , Niño , Preescolar , Femenino , Pruebas de Inhibición de Hemaglutinación , Humanos , Lactante , Subtipo H1N1 del Virus de la Influenza A/genética , Subtipo H1N1 del Virus de la Influenza A/inmunología , Vacunas contra la Influenza/inmunología , Gripe Humana/epidemiología , Gripe Humana/virología , Masculino , Persona de Mediana Edad , Nasofaringe/virología , Nariz/virología , Evaluación de Resultado en la Atención de Salud , Reacción en Cadena en Tiempo Real de la Polimerasa , Estaciones del Año , Sensibilidad y Especificidad , Vigilancia de Guardia , Análisis de Secuencia de ADNRESUMEN
IntroductionThe Canadian Sentinel Practitioner Surveillance Network reports vaccine effectiveness (VE) for the 2018/19 influenza A(H3N2) epidemic.AimTo explain a paradoxical signal of increased clade 3C.3a risk among 35-54-year-old vaccinees, we hypothesise childhood immunological imprinting and a cohort effect following the 1968 influenza A(H3N2) pandemic.MethodsWe assessed VE by test-negative design for influenza A(H3N2) overall and for co-circulating clades 3C.2a1b and 3C.3a. VE variation by age in 2018/19 was compared with amino acid variation in the haemagglutinin glycoprotein by year since 1968.ResultsInfluenza A(H3N2) VE was 17% (95% CI: -13 to 39) overall: 27% (95% CI: -7 to 50) for 3C.2a1b and -32% (95% CI: -119 to 21) for 3C.3a. Among 20-64-year-olds, VE was -7% (95% CI: -56 to 26): 6% (95% CI: -49 to 41) for 3C.2a1b and -96% (95% CI: -277 to -2) for 3C.3a. Clade 3C.3a VE showed a pronounced negative dip among 35-54-year-olds in whom the odds of medically attended illness were > 4-fold increased for vaccinated vs unvaccinated participants (p < 0.005). This age group was primed in childhood to influenza A(H3N2) viruses that for two decades following the 1968 pandemic bore a serine at haemagglutinin position 159, in common with contemporary 3C.3a viruses but mismatched to 3C.2a vaccine strains instead bearing tyrosine.DiscussionImprinting by the first childhood influenza infection is known to confer long-lasting immunity focused toward priming epitopes. Our findings suggest vaccine mismatch may negatively interact with imprinted immunity. The immunological mechanisms for imprint-regulated effect of vaccine (I-REV) warrant investigation.
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Memoria Inmunológica , Subtipo H3N2 del Virus de la Influenza A/aislamiento & purificación , Vacunas contra la Influenza/administración & dosificación , Gripe Humana/prevención & control , Vigilancia de la Población/métodos , Vacunación/estadística & datos numéricos , Potencia de la Vacuna , Adulto , Factores de Edad , Canadá/epidemiología , Femenino , Glicoproteínas Hemaglutininas del Virus de la Influenza/genética , Humanos , Subtipo H3N2 del Virus de la Influenza A/genética , Subtipo H3N2 del Virus de la Influenza A/inmunología , Vacunas contra la Influenza/inmunología , Gripe Humana/epidemiología , Gripe Humana/inmunología , Gripe Humana/virología , Masculino , Persona de Mediana Edad , Vigilancia de GuardiaRESUMEN
Using a test-negative design, we assessed interim vaccine effectiveness (VE) for the 2017/18 epidemic of co-circulating influenza A(H3N2) and B(Yamagata) viruses. Adjusted VE for influenza A(H3N2), driven by a predominant subgroup of clade 3C.2a viruses with T131K + R142K + R261Q substitutions, was low at 17% (95% confidence interval (CI): -14 to 40). Adjusted VE for influenza B was higher at 55% (95% CI: 38 to 68) despite prominent use of trivalent vaccine containing lineage-mismatched influenza B(Victoria) antigen, suggesting cross-lineage protection.
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Subtipo H3N2 del Virus de la Influenza A/inmunología , Virus de la Influenza B/inmunología , Vacunas contra la Influenza/inmunología , Gripe Humana/prevención & control , Gripe Humana/virología , Vacunación/estadística & datos numéricos , Potencia de la Vacuna , Adolescente , Adulto , Canadá/epidemiología , Estudios de Casos y Controles , Niño , Epidemias , Femenino , Humanos , Subtipo H3N2 del Virus de la Influenza A/clasificación , Subtipo H3N2 del Virus de la Influenza A/genética , Virus de la Influenza B/clasificación , Virus de la Influenza B/genética , Gripe Humana/epidemiología , Gripe Humana/inmunología , Masculino , Persona de Mediana Edad , Estaciones del Año , Vigilancia de Guardia , Adulto JovenRESUMEN
Background: Vaccine effectiveness (VE) estimates for 2015-2016 seasonal influenza vaccine are reported from Canada's Sentinel Practitioner Surveillance Network (SPSN). This season was characterized by a delayed 2009 pandemic influenza A(H1N1) virus (A[H1N1]pdm09) epidemic and concurrent influenza B(Victoria) virus activity. Potential influences on VE beyond antigenic match are explored, including viral genomic variation, birth cohort effects, prior vaccination, and epidemic period. Methods: VE was estimated by a test-negative design comparing the adjusted odds ratio for influenza test positivity among vaccinated compared to unvaccinated participants. Vaccine-virus relatedness was assessed by gene sequencing and hemagglutination inhibition assay. Results: Analyses included 596 influenza A(H1N1)pdm09 and 305 B(Victoria) cases and 926 test-negative controls. A(H1N1)pdm09 viruses were considered antigenically related to vaccine (unchanged since 2009), despite phylogenetic clustering within emerging clade 6B.1. The adjusted VE against A(H1N1)pdm09 was 43% (95% confidence interval [CI], 25%-57%). Compared to other age groups, VE against A(H1N1)pdm09 was lower for adults born during 1957-1976 (25%; 95% CI, -16%-51%). The VE against A(H1N1)pdm09 was also lower for participants consecutively vaccinated during both the current and prior seasons (41%; 95% CI, 18%-57%) than for those vaccinated during the current season only (75%; 95% CI, 45%-88%), and the VE among participants presenting in March-April 2016 (19%; 95% CI, -15%-44%) was lower than that among those presenting during January-February 2016 (62%; 95% CI, 44%-74%). The adjusted VE for B(Victoria) viruses was 54% (95% CI, 32%-68%), despite lineage-level mismatch to B(Yamagata) vaccine. The further variation in VE as observed for A(H1N1)pdm09 was not observed for B(Victoria). Conclusions: Influenza VE findings may require consideration of other agent-host and immuno-epidemiologic influences on vaccine performance beyond antigenic match, including viral genomic variation, repeat vaccination, birth (immunological) cohort effects, and potential within-season waning of vaccine protection.