Influenza Vaccine Effectiveness by A(H3N2) Phylogenetic Subcluster and Prior Vaccination History: 2016-2017 and 2017-2018 Epidemics in Canada.

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.

Influenza Vaccine Does Not Increase the Risk of Coronavirus or Other Noninfluenza Respiratory Viruses: Retrospective Analysis From Canada, 2010-2011 to 2016-2017.

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.

Getting a grippe on severity: a retrospective comparison of influenza-related hospitalizations and deaths captured in reportable disease and administrative data sources in Ontario, Canada.

BACKGROUND: Since 2009, in Ontario, reportable disease surveillance data has been used for timely in-season estimates of influenza severity (i.e., hospitalizations and deaths). Due to changes in reporting requirements influenza reporting no longer captures these indicators of severity, necessitating exploration of other potential sources of data. The purpose of this study was to complete a retrospective analysis to assess the comparability of influenza-related hospitalizations and deaths captured in the Ontario reportable disease information system to those captured in Ontario's hospital-based discharge database. METHODS: Hospitalizations and deaths of laboratory-confirmed influenza cases reported during the 2010-11 to 2013-14 influenza seasons were analyzed. Information on hospitalizations and deaths for laboratory-confirmed influenza cases were obtained from two databases; the integrated Public Health Information System, which is the provincial reportable disease database, and the Discharge Abstract Database, which contains information on all in-patient hospital visits using the International Classification of Diseases, 10th Revision, Canada (ICD-10-CA) coding standards. Analyses were completed using the ICD-10 J09 and J10 diagnosis codes as an indicator for laboratory-confirmed influenza, and a secondary analysis included the physician-diagnosed influenza J11 diagnosis code. RESULTS: For each season, reported hospitalizations for laboratory-confirmed influenza cases in the reportable disease data were higher compared to hospitalizations with J09 and J10 diagnoses codes, but lower when J11 codes were included. The number of deaths was higher in the reportable disease data, whether or not J11 codes were included. For all four seasons, the weekly trends in the number of hospitalizations and deaths were similar for the reportable disease and hospital data (with and without J11), with seasonal peaks occurring during the same week or within 1 week of each other. CONCLUSION: In our retrospective analyses we found that hospital data provided a reliable estimate of the trends of influenza-related hospitalizations and deaths compared to the reportable disease data for the 2010-11 to 2013-14 influenza seasons in Ontario, but may under-estimate the total seasonal number of deaths. Hospital data could be used for retrospective end-of-season assessments of severity, but due to delays in data availability are unlikely to be timely estimates of severity during in-season surveillance.

Children under 10 years of age were more affected by the 2018/19 influenza A(H1N1)pdm09 epidemic in Canada: possible cohort effect following the 2009 influenza pandemic.

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.

Effects of Absolute Humidity, Relative Humidity, Temperature, and Wind Speed on Influenza Activity in Toronto, Ontario, Canada.

The occurrence of influenza in different climates has been shown to be associated with multiple meteorological factors. The incidence of influenza has been reported to increase during rainy seasons in tropical climates and during the dry, cold months of winter in temperate climates. This study was designed to explore the role of absolute humidity (AH), relative humidity (RH), temperature, and wind speed (WS) on influenza activity in the Toronto, ON, Canada, area. Environmental data obtained from four meteorological stations in the Toronto area over the period from 1 January 2010 to 31 December 2015 were linked to patient influenza data obtained for the same locality and period. Data were analyzed using correlation, negative binomial regressions with linear predictors, and splines to capture the nonlinear relationship between exposure and outcomes. Our study found a negative association of both AH and temperature with influenza A and B virus infections. The effect of RH on influenza A and B viruses was controversial. Temperature fluctuation was associated with increased numbers of influenza B virus infections. Influenza virus was less likely to be detected from community patients than from patients tested as part of an institutional outbreak investigation. This could be more indicative of nosocomial transmission rather than climactic factors. The nonlinear nature of the relationship of influenza A virus with temperature and of influenza B virus with AH, RH, and temperature could explain the complexity and variation between influenza A and B virus infections. Predicting influenza activity is important for the timing of implementation of disease prevention and control measures as well as for resource allocation.IMPORTANCE This study examined the relationship between environmental factors and the occurrence of influenza in general. Since the seasonality of influenza A and B viruses is different in most temperate climates, we also examined each influenza virus separately. This study reports a negative association of both absolute humidity and temperature with influenza A and B viruses and tries to understand the controversial effect of RH on influenza A and B viruses. This study reports a nonlinear relation between influenza A and B viruses with temperature and influenza B virus with absolute and relative humidity. The nonlinear nature of these relations could explain the complexity and difference in seasonality between influenza A and B viruses, with the latter predominating later in the season. Separating community-based specimens from those obtained during outbreaks was also a novel approach in this research. These findings provide a further understanding of influenza virus transmission in temperate climates.

Vaccine Effectiveness Against Lineage-matched and -mismatched Influenza B Viruses Across 8 Seasons in Canada, 2010-2011 to 2017-2018.

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.

Should Sex Be Considered an Effect Modifier in the Evaluation of Influenza Vaccine Effectiveness?

We investigated sex as a potential modifier of influenza vaccine effectiveness (VE) between 2010-2011 and 2016-2017 in Canada. Overall VE was 49% (95% confidence interval [CI], 43% to 55%) for females and 38% (95% CI, 28% to 46%) for males (absolute difference [AD], 11%; P = .03). Sex differences were greatest for influenza A(H3N2) (AD, 17%; P = .07) and B(Victoria) (AD, 20%; P = .08) compared with A(H1N1)pdm09 (AD, 10%; P = .19) or B(Yamagata) (AD, -3%; P = .68). They were also more pronounced in older adults ≥50 years (AD, 19%; P = .03) compared with those <20 years (AD, 4%; P = .74) or 20-49 years (AD, -1%; P = .90) but with variation by subtype/lineage. More definitive investigations of VE by sex and age are warranted to elucidate these potential interactions.

Early season co-circulation of influenza A(H3N2) and B(Yamagata): interim estimates of 2017/18 vaccine effectiveness, Canada, January 2018.

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.

Beyond Antigenic Match: Possible Agent-Host and Immuno-epidemiological Influences on Influenza Vaccine Effectiveness During the 2015-2016 Season in Canada.

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.

Age-Related Differences in Influenza B Infection by Lineage in a Community-Based Sentinel System, 2010-2011 to 2015-2016, Canada.

Age-related differences in influenza B lineage detection were explored in the community-based Canadian Sentinel Practitioner Surveillance Network (SPSN) from 2010-2011 to 2015-2016. Whereas >80% of B(Victoria) cases were <40 years old, B(Yamagata) cases showed a bimodal age distribution with 27% who were <20 years old and 61% who were 30-64 years old, but with a notable gap in cases between 20 and 29 years old (4%). Overall, the median age was 20 years lower for B(Victoria) vs B(Yamagata) cases (20 vs 40 years; P < .01). Additional phylodynamic and immuno-epidemiological research is needed to understand age-related variation in influenza B risk by lineage, with potential implications for prevention and control across the lifespan.

Interim estimates of 2016/17 vaccine effectiveness against influenza A(H3N2), Canada, January 2017.

Using a test-negative design, the Canadian Sentinel Practitioner Surveillance Network (SPSN) assessed interim 2016/17 influenza vaccine effectiveness (VE) against dominant influenza A(H3N2) viruses considered antigenically matched to the clade 3C.2a vaccine strain. Sequence analysis revealed substantial heterogeneity in emerging 3C.2a1 variants by province and over time. Adjusted VE was 42% (95% confidence interval: 18-59%) overall, with variation by province. Interim virological and VE findings reported here warrant further investigation to inform potential vaccine reformulation.

Serial Vaccination and the Antigenic Distance Hypothesis: Effects on Influenza Vaccine Effectiveness During A(H3N2) Epidemics in Canada, 2010-2011 to 2014-2015.

Background: The antigenic distance hypothesis (ADH) predicts that negative interference from prior season's influenza vaccine (v1) on the current season's vaccine (v2) protection may occur when the antigenic distance is small between v1 and v2 (v1 ≈ v2) but large between v1 and the current epidemic (e) strain (v1 ≠ e). Methods: Vaccine effectiveness (VE) against medically attended, laboratory-confirmed influenza A(H3N2) illness was estimated by test-negative design during 3 A(H3N2) epidemics (2010-2011, 2012-2013, 2014-2015) in Canada. Vaccine effectiveness was derived with covariate adjustment across v2 and/or v1 categories relative to no vaccine receipt among outpatients aged ≥9 years. Prior vaccination effects were interpreted within the ADH framework. Results: Prior vaccination effects varied significantly by season, consistent with the ADH. There was no interference by v1 in 2010-2011 when v1 ≠ v2 and v1 ≠ e, with comparable VE for v2 alone or v2 + v1: 34% (95% confidence interval [CI] = -51% to 71%) versus 34% (95% CI = -5% to 58%). Negative interference by v1 was suggested in 2012-2013 with nonsignificant reduction in VE when v1 ≈ v2 and v1 ≠ e: 49% (95% CI = -47% to 83%) versus 28% (95% CI = -12% to 54%). Negative effects of prior vaccination were pronounced and statistically significant in 2014-2015 when v1 ≡ v2 and v1 ≠ e: 65% (95% CI = 25% to 83%) versus -33% (95% CI = -78% to 1%). Conclusions: Effects of repeat influenza vaccination were consistent with the ADH and may have contributed to findings of low VE across recent A(H3N2) epidemics since 2010 in Canada.

Evaluation and Comparison of Multiple Test Methods, Including Real-time PCR, for Legionella Detection in Clinical Specimens.

Legionella is a Gram-negative bacterium that can cause Pontiac fever, a mild upper respiratory infection and Legionnaire's disease, a more severe illness. We aimed to compare the performance of urine antigen, culture, and polymerase chain reaction (PCR) test methods and to determine if sputum is an acceptable alternative to the use of more invasive bronchoalveolar lavage (BAL). Data for this study included specimens tested for Legionella at Public Health Ontario Laboratories from 1st January, 2010 to 30th April, 2014, as part of routine clinical testing. We found sensitivity of urinary antigen test (UAT) compared to culture to be 87%, specificity 94.7%, positive predictive value (PPV) 63.8%, and negative predictive value (NPV) 98.5%. Sensitivity of UAT compared to PCR was 74.7%, specificity 98.3%, PPV 77.7%, and NPV 98.1%. Out of 146 patients who had a Legionella-positive result by PCR, only 66 (45.2%) also had a positive result by culture. Sensitivity for culture was the same using either sputum or BAL (13.6%); sensitivity for PCR was 10.3% for sputum and 12.8% for BAL. Both sputum and BAL yield similar results regardless testing methods (Fisher Exact p-values = 1.0, for each test). In summary, all test methods have inherent weaknesses in identifying Legionella; therefore, more than one testing method should be used. Obtaining a single specimen type from patients with pneumonia limits the ability to diagnose Legionella, particularly when urine is the specimen type submitted. Given ease of collection and similar sensitivity to BAL, clinicians are encouraged to submit sputum in addition to urine when BAL submission is not practical from patients being tested for Legionella.

A Perfect Storm: Impact of Genomic Variation and Serial Vaccination on Low Influenza Vaccine Effectiveness During the 2014-2015 Season.

BACKGROUND: The 2014-2015 influenza season was distinguished by an epidemic of antigenically-drifted A(H3N2) viruses and vaccine components identical to 2013-2014. We report 2014-2015 vaccine effectiveness (VE) from Canada and explore contributing agent-host factors. METHODS: VE against laboratory-confirmed influenza was derived using a test-negative design among outpatients with influenza-like illness. Sequencing identified amino acid mutations at key antigenic sites of the viral hemagglutinin protein. RESULTS: Overall, 815/1930 (42%) patients tested influenza-positive: 590 (72%) influenza A and 226 (28%) influenza B. Most influenza A viruses with known subtype were A(H3N2) (570/577; 99%); 409/460 (89%) sequenced viruses belonged to genetic clade 3C.2a and 39/460 (8%) to clade 3C.3b. Dominant clade 3C.2a viruses bore the pivotal mutations F159Y (a cluster-transition position) and K160T (a predicted gain of glycosylation) compared to the mismatched clade 3C.1 vaccine. VE against A(H3N2) was -17% (95% confidence interval [CI], -50% to 9%) overall with clade-specific VE of -13% (95% CI, -51% to 15%) for clade 3C.2a but 52% (95% CI, -17% to 80%) for clade 3C.3b. VE against A(H3N2) was 53% (95% CI, 10% to 75%) for patients vaccinated in 2014-2015 only, significantly lower at -32% (95% CI, -75% to 0%) if also vaccinated in 2013-2014 and -54% (95% CI, -108% to -14%) if vaccinated each year since 2012-2013. VE against clade-mismatched B(Yamagata) viruses was 42% (95% CI, 10% to 62%) with less-pronounced reduction from prior vaccination compared to A(H3N2). CONCLUSIONS: Variation in the viral genome and negative effects of serial vaccination likely contributed to poor influenza vaccine performance in 2014-2015.

Interim estimates of 2015/16 vaccine effectiveness against influenza A(H1N1)pdm09, Canada, February 2016.

Using a test-negative design, the Canadian Sentinel Practitioner Surveillance Network (SPSN) assessed interim 2015/16 vaccine effectiveness (VE) against influenza A(H1N1)pdm09 viruses. Adjusted VE showed significant protection of 64% (95% confidence interval (CI): 44-77%) overall and 56% (95%CI: 26-73%) for adults between 20 and 64 years-old against medically attended, laboratory-confirmed A(H1N1)pdm09 illness. Among the 67 A(H1N1)pdm09-positive specimens that were successfully sequenced, 62 (> 90%) belonged to the emerging genetic 6B.1 subclade, defined by S162N (potential gain of glycosylation) and I216T mutations in the haemagglutinin protein. Findings from the Canadian SPSN indicate that the 2015/16 northern hemisphere vaccine provided significant protection against A(H1N1)pdm09 illness despite genetic evolution in circulating viruses.

Mutations acquired during cell culture isolation may affect antigenic characterisation of influenza A(H3N2) clade 3C.2a viruses.

As elsewhere, few (< 15%) sentinel influenza A(H3N2) clade 3C.2a viruses that dominated in Canada during the 2014/15 season could be antigenically characterised by haemagglutination inhibition (HI) assay. Clade 3C.2a viruses that could be HI-characterised had acquired genetic mutations during in vitro cell culture isolation that modified the potential glycosylation motif found in original patient specimens and the consensus sequence of circulating viruses at amino acid positions 158-160 of the haemagglutinin protein. Caution is warranted in extrapolating antigenic relatedness based on limited HI findings for clade 3C.2a viruses that continue to circulate globally.

Epidemiology of Enterovirus D68 in Ontario.

In August 2014, children's hospitals in Kansas City, Missouri and Chicago, Illinois notified the Centers for Disease Control and Prevention (CDC) about increased numbers of pediatric patients hospitalized with severe respiratory illness (SRI). In response to CDC reports, Public Health Ontario Laboratories (PHOL) launched an investigation of patients being tested for enterovirus D-68 (EV-D68) in Ontario, Canada. The purpose of this investigation was to enhance our understanding of EV-D68 epidemiology and clinical features. Data for this study included specimens submitted for EV-D68 testing at PHOL from September 1, 2014 to October 31, 2014. Comparisons were made between patients who tested positive for the virus (cases) and those testing negative (controls). EV-D68 was identified in 153/907 (16.8%) of patients tested. In the logistic regression model adjusting for age, sex, setting and time to specimen collection, individuals younger than 20 years of age were more likely to be diagnosed with EV-D68 compared to those 20 and over, with peak positivity at ages 5-9 years. Cases were not more likely to be hospitalized than controls. Cases were more likely to be identified in September than October (OR 8.07; 95% CI 5.15 to 12.64). Routine viral culture and multiplex PCR were inadequate methods to identify EV-D68 due to poor sensitivity and inability to differentiate EV-D68 from other enterovirus serotypes or rhinovirus. Testing for EV-D68 in Ontario from July to December, 2014 detected the presence of EV-D68 virus among young children during September-October, 2014, with most cases detected in September. There was no difference in hospitalization status between cases and controls. In order to better understand the epidemiology of this virus, surveillance for EV-D68 should include testing of symptomatic individuals from all treatment settings and patient age groups, with collection and analysis of comprehensive clinical and epidemiological data.

Randomized evaluation of live attenuated vs. inactivated influenza vaccines in schools (RELATIVES) cluster randomized trial: Pilot results from a household surveillance study to assess direct and indirect protection from influenza vaccination.

BACKGROUND: Children are key drivers of influenza transmission. Vaccinating school age children decreases influenza in the community. OBJECTIVE: To pilot-test the methods for a future trial to compare the direct and indirect benefits of inactivated influenza vaccine (IIV) vs. live attenuated influenza vaccine (LAIV) in preventing influenza infection. METHODS: During the 2013-14 influenza vaccination campaign, we piloted an open-label cluster randomized trial involving 10 elementary schools in Peterborough, Ontario, Canada. We randomized schools on a 1:1 basis to have students receive IIV or LAIV. We invited a subset of vaccinated students and their households to participate in a surveillance sub-study, which involved completing daily symptom diaries during influenza season and collecting mid-turbinate swabs from symptomatic individuals to detect influenza infection. The main outcome measure was confirmed influenza infection using a real-time reverse transcriptase polymerase chain reaction (PCR) assay. RESULTS: One hundred and nineteen households (166 students and 293 household members) participated. During 15 weeks of surveillance, we detected 22 episodes of PCR-confirmed influenza (21 influenza A/H1N1 and 1 influenza B). The incidence of influenza per 1000 person-days was 1.24 (95% CI, 0.40-2.89) for IIV-vaccinated students, compared to 0.13 (95% CI, 0.003-0.72) for LAIV-vaccinated students; the incidence rate ratio was 0.10 (95% CI, 0.002-0.94). Similarly, the incidence of influenza per 1000 person-days was 1.33 (95% CI, 0.64-2.44) for IIV household members, compared to 0.47 (95% CI, 0.17-1.03) for LAIV household members; the incidence rate ratio was 0.36 (95% CI, 0.11-1.08). The overall incidence rate ratio (combining students and household members) was 0.27 (95% CI, 0.09-0.69). CONCLUSIONS: Household surveillance involving participant monitoring and reporting of symptoms and self-collection of mid-turbinate swabs is feasible. A larger study is required to validate the suggestion that vaccinating children with LAIV might confer more protection against influenza for both children and their household contacts, compared to IIV. TRIAL REGISTRATION: ClinicalTrials.gov NCT01995851.

Acute Respiratory Infections in Travelers Returning from MERS-CoV-Affected Areas.

We examined which respiratory pathogens were identified during screening for Middle East respiratory syndrome coronavirus in 177 symptomatic travelers returning to Ontario, Canada, from regions affected by the virus. Influenza A and B viruses (23.1%) and rhinovirus (19.8%) were the most common pathogens identified among these travelers.

Integrated Sentinel Surveillance Linking Genetic, Antigenic, and Epidemiologic Monitoring of Influenza Vaccine-Virus Relatedness and Effectiveness During the 2013-2014 Influenza Season.

BACKGROUND: Canada's Sentinel Physician Surveillance Network links genetic, antigenic, and vaccine effectiveness (VE) measures in an integrated platform of influenza monitoring, described here for the 2013-2014 influenza season of resurgent A(H1N1)pdm09 and late-season type B activity. METHODS: VE was estimated as [1 - odds ratio] × 100% and compared vaccination status between individuals who tested positive (cases) and those who tested negative (controls) for influenza virus. Vaccine-virus relatedness was assessed by genomic sequence analysis and hemagglutination inhibition assays. RESULTS: Analyses included 1037 controls (of whom 33% were vaccinated) and 663 cases (of whom 14% were vaccinated). A total of 415 cases tested positive for A(H1N1)pdm09 virus, 15 tested positive for A(H3N2) virus, 191 tested positive for B/Yamagata-lineage virus, 6 tested positive for B/Victoria-lineage virus, and 36 tested positive for viruses of unknown subtype or lineage. A(H1N1)pdm09 viruses belonged to clade 6B, distinguished by a K163Q substitution, but remained antigenically similar to the A/California/07/2009-like vaccine strain, with an adjusted VE of 71% (95% confidence interval [CI], 58%-80%). Most B/Yamagata-lineage viruses (83%) clustered phylogenetically with the prior (ie, 2012-2013) season's B/Wisconsin/01/2010-like clade 3 vaccine strain, while only 17% clustered with the current (ie, 2013-2014) season's B/Massachusetts/02/2012-like clade 2 vaccine strain. The adjusted VE for B/Yamagata-lineage virus was 73% (95% CI, 57%-84%), with a lower VE obtained after partial calendar-time adjustment for clade-mismatched B/Wisconsin/01/2010-like virus (VE, 63%; 95% CI, 41%-77%), compared with that for clade-matched B/Massachusetts/02/2012-like virus (VE, 88%; 95% CI, 48%-97%). No A(H3N2) viruses clustered with the A/Texas/50/2012-like clade 3C.1 vaccine strain, and more than half were antigenically mismatched, but sparse data did not support VE estimation. CONCLUSIONS: VE corresponded with antigenically conserved A(H1N1)pdm09 and lineage-matched B/Yamagata viruses with clade-level variation. Surveillance linking genotypic, phenotypic, and epidemiologic measures of vaccine-virus relatedness and effectiveness could better inform predictions of vaccine performance and reformulation.