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This population-based cohort study evaluated whether differences in COVID-19 incidence between children and adults in Ontario could be accounted for by differences in testing. The authors developed an approach that permits adjustment for differential relationships between testing and risk in different age and sex groups in the population., Background: Despite expected initial universal susceptibility to a novel pandemic pathogen like SARS-CoV-2, the pandemic has been characterized by higher observed incidence in older persons and lower incidence in children and adolescents. Objective: To determine whether differential testing by age group explains observed variation in incidence. Design: Population-based cohort study. Setting: Ontario, Canada. Participants: Persons diagnosed with SARS-CoV-2 and those tested for SARS-CoV-2. Measurements: Test volumes from the Ontario Laboratories Information System, number of laboratory-confirmed SARS-CoV-2 cases from the Integrated Public Health Information System, and population figures from Statistics Canada. Demographic and temporal patterns in incidence, testing rates, and test positivity were explored using negative binomial regression models and standardization. Sources of variation in standardized ratios were identified and test-adjusted standardized infection ratios (SIRs) were estimated by metaregression. Results: Observed disease incidence and testing rates were highest in the oldest age group and markedly lower in those younger than 20 years; no differences in incidence were seen by sex. After adjustment for testing frequency, SIRs were lowest in children and in adults aged 70 years or older and markedly higher in adolescents and in males aged 20 to 49 years compared with the overall population. Test-adjusted SIRs were highly correlated with standardized positivity ratios (Pearson correlation coefficient, 0.87 [95% CI, 0.68 to 0.95]; P < 0.001) and provided a case identification fraction similar to that estimated with serologic testing (26.7% vs. 17.2%). Limitations: The novel methodology requires external validation. Case and testing data were not linkable at the individual level. Conclusion: Adjustment for testing frequency provides a different picture of SARS-CoV-2 infection risk by age, suggesting that younger males are an underrecognized group at high risk for SARS-CoV-2 infection. Primary Funding Source: Canadian Institutes of Health Research.

In late 2019 the respiratory illness, Corona Virus Disease-19 caused by the SARS-CoV-2 virus emerged in China and quickly spread to other countries. The primary mode of transmission is person-to-person via respiratory droplets. SARS-CoV-2 has been identified in conjunctiva. Transmission by cornea transplant has not been reported but is theoretically possible. We aimed to estimate the possible risk of transmission in Canada via cornea transplant during the first wave of the pandemic, and the potential risk reduction from testing decedents. We constructed a deterministic model in which the risk of transmission was estimated as the product of three proportions: decedents with SARS-CoV-2 infection, corneas that are NAT positive, and NAT positive corneas presumed to transmit. Risk was estimated according to 3 scenarios: most likely, optimistic and pessimistic. At the peak of the first wave of the pandemic risk was estimated to be 1 in 63,031 cornea transplants in Canada but could be as low as 1 in 175,821 or as high as 1 in 10,129. It would take 16 years at the peak infection of the first wave of the pandemic to observe 1 transmission. Testing would reduce the risk of 1 in 63,031 to 1 in 210,104 assuming 70% test sensitivity. The theoretical risk of SARS-CoV-2 transmission by cornea transplant is extremely low and decedent testing is unlikely to be beneficial.

BACKGROUND Babesia microti has gained a foothold in Canada as tick vectors become established in broader geographic areas. B. microti infection is associated with mild or no symptoms in healthy individuals but is transfusion-transmissible and can be fatal in immunocompromised individuals. This is the first estimate of clinically significant transfusion-transmitted babesiosis (TTB) risk in Canada. STUDY DESIGN AND METHODS The proportion of B. microti-antibody (AB)/nucleic acid amplification test (NAT)-positive whole blood donations was estimated at 5.5% of the proportion of the general population with reported Lyme Disease (also tick-borne) based on US data. Monte Carlo simulation estimated the number and proportion of infectious red cell units for three scenarios: base, localized incidence (risk in Manitoba only), and donor study informed (prevalence from donor data). The model simulated 1,029,800 donations repeated 100,000 times for each. RESULTS In the base scenario 0.5 (0.01, 1.75), B. microti-NAT-positive donations would be expected per year, with 0.08 (0, 0.38) recipients suffering clinically significant TTB (1 every 12.5 years). In the localized incidence scenario, there were 0.21(0, 0.7) B. microti-NAT-positive donations, with 0.04 (0, 0.14) recipient infections (about 1 every 25 years). In the donor study informed scenario, there were 4.6 (0.3, 15.8) B. microti-NAT-positive donations expected, and 0.81 (0.05, 3.14) clinically significant TTB cases per year. DISCUSSION The likelihood of clinically relevant TTB is low. Testing would have very little utility in Canada at this time. Ongoing pathogen surveillance in tick vectors is important as B. microti prevalence appears to be slowly increasing in Canada.

The emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus responsible for the coronavirus disease 2019 (COVID-19) pandemic has raised concerns for programs overseeing donation and transplantation of cells, tissues, and organs (CTO) that this virus might be transmissible by transfusion or transplantation. Transplant recipients are considered particularly vulnerable to pathogens because of immunosuppression, and SARS-CoV-2 is likely to generate complications if contracted. Several signs and symptoms observed in COVID-19 positive patients reflect damage to multiple organs and tissues, raising the possibility of extrapulmonary SARS-CoV-2 infections and risk of transmission. At the beginning of the pandemic, a consensus has emerged not to consider COVID-19 positive patients as potential living or deceased donors, resulting in a global decrease in transplantation procedures. Medical decision-making at the time of organ allocation must consider safely alongside the survival advantages offered by transplantation. To address the risk of transmission by transplantation, this review summarizes the published cases of transplantation of cells or organs from donors infected with SARS-CoV-2 until January 2021 and assesses the current state of knowledge for the detection of this virus in different biologic specimens, cells, tissues, and organs. Evidence collected to date raises the possibility of SARS-CoV-2 infection and replication in some CTO, which makes it impossible to exclude transmission through transplantation. However, most studies focused on evaluating transmission under laboratory conditions with inconsistent findings, rendering the comparison of results difficult. Improved standardization of donors and CTO screening practices, along with a systematic follow-up of transplant recipients could facilitate the assessment of SARS-CoV-2 transmission risk by transplantation.

Background Case detection underestimates the burden of the COVID‐19 pandemic. Following the first COVID‐19 wave, we estimated the seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) among blood donors across Canada. Study Design and Methods This serial cross‐sectional study was conducted between May 9 and July 21, 2020 from blood donors donating at all Canadian Blood Services locations. We used the Abbott Architect assay to detect SARS‐CoV‐2 IgG antibodies from retention plasma. Seroprevalence was standardized to population‐level demographics and assay characteristics were adjusted using the Rogan‐Gladen equation. Results were stratified by region, age, ethnicity, ABO groups, and quantiles of material and social deprivation indices. Temporal trends were evaluated at 2‐week intervals. Univariate and multivariate logistic regression compared SARS‐CoV‐2 reactive to non‐reactive donors by sociodemographic variables. Results Overall 552/74642 donors, had detectable antibodies, adjusted seroprevalence was 7.0/1000 donors (95% CI; 6.3, 7.6). Prevalence was differential by geography, Ontario had the highest rate, 8.8/1000 donors (7.8, 9.8), compared to the Atlantic region 4.5/1000 donors (2.6, 6.4); adjusted odds ratio (aOR) 2.2 (1.5, 3.3). Donors that self‐identified as an ethnic minority were more likely than white donors to be sero‐reactive aOR 1.5 (1.2, 1.9). No temporal trends were observed. Discussion Worldwide, blood services have leveraged their operational capacity to inform public health. While >99% of Canadians did not show humoral evidence of past infection, we found regional variability and disparities by ethnicity. Seroprevalence studies will continue to play a pivotal role in evaluating public health policies by identifying trends and monitor disparities.

Background An obstacle in influenza therapeutics development is the lack of clinical endpoints, especially in hospitalized patients. A single time-point binary outcome measure is limited by patients’ diverse clinical trajectories and low event rates. Methods A 6-point ordinal scale with ascending clinical status severity (scoring: discharged; subacute care; acute care without/with respiratory failure; intensive care unit [ICU]; death) was proposed to study outcomes of adults hospitalized with influenza. Individual patient data from 2 active surveillance cohorts’ datasets (2015/2016−2017/2018; Edmonton, Hong Kong) was used for evaluation. The impact of neuraminidase inhibitor (NAI) treatment on longitudinal ordinal outcome changes over 30 days was analyzed using mixed-effects ordinal logistic regression and group-based trajectory models. Results Patient (n = 1226) baseline characteristics included age (mean 68.0 years), virus-type (A 78.1%, B 21.9%), respiratory failure (57.2%), ICU admittance (14.4%), and NAI treatment within 5 days of illness (69.2%). Outcomes at 30 days included discharged (75.2%), subacute care (13.7%), acute care (4.5%), and death (6.6%). Two main clinical trajectories were identified, predictive by baseline scoring (mean ± SD, 4.3 ± 0.6 vs 3.5 ± 0.6, P Conclusions The ordinal outcome scale is a potentially useful clinical endpoint for influenza therapeutic trials, which could account for the diverse clinical trajectories of hospitalized patients, warranting further development.

Background West Nile Virus (WNV) is a member of the Japanese Encephalitis (JE) serocomplex within the Flaviviridae family. We report four whole blood donors and one plasma donor with WNV nucleic acid test (NAT)-reactive donations between September 2018 and November 2019, following recent Japanese Encephalitis virus (JEV) vaccination. Case series Cases 1 and 4 had reactive WNV NAT donations 1 day after receiving the JEV vaccine. Case 2 had a reactive WNV donation 3 days after receiving the JEV vaccine. Case 3 had a reactive WNV NAT donation 3 days after returning from Arizona and 1 day after receiving the JEV vaccine. Case 5 had a reactive WNV donation the same day as receiving the JEV vaccine. Study design and methods WNV screening used the Roche cobas WNV nucleic acid test (NAT) (Roche Molecular Systems). Reference testing on WNV-reactive donations was carried out by the National Microbiology Laboratory (NML). JEV vaccine dilutions were also analyzed. Results Supplemental NAT was negative for WNV and JEV for Cases 1, 3, and 5. Case 2 had a weak amplification curve for one of two JEV NAT targets. Case 4 was JEV NAT-positive, WNV NAT-negative. Serologic testing on donation specimens for Cases 2, 4, and 5 did not support recent or remote WNV infection. JEV vaccine dilutions were detected by both cobas and supplemental NAT. Conclusions We recommend implementing a temporary blood donor deferral following a JEV vaccination, if screening utilizes a WNV assay with the capability of detecting other members of the JE serocomplex.

Background Vancomycin-resistant enterococci (VRE) are antibiotic-resistant organisms associated with both colonization and serious life-threatening infection in health care settings. Contamination of platelet concentrates (PCs) with Enterococcus can result in transfusion-transmitted infection. Case presentation This report describes the investigation of a septic transfusion case involving a 27-year-old male patient with relapsed acute leukemia who was transfused with a 5-day-old buffy coat PC pool and developed fever and rigors. Discussion Microbiology testing and pulse-field gel electrophoresis (PFGE) was done on patient blood cultures obtained from peripheral and central lines. Microbiology and molecular testing were also performed on the remaining posttransfusion PC pool, which was refrigerated for 24 hours before microbiology testing. Red blood cell (RBC) and plasma units associated with the implicated PCs were screened for microbial contamination. Patient blood cultures obtained from peripheral and central lines yielded vancomycin-resistant Enterococcus faecium. Gram stain of a sample from the platelet pool was negative but coagulase-negative Staphylococcus (CNST) and VRE were isolated on culture. Antibiotic sensitivity and PFGE profiles of several VRE isolates from the patient before and after transfusion, and the PC pool, revealed that all were closely related. Associated RBC and plasma components tested negative for microbial contamination. Conclusions Microbiological and molecular investigations showed a relationship between VRE isolated from the patient before and after transfusion, and therefore it is postulated that a patient-to-PC retrograde contamination (from either blood or skin) occurred. As the CNST isolated from the PC pool was not isolated from patient samples, its implication in the transfusion event is unknown.

Background This pilot study assesses the ability of plasma collected from Canadian blood donors in the first wave of the SARS-CoV-2 pandemic to neutralize later SARS-CoV-2 variants of concern (VOCs). Study design and methods A repeated cross-sectional design was employed, and a random cross-sectional sample of all available Canadian Blood Services retention samples (n=1500/month) was drawn monthly for April and May of 2020. Qualitative IgG analysis was performed on aliquots of specimens using anti-spike, anti-receptor binding domain and anti-nucleocapsid protein enzyme-linked immunosorbent assays as well as the Abbott Architect SARS CoV-2 IgG assay (Abbott Laboratories, USA) against anti-nucleocapsid protein. Selected plasma specimens were then assessed for neutralization against VOCs using pseudotyped lentivirus inhibition assays as well as plaque reduction neutralization test 50% (PRNT50 ). Results Six specimens with a high neutralizing titer against wild-type SARS-CoV-2 and three specimens with a low neutralizing titer against wild-type SARS-CoV-2 were chosen for further analysis against VOCs. Four of six high neutralizing titer specimens had a reduced neutralizing capacity against Beta VOCs by both neutralization methods. Three of six high neutralizing titer specimens had reduced neutralization capacity against Gamma VOCs. Conclusions This preliminary data can be used as a justification for limiting the use of first wave plasma products in upcoming clinical trials but cannot be used to speculate on general trends in the immunity of Canadian blood donors to SARS-CoV-2. This article is protected by copyright. All rights reserved.

Although pertussis vaccines have been widely used for many decades, a burden of illness persists. Resurgences in Ontario, Canada, have not been substantial in the past decade, but an outbreak of pertussis occurred in Toronto between 1 October 2005 and 31 March 2006. Previous Ontario studies found high vaccine effectiveness (VE) in the initial years post-immunization. In order to explore the impact of outbreaks and external factors on VE, we investigated pertussis VE during the period 2006-2008.We assessed pertussis VE using a frequency-matched case-control study for the period 1 March 2006 to 31 December 2008. We used logistic regression to estimate VE by age, time since last vaccination, and vaccination status according to the Ontario recommended schedule. We compared analyses including and excluding cases from Toronto, and to two recent Ontario pertussis VE studies.We included 1797 confirmed cases and 7188 matched controls. Most cases were under 4 years of age during the study period. Pertussis VE was 3.8% (95% CI: - 21.0, 24.0) in the period 15-364 days following the last pertussis vaccine dose, and increased with increasing time since vaccination. Pertussis VE in the first 15-364 days excluding Toronto increased to 57.1% (95% CI: 26.0, 75.1), but the trend of increasing VE with time since vaccination persisted. Although VE was higher in older (6-11 years) than younger (0-5 years) children, it was lower at 12-13 years than after 14 years.VE was lower in comparison with other studies conducted in Ontario, particularly in younger children. Various factors occurring during the study period may have influenced the results, including clinical testing of asymptomatic contacts, laboratory testing and methods and reporting practice, and a sensitive case definition. Further studies are needed to optimize methods for measuring VE to inform pertussis vaccine policy.RéSUMé: OBJECTIFS: Bien que les vaccins anticoquelucheux soient couramment utilisés depuis des dizaines d’années, la charge de morbidité de la coqueluche persiste. Sa réapparition en Ontario, au Canada, a été modérée au cours des 10 dernières années, mais une éclosion de coqueluche s’est produite à Toronto entre le 1

Background and objectives We describe the third documented case of autochthonous human babesiosis in Canada and the second in a Canadian blood donor. Materials and methods Multiple laboratory investigations were carried out on the donor and the immunocompromised recipient of an associated, potentially infectious red blood cell product. Results The donor had not travelled except for outdoor exposure in south-eastern Manitoba, followed by illness and hospital admission. The donor had a notable parasitaemia, positive for Babesia microti using whole blood nucleic acid testing (NAT). The recipient was negative for B. microti by both serology and NAT. Conclusion There was no evidence of transfusion-transmitted babesiosis.

IntroductionThe COVID-19 pandemic has an excessive impact on residents in long-term care facilities (LTCF), causing high morbidity and mortality. Early detection of presymptomatic and asymptomatic COVID-19 cases supports the timely implementation of effective outbreak control measures but repetitive screening of residents and staff incurs costs and discomfort. Administration of vaccines is key to controlling the pandemic but the robustness and longevity of the antibody response, correlation of neutralising antibodies with commercial antibody assays, and the efficacy of current vaccines for emerging COVID-19 variants require further study. We propose to monitor SARS-CoV-2 in site-specific sewage as an early warning system for COVID-19 in LTCF and to study the immune response of the staff and residents in LTCF to COVID-19 vaccines.Methods and analysisThe study includes two parts: (1) detection and quantification of SARS-CoV-2 in LTCF site-specific sewage samples using a molecular assay followed by notification of Public Health within 24 hours as an early warning system for appropriate outbreak investigation and control measures and cost–benefit analyses of the system and (2) testing for SARS-CoV-2 antibodies among staff and residents in LTCF at various time points before and after COVID-19 vaccination using commercial assays and neutralising antibody testing performed at a reference laboratory.Ethics and disseminationEthics approval was obtained from the University of Alberta Health Research Ethics Board with considerations to minimise risk and discomforts for the participants. Early recognition of a COVID-19 case in an LTCF might prevent further transmission in residents and staff. There was no direct benefit identified to the participants of the immunity study. Anticipated dissemination of information includes a summary report to the immunity study participants, sharing of study data with the scientific community through the Canadian COVID-19 Immunity Task Force, and prompt dissemination of study results in meeting abstracts and manuscripts in peer-reviewed journals.

Background The erythrocytic protozoan parasite Babesia microti, the cause of human babesiosis, is transmitted not only by tick bites but also via blood transfusion. B. microti is endemic in the northeastern/upper midwestern United States, where partial screening of blood donations has been implemented. In Canada, a 2013 study of approximately 14,000 donors found no B. microti antibody-positive samples, suggesting low risk at that time. Methods Between June and October 2018, 50,752 Canadian donations collected from sites near the US border were tested for Babesia nucleic acid by transcription-mediated amplification (TMA). Reactive donations were tested for B. microti by IgG immunofluorescence assay and polymerase chain reaction. A subset of 14,758 TMA nonreactive samples was also screened for B. microti antibody. Donors who tested reactive/positive were deferred, asked about risk factors, and were requested to provide a follow-up sample for supplemental testing. Results One sample from Winnipeg, Manitoba, was TMA and antibody reactive. Of the 14,758 TMA-nonreactive donations tested for antibody, four reactive donations were identified from southwestern Ontario near Lake Erie. None of the interviewed donors remembered any symptoms, likely tick exposure, or relevant travel within Canada or the United States. Conclusions This is the largest B. microti prevalence study performed in Canada. The results indicate very low prevalence, with only one TMA-confirmed-positive donation of 50,752 tested. This donor was from the only region in Canada where autochthonous infection has been reported. Seropositive donations in southwestern Ontario suggest low prevalence; travel should not be ruled out given the proximity to the US border.

Lower respiratory tract infections are a leading cause of hospitalization and viruses are important causal pathogens, especially in the elderly, immunocompromised patients and those with respiratory or cardiovascular comorbidities. Respiratory syncytial virus (RSV) is recognized as comprising a substantial burden of morbidity and mortality in older and at-risk adults, and the emergence of rapid point-of-care molecular testing has made it possible to confirm an RSV diagnosis accurately, in a clinically actionable timeframe. RSV patients have significantly higher healthcare resource use (including hospital stays and emergency room/urgent care visits) than non-RSV matched controls, especially if aged ≥65 years, a longer length of hospitalization than those with influenza, and associated costs nearly three times higher. We found no direct clinical outcome data specific to rapid molecular testing for RSV in adults and very little in children. There is very limited evidence that prompt diagnosis may reduce hospital length of stay but this and other outcome parameters need confirmation in larger, prospective clinical trials. Regarding reducing inappropriate antibiotic prescribing, the picture is mixed and testing alone is unlikely to change entrenched habits. There is little incentive for clinicians to order routine RSV tests in adults given the absence of a specific antiviral therapy. However, with numerous vaccine and antiviral candidates in clinical development, we believe it is good practice to plan and start establishing standardized testing protocols – perhaps as part of outcome studies. For especially vulnerable patients, e.g., immunocompromised and transplant patients, prompt accurate RSV diagnosis may prevent disease spread and save lives.

Background The purpose of this paper is to systematically review the literature on the relationship between socioeconomic status (SES) and influenza immunization and to examine how certain measures of SES may influence interpretations of this relationship. Methods We conducted a systematic review of existing peer-reviewed literature to evaluate the above relationship in the general population. Electronic databases (MEDLINE and EMBASE) were searched from January 2012 to May 2017 to identify English-language studies relevant to this review. Studies were included where influenza vaccination was explicitly reported as the dependent variable and SES as the independent variable. We limited our review to measures of SES that focus on education, income, social class, occupation, and deprivation. Studies that measured SES using other variables (e.g., race, ethnicity, geographic location, rural or urban status, or insurance status) were excluded. Studies were also excluded if they did not report on the human population or did not analyze original data. The population of interest included all age groups, levels of health status, and sociodemographic backgrounds. The review was also limited to World Bank high-income countries. Two authors independently screened full-text articles after obtaining a Kappa score of K = 0.867. The methodological quality of manuscripts was assessed using the appraisal tools developed by the Joanna Briggs Institute. Results were qualitatively reported and synthesized. Results Of the 42 articles included in this review, 52.4% (n = 22) found that higher levels of SES resulted in higher levels of influenza vaccination; 4.5% (n = 2) reported a negative association; and 14.3% (n = 6) found no association. Just over a quarter (26.2%, n = 12) of articles reported mixed results. Conclusions There was consistently a relationship between SES and influenza immunization, which varied according to how SES was measured. It is recommended that authors be explicit in defining the SES concept they are trying to capture and that they utilize multiple measures of SES (e.g., education, income, class). Electronic supplementary material The online version of this article (10.1186/s12874-019-0801-1) contains supplementary material, which is available to authorized users.

International audience; ObjectivesTo improve our understanding of the global epidemiology of common respiratory viruses by analysing their contemporaneous incidence at multiple sites.Methods2010–2015 incidence data for influenza A (IAV), influenza B (IBV), respiratory syncytial (RSV) and parainfluenza (PIV) virus infections were collected from 18 sites (14 countries), consisting of local (n = 6), regional (n = 9) and national (n = 3) laboratories using molecular diagnostic methods. Each site submitted monthly virus incidence data, together with details of their patient populations tested and diagnostic assays used.ResultsFor the Northern Hemisphere temperate countries, the IAV, IBV and RSV incidence peaks were 2–6 months out of phase with those in the Southern Hemisphere, with IAV having a sharp out-of-phase difference at 6 months, whereas IBV and RSV showed more variable out-of-phase differences of 2–6 months. The tropical sites Singapore and Kuala Lumpur showed fluctuating incidence of these viruses throughout the year, whereas subtropical sites such as Hong Kong, Brisbane and Sydney showed distinctive biannual peaks for IAV but not for RSV and PIV.ConclusionsThere was a notable pattern of synchrony of IAV, IBV and RSV incidence peaks globally, and within countries with multiple sampling sites (Canada, UK, Australia), despite significant distances between these sites.

Background Resurgences of pertussis have occurred in several high-income countries, often linked to waning of immunity from acellular pertussis vaccines. The degree of waning observed has varied by study design and setting. In Ontario, pertussis has not shown a substantial resurgence in the past decade. The routine immunization schedule comprises three priming doses in infancy, toddler and pre-school doses, and an adolescent dose at 14–16 years of age. Methods We estimated pertussis vaccine effectiveness (VE) through a case-control study of 1335 cases statutorily reported to public health in Ontario and occurring between January 1, 2009 and March 31, 2015, compared with 5340 randomly selected population controls, frequency-matched by age, primary-care provider and year of diagnosis. Pertussis cases met provincial confirmed or probable case definitions. We used multivariable logistic regression to estimate crude and adjusted odds ratios (aOR). Results VE against pertussis was sustained between 92% (95% confidence interval (95%CI) 88–95%) in 2–3 year olds and 90% (95%CI: 80–95%) in 8–9 year olds, but fell rapidly to 49% (95%CI: 2–73%) in children 12–13 years of age. VE following the teenage booster given at 14–16 years in Ontario reached 76% (95%CI: 52–88%) in 14–16 year olds and 78% (95%CI: −31 to 96%) in those 16–22 years old. For children who were up-to-date with the immunization schedule, VE declined from 87% (95%CI: 84–90%) during the first year to 74% (95%CI: 63–82%) after 8 or more years following their last dose of immunization. Conclusions VE is high during the first decade of life but then falls rapidly. Protection is not fully restored by the teenage booster. Our findings are consistent with the localized outbreaks we observe in high school children and underline the importance of additional policies to protect infants.

Background To date, no study has examined influenza vaccine effectiveness (IVE) against laboratory-confirmed influenza-associated hospitalizations during pregnancy. Methods The Pregnancy Influenza Vaccine Effectiveness Network (PREVENT) consisted of public health or healthcare systems with integrated laboratory, medical, and vaccination records in Australia, Canada (Alberta and Ontario), Israel, and the United States (California, Oregon, and Washington). Sites identified pregnant women aged 18 through 50 years whose pregnancies overlapped with local influenza seasons from 2010 through 2016. Administrative data were used to identify hospitalizations with acute respiratory or febrile illness (ARFI) and clinician-ordered real-time reverse transcription polymerase chain reaction (rRT-PCR) testing for influenza viruses. Overall IVE was estimated using the test-negative design and adjusting for site, season, season timing, and high-risk medical conditions. Results Among 19450 hospitalizations with an ARFI discharge diagnosis (across 25 site-specific study seasons), only 1030 (6%) of the pregnant women were tested for influenza viruses by rRT-PCR. Approximately half of these women had pneumonia or influenza discharge diagnoses (54%). Influenza A or B virus infections were detected in 598/1030 (58%) of the ARFI hospitalizations with influenza testing. Across sites and seasons, 13% of rRT-PCR-confirmed influenza-positive pregnant women were vaccinated compared with 22% of influenza-negative pregnant women; the adjusted overall IVE was 40% (95% confidence interval = 12%-59%) against influenza-associated hospitalization during pregnancy. Conclusion Between 2010 and 2016, influenza vaccines offered moderate protection against laboratory-confirmed influenza-associated hospitalizations during pregnancy, which may further inform the benefits of maternal influenza vaccination programs.

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.

BACKGROUND AND OBJECTIVES: Access to large pools of healthy adult donors advantageously positions blood component providers to undertake anti-SARS-CoV-2 seroprevalence studies. While numerous seroprevalence reports have been published by blood operators during the COVID-19 pandemic, details on the assay used has not been well documented. The objectives of this study were to evaluate the diversity of assays being used by blood operators and assess how this may affect seroprevalence estimates.MATERIALS AND METHODS: We surveyed 49 blood component providers from 39 countries. Questionnaire included information on the number and identity of assays used, the detected immunoglobulin(s) and target antigen, and performance characteristics (sensitivity, specificity).RESULTS: Thirty-eight of the 49 contacted blood suppliers provided at least partial responses. The results indicate that 19 commercial and five in-house serology assays have been used by surveyed blood operators. The Abbott SARS-CoV-2 IgG assay was the most commonly used kit and utilized by 15 blood suppliers. Two assays did not detect IgG, but detected either IgM/IgA or IgM. 68·2% of assays targeted the spike protein and 50% the nucleocapsid protein, while 18·2% targeted both viral proteins. The sensitivity and specificity of IgG-specific assays ranged from 71·9% to 100% and from 96·2% to 100%, respectively. As of 18 October 2020, the seroprevalence was below 5% in 10 of 14 countries reporting.CONCLUSION: Our results highlight the diversity of assays being used. Analyses comparing blood donor seroprevalence across countries should consider assay characteristics with optimization of signal/cut-off ratios and consistent methodology to adjust for waning antibody.

Background and objectives Filariae are parasitic worms that include the pathogens Loa loa, Onchocerca volvulus, Wuchereria bancrofti, Brugia spp. and Mansonella spp. which are endemic in parts of Africa, Asia, Asia-Pacific, South and Central America. Filariae have a wide clinical spectrum spanning asymptomatic infection to chronic debilitating disease including blindness and lymphedema. Despite successful eradication programmes, filarial infections remain an important -albeit neglected - source of morbidity. We sought to characterize the risk of transfusion transmission of microfilaria with a view to guide mitigation practices in both endemic and non-endemic countries. Materials and methods A scoping review of scientific publications as well as grey literature was carried out by a group of domain experts in microbiology, transfusion medicine and infectious diseases, representing the parasite subgroup of the International Society of Blood Transfusion. Results Cases of transfusion-transmitted filariasis are rare and confined to case reports of variable quality. Transfusion-associated adverse events related to microfilariae are confined to isolated reports of transfusion reactions. Serious outcomes have not been reported. No known strategies have been implemented, specifically, to mitigate transfusion-transmitted filariasis yet routine blood donor screening for other transfusion-transmissible infections (e.g. hepatitis B, malaria) may indirectly defer donors with microfilaremia in endemic areas. Conclusion Rare examples of transfusion-transmitted filariasis, without serious clinical effect, suggest that filariasis poses low transfusion risk. Dedicated mitigation strategies against filarial transfusion transmission are not recommended. Given endemicity in low-resource regions, priority should be on the control of filariasis with public health measures.

BACKGROUND: Convalescent plasma products are a potential passive immunotherapy for Coronavirus disease 2019 (COVID-19) disease. Various approaches have been utilized to determine the concentration of Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-neutralizing antibodies in plasma products. The Canadian Blood Services used Plaque Reduction Neutralization Test 50 (PRNT50) -generated values to qualify convalescent plasma donations supporting clinical trials in Canada. This manuscript describes changes in PRNT50 titers of repeat male plasma donations collected approximately 1-4 months after onset of COVID-19 signs and symptoms in donors. STUDY DESIGN AND METHODS: Men were eligible to donate if they: met standard criteria, were < 67 years of age, reported a previous SARS-CoV-2-positive nucleic acid test, and recovered and were symptom free for at least 28 days prior to donation. Repeat donation analysis required at least one original and one repeat donation where a PRNT50 was performed. RESULTS: From April 29, 2020 to July 25, 2020, 156 donors donated once, with 78 (50%) of the donated plasma having PRNT50 titers of ≥1:160. Thirty-seven (23.7%) of the donated plasma had a titer of 1:40 or 1:80 (individuals donating this plasma were asked to donate a second time only). A total of 30 donors (19.2%) had repeat donations. Of the repeat donors, 15 (50%) had at least an eightfold change from peak to trough PRNT50 titers within greater than 90 days after onset of COVID-19 symptoms. CONCLUSIONS: Blood operators cannot infer that SARS-CoV-2 PRNT50 will remain high in repeat plasma donors 3-4 months after onset of COVID-19 symptoms.

BACKGROUND Pertussis remains poorly controlled relative to other diseases targeted by childhood vaccination programs. We combined estimates from four population-based studies of pertussis vaccine effectiveness (VE) in three Canadian provinces using a meta-analytic approach to improve precision and explore regional variation in VE and durability of protection. METHODS Studies were conducted in Alberta, Manitoba, and Ontario over periods ranging from 1996 to 2015. Adjusted log odds ratios (OR; VE = 100*[1-OR]) of the effect of vaccination on pertussis risk were estimated by time since last vaccination in each study and pooled using DerSimonian and Laird random-effects models. We used the I2 statistic to estimate between-study heterogeneity and assessed methodological and clinical heterogeneity through subgroup analyses of study design and age. RESULTS Data on 3,270 pertussis cases and 23,863 controls were available. Pertussis VE declined from 86% (95% CI 79%-90%, I2 = 81.5%) at

Saliva is an alternative biofluid to serum for detecting and monitoring IgG to SARS-CoV-2 spike and RBD antigens in COVID-19., While the antibody response to SARS-CoV-2 has been extensively studied in blood, relatively little is known about the antibody response in saliva and its relationship to systemic antibody levels. Here, we profiled by enzyme-linked immunosorbent assays (ELISAs) IgG, IgA and IgM responses to the SARS-CoV-2 spike protein (full length trimer) and its receptor-binding domain (RBD) in serum and saliva of acute and convalescent patients with laboratory-diagnosed COVID-19 ranging from 3–115 days post-symptom onset (PSO), compared to negative controls. Anti-SARS-CoV-2 antibody responses were readily detected in serum and saliva, with peak IgG levels attained by 16–30 days PSO. Longitudinal analysis revealed that anti-SARS-CoV-2 IgA and IgM antibodies rapidly decayed, while IgG antibodies remained relatively stable up to 105 days PSO in both biofluids. Lastly, IgG, IgM and to a lesser extent IgA responses to spike and RBD in the serum positively correlated with matched saliva samples. This study confirms that serum and saliva IgG antibodies to SARS-CoV-2 are maintained in the majority of COVID-19 patients for at least 3 months PSO. IgG responses in saliva may serve as a surrogate measure of systemic immunity to SARS-CoV-2 based on their correlation with serum IgG responses.

Most of the patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mount a humoral immune response to the virus within a few weeks of infection, but the duration of this response and how it correlates with clinical outcomes has not been completely characterized. Of particular importance is the identification of immune correlates of infection that would support public health decision-making on treatment approaches, vaccination strategies, and convalescent plasma therapy. While ELISA-based assays to detect and quantitate antibodies to SARS-CoV-2 in patient samples have been developed, the detection of neutralizing antibodies typically requires more demanding cell-based viral assays. Here, we present a safe and efficient protein-based assay for the detection of serum and plasma antibodies that block the interaction of the SARS-CoV-2 spike protein receptor binding domain (RBD) with its receptor, angiotensin-converting enzyme 2 (ACE2). The assay serves as a surrogate neutralization assay and is performed on the same platform and in parallel with an ELISA for the detection of antibodies against the RBD, enabling a direct comparison. The results obtained with our assay correlate with those of 2 viral-based assays, a plaque reduction neutralization test (PRNT) that uses live SARS-CoV-2 virus and a spike pseudotyped viral vector–based assay., An ELISA-type competition assay serves as a neutralization surrogate for SARS-CoV-2 infection and was validated against standard neutralization assays on cohorts of convalescent patients.

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is a novel human coronavirus responsible for coronavirus disease 2019 (COVID‐19). The emergence of this virus in Wuhan (China) at the end of 2019, and its worldwide spread to reach the pandemic stage, has raised concerns about the possible risk that it might be transmissible by transfusion. This theoretical risk is further supported by reports of the detection of viral RNA in the blood of some infected individuals. To further address this risk, a thorough PubMed literature search was performed to systematically identify studies reporting data on the detection of SARS‐CoV‐2 RNA in blood or its components. Complementary searches were done to identify articles reporting data on the in vitro infectivity of blood components. At least 23 articles presenting data on the detection of SARS‐CoV‐2 RNA in blood, plasma, or serum were identified. Of these, three studies reported on blood donors with COVID‐19 infection identified post‐donation, and no cases of transfusion transmission were identified. A few studies mentioned results of in vitro infectivity assays of blood components in permissive cell lines, none of which were able to detect infectious virus in blood or its components. Complementary searches have identified reports demonstrating that the correlation between the presence of viral RNA in a biological sample and infectivity requires a minimal RNA load, which is rarely, if at all observed, in blood components. Overall, the available evidence suggests that the risk of transmission of SARS‐CoV‐2 by transfusion remains theoretical.

While the antibody response to SARS-CoV-2 has been extensively studied in blood, relatively little is known about the mucosal immune response and its relationship to systemic antibody levels. Since SARS-CoV-2 initially replicates in the upper airway, the antibody response in the oral cavity is likely an important parameter that influences the course of infection, but how it correlates to the antibody response in serum is not known. Here, we profile by enzyme linked immunosorbent assays (ELISAs) IgG, IgA and IgM responses to the SARS-CoV-2 spike protein (full length trimer) and its receptor binding domain (RBD) in serum (n=496) and saliva (n=90) of acute and convalescent patients with laboratory-diagnosed COVID-19 ranging from 3–115 days post-symptom onset (PSO), compared to negative controls. Anti-CoV-2 antibody responses were readily detected in serum and saliva, with peak IgG levels attained by 16–30 days PSO. Whereas anti-CoV-2 IgA and IgM antibodies rapidly decayed, IgG antibodies remained relatively stable up to 105 days PSO in both biofluids. In a surrogate neutralization ELISA (snELISA), neutralization activity peaks by 31–45 days PSO and slowly declines, though a clear drop is detected at the last blood draw (105–115 days PSO). Lastly, IgG, IgM and to a lesser extent IgA responses to spike and RBD in the serum positively correlated with matched saliva samples. This study confirms that systemic and mucosal humoral IgG antibodies are maintained in the majority of COVID-19 patients for at least 3 months PSO. Based on their correlation with each other, IgG responses in saliva may serve as a surrogate measure of systemic immunity.One Sentence SummaryIn this manuscript, we report evidence for sustained SARS-CoV-2-specific IgG and transient IgA and IgM responses both at the site of infection (mucosae) and systemically in COVID-19 patients over 3 months and suggest that saliva could be used as an alternative biofluid for monitoring IgG to SARS-CoV-2 spike and RBD antigens.

Most of the patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mount a humoral immune response to the virus within a few weeks of infection, but the duration of this response and how it correlates with clinical outcomes has not been completely characterized. Of particular importance is the identification of immune correlates of infection that would support public health decision-making on treatment approaches, vaccination strategies, and convalescent plasma therapy. While ELISA-based assays to detect and quantitate antibodies to SARS-CoV-2 in patient samples have been developed, the detection of neutralizing antibodies typically requires more demanding cell-based viral assays. Here, we present a safe and efficient protein-based assay for the detection of serum and plasma antibodies that block the interaction of the SARS-CoV-2 spike protein receptor binding domain (RBD) with its receptor, angiotensin converting-enzyme 2 (ACE2). The assay serves as a surrogate neutralization assay and is performed on the same platform and in parallel with an enzyme-linked immunosorbent assay (ELISA) for the detection of antibodies against the RBD, enabling a direct comparison. The results obtained with our assay correlate with those of two viral based assays, a plaque reduction neutralization test (PRNT) that uses live SARS-CoV-2 virus, and a spike pseudotyped viral-vector-based assay.

Key Points Question What is the association of influenza activity and environmental conditions with invasive pneumococcal disease risk in temperate countries, and are these associations generalizable? Findings In this case-crossover study of 19 566 patients from Australia, Canada, and the United States, influenza activity was associated with a short-term increase in risk of invasive pneumococcal disease, while absolute humidity was associated with a short-term decrease in invasive pneumococcal disease risk. These results were generalizable across the 3 temperate countries. Meaning This study’s finding that influenza was associated with increased risk of invasive pneumococcal disease has important implications for disease control policy and practice., This case-crossover study evaluates the short-term associations of influenza activity and environmental exposures with invasive pneumococcal disease risk in temperate countries and examines the generalizability of such associations across multiple jurisdictions., Importance Streptococcus pneumoniae is the most commonly identified cause of bacterial pneumonia, and invasive pneumococcal disease (IPD) has a high case fatality rate. The wintertime coseasonality of influenza and IPD in temperate countries has suggested that pathogen-pathogen interaction or environmental conditions may contribute to IPD risk. Objectives To evaluate the short-term associations of influenza activity and environmental exposures with IPD risk in temperate countries and to examine the generalizability of such associations across multiple jurisdictions. Design, Setting, and Participants This case-crossover analysis of 19 566 individuals with IPD from 1998 to 2011 combined individual-level outcomes of IPD and population-level exposures. Participants lived in 12 jurisdictions in Canada (the province of Alberta and cities of Toronto, Vancouver, and Halifax), Australia (Perth, Sydney, Adelaide, Brisbane, and Melbourne), and the United States (Baltimore, Providence, and Philadelphia). Data were analyzed in 2019. Exposures Influenza activity, mean temperature, absolute humidity, and UV radiation at delays of 1 to 3 weeks before case occurrence in each jurisdiction. Main Outcomes and Measures Matched odds ratios (ORs) for IPD associated with changes in exposure variables, estimated using multivariable conditional logistic regression models. Heterogeneity in effects across jurisdictions were evaluated using random-effects meta-analytic models. Results This study included 19 566 patients: 9629 from Australia (mean [SD] age, 42.8 [30.8] years; 5280 [54.8%] men), 8522 from Canada (only case date reported), and 1415 from the United States (only case date reported). In adjusted models, increased influenza activity was associated with increases in IPD risk 2 weeks later (adjusted OR [aOR] per SD increase, 1.07; 95% CI, 1.01-1.13). Increased humidity was associated with decreased IPD risk 1 week later (aOR per 1 g/m3, 0.98; 95% CI, 0.96-1.00). Other associations were heterogeneous; metaregression suggested that combinations of environmental factors might represent unique local risk signatures. For example, the heterogeneity in effects of UV radiation and humidity at a 2-week lag was partially explained by variation in temperature (UV index: coefficient, 0.0261; 95% CI, 0.0078 to 0.0444; absolute humidity: coefficient, −0.0077; 95% CI, −0.0125 to −0.0030). Conclusions and Relevance In this study, influenza was associated with increased IPD risk in temperate countries. This association was not explained by coseasonality or case characteristics and appears generalizable. Absolute humidity was associated with decreased IPD risk in the same jurisdictions. The generalizable nature of these associations has important implications for influenza control and advances the understanding of the seasonality of this important disease.

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.

Background Epstein-Barr virus (EBV) is carried in the blood of most adults, and transfusion-related infections have been reported. EBV is particularly deleterious in immunosuppressed transplant patients. The aim was to determine if EBV transmission occurred through leukodepleted blood product transfusion in pediatric recipients of hematopoietic stem cell transplants (HSCT). Study design and methods This prospective Canadian multi-center cohort study includes 156 allogeneic HSCT pediatric recipients. The association between EBV and transfusion was analyzed using Cox regressions. EBV infection, defined by a PCR+ test in the blood of seronegative recipients of an EBV-negative graft, was monitored in order to correlate the recipient EBV strain with that of the blood donors. EBV genotypes were determined by PCR amplification followed by DNA sequencing at two loci (EBNA3b and LMP1). Results No statistically significant associations were found between transfusions and EBV. One case of post-transplant EBV infection was identified among the 21 EBV-seronegative recipients receiving an EBV-negative graft. A total of 22 blood donors were retraced to determine whether the recipient's EBV strain matched that of a donor. One donor strain showed 100% sequence homology at the EBNA3b locus, but differed by one or two point mutations and by a 132-bp deletion at the LMP1 locus. The blood donor in question was alone among the 22 donors to show amplifiable virus in plasma. Blood from this donor readily produced an immortalized lymphoblastoid cell line in culture. Conclusion While considered a rare event, EBV transmission through transfusion may occur in the context of severe immunosuppression.

This study evaluated the effect of T regulatory cells (Treg cells) and the impact of BCG vaccination history of donors using an in vitro model of Mycobacterium tuberculosis H37Ra infection of peripheral blood mononuclear cells (PBMCs). PBMCs from donors with or without prior BCG vaccination were depleted of Treg cells (PBMCs-Tregs) or not depleted with Treg cells (PBMCs + Tregs) were infected up to 8 days with Mtb H37Ra. Cell aggregates were smaller in PBMCs-Tregs compared to PBMCs + Tregs at day 8 post-infection. Mtb CFUs were higher in the PBMCs-Tregs compared to PBMCs + Tregs at days 3, 5 and 8. The levels of IL-17, IFN-γ (at days 3 and 5), and TNF-α and IL-6 (at day 3) were lower in PBMCs-Tregs compared to PBMCs + Tregs. In contrast, the levels of IL-10 and IL-4 cytokines were higher at day 3 in PBMCs-Tregs compared to PBMCs + Tregs. BCG vaccination status of donors had no impact on the mycobacterial culture, level of cytokines and immune cell populations. This study shows that depletion of Tregs in human PBMCs infected with Mtb H37Ra in vitro leads to a shift from a Th1 to a Th2 cytokine rich environment that supports the survival of Mtb in this model.

Background Vaccine effectiveness (VE) studies provide essential evidence on waning vaccine-derived immunity, a major threat to pertussis control. We evaluated how study design affects estimates by comparing 2 case-control studies conducted in Ontario, Canada. Methods We compared results from a test-negative design (TND) with a frequency-matched design (FMD) case-control study using pertussis cases from 2005–2015. In the first study, we identified test-negative controls from the public health laboratory that diagnosed cases and, in the second, randomly selected controls from patients attending the same physicians that reported cases, frequency matched on age and year. We compared characteristics of cases and controls using standardized differences. Results In both designs, VE estimates for the early years postimmunization were consistent with clinical trials (TND, 84%; FMD, 89% at 1–3 years postvaccination) but diverged as time since last vaccination increased (TND, 41%; FMD, 74% by 8 years postvaccination). Overall, we observed lower VE and faster waning in the TND than the FMD. In the TND but not FMD, controls differed from cases in important confounders, being younger, having more comorbidities, and higher healthcare use. Differences between the controls of each design were greater than differences between cases. TND controls were more likely to be unvaccinated or incompletely vaccinated than FMD controls (P Conclusions The FMD adjusted better for healthcare-seeking behavior than the TND. Duration of protection from pertussis vaccines is unclear because estimates vary by study design. Caution should be exercised by experts, researchers, and decision makers when evaluating evidence on optimal timing of boosters.

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.

Stool is the diagnostic specimen of choice to identify enteropathogens in pediatric gastroenteritis. However, stool collection is challenging and its diagnostic characteristics in patients with isolated vomiting are unknown. Therefore, we evaluated if oral swabs are a suitable alternative specimen to stools. In total, 738 oral swabs and 577 stool specimens were collected from 738 children with vomiting and/or diarrhea. All specimens were tested by a laboratory-developed quantitative RT-PCR Gastroenteritis Virus Panel; 150 oral swabs and 577 stool specimens were tested by the commercial gastroenteritis pathogen panel. The Gastroenteritis Virus Panel identified adenovirus (n = 38), norovirus (n = 21), and rotavirus (n = 16) commonly in oral swabs. In stool specimens, rotavirus (n = 139), norovirus (n = 86), and adenovirus (n = 69) were detected commonly. Compared with stool specimens, the specificity of oral swabs was 99% (95% CI, 96%-100%); the sensitivity of oral swabs was 18% (95% CI, 14%-22%) for the detection of enteric viruses. The Gastrointestinal Pathogen Panel identified enteric bacteria and parasites in stool but not in oral swabs. Given the lower sensitivity of oral swabs, stool remains a preferable specimen to detect enteric viruses. However, with their high specificity, oral swabs can be considered as a suitable specimen if stool specimens are unavailable. Nevertheless, negative oral swabs require a confirmative test of stool specimens.

Background There is mounting evidence that the recent resurgence of pertussis in many countries is in part related to the acellular vaccine, which has been administered in Canada since 1997. This vaccine elicits a different cell-mediated immune response than the previously used whole-cell vaccine, and its effectiveness wanes over time. The aim of this study is to understand the immunological, demographic and clinical factors that mediate protection from pertussis on exposure. Methods This is a household case-control study protocol. Following notification of an index case in a household, a study team will conduct a home visit to collect data and biological specimens. The study team will return to the household 8 weeks from the onset of illness in the index case. The Th1, Th2 and Th17 responses, cytokine expression, IgG subclass, blood cell counts and presence of Bordetella pertussis will be determined. We will use laboratory and statistical analyses to determine immunological differences between contacts who are infected with B. pertussis and contacts who remain healthy, and to determine which clinical and demographic covariates are associated with a reduced risk of infection. Interpretation The results of this study will be essential for understanding the immune response required for protection from infection with B. pertussis and will contribute to our understanding of the shortcomings of the current vaccine.

Aim To describe the epidemiology of critically ill children admitted to a paediatric intensive care unit (PICU) with acute respiratory disease. The association with intubation was analysed for the three most prevalent viruses and in those with and without viral co‐infection. Methods Patients admitted to the PICU (2004–2014) with acute respiratory disease were included. Analyses were performed utilising each respiratory viral infection or multiple viral infections as an exposure. Results There were 1766 admissions with acute respiratory disease of which 1372 had respiratory virus testing and 748 had one or more viruses detected. The risk of intubation before or during the PICU stay was higher if parainfluenza virus was detected compared to respiratory syncytial virus (RSV) (OR: 2.20; 95% CI: 1.06–4.56). Sixty‐three admissions had two or more viruses detected, and the combination of RSV and Rhinovirus/enterovirus was the most common. No significant difference was observed in the risk of intubation between patients with multiple and single viral infections. Conclusion Higher risk of intubation was found in patients with parainfluenza as compared to RSV. The risk of intubation comparing parainfluenza virus to other viruses and for patients with multiple versus single virus needs to be further studied.

BackgroundMultiple anti-SARS-CoV-2 immunoassays are available, but no gold standard exists. We assessed four assays using various methodological approaches to estimate SARS-COV-2 seroprevalence during the first COVID-19 wave in Canada.MethodsThis serial cross-sectional study was conducted using plasma samples from healthy blood donors between April-September 2020. Qualitative assessment of SARS-CoV-2 IgG antibodies was based on four assays: Abbott Architect SARS-Cov-2 IgG assay (target nucleocapsid) (Abbott-NP) and three in-house IgG ELISA assays (target spike glycoprotein (Spike), spike receptor binding domain (RBD), and nucleocapsid (NP)). Seroprevalence was estimated using multiple composite reference standards (CRS) and by a series of Bayesian Latent Class Models (BLCM) (using uninformative, weakly, and informative priors).Results8999 blood samples were tested. The Abbott-NP assay consistently estimated seroprevalence to be lower than the ELISA-based assays. Discordance between assays was common, 13 unique diagnostic phenotypes were observed. Only 32 samples (0.4%) were positive by all four assays. BLCM using uninformative priors predicted seroprevalence increased from 0.7% (95% credible interval (CrI); 0.4, 1.0%) in April/May to 0.8% (95% CrI 0.5, 1.2%) in June/July to 1.1% (95% CrI 0.7, 1.6) in August/September. Results from CRS were very similar to the BLCM. Assay characteristics varied considerably over time. Overall spike had the highest sensitivity (89.1% (95% CrI 79.2, 96.9%), while the sensitivity of the Abbott-NP assay waned from 65.3% (95% CrI 43.6, 85.0%) in April/May to 45.9% (95% CrI 27.8, 65.6) by August/September.DiscussionWe found low SARS-CoV-2 seroprevalence rates at the end of the first wave and estimates derived from single assays may be biased.SummaryMultiple anti-SARS-CoV-2 immunoassays are available, but no gold standard exists. We used four unique assays to estimate very low SARS-COV-2 seroprevalence during the first COVID-19 wave in Canada. Caution should be exercised when interpretating seroprevalence estimates from single assays.

Summary Age-related differences in influenza B lineage infection were assessed by the community-based Canadian Sentinel Practitioner Surveillance Network between 2010–2011 and 2015–2016. Influenza B(Victoria) cases were on average 20 years younger than B(Yamagata) cases, with the latter showing a bimodal age distribution., 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

Aim: To evaluate the Alere™ i Influenza A&B assay and the Xpert®Flu/RSV XC assay using nasopharyngeal aspirates and swabs not provided in the commercial kits. Methods: Specimens were tested with the Alere i Influenza A&B and the Xpert Flu/RSV XC assays and compared with reference methods. Results: Compared with the comparator methods and following discordant analysis, the sensitivity of the i Influenza A&B assay was 63.3% for influenza A and 83.3% for influenza B. For the Xpert Flu/RSV XC assay, sensitivity was 100% for influenza A and B and respiratory syncytial virus. The specificity for all test systems was 100%. Conclusion: The Xpert Flu/RSV XC assay out-performed the Alere i Influenza A&B assay in all diagnostic characteristics evaluated.

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.

International audience; Together with influenza, the non-influenza RNA respiratory viruses (NIRVs), which include respiratory syncytial virus, parainfluenza viruses, coronavirus, rhinovirus, and human metapneumovirus, represent a considerable global health burden, as recognised by WHO's Battle against Respiratory Viruses initiative. By contrast with influenza viruses, little is known about the contemporaneous global diversity of these viruses, and the relevance of such for development of pharmaceutical interventions. Although far less advanced than for influenza, antiviral drugs and vaccines are in different stages of development for several of these viruses, but no interventions have been licensed. This scarcity of global genetic data represents a substantial knowledge gap and impediment to the eventual licensing of new antiviral drugs and vaccines for NIRVs. Enhanced genetic surveillance will assist and boost research and development into new antiviral drugs and vaccines for these viruses. Additionally, understanding the global diversity of respiratory viruses is also part of emerging disease preparedness, because non-human coronaviruses and paramyxoviruses have been listed as priority concerns in a recent WHO research and development blueprint initiative for emerging infectious diseases. In this Personal View, we explain further the rationale for expanding the genetic database of NIRVs and emphasise the need for greater investment in this area of research.

SUMMARYAn outbreak of Legionnaires' disease occurred in an inner city district in Calgary, Canada. This outbreak spanned a 3-week period in November–December 2012, and a total of eight cases were identified. Four of these cases were critically ill requiring intensive care admission but there was no associated mortality. All cases tested positive forLegionella pneumophilaserogroup 1 (LP1) by urinary antigen testing. Five of the eight patients were culture positive for LP1 from respiratory specimens. These isolates were further identified as Knoxville monoclonal subtype and sequence subtype ST222. Whole-genome sequencing revealed that the isolates differed by no more than a single vertically acquired single nucleotide variant, supporting a single point-source outbreak. Hypothesis-based environmental investigation and sampling was conducted; however, a definitive source was not identified. Geomapping of case movements within the affected urban sector revealed a 1·0 km common area of potential exposure, which coincided with multiple active construction sites that used water spray to minimize transient dust. This community point-source Legionnaires' disease outbreak is unique due to its ST222 subtype and occurrence in a relatively dry and cold weather setting in Western Canada. This report suggests community outbreaks ofLegionellashould not be overlooked as a possibility during late autumn and winter months in the Northern Hemisphere.

BACKGROUND Pertussis is still frequently reported in Canada. In Alberta, pertussis incidence ranged from 1.8 to 20.5 cases per 100,000 persons for 2004-2015. Most cases occurred in those aged

Background: Streptococcus pneumoniae is the most commonly identified cause of bacterial pneumonia, and invasive pneumococcal disease (IPD) has a high case fatality rate. The wintertime co-seasonality of influenza and IPD in temperate countries has suggested that pathogen-pathogen interaction or environmental conditions contribute to IPD risk. We evaluated the contribution of influenza and environmental conditions, using standardized methodology, across multiple geographical regions. Methods: Case data for 25,292 cases from jurisdictions in Canada, the United States and Australia were available. Associations between influenza, temperature, absolute humidity and ultraviolet radiation and IPD were evaluated using a case-crossover design. Identical models were used in all jurisdictions; heterogeneity of effects was explored using meta-analytic methods. Findings: In adjusted models, elevated influenza activity at a 2-week lag was associated with increases in IPD risk (adjusted OR (aOR) per standard deviation increase 1.07, 95% CI: 1.01-1.13). Increased humidity decreased IPD risk at a 1-week lag (aOR per gram.m-3 of water 0.98, 95% CI 0.96-1.00). Other effects were heterogeneous; meta-regression suggested that combinations of environmental factors might represent unique local "risk signatures". Interpretation: Influenza drives IPD risk in temperate countries. This association is not explained by co-seasonality or case characteristics and appears generalizable. Absolute humidity attenuates IPD risk in the same jurisdictions. The generalizable nature of these associations has important implications for influenza control and advances the understanding of seasonality of this important disease. Funding Statement: Supported by Canadian Institutes for Health Research Operating Grants (#222287 and #337516) and by the Canadian Immunization Research Network. Declaration of Interests: The authors state: "None." Ethics Approval Statement: Ethical approval for this study was obtained by the University of Toronto Research Ethics Board.

Introduction Findings from the community-based Canadian Sentinel Practitioner Surveillance Network (SPSN) suggest children were more affected by the 2018/19 influenza A(H1N1)pdm09 epidemic. Aim To compare the age distribution of A(H1N1)pdm09 cases in 2018/19 to prior seasonal influenza epidemics in Canada. Methods The 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. Results In 2018/19, more influenza A(H1N1)pdm09 cases were under 10 years old than controls (29% vs 16%; p Conclusion Children 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.