Background:Despite widespread vaccination, pertussis remains a poorly controlled disease globally and results in substantial annual morbidity and mortality, particularly in young children. Controlled human infection models (CHIMs) using the causative agent Bordetella pertussis are promising systems to enable the study of pertussis disease pathogenesis and immunology and to rapidly assess vaccines and therapeutics. While a pertussis CHIM that produces asymptomatic infection has been established in Europe, the development of a CHIM that leads to symptomatic illness would be advantageous for evaluating vaccine efficacy against both infection and disease. Methods:Healthy participants 18-40 years of age were inoculated intranasally with one of eight doses (ranging from 104 to 108 colony forming units (CFU)) of the pertactin-producing B. pertussis isolate D420 at the challenge facility within the Canadian Center for Vaccinology (Nova Scotia, Canada). The study occurred in two stages. In stage one, the B. pertussis dose was escalated in cohort groups of five to six participants until reaching an endpoint where 70-90% of participants exhibited mild (non-severe, Grade 1 or 2) symptomatic infection, defined as the Human Infectious Dose 70-90 (HID70-90). In stage two, additional challenges were conducted for doses below, at, and above the identified HID70-90 to characterize the emerging pertussis model. For all challenge doses, participants were closely monitored during an inpatient stay of up to 24 days and post-discharge for laboratory-confirmed infection, pertussis symptoms, safety, and IgG antibody responses to four B. pertussis antigens including pertussis toxin, filamentous hemagglutinin, fimbriae, and pertactin. All participants received a five-day course of azithromycin, where timing of initiation depended on B. pertussis testing and symptoms. The study was conducted between July 4, 2022 and March 19, 2025. Findings:Seventy-five participants were inoculated with one of the eight B. pertussis D420 challenge doses and completed the inpatient stay. From the stage-one dose escalation, we found that 107 CFU of B. pertussis D420 was the lowest dose that achieved the HID70-90, where 9 of 12 participants (75·0%) exhibited mild symptomatic infection. Following stage-two challenges, 16 of 22 total participants at 107 CFU (72·7%) developed mild symptomatic infection, thus verifying the HID70-90. The symptomatic infection rate below the HID70-90 at 5×106 CFU of D420 was 20·0% and above the HID70-90 at 5×107 and 108 CFU were 58·3% and 55·6%, respectively. Symptoms with elevated frequency for symptomatic infection (relative to background symptoms in non-infected) included nasal congestion, runny nose, fatigue, malaise, and cough. At the HID70-90, 50% of symptomatic infections included cough. Serological analyses of the four highest (stage-two) challenge doses (5×106, 107, 5×107, 108 CFU) revealed that antibody titres increased over time post-challenge. Seroconversion for at least one of the four studied antibodies was nearly twice as common for symptomatic (70·0%) than asymptomatic (35·7%) infection and was absent (0%) for non-infected. All infections were cleared following azithromycin treatment (100%) and there were no study-related serious adverse events. Interpretation:A safe and reproducible symptomatic pertussis CHIM was achieved, providing a model for research on pertussis disease pathogenesis and immunology and for assessing vaccines and therapeutics. (Clinicaltrials.gov, NCT05136599).

Bartonella quintana is a louse-borne Gram-negative bacterium first discovered as the cause of trench fever during World War I. As B. quintana is not identified using routine culture with 5-day incubation, the pathogen is an agent of blood culture-negative endocarditis, particularly among individuals experiencing homelessness. Here, we describe a case of an 80-year-old man who presented in the winter of 2017 with severe aortic valve regurgitation resulting in exercise intolerance, requiring aortic valve replacement. Pathological assessment of the explanted aortic valve revealed changes of infective endocarditis. The presence of B. quintana in the valve tissue was confirmed using molecular methods including B. quintana-specific polymerase chain reaction (PCR) as well as PCR and sequencing of the 16S rRNA, heat shock protein (hsp), and RNA polymerase (rpoB) genes. The organism was subsequently grown from the patient's blood. Serology revealed B. quintana IgG titres that were initially elevated at 1:4096, but decreased and were sustained at 1:1024, as the patient recovered following treatment with doxycycline and rifampin. Bartonella quintana endocarditis is recognized as a cause of culture-negative endocarditis, but the diagnosis can be difficult, as symptoms may be non-specific, and the organism requires special conditions (and media) for routine growth. This case emphasizes the value of pathological investigations and microbiology laboratory support in the setting of low clinical and intraoperative suspicion of infective endocarditis.

INTRODUCTION:The Quadrivalent human papillomavirus (HPV) Vaccine Evaluation Study with Addition of the Nonavalent Vaccine Study (QUEST-ADVANCE) aims to provide insight into the long-term immunogenicity and effectiveness of one, two and three HPV vaccine doses. Here, we describe the protocol for QUEST-ADVANCE. METHODS AND ANALYSIS:QUEST-ADVANCE is an observational cohort study including males and females who are unvaccinated or vaccinated with the quadrivalent or nonavalent HPV vaccine in British Columbia, Canada. Female participants who are unvaccinated or vaccinated with 1-3 doses of the quadrivalent or nonavalent HPV vaccine at 9-14 years of age will be recruited approximately 5 or 12 years postvaccination eligibility. Male participants who are unvaccinated or vaccinated with 1 or 2 doses of the nonavalent HPV vaccine at 9-14 years of age will be recruited at approximately 5 years postvaccination eligibility. The study involves a maximum of four visits over a period of 4-5 years for female participants, and two visits over a 12-month period for male participants. At each visit, self-collected swabs (cervico-vaginal or penile) and questionnaire data will be collected. In each study group, a subset of participants will be invited to participate in a substudy evaluating the long-term humoral immunogenicity of the HPV vaccine. Additional blood samples will be collected from participants who are part of the immunogenicity substudy. The total required sample size is 7180 individuals. The primary objectives are (1) to examine vaccine effectiveness in males and females against prevalent genital HPV infections for one, two and three doses of the HPV vaccine compared with unvaccinated participants and (2) to evaluate if there is non-inferior immunogenicity as indicated by type-specific antibody response of one dose of the HPV vaccine in 20-27-year-old females vaccinated at 9-14 years of age compared with historical data of three doses of the HPV vaccine females vaccinated at 16-26 years of age up to 12 years postvaccination. ETHICS AND DISSEMINATION:QUEST-ADVANCE was approved by the Research Ethics Board of the University of British Columbia/Children's and Women's Health Centre of British Columbia (H20-02111). Individual electronic informed consent or assent will be obtained from each participant before any study-specific procedures are undertaken. Results will be published in an international peer-reviewed journal and on the study website.

Background:This study aimed to evaluate the impact of frailty on clinical outcomes and disease severity of respiratory syncytial virus (RSV) infection in older adults using data from the CIRN SOS Network (Serious Outcomes Surveillance Network; Canadian Immunization Research Network). Methods:This cohort study used data from the CIRN SOS Network collected during the 2012-2013, 2013-2014, and 2014-2015 influenza seasons. Patients aged ≥50 years who were hospitalized for acute respiratory illness were tested for RSV by multiplex reverse transcription-polymerase chain reaction. The analysis focused on frailty to assess its association with RSV disease severity and clinical outcomes. Frailty was categorized as nonfrail, prefrail, and frail according to validated cutoffs based on baseline frailty index. Results:Among 365 older adults hospitalized for RSV-related acute respiratory infections, most were classified as frail (61.1%), with fewer classified as prefrail (28.5%) or nonfrail (10.4%). Frailty was significantly associated with severe RSV outcomes, such as prolonged hospitalization and increased oxygen therapy requirements. Specifically, frail patients experienced longer hospitalizations and higher intensive care unit admission rates, with an odds ratio of 3.48 (95% CI, 1.30-9.12) for the association between frailty and severe disease. While RSV types A and B showed no significant differences in clinical outcomes, chronic obstructive pulmonary disease and chronic kidney disease emerged as factors associated with disease severity, alongside frailty. Conclusions:Frailty is an important predictor of RSV severity in older adults and is associated with longer hospital stays and increased health care needs. This highlights the need to consider frailty in RSV vaccine and therapeutic trials and suggests the potential benefits of interventions and public health and programmatic messaging tailored to older adults living with frailty.

BACKGROUND:Respiratory syncytial virus (RSV) causes substantial morbidity and mortality among adults. Given recent RSV vaccine authorizations, data on groups at highest risk are needed to support vaccine program decision making. METHODS:We identified adults aged ≥ 18 years hospitalized with laboratory-confirmed RSV and hospitalizations with RSV-related diagnostic codes in Ontario, Canada (2017-2019). We calculated incidence of hospitalization with 95% confidence intervals (CIs) using Poisson regression stratified by demographic and clinical risk factors, and substratified by age. We reported secondary outcomes including the proportion of individuals with fatal outcomes. RESULTS:Over 2 respiratory virus seasons, we identified 3928 RSV-associated hospitalizations. Incidence increased steadily with age from 2.0 (95% CI, 1.8-2.3) per 100 000 for those aged 18-49 years to 43.7 (95% CI, 41.0-46.6) per 100 000 for those aged 70-79 years, with a sharp increase to 134.7 (95% CI, 128.6-141.1) per 100 000 for those aged ≥ 80 years. Incidence was higher for those with comorbidities, including chronic kidney disease (receiving dialysis) (494.7; 95% CI, 410.7-595.8) and transplant recipients (370.9; 95% CI, 318.0-432.6), as well as for those living in lower (22.4; 95% CI, 21.1-23.7) versus higher-income neighborhoods (11.8; 95% CI, 10.8-12.8). Among those hospitalized, 10.3% (n = 403) died within 30 days of admission, and 93.1% of deaths occurred in those aged ≥ 60 years. Of survivors, 44.6% of community-dwelling adults aged ≥ 60 years had functional decline requiring formal supports at discharge. DISCUSSION:We found a substantial burden of RSV among older adults, particularly among those with preexisting medical conditions and those of lower socioeconomic status. These results will inform equitable vaccine recommendations for adults.

Background Herpes zoster (HZ) vaccines should provide durable protection against HZ and HZ-related complications. We report the final analysis of a long-term follow-up (LTFU) study (ZOE-LTFU) including 11 years of follow-up after primary vaccination with recombinant zoster vaccine (RZV). Methods ZOE-LTFU (NCT02723773) was an open-label, phase 3b study following participants of two phase 3 trials, ZOE-50 and ZOE-70. ZOE-LTFU started approximately 5 years post-vaccination in ZOE-50/70 and participants were followed for 6 years. The primary objective was to assess vaccine efficacy (VE) against HZ during ZOE-LTFU. Secondary objectives included VE against HZ from 1 month post-dose 2 in ZOE-50/70 until end of ZOE-LTFU, VE against post-herpetic neuralgia (PHN) and non-PHN complications, immunogenicity, and long-term safety. The VE calculation used a historical control constructed with ZOE-50/70 placebo data. Findings VE was assessed in the modified total vaccinated cohort (n = 7273 [mean age 67·3 years at first vaccination]). During ZOE-LTFU, VE was 79·8% (95% confidence interval [CI]: 73·7, 84·6) and 73·2% (95% CI: 62·9, 80·9) against HZ in participants ≥50 and ≥70 years at first vaccination, respectively, and was 87·5% (95% CI: 64·8, 96·8) against PHN and 91·7% (95% CI: 43·7, 99·8) against other HZ-related complications in participants ≥50 years. From 1 month post-dose 2 in ZOE-50/70 to the end of ZOE-LTFU, VE against HZ was 87·7% (95% CI: 84·9, 90·1) in participants ≥50 years and sustained at 82·0% (95% CI: 63·0, 92·2) in the eleventh year post-vaccination. Humoural and cell-mediated immune responses plateaued at over 5-fold and ∼7-fold, respectively, above pre-vaccination levels in ZOE-50/70. No RZV-related serious adverse events occurred. Interpretation Efficacy of RZV against HZ and associated complications remained high through 11 years post-vaccination, indicating sustained clinical benefit. Funding The funder of the study was GSK who was involved in study design, data collection, data analysis, data interpretation, writing of the report, and the decision to submit for publication.

BACKGROUND:Human metapneumovirus (hMPV) significantly impacts young children, older adults, and those with preexisting conditions. This study examines frailty and clinical outcomes in middle-aged and older adults hospitalized due to hMPV infections. METHODS:Data from the Canadian Immunization Research Network's Serious Outcomes Surveillance Network were analyzed. Included were adults aged ≥50 with lab-confirmed hMPV infection. Severe infection was marked by pneumonia, oxygen need, intensive care unit admission, mechanical ventilation, or death within 30 days. The Frailty Index (FI) categorized individuals as nonfrail (FI < 0.08), prefrail (FI ≥ 0.08, FI < 0.21), and frail (FI ≥ 0.21). Multivariate ridge regression identified factors linked to disease severity. RESULTS:Among 212 patients (median age 76), 85.4% had severe disease and 61.3% were frail. Frail patients had higher rates of severe disease (80.8% vs. 63.4%), oxygen therapy need (80.8% vs. 63.4%), and longer hospital stays (median 8 vs. 4 days) than patients who were nonfrail. Any cardiac illness (odds ratio [OR], 1.76; 95% confidence interval [CI], 1.02-3.09), congestive heart failure (OR, 1.91; 95% CI, 1.12-3.09), chronic obstructive pulmonary disease (OR, 1.93; 95% CI, 1.14-3.35), and frailty (OR, 1.99; 95% CI, 1.18-3.38) were significantly associated with increased odds of severe disease. CONCLUSIONS:Frailty, assessable with standardized tools, is associated with severe hMPV infections in middle-aged and older adults. Recognizing frailty in clinical management and as a vaccination criterion is necessary as hMPV vaccines become available. CLINICAL TRIALS REGISTRATION:NCT01517191 (ClinicalTrials.gov).

Respiratory viruses represent a significant public health threat. There is the need for robust and coordinated surveillance to guide global health responses. Established in 2012, the Global Influenza Hospital Surveillance Network (GIHSN) addresses this need by collecting clinical and virological data on persons with acute respiratory illnesses across a network of hospitals worldwide. GIHSN utilizes a standardized patient enrolment and data collection protocol across its study sites. It leverages pre-existing national infrastructures and expert collaborations to facilitate comprehensive data collection. This includes demographic, clinical, epidemiological, and virologic data, and whole genome sequencing (WGS) for a subset of viruses. Sequencing data are shared in the Global Initiative on Sharing All Influenza Data (GISAID). GIHSN uses financing and governance approaches centered around public-private partnerships. Over time, GIHSN has included more than 100 hospitals across 27 countries and enrolled more than 168,000 hospitalized patients, identifying 27,562 cases of influenza and 44,629 of other respiratory viruses. GIHSN has expanded beyond influenza to include other respiratory viruses, particularly since the COVID-19 pandemic. In November 2023, GIHSN strengthened its global impact through a memorandum of understanding with the World Health Organization, aimed at enhancing collaborative efforts and data sharing for improved health responses. GIHSN exemplifies the value of integrating scientific research with public health initiatives through global collaboration and public-private partnerships governance. Future efforts should enhance the scalability of such models and ensure their sustainability through continued public and private support.

Background. Oseltamivir is recommended for the treatment of adults hospitalized with influenza, but adherence is often suboptimal. This may be due to doubts about the reliability of the evidence supporting its benefits, particularly when initiation is delayed. We aimed to assess the effectiveness of oseltamivir in reducing mortality in older adults hospitalized with influenza, with a focus on the timing of initiation. Methods. The CIRN-SOS Network gathered data on severe respiratory illnesses across 5 Canadian provinces during the influenza seasons 2012-2019. Individuals aged >= 65 years with confirmed influenza and available antiviral prescription data were included. We compared the 30-day survival rates of hospitalized patients based on oseltamivir prescription status. Kaplan-Meier estimated survival probability and inverse probability of treatment (IPT)-weighted Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality. The analyses considered the time to antiviral initiation (>48 vs <= 48 hours). Results. Among the 8135 influenza patients studied, 2126 did not receive antiviral treatment, whereas 6009 were treated with oseltamivir. A total of 395 patients were hospitalized for >30 days. The overall mortality rate was 8.32 per 1000 person-days, with 53.9% of the deaths occurring within the first week. Oseltamivir recipients had a 18% lower risk of 30-day mortality (IPT-weighted HR, 0.82 [95% CI, .69-.98]). The benefit was significant for influenza A (IPT-weighted HR, 0.74 [95% CI, .61-.91]) but not for influenza B (IPT-weighted HR, 1.12 [95% CI, .81-1.56]). Oseltamivir remained effective even when initiated after 48 hours (IPT-weighted HR, 0.66 [95% CI, .49-.90]). Influenza vaccination did not mediate the effectiveness of oseltamivir in reducing mortality. Conclusions. Oseltamivir significantly reduces mortality risk in older adults hospitalized with influenza, even when administered after 48 hours, independent of vaccination status.

This study aimed to establish a Severity Scale for influenza and other acute respiratory infections (ARI), requiring hospitalization, for surveillance and research purposes (the SevScale). Such a scale could aid the interpretation of data gathered from disparate settings. This could facilitate pooled analyses linking viral genetic sequencing data to clinical severity, bringing insights to inform influenza surveillance and the vaccine strain selection process. We used a subset of data from the Global Influenza Hospital Surveillance Network database, including data from different geographical areas and income levels. To quantify the underlying concept of severity, an item response model was developed using 16 indicators of severity related to the hospital stay. Each patient in the dataset was assigned a Severity Score and a Severity Category (low, medium, or high severity). Finally, we compared the model scores across different subgroups. Data from 9 countries were included, covering between 4 and 11 seasons from 2012 to 2022, with a total of 96,190 ARI hospitalizations. Not for all severity indicators data were available for all included seasons. Subgroups with a high percentage of patients in the high Severity Category included influenza A(H1N1)pdm09, age ≥ 50, lower-middle income countries, and admission since the start of the COVID-19 pandemic. The initial model successfully highlighted severity disparities across patient subgroups. Repeating this exercise with new, more complete data would allow recalibration and validation of the current model. The SevScale proved to be a promising method to define severity for influenza vaccine strain selection, surveillance, and research.

Background Influenza and RSV coinfections are not commonly seen but are concerning as they can lead to serious illness and adverse clinical outcomes among vulnerable populations. Here we describe the clinical features and outcomes of influenza and RSV coinfections in hospitalized adults. Methods A cohort study was performed with pooled active surveillance in hospitalized adults ≥ 50 years from the Serious Outcomes Surveillance Network of the Canadian Immunization Research Network (CIRN SOS) during the 2012/13, 2013/14, and 2014/15 influenza seasons. Descriptive statistics summarized the characteristics of influenza/RSV coinfections. Kaplan-Meier estimated the probability of survival over the first 30 days of hospitalization. Results Over three influenza seasons, we identified 33 cases of RSV and influenza coinfection, accounting for 2.39 cases per 1,000 hospitalizations of patients with acute respiratory illnesses. Adults aged 50 + years commonly reported cough (81.8%), shortness of breath (66.7%), sputum production (45.5%), weakness (33.3%), fever (27.3%), and nasal congestion (24.2%) as constitutional and lower respiratory tract infection symptoms. The mortality rate was substantial (12.1%), and age, comorbidity burden, and frailty were associated with a higher risk for adverse clinical outcomes. Conclusions Older adults are at higher risk for complications from influenza and RSV coinfections, especially those over 65 with a high comorbidity burden and frailty.

Background: The demand for COVID-19 vaccines has diminished as the pandemic lingers. Understanding vaccine hesitancy among essential workers is important in reducing the impact of future pandemics by providing effective immunization programs delivered expeditiously. Method: Two surveys exploring COVID-19 vaccine acceptance in 2021 and 2022 were conducted in cohorts of health care providers (HCP) and education workers participating in prospective studies of COVID-19 illnesses and vaccine uptake. Demographic factors and opinions about vaccines (monovalent and bivalent) and public health measures were collected in these self-reported surveys. Modified multivariable Poisson regression was used to determine factors associated with hesitancy. Results: In 2021, 3 % of 2061 HCP and 6 % of 3417 education workers reported hesitancy (p < 0.001). In December 2022, 21 % of 868 HCP and 24 % of 1457 education workers reported being hesitant to receive a bivalent vaccine (p = 0.09). Hesitance to be vaccinated with the monovalent vaccines was associated with earlier date of survey completion, later receipt of first COVID-19 vaccine dose, no influenza vaccination, and less worry about becoming ill with COVID-19. Factors associated with hesitance to be vaccinated with a bivalent vaccine that were common to both cohorts were receipt of two or fewer previous COVID-19 doses and lower certainty that the vaccines were safe and effective. Conclusion: Education workers were somewhat more likely than HCP to report being hesitant to receive COVID-19 vaccines but reasons for hesitancy were similar. Hesitancy was associated with non-receipt of previous vaccines (i.e., previous behaviour), less concern about being infected with SARS-CoV-2, and concerns about the safety and effectiveness of vaccines for both cohorts. Maintaining inter-pandemic trust in vaccines, ensuring rapid data generation during pandemics regarding vaccine safety and effectiveness, and effective and transparent communication about these data are all needed to support pandemic vaccination programs.

BACKGROUND:The Global Influenza Hospital Surveillance Network (GIHSN) has since 2012 provided patient-level data on severe influenza-like-illnesses from >100 participating clinical sites worldwide based on a core protocol and consistent case definitions. METHODS:We used multivariable logistic regression to assess the risk of intensive care unit admission, mechanical ventilation, and in-hospital death among hospitalized patients with influenza and explored the role of patient-level covariates and country income level. RESULTS:The data set included 73 121 patients hospitalized with respiratory illness in 22 countries, including 15 660 with laboratory-confirmed influenza. After adjusting for patient-level covariates we found a 7-fold increase in the risk of influenza-related intensive care unit admission in lower middle-income countries (LMICs), compared with high-income countries (P = .01). The risk of mechanical ventilation and in-hospital death also increased by 4-fold in LMICs, though these differences were not statistically significant. We also find that influenza mortality increased significantly with older age and number of comorbid conditions. Across all severity outcomes studied and after controlling for patient characteristics, infection with influenza A/H1N1pdm09 was more severe than with A/H3N2. CONCLUSIONS:Our study provides new information on influenza severity in underresourced populations, particularly those in LMICs.

Abstract We developed and validated the Influenza Severity Scale (ISS), a standardized risk assessment for influenza, to estimate and predict the probability of major clinical events in patients with laboratory-confirmed infection. Data from the Canadian Immunization Research Network’s Serious Outcomes Surveillance Network (2011/2012–2018/2019 influenza seasons) enabled the selecting of all laboratory-confirmed influenza patients. A machine learning-based approach then identified variables, generated weighted scores, and evaluated model performance. This study included 12,954 patients with laboratory-confirmed influenza infections. The optimal scale encompassed ten variables: demographic (age and sex), health history (smoking status, chronic pulmonary disease, diabetes mellitus, and influenza vaccination status), clinical presentation (cough, sputum production, and shortness of breath), and function (need for regular support for activities of daily living). As a continuous variable, the scale had an AU-ROC of 0.73 (95% CI, 0.71–0.74). Aggregated scores classified participants into three risk categories: low (ISS < 30; 79.9% sensitivity, 51% specificity), moderate (ISS ≥ 30 but < 50; 54.5% sensitivity, 55.9% specificity), and high (ISS ≥ 50; 51.4% sensitivity, 80.5% specificity). ISS demonstrated a solid ability to identify patients with hospitalized laboratory-confirmed influenza at increased risk for Major Clinical Events, potentially impacting clinical practice and research.

Background: Studies have shown an association between workplace safety climate scores and patient outcomes. This study aimed to investigate (1) performance of the hospital safety climate scale that was adapted to assess acute respiratory illness safety climate, (2) factors associated with safety climate scores, and (3) whether the safety scores were associated with following recommended droplet and contact precautions.Methods: A survey of Canadian healthcare personnel participating in a cohort study of influenza during the 2010/2011-2013/2014 winter seasons. Factor analysis and structural equation modeling were used for analyses.Results: Of the 1359 participants eligible for inclusion, 88% were female and 52% were nurses. The adapted items loaded to the same factors as the original scale. Personnel working on higher risk wards, nurses, and younger staff rated their hospital's safety climate lower than other staff. Following guidelines for droplet and contact precautions was positively associated with ratings of management support and absence of job hindrances.Conclusion: The adapted tool can be used to assess hospital safety climates regarding respiratory pathogens. Management support and the absence of job hindrances are associated with hospital staff's propensity and ability to follow precautions against the transmission of respiratory illnesses.

This qualitative, cross-sectional study aimed to understand the barriers and facilitators related to the adherence and completion of the recombinant zoster vaccine (RZV) two-dose series in Canada, as perceived by healthcare providers (HCPs) and patients. Data collection occurred via 60-minute concept elicitation interviews with 12 HCPs (4 physicians, 2 nurse practitioners, 6 pharmacists) who had prescribed and/or administered RZV in Canada, and 21 patients aged >= 50 years who had received >= 1 dose of RZV. Patients were categorized as adherent (received both doses within the recommended 2-to-6-month timeframe; n = 11) or non-adherent (received only one dose or second dose outside the recommended timeframe; n = 10). Interview transcripts were coded and analyzed using a two-part thematic analysis approach. HCP-identified barriers to RZV adherence included high out-of-pocket cost, inconsistent/lack of health plan coverage, inconvenient processes for accessing RZV, and patient forgetfulness. HCP-identified facilitators included desire for shingles protection, HCP encouragement, and reminders. Barriers to RZV adherence identified by patients included lack of HCP knowledge/experience with RZV, receiving unreliable/confusing information, having unpleasant/severe side effects following the first dose, high out-of-pocket cost, lack of insurance coverage, and forgetfulness. Patient-identified facilitators included self-motivation, financial support, convenient processes for obtaining RZV, and reminders. In conclusion, many factors can influence RZV series completion and adherence among adults in Canada, including cost, insurance coverage, HCP knowledge and encouragement, and reminders. Awareness of these factors may inform HCPs in helping patients overcome barriers and identify opportunities for future consideration, facilitating protection against herpes zoster.

INTRODUCTION:Cytomegalovirus (CMV) is the most common cause of congenital infection and affected children often have permanent neurodevelopmental sequelae, including hearing loss and intellectual disability. Vaccines to prevent transmission of CMV during pregnancy are a public health priority. This first-in-humans dose-ranging, randomized, placebo-controlled, observer-blinded study evaluated the safety and immunogenicity of an enveloped virus-like particle (eVLP) vaccine expressing a modified form of the CMV glycoprotein B (gB). METHODS:Healthy CMV-seronegative 18 to 40-year-olds at 3 Canadian study sites were randomized to one of 4 dose formulations (0.5 µg, 1 µg, or 2 µg gB content with alum) or 1 µg gB without alum, or placebo, given intramuscularly on days 0, 56 and 168. Outcome measures were solicited and unsolicited adverse events (AE), severe AE, gB and AD-2 epitope binding antibody titers and avidity, and neutralizing antibody (nAb) titers to CMV measured in fibroblast and epithelial cell infection assays. RESULTS:Among 125 participants, the most common solicited local and general AEs were pain and headache, respectively. A dose-dependent increase in gB binding, avidity and nAb titers was observed after doses 2 and 3, with the highest titers in the alum-adjuvanted 2.0 µg dose recipients after the third dose; in the latter 24 % had responses to the broadly neutralizing AD-2 epitope. Neutralizing activity to CMV infection of fibroblasts was seen in 100 % of 2.0 µg alum-adjuvanted dose recipients, and to epithelial cell infection in 31 %. Epithelial cell nAb titers were positively correlated with higher geometric mean CMV gB binding titers. CONCLUSIONS:An eVLP CMV vaccine was immunogenic in healthy CMV-seronegative adults and no safety signals were seen. Alum adjuvantation increased immunogenicity as did higher antigen content and a three dose schedule. This phase 1 trial supports further development of this eVLP CMV vaccine candidate.

Background The Global Influenza Hospital Surveillance Network (GIHSN) was established in 2012 to conduct coordinated worldwide influenza surveillance. In this study, we describe underlying comorbidities, symptoms, and outcomes in patients hospitalized with influenza. Methods Between November 2018 and October 2019, GIHSN included 19 sites in 18 countries using a standardized surveillance protocol. Influenza infection was laboratory-confirmed with reverse-transcription polymerase chain reaction. A multivariate logistic regression model was utilized to analyze the extent to which various risk factors predict severe outcomes. Results Of 16 022 enrolled patients, 21.9% had laboratory-confirmed influenza; 49.2% of influenza cases were A/H1N1pdm09. Fever and cough were the most common symptoms, although they decreased with age (P < .001). Shortness of breath was uncommon among those <50 years but increased with age (P < .001). Middle and older age and history of underlying diabetes or chronic obstructive pulmonary disease were associated with increased odds of death and intensive care unit (ICU) admission, and male sex and influenza vaccination were associated with lower odds. The ICU admissions and mortality occurred across the age spectrum. Conclusions Both virus and host factors contributed to influenza burden. We identified age differences in comorbidities, presenting symptoms, and adverse clinical outcomes among those hospitalized with influenza and benefit from influenza vaccination in protecting against adverse clinical outcomes. The GIHSN provides an ongoing platform for global understanding of hospitalized influenza illness.

Background: Influenza vaccines prevent influenza-related morbidity and mortality; however, suboptimal vaccine effectiveness (VE) of non-adjuvanted trivalent inactivated influenza vaccine (naTIV) or quadrivalent formulations in older adults prompted the use of enhanced products such as adjuvanted TIV (aTIV). Here, the VE of aTIV is compared to naTIV for preventing influenza-associated hospitalization among older adults. Methods: A test-negative design study was used with pooled data from the 2012 to 2015 influenza seasons. An inverse probability of treatment (IPT)-weighted logistic regression estimated the Odds Ratio (OR) for laboratory-confirmed influenza-associated hospitalization. VE was calculated as (1-OR)*100% with accompanying 95% confidence intervals (CI). Results: Of 7,101 adults aged > 65, 3,364 received naTIV and 526 received aTIV. The overall VE against influenza hospitalization was 45.9% (95% CI: 40.2%-51.1%) for naTIV and 53.5% (42.8%-62.3%) for aTIV. No statistically significant differences in VE were found between aTIV and naTIV by age group or influenza season, though a trend favoring aTIV over naTIV was noted. Frailty may have impacted VE in aTIV recipients compared to those receiving naTIV, according to an exploratory analysis; VE adjusted by frailty was 59.1% (49.6%-66.8%) for aTIV and 44.8% (39.1%-50.0%) for naTIV. The overall relative VE of aTIV to naTIV against laboratory-confirmed influenza hospital admission was 25% (OR 0.75; 0.61-0.92), demonstrating statistically significant benefit favoring aTIV. Conclusions: Adjusting for frailty, aTIV showed statistically significantly better protection than naTIV against influenza-associated hospitalizations in older adults. In future studies, it is important to consider frailty as a significant confounder of VE.