Search

While molecular testing is recommended for symptomatic patients suspected of having coronavirus disease 2019 (COVID-19), limited data are available examining real-world use of tests for severe acute respiratory syndrome coronavirus (SARS-CoV-2) and the impact of SARS-CoV-2 testing on patient outcomes. In this retrospective cohort study using de-identified administrative claims data in the Optum Labs Data Warehouse, we identified 2 groups of patients with ≥1 outpatient claims with a procedure code for SARS-CoV-2 testing between January 2021 and September 2022. Group 1 had ≥1 claims with CPT code 0240U or 0241U ("Xpert Xpress") (N = 51,602); Group 2 had ≥1 claims for laboratory-based molecular testing (N = 317,192). Outcomes assessed on the identification date and through the 90-day follow-up included claims evidence of use of SARS-CoV-2, influenza, and respiratory syncytial virus (RSV) tests, diagnosis of active COVID-19, influenza, or RSV, and use of treatments (antivirals for COVID-19, influenza, and RSV and other treatments for COVID-19 and RSV). Patients in Group 1 had fewer tests for SARS-CoV-2, influenza, or RSV (mean ± standard deviation 1.6±1.4 versus 2.6±2.6, standardized difference -0.45), faster time to diagnosis of COVID-19 (median 0 versus 4 days, standardized difference -0.27) or influenza (median 0 versus 5 days, standardized difference -0.74), and faster time to treatment of COVID-19, influenza, or RSV (median 1 versus 5 days, standardized difference 0.16) than patients in Group 2. In this nationwide real-world study of outpatient testing, use of point-of-care molecular multiplex SARS-CoV-2 testing resulted in fewer claims for SARS-CoV-2, influenza, and RSV tests, faster time to diagnosis, and faster time to treatment than laboratory-based molecular testing. [ABSTRACT FROM AUTHOR]

Introduction: Influenza (Flu) causes considerable morbidity and mortality globally, and in Bhutan, Flu viruses are a leading cause of acute respiratory infection and cause outbreaks during Flu seasons. In this study, we aim to analyze the epidemiology and the genetic characterization of Flu viruses circulated in Bhutan in 2022. Method: Respiratory specimens were collected from patients who meet the case definition for influenza-like illness (ILI) and severe acute respiratory infection (SARI) from sentinel sites. Specimens were tested for Flu and SARS-CoV-2 viruses by RT-PCR using the Multiplex Assay. Selected positive specimens were utilized for Flu viral genome sequencing by next-generation sequencing. Descriptive analysis was performed on patient demographics to see the proportion of Flu-associated ILI and SARI. All data were analyzed using Epi Info7 and QGIS 3.16 software. Result: A weekly average of 16.2 ILI cases per 1000 outpatient visits and 18 SARI cases per 1000 admitted cases were reported in 2022. The median age among ILI was 12 years (IQR: 5–28) and SARI was 6.2 (IQR: 2.5–15) years. Flu A(H3N2) (70.2%) subtype was the most predominant circulating strain. Flu A(H1N1)pdm09 and Flu B viruses belonged to subclades that were mismatched to the vaccine strains recommended for the 2021–2022 season but matched the vaccine strain for the 2022–2023 season with vaccine efficacy 85.14% and 88.07% respectively. Flu A(H3N2) virus belonged to two subclades which differed from the vaccine strains recommended in both the 2021–2022 and 2022–2023 seasons with vaccine efficacy 68.28%. Conclusion: Flu virus positivity rates were substantially elevated during the Flu season in 2022 compared to 2021. Flu A(H3N2) subtype was the most predominant circulating strain in the country and globally. Genetic characterization of the Flu viruses in Bhutan showed a close relatedness of high vaccine efficacy with the vaccine strain that WHO recommended for the 2022–23 season. [ABSTRACT FROM AUTHOR]

From 2011-2018, we conducted surveillance in marine mammals along the California coast for influenza A virus (IAV), frequently detecting anti-influenza antibodies and intermittently detecting IAV. In spring 2019, this pattern changed. Despite no change in surveillance intensity, we detected IAV RNA in 10 samples in March and April, mostly in nasal and rectal swabs from northern elephant seals (Mirounga angustirostris). Although virus isolation was unsuccessful, IAV sequenced from one northern elephant seal nasal swab showed close genetic identity with pandemic H1N1 IAV subclade 6B.1A.1 that was concurrently circulating in humans in the 2018/19 influenza season. This represents the first report of human A(H1N1)pdm09 IAV in northern elephant seals since 2010, suggesting IAV continues to spill over from humans to pinnipeds.

This study was aimed to explore the association between potential factors including public health and social measures and the number of influenza patients in Thailand between 2014–2021. Secondary data from relevant agencies were collected. Generalized Estimating Equation (GEE) and regression coefficient (β) were performed at a significance level of 0.05. We found factors associated with number of influenza patients during the time prior to COVID-19 pandemic were monthly income per household (Adjusted β = -0.02; 95% CI: -0.03, -0.01), population density (Adjusted β = 1.00; 95% CI: 0.82, 1.18), rainy season (Adjusted β = 137.15; 95% CI: 86.17, 188.13) and winter time (Adjusted β = 56.46; 95% CI: 3.21, 109.71). During the time of COVID-19 pandemic, population density (Adjusted β = 0.20; 95% CI: 0.15, 0.26), rainy season (Adjusted β = -164.23; 95% CI: -229.93, -98.52), winter time (Adjusted β = 61.06; 95% CI: 0.71, 121.41), public health control measures (prohibition of entering to into an area with high number of COVID-19 infections (Adjusted β = -169.34; 95% CI: -233.52, -105.16), and restriction of travelling also reduced the number of influenza patients (Adjusted β = -66.88; 95% CI: -125.15, -8.62) were associated with number of influenza patients. This study commends strategies in monitoring influenza patients to focus on the areas with low income, high population density, and in specific seasons. Public health and social measures which can be implemented are prohibition of entering to risk-areas (lock down), and restriction of travelling across provinces which their effectiveness in reducing influenza infections. [ABSTRACT FROM AUTHOR]

Influenza A viruses (IAVs) continue to pose a huge threat to public health, and their prevention and treatment remain major international issues. Neuraminidase (NA) is the second most abundant surface glycoprotein on influenza viruses, and antibodies to NA have been shown to be effective against influenza infection. In this study, we generated a monoclonal antibody (mAb), named FNA1, directed toward N1 NAs. FNA1 reacted with H1N1 and H5N1 NA, but failed to react with the NA proteins of H3N2 and H7N9. In vitro, FNA1 displayed potent antiviral activity that mediated both NA inhibition (NI) and blocking of pseudovirus release. Moreover, residues 219, 254, 358, and 388 in the NA protein were critical for FNA1 binding to H1N1 NA. However, further validation is necessary to confirm whether FNA1 mAb is indeed a good inhibitor against NA for application against H1N1 and H5N1 viruses. [ABSTRACT FROM AUTHOR]

Purpose: To assess the epidemiology of seasonal influenza in Huzhou City, Zhejiang Province, China, during 2018–2022 and provide insights for influenza prevention. Methods: Following the National Influenza Surveillance Program, we conducted pathogen surveillance by randomly sampling throat swabs from cases with influenza-like illness (ILI) at two sentinel hospitals. Results: From 2018 to 2022, a total of 3,813,471 cases were treated at two hospitals in Huzhou, China. Among them, there were 112,385 cases of Influenza-Like Illness (ILI), accounting for 2.95% of the total number of cases. A total of 11,686 ILI throat swab samples were tested for influenza viruses, with 1,602 cases testing positive for influenza virus nucleic acid, resulting in a positivity rate of 13.71%. Among the positive strains, there were 677 strains of A(H3N2) virus, 301 strains of A(H1N1) virus, 570 strains of B/Victoria virus, and 54 strains of B/Yamagata virus. The ILI percentage (ILI%) and influenza nucleic acid positivity rate showed winter-spring peaks in the years 2018, 2019, 2021, and 2022, with the peaks concentrated in January and February. Additionally, a small peak was observed in August 2022 during the summer season. No peak was observed during the winter-spring season of 2020. The highest proportion of ILI cases was observed in children aged 0–4 years, followed by school-age children aged 5–14 years. There was a positive correlation between ILI% and influenza virus nucleic acid positivity rate (r = 0.60, p < 0.05). Conclusions: The influenza outbreak in Huzhou from 2020 to 2022 was to some extent influenced by the COVID-19 pandemic and public health measures. After the conclusion of the COVID-19 pandemic, the influenza outbreak in Huzhou may become more severe. Therefore, it is crucial to promptly assess the influenza outbreak trends based on the ILI% and the positivity rate of influenza virus nucleic acid tests. [ABSTRACT FROM AUTHOR]

The World Health Organization (WHO) raised the global alert level for the A(H1N1) influenza pandemic in June 2009. However, since the beginning of the epidemic, the fight against the epidemic lacked foundations for managing cases to reduce the disease lethality. It was urgent to carry out studies that would indicate a model for predicting severe forms of influenza. This study aimed to identify risk factors for severe forms during the 2009 influenza epidemic and develop a prediction model based on clinical epidemiological data. A case-control of cases notified to the health secretariats of the states of Rio de Janeiro, São Paulo, Minas Gerais, Paraná, and Rio Grande do Sul was conducted. Cases had fever, respiratory symptoms, positive confirmatory test for the presence of the virus associated with one of the three conditions: (i) presenting respiratory complications such as pneumonia, ventilatory failure, severe acute respiratory distress syndrome, sepsis, acute cardiovascular complications or death; or respiratory failure requiring invasive or non-invasive ventilatory support, (ii) having been hospitalized or (iii) having been admitted to an Intensive Care Unit. Controls were individuals diagnosed with the disease on the same date (or same week) as the cases. A total of 1653 individuals were included in the study, (858 cases/795 controls). These participants had a mean age of 26 years, a low level of education, and were mostly female. The most important predictors identified were systolic blood pressure in mmHg, respiratory rate in bpm, dehydration, obesity, pregnancy (in women), and vomiting (in children). Three clinical prediction models of severity were developed, for adults, adult women, and for children. The performance evaluation of these models indicated good predictive capacity. The area values under the ROC curve of these models were 0.89; 0.98 and 0.91 respectively for the model of adults, adult women, and children respectively. [ABSTRACT FROM AUTHOR]

The coronavirus disease (COVID-19) pandemic has considerably impacted public health, including the transmission patterns of other respiratory pathogens, such as the 2009 pandemic influenza (H1N1). COVID-19 and influenza are both respiratory infections that started with a lack of vaccination-based immunity in the population. However, vaccinations have been administered over time, resulting in a transition of the status of both diseases from a pandemic to an endemic. In this study, unsupervised clustering techniques were used to identify clusters of disease trends in Thailand. The analysis incorporated three distinct surveillance datasets: the pandemic influenza outbreak, influenza in the endemic stage, and the early stages of COVID-19. The analysis demonstrated a significant difference in the distribution of provinces between Cluster -1, representing those with unique transmission patterns, and the other clusters, indicating provinces with similar transmission patterns among their members. Specifically, for Pandemic Influenza, the ratio was 61:16, while for Pandemic COVID-19, it was 65:12. In contrast, Endemic Influenza exhibited a ratio of 46:31, with a notable emergence of more clustered provinces in the southern, western, and central regions. Furthermore, a pair of provinces with highly similar spreading patterns were identified during the pandemic stages of both influenza and COVID-19. Although the similarity decreased slightly for endemic influenza, they still belonged to the same cluster. Our objective was to identify the transmission patterns of influenza and COVID-19, with the aim of providing quantitative and spatial information to aid public health management in preparing for future pandemics or transitioning into an endemic phase. [ABSTRACT FROM AUTHOR]

BACKGROUND: Respiratory syncytial virus (RSV) can cause severe disease in adults with cardiopulmonary conditions, such as congestive heart failure (CHF). We quantified the rate of RSV-associated hospitalization in adults by CHF status using population-based surveillance in the United States. METHODS: Population-based surveillance for RSV (RSV-NET) was performed in 35 counties in seven sites during two respiratory seasons (2015-2017) from October 1-April 30. Adults (≥18 years) admitted to a hospital within the surveillance catchment area with laboratory-confirmed RSV identified by clinician-directed testing were included. Presence of underlying CHF was determined by medical chart abstraction. We calculated overall and age-stratified (

A previous report demonstrated the strong association between the presence of antibodies binding to an epitope region from SARS-CoV-2 nucleocapsid, termed Ep9, and COVID-19 disease severity. Patients with anti-Ep9 antibodies (Abs) had hallmarks of antigenic interference (AIN), including early IgG upregulation and cytokine-associated injury. Thus, the immunological memory of a prior infection was hypothesized to drive formation of suboptimal anti-Ep9 Abs in severe COVID-19 infections. This study identifies a putative primary antigen capable of stimulating production of cross-reactive, anti-Ep9 Abs. Binding assays with patient blood samples directly show cross-reactivity between Abs binding to Ep9 and only one bioinformatics-derived, homologous putative antigen, a sequence derived from the neuraminidase protein of H3N2 influenza A virus. This cross-reactive binding is highly influenza strain specific and sensitive to even single amino acid changes in epitope sequence. The neuraminidase protein is not present in the influenza vaccine, and the anti-Ep9 Abs likely resulted from the widespread influenza infection in 2014. Therefore, AIN from a previous infection could underlie some cases of COVID-19 disease severity.

How do attitudes toward vaccination change over the course of a public health crisis? We report results from a longitudinal survey of United States residents during six months (March 16 -August 16, 2020) of the COVID-19 pandemic. Contrary to past research suggesting that the increased salience of a disease threat should improve attitudes toward vaccines, we observed a decrease in intentions of getting a COVID-19 vaccine when one becomes available. We further found a decline in general vaccine attitudes and intentions of getting the influenza vaccine. Analyses of heterogeneity indicated that this decline is driven by participants who identify as Republicans, who showed a negative trend in vaccine attitudes and intentions, whereas Democrats remained largely stable. Consistent with research on risk perception and behavior, those with less favorable attitudes toward a COVID-19 vaccination also perceived the virus to be less threatening. We provide suggestive evidence that differential exposure to media channels and social networks could explain the observed asymmetric polarization between self-identified Democrats and Republicans.

Effective and timely disease surveillance systems have the potential to help public health officials design interventions to mitigate the effects of disease outbreaks. Currently, healthcare-based disease monitoring systems in France offer influenza activity information that lags real-time by one to three weeks. This temporal data gap introduces uncertainty that prevents public health officials from having a timely perspective on the population-level disease activity. Here, we present a machine-learning modeling approach that produces real-time estimates and short-term forecasts of influenza activity for the twelve continental regions of France by leveraging multiple disparate data sources that include, Google search activity, real-time and local weather information, flu-related Twitter micro-blogs, electronic health records data, and historical disease activity synchronicities across regions. Our results show that all data sources contribute to improving influenza surveillance and that machine-learning ensembles that combine all data sources lead to accurate and timely predictions.

The "Russian Influenza"-coronavirus theory (RICT) proposes that the pandemic of 1889–1892, conventionally regarded as an influenza pandemic, was caused by the emergence of human coronavirus OC43 (HCoV-OC43) as a zoonosis of bovine coronavirus (BCoV). RICT is based on a Bayesian phylogenetic calculation of the date of the most recent common ancestor (MRCA) of HCoV-OC43 and BCoV. The theory also draws on comparison of both symptoms and some epidemiological parameters of the best studied coronavirus pandemic, i.e. COVID-19, with those reported in 1889–1892. The case is completed with circumstantial evidence involving a panzoonotic among cattle in the decade prior to the "Russian Influenza", with characteristics suggesting it may have been caused by BCoV. In this paper, we review the Bayesian phylogenetic evidence for RICT, replicating previous studies and adding our own, in each case critically reviewing the suitability of the datasets used and the parameters applied. We conclude that the most probable date for the MRCA of HCoV-OC43 and BCoV is 1898–1902. This is a decade too late for compatibility with RICT but happens to coincide with another serious outbreak of respiratory illness, reported in both the USA and the UK, in the winter of 1899–1900. [ABSTRACT FROM AUTHOR]

Common in swine production worldwide, influenza causes significant clinical disease and potential transmission to the workforce. Swine vaccines are not universally used in swine production, due to their limited efficacy because of continuously evolving influenza viruses. We evaluated the effects of vaccination, isolation of infected pigs, and changes to workforce routine (ensuring workers moved from younger pig batches to older pig batches). A Susceptible-Exposed-Infected-Recovered model was used to simulate stochastic influenza transmission during a single production cycle on an indoor hog growing unit containing 4000 pigs and two workers. The absence of control practices resulted in 3,957 pigs [0–3971] being infected and a 0.61 probability of workforce infection. Assuming incoming pigs had maternal-derived antibodies (MDAs), but no control measures were applied, the total number of infected pigs reduced to 1 [0–3958] and the probability of workforce infection was 0.25. Mass vaccination (40% efficacious) of incoming pigs also reduced the total number of infected pigs to 2362 [0–2374] or 0 [0–2364] in pigs assumed to not have MDAs and have MDAs, respectively. Changing the worker routine by starting with younger to older pig batches, reduced the number of infected pigs to 996 [0–1977] and the probability of workforce infection (0.22) in pigs without MDAs. In pigs with MDAs the total number of infected pigs was reduced to 0 [0–994] and the probability of workforce infection was 0.06. All other control practices alone, showed little improvement in reducing total infected pigs and the probability of workforce infection. Combining all control strategies reduced the total number of infected pigs to 0 or 1 with a minimal probability of workforce infection (<0.0002–0.01). These findings suggest that non-pharmaceutical interventions can reduce the impact of influenza on swine production and workers when efficacious vaccines are unavailable. [ABSTRACT FROM AUTHOR]

Global mitigation strategies to tackle the threat posed by SARS-CoV-2 have produced a significant decrease of the severity of 2020/21 seasonal influenza, which might result in a reduced population natural immunity for the upcoming 2021/22 influenza season. To predict the spread of influenza virus in Italy and the impact of prevention and control measures, we present an age-structured Susceptible-Exposed-Infectious-Removed (SEIR) model including the role of social mixing patterns and the impact of age-stratified vaccination strategies and Non-Pharmaceutical Interventions (NPIs) such as school closures, partial lockdown, as well as the adoption of personal protective equipment and the practice of hand hygiene. We find that vaccination campaigns with standard coverage would produce a remarkable mitigation of the spread of the disease in moderate influenza seasons, making the adoption of NPIs unnecessary. However, in case of severe seasonal epidemics, a standard vaccination coverage would not be sufficiently effective in fighting the epidemic, thus implying that a combination with the adoption of NPIs is necessary to contain the disease. Alternatively, our results show that the enhancement of the vaccination coverage would reduce the need to adopt NPIs, thus limiting the economic and social impacts that NPIs might produce. Our results highlight the need to respond to the influenza epidemic by strengthening the vaccination coverage. [ABSTRACT FROM AUTHOR]

Background: Vaccination during pregnancy has been repeatedly demonstrated to be safe and effective in protecting against infection and associated harms for the mother, developing baby, and subsequent infant. However, maternal vaccination uptake remains low compared to the general population. Objectives: An umbrella review to explore the barriers and facilitators to Influenza, Pertussis and COVID-19 vaccination during pregnancy and within 2 years after childbirth, and to inform interventions to encourage uptake (PROSPERO registration number: CRD42022327624). Methods: Ten databases were searched for systematic reviews published between 2009 and April 2022 exploring the predictors of vaccination or effectiveness of interventions to improve vaccination for Pertussis, Influenza, or COVD-19. Both pregnant women and mothers of infants under two years were included. Barriers and facilitators were organised using the WHO model of determinants of vaccine hesitancy through narrative synthesis, the Joanna Briggs Institute checklist assessed review quality, and the degree of overlap of primary studies was calculated. Results: 19 reviews were included. Considerable overlap was found especially for intervention reviews, and the quality of the included reviews and their primary studies varied. Sociodemographic factors were specifically researched in the context of COVID-19, exerting a small but consistent effect on vaccination. Concerns around the safety of vaccination particularly for the developing baby were a main barrier. While key facilitators included recommendation from a healthcare professional, previous vaccination, knowledge around vaccination, and communication with and support from social groups. Intervention reviews indicated multi-component interventions involving human interaction to be most effective. Conclusion: The main barriers and facilitators for Influenza, Pertussis and COVID-19 vaccination have been identified and constitute the foundation for policy development at the international level. Ethnicity, socioeconomic status, concerns about vaccine safety and side effects, and lack of healthcare professionals' recommendations, are the most relevant factors of vaccine hesitancy. Adapting educational interventions to specific populations, person-to-person interaction, healthcare professionals' involvement, and interpersonal support are important strategies to improve uptake. [ABSTRACT FROM AUTHOR]

BackgroundSeasonality in tuberculosis (TB) has been described, especially in children. However, few studies have assessed seasonality of TB in the equatorial region, and none in children.ObjectivesTo assess for seasonality of childhood TB cases in Kampala, Uganda, and determine the role of temperature, rainfall patterns, and influenza cases on TB diagnoses.MethodsWe retrospectively analyzed demographic and clinical data of children (under 15 years) diagnosed with TB at a pediatric TB clinic in Kampala, Uganda from 2010 to 2015. We performed decomposition analysis of the monthly case time series to assess seasonality. We compared monthly mean plots and performed Poisson regression to assess any association between TB diagnoses and temperature, rainfall, and influenza.ResultsOf the 713 childhood TB cases diagnosed at the clinic, 609 (85%) were clinically diagnosed and 492 (69%) were pulmonary cases. There were minimal monthly variations in TB cases, with a trough in December and peaks in July and October, but there was no significant seasonality. Temperature variations did not show a clear pattern with TB diagnoses. Rainfall alternated with TB diagnoses in the first half of the year, but then overlapped in the second half and was significantly associated with TB diagnoses. Influenza cases were significantly related to TB diagnoses with (β = 0.05, 95% CI 0.01 to 0.09, p = 0.01) or without (β = 0.06, 95% CI 0.01 to 0.1, p = 0.01) rainfall, and had particular overlap with pulmonary TB cases.ConclusionsSeasonal variations in childhood TB diagnoses were non-significant. Temperature did not have a clear pattern with TB diagnoses, but rainfall and influenza cases correlated with the primarily clinically diagnosed childhood TB cases.

Background: The prediction and prevention of influenza is a public health issue of great concern, and the study of timely acquisition of influenza transmission trend has become an important research topic. For achieving more quicker and accurate detection and prediction, the data recorded on the Internet, especially on the search engine from Google or Baidu are widely introduced into this field. Moreover, with the development of intelligent technology and machine learning algorithm, many updated and advanced trend tracking and forecasting methods are also being used in this research problem. Methods: In this paper, a new recurrent neural network architecture, attention-based long short-term memory model is proposed for influenza surveillance. This is a kind of deep learning model which is trained by processing from Baidu Index series so as to fit the real influenza survey time series. Previous studies on influenza surveillance by Baidu Index mostly used traditional autoregressive moving average model or classical machine learning models such as logarithmic linear regression, support vector regression or multi-layer perception model to fit influenza like illness data, which less considered the deep learning structure. Meanwhile, some new model that considered the deep learning structure did not take into account the application of Baidu index data. This study considers introducing the recurrent neural network with long short-term memory combined with attention mechanism into the influenza surveillance research model, which not only fits the research problems well in model structure, but also provides research methods based on Baidu index. Results: The actual survey data and Baidu Index data are used to train and test the proposed attention-based long short-term memory model and the other comparison models, so as to iterate the value of the model parameters, and to describe and predict the influenza epidemic situation. The experimental results show that our proposed model has better performance in the mean absolute error, mean absolute percentage error, index of agreement and other indicators than the other comparison models. Conclusion: Our proposed attention-based long short-term memory model vividly verifies the ability of this attention-based long short-term memory structure for better surveillance and prediction the trend of influenza. In comparison with some of the latest models and methods in this research field, the model we proposed is also excellent in effect, even more lightweight and robust. Future research direction can consider fusing multimodal data based on this model and developing more application scenarios. [ABSTRACT FROM AUTHOR]

Influenza B viruses (IBV) are responsible for a considerable part of the burden caused by influenza virus infections. Since their emergence in the 1980s, the Yamagata and Victoria antigenic lineages of influenza B circulate in alternate patterns across the globe. Furthermore, their evolutionary divergence and the appearance of new IBV subclades complicates the prediction of future influenza vaccines compositions. It has been proposed that the addition of the neuraminidase (NA) antigen could potentially induce a broader protection and compensate for hemagglutinin (HA) mismatches in the current vaccines. Here we show that anti-NA and -HA sera against both Victoria and Yamagata lineages have limited inter-lineage cross-reactivity. When transferred to mice prior to infection with a panel of IBVs, anti-NA sera were as potent as anti-HA sera in conferring protection against homologous challenge and, in some cases, conferred superior protection against challenge with heterologous IBV strains. [ABSTRACT FROM AUTHOR]

Manufactured influenza vaccines have to contain a defined amount of hemagglutinin (HA) antigen. Therefore, vaccine viruses with a high HA antigen yield (HAY) are preferable for manufacturing vaccines, particularly vaccines in response to a pandemic, when vaccines need to be rapidly produced. However, the viral properties associated with a high HAY have not yet been fully clarified. To identify the HAY-associated traits, we first propagated 26 H5 candidate vaccine viruses (CVVs) in eggs, which were previously developed based on genetic reassortment methods using master viruses, to determine their total protein yield (TPY), ratio of HA to total viral protein (%-HA content) and HAY. The results revealed that the HAY was correlated with the TPY but not with the %-HA content. We further found that altering the sequences of the 3' noncoding region of HA vRNA or replacing the master virus improved the HAYs and TPYs of the low-HAY CVVs to approximately double the values of the original CVVs but did not change the %-HA content, which a previous study suggested was associated with the HAY. Analyses based on real-time PCR assays and scanning electron microscopy revealed that the virus samples with an improved HAY contained more copies of the virus genome and viral particles than the original samples. The results suggest that an improvement in virus growth (i.e., an increase in the amount of viral particles) leads to an increase in the TPY and thus in the HAY, regardless of the %-HA content. The approximately twofold increase in the HAY shown in this study may not appear to represent a large improvement, but the impact will be significant given the millions of chicken eggs used to produce vaccines. These findings will be informative for developing high-HAY vaccine viruses. [ABSTRACT FROM AUTHOR]

The screening of flu-like syndrome is difficult due to nonspecific symptoms or even oligosymptomatic presentation and became even more complex during the Covid-19 pandemic. However, an efficient screening tool plays an important role in the control of highly contagious diseases, allowing more efficient medical-epidemiological approaches and rational management of global health resources. Infrared thermography is a technique sensitive to small alterations in the skin temperature which may be related to early signs of inflammation and thus being relevant in the detection of infectious diseases. Thus, the objective of this study was to evaluate the potential of facial thermal profiles as a risk evaluator of symptoms and signs of SARs diseases, using COVID-19 as background disease. A total of 136 patients were inquired about the most common symptoms of COVID-19 infection and were submitted to an infrared image scanning, where the temperatures of 10 parameters from different regions of the face were captured. We used RT-qPCR as the ground truth to compare with the thermal parameters, in order to evaluate the performance of infrared imaging in COVID-19 screening. Only 16% of infected patients had fever at the hospital admission, and most infrared thermal variables presented values of temperature significantly higher in infected patients. The maximum eye temperature (MaxE) showed the highest predictive value at a cut-off of >35.9°C (sn = 71.87%, sp = 86.11%, LR+ = 5.18, LR- = 0.33, AUC = 0.850, p < 0.001). Our predictive model reached an accuracy of 86% for disease detection, indicating that facial infrared thermal scanning, based on the combination of different facial regions and the thermal profile of the face, has potential to act as a more accurate diagnostic support method for early COVID-19 screening, when compared to classical infrared methods, based on a single spot with the maximum skin temperature of the face. [ABSTRACT FROM AUTHOR]

Humans are susceptible to influenza. The influenza virus spreads quickly and behave seasonally. The seasonality and spread of influenza are often associated with meteorological factors and have spatio-temporal differences. Based on the influenza cases and daily average meteorological factors in Lanzhou from 2014 to 2017, this study firstly aimed to analyze the characteristics of influenza incidence in Lanzhou and the impact of meteorological factors on influenza activities. Then, SARIMA(X) models for the prediction were established. The influenza cases in Lanzhou from 2014 to 2017 was more male than female, and the younger the age, the higher the susceptibility; the epidemic characteristics showed that there is a peak in winter, a secondary peak in spring, and a trough in summer and autumn. The influenza cases in Lanzhou increased with increasing daily pressure, decreasing precipitation, average relative humidity, hours of sunshine, average daily temperature and average daily wind speed. Low temperature was a significant driving factor for the increase of transmission intensity of seasonal influenza. The SARIMAX (1,0,0)(1,0,1)[12] multivariable model with average temperature has better prediction performance than the university model. This model is helpful to establish an early warning system, and provide important evidence for the development of influenza control policies and public health interventions. [ABSTRACT FROM AUTHOR]

Background: Co-circulation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other respiratory viruses, such as influenza and respiratory syncytial virus (RSV), can be a severe threat to public health. The accurate detection and differentiation of these viruses are essential for clinical laboratories. Herein, we comparatively evaluated the performance of the Kaira COVID-19/Flu/RSV Detection Kit (Kaira; Optolane, Seongnam, Korea) for detection of SARS-CoV-2, influenza A and B, and RSV in nasopharyngeal swab (NPS) specimens with that of the PowerChek SARS-CoV-2, Influenza A&B, RSV Multiplex Real-time PCR Kit (PowerChek; Kogene Biotech, Seoul, Korea). Methods: A total of 250 archived NPS specimens collected for routine clinical testing were tested in parallel by the Kaira and PowerChek assays. RNA standards were serially diluted and tested by the Kaira assay to calculate the limit of detection (LOD). Results: The positive and negative percent agreements between the Kaira and PowerChek assays were as follows: 100% (49/49) and 100% (201/201) for SARS-CoV-2; 100% (50/50) and 99.0% (198/200) for influenza A; 100% (50/50) and 100% (200/200) for influenza B; and 100% (51/51) and 100% (199/199) for RSV, respectively. The LODs of the Kaira assay for SARS-CoV-2, influenza A and B, and RSV were 106.1, 717.1, 287.3, and 442.9 copies/mL, respectively. Conclusions: The Kaira assay showed comparable performance to the PowerChek assay for detection of SARS-CoV-2, influenza A and B, and RSV in NPS specimens, indicating that the Kaira assay could be a useful diagnostic tool when these viruses are co-circulating. [ABSTRACT FROM AUTHOR]

Introduction: Seasonal influenza is a significant public health challenge worldwide. This study aimed to investigate the epidemiological characteristics and spatial patterns of severe hospitalized influenza cases confirmed by polymerase chain reaction (PCR) in Iran. Methods: Data were obtained from Iran's Ministry of Health and Medical Education and included all hospitalized lab-confirmed influenza cases from January 1, 2016, to December 30, 2018 (n = 9146). The Getis-Ord Gi* and Local Moran's I statistics were used to explore the hotspot areas and spatial cluster/outlier patterns of influenza. We also built a multivariable logistic regression model to identify covariates associated with patients' mortality. Results: Cumulative incidence and mortality rate were estimated at 11.44 and 0.49 (per 100,000), respectively, and case fatality rate was estimated at 4.35%. The patients' median age was 40 (interquartile range: 22–63), and 55.5% (n = 5073) were female. The hotspot and cluster analyses revealed high-risk areas in northern parts of Iran, especially in cold, humid, and densely populated areas. Moreover, influenza hotspots were more common during the colder months of the year, especially in high-elevated regions. Mortality was significantly associated with older age (adjusted odds ratio [aOR]: 1.01, 95% confidence interval [CI]: 1.01–1.02), infection with virus type-A (aOR: 1.64, 95% CI: 1.27–2.15), male sex (aOR: 1.77, 95% CI: 1.44–2.18), cardiovascular disease (aOR: 1.71, 95% CI: 1.33–2.20), chronic obstructive pulmonary disease (aOR: 1.82, 95% CI: 1.40–2.34), malignancy (aOR: 4.77, 95% CI: 2.87–7.62), and grade-II obesity (aOR: 2.11, 95% CI: 1.09–3.74). Conclusions: We characterized the spatial and epidemiological heterogeneities of severe hospitalized influenza cases confirmed by PCR in Iran. Detecting influenza hotspot clusters could inform prioritization and geographic specificity of influenza prevention, testing, and mitigation resource management, including vaccination planning in Iran. [ABSTRACT FROM AUTHOR]

Introduction: Influenza vaccination of children with medical comorbidities is critical due their increased risks for severe influenza disease. In Australia, hospitals are an avenue for influenza vaccine delivery to children with comorbidities but are not always effectively utilised. Qualitative enquiry sought to ascertainment the barriers and enablers for influenza vaccination recommendation, delivery, and recording of these children at Australian hospitals. Methods: Semi-structured interviews and discussion group sessions were conducted with paediatricians and nurses at four tertiary paediatric specialist hospitals and two general community hospitals in three Australian states. Transcripts from interviews and group sessions were inductively analysed for themes. The Capability, Opportunity, Motivation, and Behaviour (COM-B) model was used to explore the elements of each theme and identify potential interventions to increase influenza vaccination recommendation and delivery behaviours by providers. Results: Fifteen discussion sessions with 28 paediatricians and 26 nurses, and nine in-depth interviews (five paediatricians and four nurses) were conducted. Two central thematic domains were identified: 1. The interaction between hospital staff and parents/patients for influenza vaccine recommendation, and 2. Vaccination delivery and recording in the hospital environment. Six themes across these domains emerged detailing the importance of dedicated immunisation services, hospital leadership, paediatricians' vaccine recommendation role, the impact of comorbidities, vaccination recording, and cocooning vaccinations. Supportive hospital leadership, engaged providers, and dedicated immunisation services were identified as essential for influenza vaccination of children with comorbidities in Australian hospital. Conclusion: Recommendation of influenza vaccination for Australian children with comorbidities is impacted by the beliefs of paediatricians and the perceived impact of influenza disease on children's comorbidities. Dedicated immunisation services and supportive hospital leadership were drivers for influenza vaccine delivery at hospitals. Future interventions targeting hospital-based influenza vaccine delivery for children with comorbidities should take a rounded approach targeting providers' attitudes, the hospital environment and leadership support. [ABSTRACT FROM AUTHOR]

Introduction: Non-pharmaceutical interventions (NPIs) such as lockdown, social distancing and use of face coverings was adopted by the United Kingdom (UK) Armed Forces (AF) during the COVID-19 pandemic. This study assessed the impact of the use of NPIs on the incidence of influenza-like illness (ILI) in the UK AF. Methods: A longitudinal study design was adopted, and secondary data was analysed retrospectively. Clinical Read codes for ILI was used to generate data for flu seasons before and during the COVID-19 pandemic (September 2017 to April 2021). Results: Before the COVID-19 pandemic, the rate of reporting ILI was ~ 4% across all flu seasons. The count of ILI was 2.9%, 2.2% and 3.1% during 2017–18, 2018–19 and 2019–20 flu seasons respectively. During the COVID-19 pandemic, both the rate of reporting ILI (0.6%) and the count of ILI (0.5%) were significantly smaller (p <.001). The rate of reporting ILI was positively correlated with the count of ILI (r (2) =.97, p =.014). Influenza vaccination rate increased by 1.3% during the COVID-19 pandemic. Vaccination rate was negatively correlated with the rate of reporting ILI (r (2) = -.52, p = 0.24) and the count of ILI (r (2) = -.61, p = 0.19). However, this correlation was not significant. The use of NPIs was negatively correlated with the rate of reporting ILI (r (2) = -.99, p = <.001) and the count of ILI (r (2) = -.95, p = 0.026). The overall multiple regression performed was statistically significant (R2 = 0.94, F (1, 2) = 33.628, p = 0.028). The rate of reporting ILI significantly predicted the count of ILI (β = 0.609, p = 0.028) while vaccination rate did not significantly predict the count of ILI (β = -0.136, p = 0.677). Conclusions: The incidence of ILI in the UK AF was significantly reduced during the COVID-19 pandemic. The use of NPIs and the rate of reporting ILI significantly reduced the count of ILI. Being vaccinated for influenza did not significantly reduce the count of ILI. [ABSTRACT FROM AUTHOR]

The coexistence of different types of poultry operations such as free range and backyard flocks, large commercial indoor farms and live bird markets, as well as the presence of many areas where wild and domestic birds co-exist, make California susceptible to avian influenza outbreaks. The 2014-2015 highly pathogenic Avian Influenza (HPAI) outbreaks affecting California and other states in the United States have underscored the need for solutions to protect the US poultry industry against this devastating disease. We applied disease distribution models to predict where Avian influenza is likely to occur and the risk for HPAI outbreaks is highest. We used observations on the presence of Low Pathogenic Avian influenza virus (LPAI) in waterfowl or water samples at 355 locations throughout the state and environmental variables relevant to the disease epidemiology. We used two algorithms, Random Forest and MaxEnt, and two data-sets Presence-Background and Presence-Absence data. The models performed well (AUCc > 0.7 for testing data), particularly those using Presence-Background data (AUCc > 0.85). Spatial predictions were similar between algorithms, but there were large differences between the predictions with Presence-Absence and Presence-Background data. Overall, predictors that contributed most to the models included land cover, distance to coast, and broiler farm density. Models successfully identified several counties as high-to-intermediate risk out of the 8 counties with observed outbreaks during the 2014-2015 HPAI epizootics. This study provides further insights into the spatial epidemiology of AI in California, and the high spatial resolution maps may be useful to guide risk-based surveillance and outreach efforts.

Background: The risk of hospitalization or death after influenza infection is higher at the extremes of age and in individuals with comorbidities. We estimated the number of hospitalizations with influenza and characterized the cumulative risk of comorbidities and age on severe outcomes in Mexico and Brazil. Methods: We used national hospital discharge data from Brazil (SIH/SUS) from 2010–2018 and Mexico (SAEH) from 2010–2017 to estimate the number of influenza admissions using ICD-10 discharge codes, stratified by age (0–4, 5–17, 18–49, 50–64, and ≥65 years). Duration of hospital stay, admission to the intensive care unit (ICU), and in-hospital case fatality rates (CFRs) defined the severe outcomes. Rates were compared between patients with or without pre-specified comorbidities and by age. Results: A total of 327,572 admissions with influenza were recorded in Brazil and 20,613 in Mexico, with peaks period most years. In Brazil, the median hospital stay duration was 3.0 days (interquartile range, 2.0–5.0), ICU admission rate was 3.3% (95% CI, 3.2–3.3%), and in-hospital CFR was 4.6% (95% CI, 4.5–4.7). In Mexico, the median duration of stay was 5.0 days (interquartile range, 3.0–7.0), ICU admission rate was 1.8% (95% CI, 1.6–2.0%), and in-hospital CFR was 6.9% (95% CI, 6.5–7.2). In Brazil, ICU admission and in-hospital CFR were higher in adults aged ≥50 years and increased in the presence of comorbidities, especially cardiovascular disease. In Mexico, comorbidities increased the risk of ICU admission by 1.9 (95% CI, 1.0–3.5) and in-hospital CFR by 13.9 (95% CI, 8.4–22.9) in children 0–4 years. Conclusion: The SIH/SUS and SAEH databases can be used to estimate hospital admissions with influenza, and the disease severity. Age and comorbidities, especially cardiovascular disease, are cumulatively associated with more severe outcomes, with differences between countries. This association should be further analyzed in prospective surveillance studies designed to support influenza vaccination strategy decisions. [ABSTRACT FROM AUTHOR]

Background: Rapid diagnosis of influenza is critical in preventing the spread of infection and ensuring patients quickly receive antiviral medication to reduce the severity and duration of influenza symptoms, whilst controlling the spread of the causative virus. In Japan patients are often administered anti-influenza medication following a positive rapid antigen detection test (RADT) result. However, the sensitivity of RADTs can lead to false negative results. The cobas® Influenza A/B Nucleic acid test for use on the cobas Liat® System (Liat) is a molecular point-of-care method that can provide a more sensitive alternative to RADTs for rapid influenza diagnosis and treatment. Methods: In this prospective multicenter study, diagnostic performance of the Liat test was compared with RADTs in patients presenting with influenza-like-illness. Test performance was also assessed by time since symptom onset. Results: Of 419 patients enrolled, 413 were evaluable for all designated tests. Most patients had type-A infection, and only one patient had influenza type B. In 413 patients, the sensitivity and specificity (95% CI) of the Liat test were 99.5% (97.2–99.9%) and 99.5% (97.4–99.9%), respectively, and were 79.7% (73.5–84.7%) and 95.4% (91.7–97.5%) for RADTs. For patients tested <12 hours from symptom onset, the Liat test had significantly higher sensitivity than RADTs (p<0.0001). Conclusion: Overall, compared with standard of care RADTs, the Liat test was more sensitive and specific in children and adults, particularly in the early stages of infection. Greater sensitivity can enable earlier diagnosis and may better inform appropriate antiviral treatment decisions. [ABSTRACT FROM AUTHOR]

The herpes simplex virus 1 (HSV-1) virion host shut-off (vhs) protein cleaves both cellular and viral mRNAs by a translation-initiation-dependent mechanism, which should spare circular RNAs (circRNAs). Here, we show that vhs-mediated degradation of linear mRNAs leads to an enrichment of circRNAs relative to linear mRNAs during HSV-1 infection. This was also observed in influenza A virus (IAV) infection, likely due to degradation of linear host mRNAs mediated by the IAV PA-X protein and cap-snatching RNA-dependent RNA polymerase. For most circRNAs, enrichment was not due to increased circRNA synthesis but due to a general loss of linear RNAs. In contrast, biogenesis of a circRNA originating from the long isoform (NEAT1_2) of the nuclear paraspeckle assembly transcript 1 (NEAT1) was induced both in HSV-1 infection–in a vhs-independent manner–and in IAV infection. This was associated with induction of novel linear splicing of NEAT1_2 both within and downstream of the circRNA. NEAT1_2 forms a scaffold for paraspeckles, nuclear bodies located in the interchromatin space, must likely remain unspliced for paraspeckle assembly and is up-regulated in HSV-1 and IAV infection. We show that NEAT1_2 splicing and up-regulation can be induced by ectopic co-expression of the HSV-1 immediate-early proteins ICP22 and ICP27, potentially linking increased expression and splicing of NEAT1_2. To identify other conditions with NEAT1_2 splicing, we performed a large-scale screen of published RNA-seq data. This uncovered both induction of NEAT1_2 splicing and poly(A) read-through similar to HSV-1 and IAV infection in cancer cells upon inhibition or knockdown of CDK7 or the MED1 subunit of the Mediator complex phosphorylated by CDK7. In summary, our study reveals induction of novel circular and linear NEAT1_2 splicing isoforms as a common characteristic of HSV-1 and IAV infection and highlights a potential role of CDK7 in HSV-1 or IAV infection. [ABSTRACT FROM AUTHOR]

The endothelial glycocalyx (EGX) contributes to the permeability barrier of vessels and regulates the coagulation cascade. EGX damage, which occurs in numerous disease states, including sepsis and trauma, results in endotheliopathy. While influenza and other viral infections are known to cause endothelial dysfunction, their effect on the EGX has not been described. We hypothesized that the H1N1 influenza virus would cause EGX degradation. Human umbilical vein endothelial cells (HUVECs) were exposed to varying multiplicities of infection (MOI) of the H1N1 strain of influenza virus for 24 hours. A dose-dependent effect was examined by using an MOI of 5 (n = 541), 15 (n = 714), 30 (n = 596), and 60 (n = 653) and compared to a control (n = 607). Cells were fixed and stained with FITC-labelled wheat germ agglutinin to quantify EGX. There was no difference in EGX intensity after exposure to H1N1 at an MOI of 5 compared to control (6.20 vs. 6.56 Arbitrary Units (AU), p = 0.50). EGX intensity was decreased at an MOI of 15 compared to control (5.36 vs. 6.56 AU, p<0.001). The degree of EGX degradation was worse at higher doses of the H1N1 virus; however, the decrease in EGX intensity was maximized at an MOI of 30. Injury at MOI of 60 was not worse than MOI of 30. (4.17 vs. 4.47 AU, p = 0.13). The H1N1 virus induces endothelial dysfunction by causing EGX degradation in a dose-dependent fashion. Further studies are needed to characterize the role of this EGX damage in causing clinically significant lung injury during acute viral infection. [ABSTRACT FROM AUTHOR]

The emergence of potentially pandemic viruses has resulted in preparedness efforts to develop candidate vaccines and adjuvant formulations. We evaluated the dose-sparing effect and safety of two distinct squalene-based oil-in-water adjuvant emulsion formulations (IB160 and SE) with influenza A/H7N9 antigen. This phase I, randomized, double-blind, placebo-controlled, dose-finding trial (NCT03330899), enrolled 432 healthy volunteers aged 18 to 59. Participants were randomly allocated to 8 groups: 1A) IB160 + 15μg H7N9, 1B) IB160 + 7.5μg H7N9, 1C) IB160 + 3.75μg H7N9, 2A) SE + 15μg H7N9, 2B) SE + 7.5μg H7N9, 2C) SE + 3.75μg H7N9, 3) unadjuvanted vaccine 15μg H7N9 and 4) placebo. Immunogenicity was evaluated through haemagglutination inhibition (HI) and microneutralization (MN) tests. Safety was evaluated by monitoring local and systemic, solicited and unsolicited adverse events (AE) and reactions (AR) 7 and 28 days after each study injection, respectively, whereas serious adverse events (SAE) were monitored up to 194 days post-second dose. A greater increase in antibody geometric mean titers (GMT) was observed in groups receiving adjuvanted vaccines. Vaccinees receiving IB160-adjuvanted formulations showed the greatest response in group 1B, which induced an HI GMT increase of 4.7 times, HI titers ≥40 in 45.2% of participants (MN titers ≥40 in 80.8%). Vaccinees receiving SE-adjuvanted vaccines showed the greatest response in group 2A, with an HI GMT increase of 2.5 times, HI titers ≥40 in 22.9% of participants (MN titers ≥40 in 65.7%). Frequencies of AE and AR were similar among groups. Pain at the administration site and headache were the most frequent local and systemic solicited ARs. The vaccine candidates were safe and the adjuvanted formulations have a potential dose-sparing effect on immunogenicity against influenza A/H7N9. The magnitude of this effect could be further explored. [ABSTRACT FROM AUTHOR]

Introduction: In Canada, pneumococcal vaccination is recommended to all adults aged ≥65 and those <65 who have one or more chronic medical conditions (CMCs). Understanding vaccine uptake and its determinants among eligible groups has important implications for reducing the burden of pneumococcal disease. Methods: Using data from a large national cohort of Canadian residents aged ≥47 years between 2015–2018, we calculated self-reported pneumococcal vaccine uptake among eligible groups, estimated associations between key factors and non-vaccination, assessed missed opportunities for vaccination (MOV) and examined risk factors for MOV. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for relevant associations were estimated through logistic regression. Results: 45.8% (95% CI: 45.2–46.5) of 22,246 participants aged ≥65 and 81.3% (95% CI: 80.5–82.0) of 10,815 individuals aged 47–64 with ≥1 CMC reported never having received a pneumococcal vaccine. Receipt of influenza vaccination in the previous year was associated with the lowest odds of pneumococcal non-vaccination (aOR = 0.14 [95% CI: 0.13–0.15] for older adults and aOR = 0.23 [95% CI: 0.20–0.26] for those aged 47–64 with ≥1 CMC). Pneumococcal vaccine uptake was also more likely in case of contact with a family doctor in the previous year (versus no contact), increased with age and varied widely across provinces. Among individuals recently vaccinated against influenza, 32.6% (95% CI: 31.9–33.4) of those aged ≥65 and 71.1% (95% CI: 69.9–72.3) of those aged 47–64 with ≥1 CMC missed an opportunity to get a pneumococcal vaccine. Among individuals who had contact with a family doctor, 44.8% (95% CI: 44.1–45.5) of those aged ≥65 and 80.4% (95% CI: 79.6–81.2) of those aged 47–64 with ≥1 CMC experienced a MOV. Conclusions: Pneumococcal vaccine uptake remains suboptimal among at-risk Canadian adults who are eligible for vaccination. Further research is needed to clarify the reasons behind missed opportunities for vaccination and adequately address the main barriers to pneumococcal vaccination. [ABSTRACT FROM AUTHOR]

Influenza is a major cause of highly contagious respiratory illness resulting in high mortality and morbidity worldwide. Annual vaccination is an effective way to prevent infection and complication from constantly mutating influenza strains. Vaccination utilizes preemptive inoculation with live virus, live attenuated virus, inactivated virus, or virus segments for optimal immune activation. The route of administration also affects the efficacy of the vaccination. Here, we evaluated the effects of inoculation with ultraviolet (UV)-inactivated or live influenza A virus strains and compared their effectiveness and cross protection when intraperitoneal and intramuscular routes of administration were used in mice. Intramuscular or intraperitoneal inoculation with UV-inactivated Influenza A/WSN/1933 provided some protection against intranasal challenge with a lethal dose of live Influenza A/WSN/1933 but only when a high dose of the virus was used in the inoculation. By contrast, inoculation with a low dose of live virus via either route provided complete protection against the same intranasal challenge. Intraperitoneal inoculation with live or UV-inactivated Influenza A/Philippines/2/1982 and intramuscular inoculation with UV-inactivated Influenza A/Philippines/2/1982 failed to produce cross-reactive antibodies against Influenza A/WSN/1933. Intramuscular inoculation with live Influenza A/Philippines/2/1982 induced small amounts of cross-reactive antibodies but could not suppress the cytokine storm produced upon intranasal challenge with Influenza A/WSN/1993. None of the tested inoculation conditions provided observable cross protection against intranasal challenge with a different influenza strain. Taken together, vaccination efficacy was affected by the state and dose of the vaccine virus and the route of administration. These results provide practical data for the development of effective vaccines against influenza virus. [ABSTRACT FROM AUTHOR]

Evidence suggests that older people aged ≥65 years and those aged 60–64 years with chronic medical conditions are at higher risk of developing severe complications due to influenza virus infection when compared with young, healthy adults. Although seasonal influenza is monitored through a nationwide passive surveillance in Japan, influenza related outcomes and medical resource consumption have not been fully documented. This retrospective database study aimed to describe the epidemiological and clinical characteristics of medically attended influenza cases aged ≥60 years and the associated medical resource consumption in Japan. We used clinically diagnosed influenza (CDI) based on the international classification of disease codes, and laboratory-confirmed influenza (LCI) based on influenza test results, to identify the patient population during a total of nine seasons (2010/2011 to 2018/2019). A total of 372,356 CDI and 31,122 LCI cases were identified from 77 medical institutions. The highest numbers of medically-attended influenza episodes were in patients aged 65–74 years and 75–84 years. On average, across seasons, 5.9% of all-cause hospitalizations were attributable to CDI and 0.4% were LCI. Influenza viruses type A and B co-circulated annually in varying degree of intensity and were associated with similar level of complications, including cardiovascular-related. Oxygen therapy increased with age; by contrast, mechanical ventilation, dialysis, blood transfusion, and intensive care unit admission were higher in the younger groups. In-hospital mortality for inpatients aged ≥ 85 years with CDI and LCI were 18.6% and 15.5%, respectively. Considering the burden associated with medically-attended influenza in this population, influenza prevention, laboratory confirmation and clinical management should be emphasized by general practicians and specialists like cardiologists to protect this aging population. [ABSTRACT FROM AUTHOR]

Background: Influenza vaccination is recommended in Canada for older adults and those with underlying health conditions due to their increased risk of severe outcomes. Further research is needed to identify who within these groups is not receiving influenza vaccine to identify opportunities to increase coverage. Objectives: We aimed to 1) estimate influenza non-vaccination prevalence and 2) assess factors associated with non-vaccination among Canadian adults aged ≥65 and adults aged 46–64 with ≥1 chronic medical condition (CMC) due to their high risk of severe influenza outcomes. Methods: We conducted a secondary analysis of cross-sectional data collected from 2015–2018 among participants of the Canadian Longitudinal Study on Aging. For both groups of interest, we estimated non-vaccination prevalence and used logistic regression models to identify factors associated with non-vaccination. We report adjusted odds ratios and 95% confidence intervals for the investigated variables. Results: Overall, 29.5% (95% CI: 28.9%, 30.1%) of the 23,226 participants aged ≥65 years and 50.4% (95% CI: 49.4%, 51.3%) of the 11,250 participants aged 46–64 years with ≥1 CMC reported not receiving an influenza vaccination in the past 12 months. For both groups, lack of recent contact with a family doctor and current smoking were independently associated with non-vaccination. Discussion: Influenza vaccination helps prevent severe influenza outcomes. Yet, half of adults aged 46–64 years with ≥1 CMC and more than one-quarter of all adults aged ≥65 years did not receive a recommended influenza vaccine in the year prior to the survey. Innovation in vaccination campaigns for routinely recommended vaccines, especially among those without annual family doctor visits, may improve coverage. Conclusion: Influenza vaccination coverage among Canadian adults aged 46–64 years with ≥1 CMC and adults aged ≥65 years remains suboptimal. Vaccination campaigns targeting those at high risk of severe outcomes without routine physician engagement should be evaluated to improve uptake. [ABSTRACT FROM AUTHOR]

Pregnant women are particularly vulnerable to infection. Furthermore, infection from pertussis, influenza and COVID-19 increases the likelihood of adverse consequences to the mother and developing baby such as stillbirth, ICU admission, and pre-term caesarean birth. Increased rates of transmission and risk of adverse consequences from infection justifies the provision of national maternal vaccination programmes. Additionally, maternal vaccination helps protect the infant until they are able to receive their own vaccinations; a time when they are most at risk of mortality from influenza and pertussis. Vaccination during pregnancy has been repeatedly demonstrated as safe and effective in reducing harm, although rates of uptake remain low compared to the general population. The current protocol describes the methodology for an umbrella review aiming to explore the barriers and facilitators of vaccination during pregnancy for pertussis, influenza, and COVID-19. Systematic reviews that investigate the barriers and facilitators of at least one of either pertussis, influenza, or COVID-19 will be included in this review. Multiple databases will be searched, and included reviews assessed for quality (using the Joanna Briggs Institute (JBI) quality assessment for systematic reviews) and degree of overlap of included primary studies. Included reviews will be analysed according to the WHO SAGE model of determinants of vaccine hesitancy and separated by whether these explore influenza and pertussis, or COVID-19. The outcomes of this review will help inform the development of interventions to increase uptake of vaccination during pregnancy, and on whether interventions need to be tailored depending on the infectious disease. The key findings will identify the specific barriers and facilitators of vaccination hesitancy by considering contextual influences (e.g. sociodemographic variables), individual/social group influences (e.g. trust in the institutions), and vaccine-specific issues (e.g. safety and recommendations). [ABSTRACT FROM AUTHOR]

Recent reports of haemagglutinin antigen (HA) mismatch between vaccine composition strains and circulating strains, have led to renewed interest in influenza B viruses. Additionally, there are concerns about resistance to neuraminidase inhibitors in new influenza B isolates. To assess the potential impact in Ghana, we characterized the lineages of influenza B viruses that circulated in Ghana between 2016 and 2017 from different regions of the country: Southern, Northern and Central Ghana. Eight representative specimens from the three regions that were positive for influenza B virus by real-time RT-PCR were sequenced and compared to reference genomes from each lineage. A total of eleven amino acids substitutions were detected in the B/Victoria lineage and six in the B/Yamagata lineage. The strains of influenza B viruses were closely related to influenza B/Brisbane/60/2008 and influenza B/Phuket/3073/2013 for the Victoria and Yamagata lineages, respectively. Three main amino acid substitutions (P31S, I117V and R151K) were found in B/Victoria lineages circulating between 2016 and 2017, while one strain of B/Victoria possessed a unique glycosylation site at amino acid position 51 in the HA2 subunit. Two main substitutions (L172Q and M251V) were detected in the HA gene of the B/Yamagata lineage. The U.S. CDC recently reported a deletion sub-group in influenza B virus, but this was not identified among the Ghanaian specimens. Close monitoring of the patterns of influenza B evolution is necessary for the efficient selection of representative viruses for the design and formulation of effective influenza vaccines. [ABSTRACT FROM AUTHOR]

There is a lack of comprehensive instruments for the assessment of compliance with influenza immunization. The purpose of this study was to examine psychometric characteristics of the Health Belief Model Applied to Influenza (HBMAI) among people with chronic diseases. We selected people residing in four municipalities of the Foča region (Republic of Srpska—Bosnia and Herzegovina) who were listed in the official records to receive the recommended influenza immunization in 2017/2018. Participants were interviewed using the HBMAI questionnaire at their homes. The HBMAI is composed of 45 items classified in 7 domains (Susceptibility, Seriousness, Benefits, Barriers, Knowledge, Health Motivation and Cue to Action). The confirmatory factor analysis (CFA) suggested that the Serbian HBMAI did not fit the original structure. The parallel analysis suggested that HBMAI in Serbian had 6 domains, instead of the original 7. The domain of "Knowledge" was removed. The domains of "Barriers", "Health Motivation" and "Cue to Action" preserved their original structure. The domains of "Susceptibility", "Seriousness" and "Benefits" were partially modified. The parameters on the CFA for the new modified HBMAI in Serbian were acceptable (goodness of fit index [GFI] = 0.946, comparative fit index [CFI] = 0.967, Tucker-Lewis index [TLI] = 0.963, root mean square error of approximation [RMSEA] = 0.044 and standardized root mean square residual [SRMR] = 0.078). This modified HBMAI version with 6 domains, not including the Knowledge domain, is recommended for use in research about influenza among people with chronic diseases in Serbian language. [ABSTRACT FROM AUTHOR]

Background: Influenza cause a clinical and economic burden for health systems and society. It is necessary to know the cost of the disease in order to perform cost-effectiveness assessments of preventive or treatment interventions. Objective: Assess the costs of the care of children with influenza in a third level hospital in Mexico. Methods: Longitudinal retrospective study based on the review of clinical files of children hospitalized with influenza. The use of resources used during their hospitalization in the emergency room, general ward, or PICU was logged, and the amount of supplies were multiplied by their corresponding prices to calculate the direct medical expenses. Descriptive statistics were used, and a GLM was adjusted in order to assess the effect of the clinical characteristics of the patients on the cost. Goodness of fit tests were performed. Results: 132 files were reviewed, out of which 95% were of subjects who had comorbidities. Subjects admitted at the PICU generates the highest cost (mean $29,608.62 USD), when analyzing the total cost summarizing the three clinical areas (Emergency room, general ward and PICU) by age group, the highest cost was for patients over age 10 (mean $49,674.53 USD). Comorbidities increase the cost of hospitalization by $10,000.00 USD. Conclusions: Influenza causes a significant financial burden on the health system. Children with comorbidities increase the costs and children over 10 years uses a significant amount of resources and they are not a priority in immunization program. It is necessary to perform studies on the use of resources in the first and second attention levels, which represent the highest incidence of the disease. [ABSTRACT FROM AUTHOR]

Objectives: To explore barriers and facilitators to COVID-19, influenza, and pneumococcal vaccine uptake in immunosuppressed adults with immune-mediated inflammatory diseases (IMIDs). Methods: Recruiting through national patient charities and a local hospital, participants were invited to take part in an in-depth, one-to-one, semi-structured interview with a trained qualitative researcher between November 2021 and January 2022. Data were analysed thematically in NVivo, cross-validated by a second coder and mapped to the SAGE vaccine hesitancy matrix. Results: Twenty participants (75% female, 20% non-white) were recruited. Barriers and facilitators spanned contextual, individual/group and vaccine/vaccination-specific factors. Key facilitators to all vaccines were higher perceived infection risk and belief that vaccination is beneficial. Key barriers to all vaccines were belief that vaccination could trigger IMID flare, and active IMID. Key facilitators specific to COVID-19 vaccines included media focus, high incidence, mass-vaccination programme with visible impact, social responsibility, and healthcare professionals' (HCP) confirmation of the new vaccines' suitability for their IMID. Novel vaccine technology was a concern, not a barrier. Key facilitators of influenza/pneumococcal vaccines were awareness of eligibility, direct invitation, and, clear recommendation from trusted HCP. Key barriers of influenza/pneumococcal vaccines were unaware of eligibility, no direct invitation or recommendation from HCP, low perceived infection risk, and no perceived benefit from vaccination. Conclusions: Numerous barriers and facilitators to vaccination, varying by vaccine-type, exist for immunosuppressed-IMID patients. Addressing vaccine benefits and safety for IMID-patients in clinical practice, direct invitation, and public-health messaging highlighting immunosuppression as key vaccination-eligibility criteria may optimise uptake, although further research should assess this. [ABSTRACT FROM AUTHOR]

A growing number of studies suggest that climate may impact the spread of COVID-19. This hypothesis is supported by data from similar viral contagions, such as SARS and the 1918 Flu Pandemic, and corroborated by US influenza data. However, the extent to which climate may affect COVID-19 transmission rates and help modeling COVID-19 risk is still not well understood. This study demonstrates that such an understanding is attainable through the development of regression models that verify how climate contributes to modeling COVID-19 transmission, and the use of feature importance techniques that assess the relative weight of meteorological variables compared to epidemiological, socioeconomic, environmental, and global health factors. The ensuing results show that meteorological factors play a key role in regression models of COVID-19 risk, with ultraviolet radiation (UV) as the main driver. These results are corroborated by statistical correlation analyses and a panel data fixed-effect model confirming that UV radiation coefficients are significantly negatively correlated with COVID-19 transmission rates. [ABSTRACT FROM AUTHOR]

Introduction: Using respiratory virus rapid diagnostic tests in the emergency department could allow better and faster clinical management. Point-of-care PCR instruments now provide results in less than 30 minutes. The objective of this study was to assess the impact of the use of a rapid molecular diagnostic test, the cobas® Influenza A/B & RSV Assay, during the clinical management of emergency department patients. Methods: Patients (adults and children) requiring admission or suffering from an underlying condition at risk of respiratory complications were prospectively recruited in the emergency department of four hospitals in the Brussels region. Physicians' intentions regarding admission, isolation, antibiotic, and antiviral use were collected before and after performing the rapid molecular test. Additionally, a comparison of the analytical performance of this test against antigen rapid tests and viral culture was performed as well as a time-to-result evaluation. Results: Among the 293 patients recruited, 90 had a positive PCR, whereas 44 had a positive antigen test. PCR yielded a sensitivity of 100% for all targets. Antigen tests yielded sensitivities ranging from 66.7% for influenza B to 83.3% for respiratory syncytial virus (RSV). The use of PCR allowed a decrease in the overall need for isolation and treatment by limiting the isolation of negative patients and antibiotic use for positive patients. Meanwhile, antiviral treatments better targeted patients with a positive influenza PCR. Conclusion: The use of a rapid influenza and RSV molecular test improves the clinical management of patients admitted to the emergency department by providing a fast and reliable result. Their additional cost compared to antigen tests should be balanced with the benefit of their analytical performance, leading to efficient reductions in the need for isolation and antibiotic use. [ABSTRACT FROM AUTHOR]

Influenza viruses (Inf-V) are an important cause of acute respiratory infection (ARI) in children. This study was undertaken to describe the clinical and epidemiological characteristics of Inf-V infections in a sample of hospitalized children with ARI. Nasopharyngeal aspirates (NPA) from 500 children between 1 month to 5 years old with symptoms of ARI were collected at the Teaching Hospital Kegalle Sri Lanka From May 2016 to June 2018, NPAs were tested for influenza A (Inf-A) and B (Inf-B) viruses, human respiratory syncytial virus (hRSV), human parainfluenza virus (hPIV) 1–3 using an immunofluorescence assay. The Inf-V were then subtyped using a multiplex RT-PCR. Inf-V were detected in 10.75% (54/502) of the hospitalized children with ARI and in that 5.57% (28/502) were positive for Inf-A and 5.17% (26/502) were positive for Inf-B. Of the 54 Inf-V positive children, 33 were aged between 6 and 20 months. Of the 28 children infected with Inf-A, 15 had uncharacterized lower respiratory infection, 7 had bronchopneumonia and 6 had bronchiolitis. Of the 26 children infected with Inf-B, 11 had uncharacterized lower respiratory infection, 10 had bronchiolitis, and 4 had bronchopneumonia. Inf-B circulated throughout the year with a few peaks, one in June and then in August followed by November to December in 2016 and one in April 2017 and January 2018. Inf-A circulated throughout the year with a major peak in March to April 2017 and July 2018. ARI was more common in boys compared to girls. Majority of the children infected with Inf-V were diagnosed with uncharacterized lower respiratory infection and mild to moderate bronchiolitis. Inf-V infections were prevalent throughout the year in the study area of Sri Lanka with variations in the type of the circulating virus. [ABSTRACT FROM AUTHOR]

Flu disease, with high mortality and morbidity, is caused by the influenza virus. Influenza infections are most effectively prevented through vaccination, but it requires annual reformulation due to the antigenic shift or drift of hemagglutinin and neuraminidase proteins. Increasing resistance to available anti-influenza drugs was also recently reported. The M2 surface protein of the influenza virus is an attractive target for universal vaccine development as it is highly conserved and multifunctional throughout the viral life cycle. This study aimed to discover a single-chain variable fragment (scFv) targeting the M2 protein of influenza A H1N1/PR8, showing neutralizing activity through plaque inhibition in virus replication. Several candidates were isolated using bio-panning, including scFv and single-domain VL target M2 protein, which was displayed on the yeast surface. The scFv/VL proteins were obtained with high yield and high purity through soluble expression in E. coli BL21 (DE3) pLysE strains. A single-domain VL-M2-specific antibody, NVLM10, exhibited the highest binding affinity to influenza virions and was engineered into a bivalent format (NVL2M10) to improve antigen binding. Both antibodies inhibited virus replication in a dose-dependent manner, determined using plaque reduction- and immunocytochemistry assays. Furthermore, bivalent anti-M2 single-domain VL antibodies significantly reduced the plaque number and viral HA protein intensity as well as viral genome (HA and NP) compared to the monovalent single-domain VL antibodies. This suggests that mono- or bivalent single-domain VL antibodies can exhibit neutralizing activity against influenza virus A, as determined through binding to virus particle activity. [ABSTRACT FROM AUTHOR]

Background: Decisions regarding the evaluation of children with influenza infection rely on the likelihood of severe disease. The role of early vital signs as predictors of severe influenza infection in children is not well known. Our objectives were to determine the value of vital signs in predicting hospitalization/recurrent emergency department (ED) visits due to influenza infection in children. Methods: We conducted a prospective study of children aged 6 months to 8 years of age with influenza like illness evaluated at an ED/UC from 2016–2018. All children underwent influenza testing by PCR. We collected heart rate, respiratory rate and temperature, and converted heart rate (HR) and respiratory rate (RR) to z-scores by age. HR z scores were further adjusted for temperature. Our primary outcome was hospitalization/recurrent ED visits within 72 hours. Vital sign predictors with p< 0.2 and other clinical covariates were entered into a multivariable logistic regression model to determine odds ratios (OR) and 95% CI; model performance was assessed using the Brier score and discriminative ability with the C statistic. Results: Among 1478 children, 411 (27.8%) were positive for influenza, of which 42 (10.2%) were hospitalized or had a recurrent ED visit. In multivariable analyses, adjusting for age, high-risk medical condition and school/daycare attendance, higher adjusted respiratory rate (OR 2.09, 95%CI 1.21–3.61, p = 0.0085) was a significant predictor of influenza hospitalization/recurrent ED visits. Conclusions: Higher respiratory rate adjusted for age was the most useful vital sign predictor of severity among young children with PCR-confirmed influenza. [ABSTRACT FROM AUTHOR]

Introduction: Influenza vaccination, besides protecting traditional risk groups, can protect employees and reduce illness-related absence, which is especially relevant in sectors with staff shortages. This study describes current knowledge of influenza vaccination in teachers and estimates its potential impact. Methods: We conducted a scoping review of the considerations for and impact of influenza vaccination of schoolteachers (grey and scientific literature up to 2020 March, complemented with interviews). We then estimated the potential impact of teacher vaccination in the Netherlands, with different scenarios of vaccine uptake for 3 influenza seasons (2016–2019). Using published data on multiple input parameters, we calculated potentially averted absenteeism notifications, averted absenteeism duration and averted doctor visits for influenza. Results: Only one scientific paper reported on impact; it showed lower absenteeism in vaccinated teachers, whereas more knowledge of vaccination impact was deemed crucial by 50% of interviewed experts. The impact for the Netherlands of a hypothetical 50% vaccine uptake was subsequently estimated: 74–293 potentially averted physician visits and 11,178–28,896 potentially averted days of influenza absenteeism (on ≈200,000 total teacher population). An estimated 12–32 vaccinations were required to prevent one teacher sick-leave notification, or 3.5–9.1 vaccinations to prevent one day of teacher absenteeism (2016–2019). Conclusion: Scientific publications on influenza vaccination in teachers are few, while public interest has increased to reduce teacher shortages. However, school boards and public health experts indicate requiring knowledge of impact when considering this vaccination. Estimations of 3.5–9.1 vaccinated teachers preventing one day of influenza-related sick leave suggest a possible substantial vaccination impact on absenteeism. Financial incentives, more accessible on-site vaccinations at workplaces, or both, are expected to increase uptake, but more research is needed on teachers' views and vaccine uptake potential and its cost-effectiveness. Piloting free on-site influenza vaccination in several schools could provide further information on teacher participation. [ABSTRACT FROM AUTHOR]

Introduction: Despite evidence suggesting an association between influenza infection and increased risk of acute myocardial infarction (AMI) in the older adult population (aged 65 years or above), little is known about its near-term risks in middle-aged adults (aged 45 to 64 years). This study aims to estimate the risks of and association between severe influenza infection requiring hospitalization and subsequent AMI within 12 months in middle-aged adults. Method: This is a retrospective case-control analysis of territorywide registry data of people aged 45 to 64 years admitting from up to 43 public hospitals in Hong Kong during a 20-year period from January 1997 to December 2017. The exposure was defined as severe influenza infection documented as the principal diagnosis using International Classification of Diseases codes and non-exposure as hospitalization for orthopedic surgery. Logistic regression was used to analyze the risk of subsequent hospitalization for AMI within 12 months following the exposure. Results: Among 30,657 middle-aged adults with an indexed hospitalization, 8,840 (28.8%) had an influenza-associated hospitalization. 81 (0.92%) were subsequently rehospitalized with AMI within 12 months after the indexed hospitalization. Compared with the control group, the risk of subsequent hospitalization for AMI was significantly increased (odds ratio [OR]: 2.54, 95% confidence interval [CI]: 1.64–3.92, p<0.001). The association remained significant even after adjusting for potential confounders (adjusted OR: 1.81, 95% CI: 1.11–2.95, p = 0.02). Patients with a history of hypertension, but not those with diabetes mellitus, dyslipidemia or atrial fibrillation/flutter, were at increased risk (adjusted OR: 5.01, 95% CI: 2.93–8.56, p<0.001). Conclusion: Subsequent hospitalization for AMI within 12 months following an indexed respiratory hospitalization for severe influenza increased nearly two-fold compared with the non-cardiopulmonary, non-exposure control. Recommendation of influenza vaccination extending to middle-aged adult population may be justified for the small but significant increased near-term risk of AMI. [ABSTRACT FROM AUTHOR]

Introduction: Health care professionals working in primary and specialized care typically search for medical information from Internet sources. In Finland, Physician's Databases are online portals aimed at professionals seeking medical information. As dosage errors may occur when prescribing medication to children, professionals' need for reliable medical information has increased in public health care centers and hospitals. Influenza continues to be a public health threat, with young children at risk of developing severe illness and easily transmitting the virus. Oseltamivir is used to treat children with influenza. The objective of this study was to compare searches for children's oseltamivir and influenza diagnoses in primary and specialized care, and to determine if the searches could aid detection of influenza outbreaks. Methods: We compared searches in Physician's Databases for children's oral suspension of oseltamivir (6 mg/mL) for influenza diagnoses of children under 7 years and laboratory findings of influenza A and B from the National Infectious Disease Register. Searches and diagnoses were assessed in primary and specialized care across Finland by season from 2012–2016. The Moving Epidemic Method (MEM) calculated seasonal starts and ends, and paired differences in the mean compared two indicators. Correlation was tested to compare seasons. Results: We found that searches and diagnoses in primary and specialized care showed visually similar patterns annually. The MEM-calculated starting weeks in searches appeared mainly in the same week. Oseltamivir searches in primary care preceded diagnoses by −1.0 weeks (95% CI: −3.0, −0.3; p = 0.132) with very high correlation (τ = 0.913). Specialized care oseltamivir searches and diagnoses correlated moderately (τ = 0.667). Conclusion: Health care professionals' searches for children's oseltamivir in online databases linked with the registers of children's influenza diagnoses in primary and specialized care. Therefore, database searches should be considered as supplementary information in disease surveillance when detecting influenza epidemics. [ABSTRACT FROM AUTHOR]

Shortly after the implementation of community mitigation measures in response to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), sharp declines in respiratory syncytial virus and influenza circulation were noted; post-mitigation circulation of other respiratory pathogens has gone unexplored. We retrospectively analyzed all records of a provider-ordered multiplex test between April 1, 2018, and July 31, 2021, in Nashville, Tennessee, and we noted disrupted historical seasonal patterns for common respiratory pathogens during the SARS-CoV-2 pandemic. [ABSTRACT FROM AUTHOR]