Moderate Influenza Research Articles

End of 2022/23 Season Influenza Vaccine Effectiveness in Primary Care in Great Britain.

The 2022/23 influenza season in the United Kingdom saw the return of influenza to prepandemic levels following two seasons with low influenza activity. The early season was dominated by A(H3N2), with cocirculation of A(H1N1), reaching a peak late December 2022, while influenza B circulated at low levels during the latter part of the season. From September to March 2022/23, influenza vaccines were offered, free of charge, to all aged 2-13 (and 14-15 in Scotland and Wales), adults up to 49 years of age with clinical risk conditions and adults aged 50 and above across the mainland United Kingdom. End-of-season adjusted vaccine effectiveness (VE) estimates against sentinel primary-care attendance for influenza-like illness, where influenza infection was laboratory confirmed, were calculated using the test negative design, adjusting for potential confounders. Results In the mainland United Kingdom, end-of-season VE against all laboratory-confirmed influenza for all those > 65 years of age, most of whom received adjuvanted quadrivalent vaccines, was 30% (95% CI: -6% to 54%). VE for those aged 18-64, who largely received cell-based vaccines, was 47% (95% CI: 37%-56%). Overall VE for 2-17 year olds, predominantly receiving live attenuated vaccines, was 66% (95% CI: 53%-76%). The paper provides evidence of moderate influenza VE in 2022/23.

Estimating the economic burden of influenza on the older population in Malaysia

Background Influenza is a contagious respiratory illness that can cause life-threatening complications among high-risk groups. Estimating the economic burden of influenza is essential to guide policy‐making on influenza vaccination programmes, especially in resource‐limited settings. This study aimed to estimate the economic burden of influenza on older adults (those aged ≥60 years) in Malaysia from the provider’s perspective. Methods The main data source in this study was the MY-DRG Casemix database of a teaching hospital in Malaysia. Cases with principal and secondary diagnoses coded in the International Classification of Diseases version 10 (ICD-10) as J09, J10.0, J10.1, J10.8, J11.0, J11.1, J11.8, J12.8, and J12.9, which represent influenza and its complications, were included in the study. The direct cost of influenza at all severity levels was calculated from the casemix data and guided by a clinical pathway developed by experts. The effect of the variations in costs and incidence rate of influenza for both the casemix and clinical pathway costing approaches was assessed with sensitivity analysis. Results A total of 1,599 inpatient and 407 outpatient influenza cases were identified from the MY-DRG Casemix database. Most hospitalised cases were aged <18 years (90.6%), while 77 cases (4.8%) involved older people. Mild, moderate, and severe cases comprised 56.5%, 35.1%, and 8.4% of cases, respectively. The estimated average annual direct costs for managing mild, moderate, and severe influenza were RM2,435 (USD579), RM6,504 (USD1,549), and RM13,282 (USD3,163), respectively. The estimated total annual economic burden of influenza on older adults in Malaysia was RM3.28 billion (USD782 million), which was equivalent to 10.7% of the Ministry of Health Malaysia budget for 2020. The sensitivity analysis indicated that the influenza incidence rate and cost of managing severe influenza were the most important factors influencing the total economic burden. Conclusions Overall, our results demonstrated that influenza imposes a substantial economic burden on the older Malaysian population. The high cost of influenza suggested that further efforts are required to implement a preventive programme, such as immunisation for older people, to reduce the disease and economic burdens.

FluTracking: Weekly online community-based surveillance of influenza-like illness in Australia, 2019 Annual Report

FluTracking provided evidence for an early, long, but moderate influenza season in the Australian community compared to prior years. Influenza-like illness (ILI) activity in 2019 peaked earlier (week ending 16 June) than any season on record in FluTracking data. ILI attack rates were above average early in the 2019 season (peak of 2.2%), and the duration of peak activity was longer than most prior years. However, ILI attack rates were lower than the five-year average in the latter half of the season. FluTracking participants reported higher vaccination coverage in 2019 (73.3%) compared with 2018 (65.7%), with the most notable increase in children aged less than five years (69.3% in 2019, compared to 55.6% in 2018). The total 2019 count of laboratory notifications (312,945) was higher than prior years (2007 onwards), and the peak weekly count of 18,429 notifications in 2019 was also higher than all prior years, except 2017. FluTracking makes a comparison to another surveillance system each year. The peak weekly percentage of calls to HealthDirect that were influenza-related was higher in 2019 (12.8%) than for 2014-2018 (range of 8.2-11.4% for peak week of activity each year). FluTracking participants reported a 2.5 times increase in influenza testing from 2018 to 2019 and a 1.5 times increase from 2017. Although 2019 was of higher activity and severity than 2018, Flutracking data indicates that 2019 was a lower activity and severity season than 2017, and notifications and influenza-related calls were heightened by increased community concern and testing.

Assessment of 2021/22 influenza epidemic scenarios in Italy during SARS-CoV-2 outbreak.

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.

Clinical Pathway for Influenza in the Elderly: A comprehensive management protocol of Malaysia

Introduction: The clinical pathway (CP) is one of the most recommended tools for ensuring the best quality of care and has been proven to reduce the cost and time spent in hospital. The development of a CP for influenza is crucial, especially for the elderly, as they are vulnerable to influenza-related complications. The main aim of this study was to provide a comprehensive protocol for each component of influenza management among the elderly in Malaysia. Methods: An expert group meeting was conducted involving family medicine specialists, public health specialists, geriatricians, respiratory physicians and infectious disease physicians. The CP was designed following a 6-step protocol: 1) Selection of expert panel, 2) discussion and information gathering, 3) development of CP draft, 4) refinement of CP draft, 5) implementation of CP, and 6) finalisation of CP. The CP for influenza was designed based on service type and disease severity. Results: The panel described both outpatient and inpatient CPs for managing elderly patients with influenza. The outpatient CP covered mild and moderate influenza cases, while the inpatient CP addressed the management of moderate and severe influenza. The estimated length of hospital stay for moderate and severe influenza cases with pneumonia was 6 and 14 days, respectively. Conclusions: The CP for influenza supports existing treatment according to illness severity leveraged on current clinical practice guidelines and the best-care practices in primary and tertiary care settings. Continuous use of the CP is required to assess its effectiveness, thereby enabling optimisation of the healthcare process in influenza treatment.

4-1BB/4-1BBL signaling pathway in patients with influenza A (H1N1) virus-associated pneumonia

Aim. To evaluate the activity of the 4-1BB/4-1BBL signaling pathway in patients with influenza A (H1N1) virus-associated pneumonia.Materials and Methods. Here we enrolled 85 patients (41 males and 44 females, median age 48 (36-62) years) with influenza A (H1N1) virus-associated pneumonia. Among the exclusion criteria were unstable hemodynamics, BMI > 30, diabetes mellitus, HIV, tuberculosis, and cancer. Control group consisted of 15 healthy donors. The diagnosis of influenza A / H1N1 was confirmed by a positive PCR test. Pneumonia was diagnosed according to the Federal Clinical Guidelines «Community-acquired pneumonia in adults». Severity of pneumonia was evaluated by using CURB-65 and SMART-COP scales as well as IDSA/ATS criteria. Plasma concentration of 4-1BB (CD137 or TNFRSF9, an inducible costimulatory receptor expressed on activated T cells and antigen-presenting cells) was determined by flow cytometry.Results. Patients with moderate and severe influenza A (H1N1) virus-associated pneumonia had 1.5- and 2.4 fold-increased concentration of plasma 4-1ВВ as compared with the healthy controls.Conclusion. The 4-1BB/4-1BBL signaling pathway, involved in multiple immune reactions, is associated with the severity of influenza A (H1N1) virus-associated pneumonia.

Influence of disease attenuation on relative influenza vaccine effectiveness by vaccine type

Benefit conferred by “enhanced” influenza vaccines is often measured by relative vaccine effectiveness, (rVE), which compares disease risk among groups of people who received alternative vaccines. Differences in attenuation of illness severity by vaccine types could manifest as differences in rVE. Using a simulated VE study and cohort of adults aged ≥ 65 years, we examined how rVE varied with assumptions about attenuation of disease severity conferred by standard and enhanced vaccines and how this variation could lead to differing estimates of rVE for prevention of moderate (i.e., outpatient) versus severe (i.e., inpatient) influenza illness. We found that if enhanced vaccines attenuated severe illness more than moderate illness, then rVE observed against severe disease could be higher than rVE observed against moderate disease. Thus, if differences in disease attenuation by vaccine type occurs, estimates of rVE may vary for influenza outcomes of differing levels of severity.

Comparison of Lung-Homing Receptor Expression and Activation Profiles on NK Cell and T Cell Subsets in COVID-19 and Influenza.

Respiratory viral infections with SARS-CoV-2 and influenza viruses commonly induce a strong infiltration of immune cells into the human lung, with potential detrimental effects on the integrity of the lung tissue. Despite comprising the largest fractions of circulating lymphocytes in the lung, rather little is known about how peripheral blood natural killer (NK) cell and T cell subsets are equipped for lung-homing in COVID-19 and influenza. Here, we provide a detailed comparative analysis of NK cells and T cells in patients infected with SARS-CoV-2 or influenza virus, focusing on the protein and gene expression of chemokine receptors known to be involved in recruitment to the lung. For this, we used 28-colour flow cytometry as well as re-analysis of a publicly available single-cell RNA-seq dataset from bronchoalveolar lavage (BAL) fluid. Frequencies of NK cells and T cells expressing CXCR3, CXCR6, and CCR5 were altered in peripheral blood of COVID-19 and influenza patients, in line with increased transcript expression of CXCR3, CXCR6, and CCR5 and their respective ligands in BAL fluid. NK cells and T cells expressing lung-homing receptors displayed stronger phenotypic signs of activation compared to cells lacking lung-homing receptors, and activation was overall stronger in influenza compared to COVID-19. Together, our results indicate a role for CXCR3+, CXCR6+, and/or CCR5+ NK cells and T cells that potentially migrate to the lungs in moderate COVID-19 and influenza patients, identifying common targets for future therapeutic interventions in respiratory viral infections.

Comprehensive Immunologic Evaluation of Bronchoalveolar Lavage Samples from Human Patients with Moderate and Severe Seasonal Influenza and Severe COVID-19.

Infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) or seasonal influenza may lead to respiratory failure requiring intubation and mechanical ventilation. The pathophysiology of this respiratory failure is attributed to local immune dysregulation, but how the immune response to viral infection in the lower airways of the human lung differs between individuals with respiratory failure and those without is not well understood. We used quantitative multiparameter flow cytometry and multiplex cytokine assays to evaluate matched blood and bronchoalveolar lavage (BAL) samples from control human subjects, subjects with symptomatic seasonal influenza who did not have respiratory failure, and subjects with severe seasonal influenza or SARS-CoV-2 infection with respiratory failure. We find that severe cases are associated with an influx of nonclassical monocytes, activated T cells, and plasmablast B cells into the lower airways. Cytokine concentrations were not elevated in the lower airways of moderate influenza patients compared with controls; however, 28 of 35 measured cytokines were significantly elevated in severe influenza, severe SARS-CoV-2 infection, or both. We noted the largest elevations in IL-6, IP-10, MCP-1, and IL-8. IL-1 family cytokines and RANTES were higher in severe influenza infection than severe SARS-CoV-2 infection. Interestingly, only the concentration of IP-10-correlated between blood and BAL during severe infection. Our results demonstrate inflammatory immune dysregulation in the lower airways during severe viral pneumonia that is distinct from lower airway responses seen in human patients with symptomatic, but not severe, illness and suggest that measurement of blood IP-10 concentration may predict this unique dysregulation.

Evaluation of a Sick Employee Online Log System for Tracking Sick Hospital Employees During Two Influenza Seasons

Background: Since 2009, Vidant Health has used a Sick Employee Online Log (SEOL) system to track illnesses among employees and to capture this information in real time. The CDC assessed the 2017–2018 influenza season as a high-severity influenza season, whereas the 2018–2019 influenza season was of moderate severity. Objective: In this research project, we sought to determine whether the influenza season severity would affect either the hospital-based employee illness surveillance system results or would correlate with state influenza-like illness (ILI) visits. Methods: The SEOL system is an internet-based system initiated in December 2008. When a hospital employee calls in sick, the department manager records whether the employee reports the following symptoms: nausea, vomiting, diarrhea, upper respiratory infection, fever, sore throat, headache, conjunctivitis, rash, and/or cough. The information is confidential, with raw data access restricted to review by occupational health and infection control leadership. The correlation value was determined for each symptom using the North Carolina Division of Human Services (NC DHHS) percentage of ILI visits in statewide emergency departments.1 The data collection dates covered January 1–May 31 for each year. In this study, only symptoms related to influenza were included: upper respiratory infection, fever, influenza-like illness, cough and self-reported influenza. Correlation values were calculated using MS Excel software. Results: There were no breaks in confidentiality. All of the correlation values had a correlation value of 0.5 or better (Fig. 1), showing good correlation with the NC DHHS ILI data for both years; however, the more severe 2017–2018 influenza season had correlation values of 0.7 for all symptoms, versus 0.52–0.59 for URI and ILI, respectively, only during 2018–2019. Conclusions: The higher-severity influenza season did correlate with a higher r values when compared to North Carolina’s DHHS ILI emergency department data than did the influenza season of moderate severity. A possible explanation is that a higher-severity influenza season would correlate better than a moderate influenza season because it shows fewer ILI peaks and troughs. In conclusion, the SEOL system served as an early warning that influenza is present among our staff, and it correlates well with the state system for ILI surveillance. Potential limitations of SEOL are that respiratory symptoms are not specific to influenza; thus, they are subject to variation due to other respiratory viruses circulating among our employees.1. The North Carolina Disease Event Tracking and Epidemiologic Collection Tool. NC DETECT website. http://www.ncdetect.org. Accessed Nov 8, 2019.Funding: NoneDisclosures: None

Severe and moderate seasonal influenza epidemics among Italian healthcare workers: A comparison of the excess of absenteeism

BackgroundThis study aims to quantify the excess of sickness absenteeism among healthcare workers (HCWs), to estimate the impact of a severe versus moderate influenza season and to determine whether the vaccination rates are associated with reduced sickness absence.MethodsWe investigated the excess absenteeism that occurred in a large Italian hospital, 5300 HCWs, during the severe influenza season of 2017/2018 and compared it with three moderate flu seasons (2010/2013). Data on influenza vaccinations and absenteeism were obtained from the hospital's databases. The data were split into two periods: the epidemic, from 42 to 17 weeks, and non‐epidemic, defined as 18 to 41 weeks, which was used as the baseline. We stratified the absenteeism among HCWs in multiple variables.ResultsOur study showed an increased absenteeism among HCWs during the epidemic period of severe season in comparison with non‐epidemic periods, the absolute increase correlated with a relative increase of 70% (from 4.05 to 6.68 days/person). Vaccinated HCWs had less excess of absenteeism in comparison with non‐vaccinated HCWs (1.74 vs 2.71 days/person). The comparison with the moderate seasons showed a stronger impact on HCW sick absenteeism in the severe season (+0.747days/person, P = .03), especially among nurses and HCWs in contact with patients (+1.53 P < .01; +1.19 P < .01).ConclusionsIn conclusion, a severe influenza epidemic has greater impacts on the absenteeism among HCWs than a moderate one. Although at a low rate, a positive effect of vaccination on absenteeism is present, it may support healthcare facilities to recommend vaccinations for their workers.

Risk of Ischemic Stroke in Patients With Coronavirus Disease 2019 (COVID-19) vs Patients With Influenza

It is uncertain whether coronavirus disease 2019 (COVID-19) is associated with a higher risk of ischemic stroke than would be expected from a viral respiratory infection. To compare the rate of ischemic stroke between patients with COVID-19 and patients with influenza, a respiratory viral illness previously associated with stroke. This retrospective cohort study was conducted at 2 academic hospitals in New York City, New York, and included adult patients with emergency department visits or hospitalizations with COVID-19 from March 4, 2020, through May 2, 2020. The comparison cohort included adults with emergency department visits or hospitalizations with influenza A/B from January 1, 2016, through May 31, 2018 (spanning moderate and severe influenza seasons). COVID-19 infection confirmed by evidence of severe acute respiratory syndrome coronavirus 2 in the nasopharynx by polymerase chain reaction and laboratory-confirmed influenza A/B. A panel of neurologists adjudicated the primary outcome of acute ischemic stroke and its clinical characteristics, mechanisms, and outcomes. We used logistic regression to compare the proportion of patients with COVID-19 with ischemic stroke vs the proportion among patients with influenza. Among 1916 patients with emergency department visits or hospitalizations with COVID-19, 31 (1.6%; 95% CI, 1.1%-2.3%) had an acute ischemic stroke. The median age of patients with stroke was 69 years (interquartile range, 66-78 years); 18 (58%) were men. Stroke was the reason for hospital presentation in 8 cases (26%). In comparison, 3 of 1486 patients with influenza (0.2%; 95% CI, 0.0%-0.6%) had an acute ischemic stroke. After adjustment for age, sex, and race, the likelihood of stroke was higher with COVID-19 infection than with influenza infection (odds ratio, 7.6; 95% CI, 2.3-25.2). The association persisted across sensitivity analyses adjusting for vascular risk factors, viral symptomatology, and intensive care unit admission. In this retrospective cohort study from 2 New York City academic hospitals, approximately 1.6% of adults with COVID-19 who visited the emergency department or were hospitalized experienced ischemic stroke, a higher rate of stroke compared with a cohort of patients with influenza. Additional studies are needed to confirm these findings and to investigate possible thrombotic mechanisms associated with COVID-19.

Efficacy of FLU-v, a broad-spectrum influenza vaccine, in a randomized phase IIb human influenza challenge study

FLU-v, developed by PepTcell (SEEK), is a peptide vaccine aiming to provide a broadly protective cellular immune response against influenza A and B. A randomized, double-blind, placebo-controlled, single-center, phase IIb efficacy and safety trial was conducted. One hundred and fifty-three healthy individuals 18–55 years of age were randomized to receive one or two doses of adjuvanted FLU-v or adjuvanted placebo subcutaneously on days −43 and −22, prior to intranasal challenge on day 0 with the A/California/04/2009/H1N1 human influenza A challenge virus. The primary objective of the study was to identify a reduction in mild to moderate influenza disease (MMID) defined as the presence of viral shedding and clinical influenza symptoms. Single-dose adjuvanted FLU-v recipients (n = 40) were significantly less likely to develop MMID after challenge vs placebo (n = 42) (32.5% vs 54.8% p = 0.035). FLU-v should continue to be evaluated and cellular immunity explored further as a possible important correlate of protection against influenza.

Pathway mapping of leukocyte transcriptome in influenza patients reveals distinct pathogenic mechanisms associated with progression to severe infection

BackgroundInfluenza infections produce a spectrum of disease severity, ranging from a mild respiratory illness to respiratory failure and death. The host-response pathways associated with the progression to severe influenza disease are not well understood.MethodsTo gain insight into the disease mechanisms associated with progression to severe infection, we analyzed the leukocyte transcriptome in severe and moderate influenza patients and healthy control subjects. Pathway analysis on differentially expressed genes was performed using a topology-based pathway analysis tool that takes into account the interaction between multiple cellular pathways. The pathway profiles between moderate and severe influenza were then compared to delineate the biological mechanisms underpinning the progression from moderate to severe influenza.Results107 patients (44 severe and 63 moderate influenza patients) and 52 healthy control subjects were included in the study. Severe influenza was associated with upregulation in several neutrophil-related pathways, including pathways involved in neutrophil differentiation, migration, degranulation and neutrophil extracellular trap (NET) formation. The degree of upregulation in neutrophil-related pathways were significantly higher in severely infected patients compared to moderately infected patients. Severe influenza was also associated with downregulation in immune response pathways, including pathways involved in antigen presentation such as CD4+ T-cell co-stimulation, CD8+ T cell and Natural Killer (NK) cells effector functions. Apoptosis pathways were also downregulated in severe influenza patients compare to moderate and healthy controls.ConclusionsThese findings showed that there are changes in gene expression profile that may highlight distinct pathogenic mechanisms associated with progression from moderate to severe influenza infection.

Moderate influenza vaccine effectiveness against A(H1N1)pdm09 virus, and low effectiveness against A(H3N2) subtype, 2018/19 season in Italy

ABSTRACTBackground: Influenza vaccines are updated every year to match the vaccine strains with currently circulating viruses; consequently influenza vaccine effectiveness (IVE) has to be assessed annually.Research design and methods: A test-negative case-control study was conducted within the context of the Italian sentinel influenza surveillance network to estimate IVE by age group, virus subtype, and vaccine brand in medically attended laboratory-confirmed influenza.Results: In Italy, the 2018/19 influenza season was characterized by the co-circulation of influenza A(H1N1)pdm09 and A(H3N2) viruses. The adjusted IVE estimate in preventing influenza was moderate (44.8%, 95% CI: 18.8 to 62.5) against A(H1N1)pdm09, whereas there was no evidence of effectiveness (1.8%, 95% CI: −37.8 to 30.1) in persons affected by A(H3N2). IVE against A(H1N1)pdm09 decreased with age ranging from 65.7% to 13.1% among children/adolescents and elderly, respectively; moreover results suggest that Vaxigrip Tetra® was more effective against A(H1N1)pdm09 compared to Fluarix Tetra® [62.5% (95% CI: 34.3 to 78.6) vs 24.5% (95% CI: −40.6 to 59.6)]. Low effectiveness (35.2%, 95% CI: −50.8 to 72.1) against A(H3N2) was detected only in the elderly immunized with Fluad®.Conclusions: Findings suggest that influenza vaccines were low to moderately effective, probably due to a mismatch between circulating and vaccine strains.

Bioassay of ferulic acid derivatives as influenza neuraminidase inhibitors.

Four series of ferulic acid derivatives were designed, synthesized, and evaluated for their neuraminidase (NA) inhibitory activities against influenza virus H1N1 in vitro. The pharmacological results showed that the majority of the target compounds exhibited moderate influenza NA inhibitory activity, which was also better than that of ferulic acid. The two most potent compounds were 1m and 4a with IC50 values of 12.77 ± 0.47 and 12.96 ± 1.34 μg/ml, respectively. On the basis of the biological results, a preliminary structure-activity relationship (SAR) was derived and discussed. Besides, molecular docking was performed to study the possible interactions of compounds 1p, 2d, 3b, and 4a with the active site of NA. It was found that the 4-OH-3-OMe group and the amide group (CON) of ferulic acid amide derivatives were two key pharmacophores for NA inhibitory activity. It is meaningful to further modify the natural product ferulic acid to improve its influenza NA inhibitory activity.

Nucleoside analogues for the treatment of influenza: history and experience

Aim. In this study we retrospectively evaluated the clinical effectiveness and safety of nucleoside analogues (Triazavirin© and ribavirin) with that of oseltamivir for treating moderate severe influenza in adults. Materials and methods. We have used data from 191 health records of patients with moderate severe PCR confirmed influenza A and B. Control group included 57 patients treated with oseltamivir, comparison groups – 53 and 81 patients, who received Triazavirin© and ribavirin accordingly. We compared infectious intoxication syndrome duration, fever duration, duration of acute rhinitis, acute pharyngitis, acute laryngitis, acute tracheitis, acute bronchitis, cough duration as well as pneumonia occurrence. Results. No statistically significant difference in the duration of developed syndromes in Triazavirin©-treated group and oseltamivir-treated group were observed. We have noticed that fever duration had been significantly longer in ribavirin group compared to control group (4,1±2,22 days vs. 3,1±1,94 days, p&lt;0,05) as well as more frequent pneumonia occurrence (1,2% vs. 0,0%, p&gt;0,05). Conclusion. New nucleoside analogue Triazavirin© showed good efficacy and safety profile in adult patients with influenza. This fact provides the opportunity to recommend it for treatment of influenza along with neuraminidase inhibitors.

Use of ambulance dispatch calls for surveillance of severe acute respiratory infections?

ObjectiveWe aim to assess whether influenza circulation, as measured through influenza-like-illness (ILI) in primary care, is reflected in ambulance dispatch (AD) calls.IntroductionSurveillance of severe influenza infections is lacking in the Netherlands. Ambulance dispatch (AD) data may provide information about severity of the influenza epidemic and its burden on emergency services.The current gold standard, primary care-based surveillance of influenza-like-illness (ILI), mainly captures mild to moderate influenza cases, and does not provide adequate information on severe disease.Monitoring the severity of the annual epidemic, particularly among groups most at risk of complications, is of importance for the planning of health services and the public health response.MethodsWe analysed all calls from four ambulance dispatch centers serving 4.3 million people in the Netherlands, between January 2014 and December 2016. The main complaint and urgency level is recorded during triage; those possibly caused by respiratory infections were grouped as respiratory syndrome calls (RSC). We modelled the proportion of all RSC calls against the weekly ILI incidence (we allowed up to 4-week lags and leads), from sentinel primary-care surveillance. We used binomial regression with identity link to obtain differences in proportions. We built separate models by age group, urgency level and time of day. We tested heterogeneity of effects by season.ResultsWe included 289,307 calls; 6.7% were RSC. Overall, proportion of RSC increased by 0.114 percentage points for each increase of 1/10,000 population in ILI incidence. In our study population, this translated into 550 ambulance calls attributable to influenza (as measured by ILI) per year. Association was stronger in the models including only out-of-office hours, children (&lt;15 years) and highest urgency level calls. In the latter two, the effect varied by season. RSC was best associated with ILI from the previous 1-3 weeks in all models, except in children where RSC preceded ILI by 1 week.ConclusionsOur results demonstrate the potential usefulness of ambulance dispatch data to complement existing influenza surveillance by providing information on the volume and timing of severe cases attributable to influenza within the yearly epidemics.

A Dose-finding Study of a Wild-type Influenza A(H3N2) Virus in a Healthy Volunteer Human Challenge Model.

The development of vaccines and therapeutics has relied on healthy volunteer influenza challenge studies. A validated human infection model with wild-type A(H1N1)pdm09 was reported previously. Our objective was to characterize a wild-type influenza A/Bethesda/MM1/H3N2 challenge virus in healthy volunteers. Participants received a single dose of a cell-based, reverse-genetics, Good Manufacturing Practices-produced wild-type influenza A(H3N2)2011 virus intranasally and were isolated at the National Institutes of Health Clinical Center for ≥9 days. Dose escalation was performed from 104 to 107 TCID50 (50% tissue culture infectious dose). Viral shedding and clinical disease were evaluated daily. Of 37 participants challenged, 16 (43%) had viral shedding and 27 (73%) developed symptoms, with 12 (32%) participants experiencing mild to moderate influenza disease (MMID), defined as shedding and symptoms. Only participants receiving 106 and 107 TCID50 experienced MMID at 44% and 40%, respectively. Symptom severity peaked on day 3, whereas most viral shedding occurred 1-2 days after challenge. Only 10 (29%) participants had a ≥4-fold rise in hemagglutination inhibition antibody titer after challenge. The A/Bethesda/MM1/H3N2 challenge virus safely induced MMID in healthy volunteers, but caused less MMID than the A(H1N1)pdm09 challenge virus even at the highest dose. There was less detection of shedding though the incidence of symptoms was similar to A(H1N1)pdm09. Fewer serum anti-hemagglutinin (HA) antibody responses with less MMID indicate that preexisting immunity factors other than anti-HA antibody may limit shedding in healthy volunteers. This A/Bethesda/MM1/H3N2 challenge virus can be utilized in future studies to further explore pathogenesis and immunity and to evaluate vaccine candidates. NCT02594189.

Predictors for influenza vaccine acceptance among patients with inflammatory rheumatic diseases

BackgroundPatients with inflammatory rheumatic diseases are at higher risk for influenza and current guidelines recommend vaccination for this group of patients. The aim of this study was to evaluate the vaccination coverage and predictors for influenza vaccination among patients with inflammatory rheumatic diseases. MethodsThis survey was conducted at the outpatient rheumatology clinic at the Medical University of Vienna between July and October 2017. All patients diagnosed with an inflammatory rheumatic disease and receiving immunosuppressive therapy were asked to complete a questionnaire about their influenza vaccination status for 2016/17. Results490 patients with rheumatic diseases completed a questionnaire (33% male, mean age 55.3 years). The influenza vaccination rate for the previous season was 25.3% (n = 124/490). Predictors for a positive influenza vaccination status were higher age (Adjusted Odds Ratio 5.0, 95% Confidence Interval 2.4–10.4) and treatment with biological disease-modifying antirheumatic drugs (AOR 2.0, 95% CI 1.3–3.1). Patients who received a recommendation for influenza vaccination by their general practitioner were significantly more likely to be vaccinated than those who did not (57% vs. 15%, AOR 6.6, 95% CI 4.1–10.8); even more so if they received a recommendation by their rheumatologist (62% vs. 19%, AOR 9.0, 95% CI 4.9–16.5). The main reasons for patients to decline influenza vaccination were fear of side effects (36%), concerns that vaccination might not be effective due to their immunosuppressed condition (38%) or that it might worsen the rheumatic disease (20%). ConclusionsA moderate influenza vaccination rate of 25.3% was detected among patients with inflammatory rheumatic diseases. Recommendation of the influenza vaccine by a physician exerts the most effective impact on a positive vaccination status.