Influenza Complications Research Articles

Comparison of severe pediatric complicated influenza patients with and without neurological involvement.

Although influenza is generally an acute, self-limited, and uncomplicated disease in healthy children, it can result in severe morbidity and mortality. The objectives of this study were to analyze and compare the clinical features and outcome of severe pediatric influenza with and without central nervous system (CNS) involvement.We conducted a retrospective observational study of children admitted to the pediatric intensive care unit (PICU) of China Medical University Children's Hospital in Taiwan with a confirmed diagnosis of influenza. The demographic data, clinical and laboratory presentations, therapeutic strategies, and neurodevelopmental outcomes for these patients were analyzed. Furthermore, comparison of patients with and without CNS involvement was conducted.A total of 32 children with severe influenza were admitted during the study periods. Sixteen children were categorized as the non-CNS (nCNS) group and 16 children were categorized as the CNS group. Nine of them had underlying disease. The most common complication in the nCNS group was acute respiratory distress syndrome, (n = 8/16), followed by pneumonia (n = 7/16, 44%). In the CNS group, the most lethal complication was acute necrotizing encephalopathy (n = 3/16) which led to 3 deaths. The overall mortality rate was higher in the CNS group (n = 6) than in the nCNS group (n = 1) (37.5% vs 6.25%, P = .03).The mortality rate of severe complicated influenza was significantly higher with CNS involvement. Children with primary cardiopulmonary abnormalities were at high risk of developing severe complicated influenza, while previously healthy children exhibited risk for influenza-associated encephalitis/encephalopathy.

Neuraminidase inhibitors and single dose baloxavir are effective and safe in uncomplicated influenza: a meta-analysis of randomized controlled trials

ABSTRACT Background Scarce evidence verifying the clinical impact of baloxavir on influenza complications is found. Methods PubMed, Cochrane Library, and Web of Science databases were searched through December 2020. Randomized-controlled trials (RCT) that enrolled patients with laboratory-confirmed influenza receiving neuraminidase inhibitors (NAI) or baloxavir comparing to placebo were assessed. PROSPERO Registration-number: CRD42021226854. Results Twenty-one RCTs (11,697 patients) were included. Antiviral administration significantly reduced time to clinical resolution (mean difference: −21.3 hours) and total influenza-related complications (OR:0.55, 95%CI: 0.42–0.73). Specifically, antivirals significantly decreased bronchitis (OR:0.54, 95%CI: 0.38–0.75), sinusitis (OR:0.51, 95%CI: 0.33–0.78), acute otitis media (OR:0.48, 95%CI: 0.30–0.77), and antibiotic prescription (OR:0.62; 95%CI: 0.48–0.80). A positive trend favored antivirals administration to reduce pneumonia (OR:0.47, 95%CI: 0.16–1.33), or hospitalization rates (OR:0.65; 95%CI: 0.34–1.24) compared to placebo, but did not reach statistical significance. Adverse events (AE) were reported in 11%, 8.9%, and 5.1% of NAIs, placebo and baloxavir recipients, respectively. Compared with NAIs, administration of baloxavir showed non-significantly reduced AEs (OR:0.74, 95%CI: 0.53–1.04). Conclusions Single-dose baloxavir and NAIs were superior to placebo to reduce complications in uncomplicated influenza, with 40% significant reduction in antibiotic prescription. Safety and efficacy of single-dose baloxavir were non-inferior to NAIs.

Influenza Vaccination and Health Outcomes in COVID-19 Patients: A Retrospective Cohort Study

COVID-19 is an infectious disease caused by the novel coronavirus SARS-CoV-2. Several measures aimed at containing the spread of this virus have been recommended by international and nation public health institutions, but whether the influenza vaccine, while not protective against COVID-19, nonetheless reduces disease severity is unclear. This study evaluated the potential role of influenza vaccine in reducing the rate of hospitalization and death in COVID-19 patients. COVID-19 cases recorded in the province of Brindisi (Apulia, Southern Italy) during the first pandemic wave (February–May 2020) and occurring in patients vaccinated with the influenza vaccine during the 2019–2020 influenza season were considered. From February 2020 to May 2020, 3872 inhabitants of the province of Brindisi underwent SARS-CoV-2 PCR testing and 664 (8.7%) tested positive. A multivariate analysis showed that among COVID-19 patients neither hospitalization nor death was significantly associated with influenza vaccination (p > 0.05), whereas within this group male sex, older age, and chronic diseases were identified as risk factors for morbidity and mortality. Our study did not show an association between the influenza vaccine and complications of COVID-19. Nonetheless, influenza vaccination must be promoted as a central public health measure, because by reducing the burden on hospitals it can greatly benefit the management of COVID-19 patients.

Differences in antibiotic and antiviral use in people with confirmed influenza: a retrospective comparison of rapid influenza PCR and multiplex respiratory virus PCR tests

BackgroundInfluenza is a highly contagious respiratory virus with clinical impacts on patient morbidity, mortality and hospital bed management. The effect of rapid nucleic acid testing (RPCR) in comparison to standard multiplex PCR (MPCR) diagnosis in treatment decisions is unclear. This study aimed to determine whether RPCR influenza testing in comparison to standard MPCR testing was associated with differences in antibiotic and antiviral (oseltamivir) utilisation and hospital length of stay in emergency department and inpatient hospital settings.MethodsA retrospective cohort study of positive influenza RPCR and MPCR patients was performed utilising data from the 2017 influenza season. Medical records of correlating patient presentations were reviewed for data collection. An analysis of RPCR versus MPCR patient outcomes was performed examining test turnaround time, antibiotic initiation, oseltamivir initiation and hospital length of stay for both emergency department and inpatient hospital stay. Subgroup analysis was performed to assess oseltamivir use in high risk populations for influenza complications. Statistical significance was assessed using Mann-Whitney test for numerical data and Chi-squared test for categorical data. Odds ratio with 95% confidence intervals were calculated where appropriate.ResultsOverall, 122 RPCR and 362 MPCR positive influenza patients were included in this study. Commencement of antibiotics was less frequent in the RPCR than MPCR cohorts (51% vs 67%; p < 0.01, OR 0.52; 95% CI 0.34–0.79). People at high risk of complications from influenza who were tested with the RPCR were more likely to be treated with oseltamivir compared to those tested with the MPCR (76% vs 63%; p = 0.03, OR 1.81; 95% CI 1.07–3.08). Hospital length of stay was not impacted when either test was used in the emergency department and inpatient settings.ConclusionsThese findings suggest utilisation of RPCR testing in influenza management can improve antibiotic stewardship through reduction in antibiotic use and improvement in oseltamivir initiation in those at higher risk of complications. Further research is required to determine other factors that may have influenced hospital length of stay and a cost-benefit analysis should be undertaken to determine the financial impact of the RPCR test.

Elderberry for prevention and treatment of viral respiratory illnesses: a systematic review

BackgroundElderberry has traditionally been used to prevent and treat respiratory problems. During the COVID-19 pandemic, there has been interest in elderberry supplements to treat or prevent illness, but also concern that elderberry might overstimulate the immune system and increase the risk of ‘cytokine storm’. We aimed to determine benefits and harms of elderberry for the prevention and treatment of viral respiratory infections, and to assess the relationship between elderberry supplements and negative health impacts associated with overproduction of pro-inflammatory cytokines.MethodsWe conducted a systematic review and searched six databases, four research registers, and two preprint sites for studies. Two reviewers independently assessed studies for inclusion, extracted data from studies, assessed risk of bias using Cochrane tools, and evaluated certainty of estimates using GRADE. Outcomes included new illnesses and the severity and duration of illness.ResultsWe screened 1187 records and included five randomized trials on elderberry for the treatment or prevention of viral respiratory illness. We did not find any studies linking elderberry to clinical inflammatory outcomes. However, we found three studies measuring production of cytokines ex vivo after ingestion of elderberry. Elderberry may not reduce the risk of developing the common cold; it may reduce the duration and severity of colds, but the evidence is uncertain. Elderberry may reduce the duration of influenza but the evidence is uncertain. Compared to oseltamivir, an elderberry-containing product may be associated with a lower risk of influenza complications and adverse events. We did not find evidence on elderberry and clinical outcomes related to inflammation. However, we found evidence that elderberry has some effect on inflammatory markers, although this effect may decline with ongoing supplementation. One small study compared elderberry to diclofenac (a nonsteroidal anti-inflammatory drug) and provided some evidence that elderberry is as effective or less effective than diclofenac in cytokine reduction over time.ConclusionsElderberry may be a safe option for treating viral respiratory illness, and there is no evidence that it overstimulates the immune system. However, the evidence on both benefits and harms is uncertain and information from recent and ongoing studies is necessary to make firm conclusions.

Influenza infections during the period of 2019–2020 -just before the COVID-19 outbreak- in a single unit

Background and Purpose: We aimed to evaluate the demographic features, clinical manifestations, course of disease, and outcome of children with Influenza and Influenza complications. Methods: In the winter season -just before the COVID 19 outbreak- between October 2019 and March 2020, the cases with Influenza diagnosed by rt-PCR (real time polymerase chain reaction) requiring hospitalization retrospectively were evaluated with hospital records. Results: A total 36 children were hospitalized with Influenza virus infection. The most frequent presentations of the subjects were malaise and fever. Other clinical presentations consisted of vomitting (36.1%), abdominal pain (30.5%), myalgia (27.7%), diarrhea (25%), dry cough (19.4%), and arthralgia (11.1%). There were respiratory distress in 19 patients (52.7%) in our cohort. The most frequent underlying disease requiring hospitalization was neurological diseases. Conclusions and Recommendation: The Influenza infection was associated with a wide variety of clinical findings during the hospital admission in pediatric patients. Immunization programs for Influenza should be considered for all children aged &gt; 6 months, and should be also targeted the pediatric population that likely to be hospitalized with predisposing medical conditions- particularly neurological- every influenza season. Encouraging the use of Influenza vaccines will provide a decrease in Influenza that have similar presentations of COVID-19.

Effectiveness of the Cell-Derived Inactivated Quadrivalent Influenza Vaccine in Individuals at High Risk of Influenza Complications in the 2018-2019 United States Influenza Season.

BackgroundHigher rates of influenza-related morbidity and mortality occur in individuals with underlying medical conditions. To improve vaccine effectiveness, cell-based technology for influenza vaccine manufacturing has been developed. Cell-derived inactivated quadrivalent influenza vaccines (cIIV4) may improve protection in seasons in which egg-propagated influenza viruses undergo mutations that affect antigenicity. This study aimed to estimate the relative vaccine effectiveness (rVE) of cIIV4 versus egg-derived inactivated quadrivalent influenza vaccines (eIIV4) in preventing influenza-related medical encounters in individuals with underlying medical conditions putting them at high risk of influenza complications during the 2018–2019 US influenza season.MethodsAn integrated dataset, linking primary care electronic medical records with claims data, was used to conduct a retrospective cohort study among individuals aged ≥4 years, with ≥1 health condition, vaccinated with cIIV4 or eIIV4 during the 2018–2019 season. Adjusted odds ratios (ORs) were derived using a doubly robust inverse probability of treatment-weighting (IPTW) model, adjusting for age, sex, race, ethnicity, geographic region, vaccination week, and health status. Relative vaccine effectiveness was estimated by (1 − OR) × 100 and presented with 95% confidence intervals (CIs).ResultsThe study cohort included 471 301 cIIV4 and 1 641 915 eIIV4 recipients. Compared with eIIV4, cIIV4 prevented significantly more influenza-related medical encounters among individuals with ≥1 health condition (rVE, 13.4% [95% CI, 11.4%–15.4%]), chronic pulmonary disease (rVE, 18.7% [95% CI, 16.0%–21.3%]), and rheumatic disease (rVE, 11.8% [95% CI, 3.6%–19.3%]).ConclusionsOur findings support the use of cIIV4 in individuals ≥4 years of age at high risk of influenza complications and provide further evidence supporting improved effectiveness of cIIV4 compared with eIIV4.

Uptake of influenza vaccination among persons with inflammatory bowel disease, multiple sclerosis or rheumatoid arthritis: a population-based matched cohort study

Background:Individuals with immune-mediated inflammatory diseases, such as inflammatory bowel disease, multiple sclerosis and rheumatoid arthritis, are at increased risk for influenza and related complications. We examined and compared the uptake of influenza vaccination among people with and without these diseases, as well as the influence of psychiatric comorbidity on vaccine uptake.Methods:Using administrative data from Apr. 1, 1984, to Mar. 31, 2016, we conducted a retrospective matched cohort study in Manitoba, Canada. We matched persons 18 years of age or older who had a diagnosis of inflammatory bowel disease, multiple sclerosis or rheumatoid arthritis (the immune-mediated inflammatory disease cohorts) with persons who did not have these diagnoses (the control cohorts) on age, sex and region. We then identified cohort members with any mood or anxiety disorder (depression, anxiety disorders, bipolar disorder). We identified influenza vaccinations through billing codes. Using binomial regression, we modelled the difference in the proportion of the immune-mediated inflammatory disease and matched cohorts vaccinated annually, with adjustment for sociodemographic characteristics, comorbidity and immune therapy. We tested additive interaction effects between a person’s cohort and presence of a mood or anxiety disorder.Results:We identified 32 880 individuals with 1 or more immune-mediated inflammatory diseases (10 148 with inflammatory bowel disease, 6158 with multiple sclerosis and 16 975 with rheumatoid arthritis) and a total of 164 152 controls. In fiscal year 2015, 8668 (41.3%, 95% confidence interval [CI] 40.6% to 42.0%) of the 20 982 persons with an immune-mediated inflammatory disease received an influenza vaccination, a rate higher than among controls (35 238 of 104 634; 33.7%, 95% CI 33.4% to 34.0%). After adjustment, participants with an immune-mediated inflammatory disease but no mood or anxiety disorder had 6.44% (95% CI 5.79% to 7.10%) greater uptake of vaccination than participants without such a disease. Among participants without an immune-mediated inflammatory disease, having a mood or anxiety disorder was associated with 4.54% (95% CI 4.20% to 4.89%) greater uptake of vaccination. However, we observed a subadditive interaction between immune-mediated inflammatory disease and psychiatric status (−1.38%, 95% CI −2.26% to −0.50%).Interpretation:Uptake of influenza vaccination was consistently low in populations with immune-mediated inflammatory disease, and although psychiatric morbidity is associated with greater vaccine uptake by Manitobans, it negatively interacts with these diseases to reduce uptake. Changes in care delivery are needed to mitigate this gap in care.

Initial Results on Lung Transplantation in a Vietnamese Hospital

Purpose Lung transplantation (LTx) is a complex technique of organ transplant, both organizational, technical, postoperative as well as the poor long-term outcome. In the world, the first LTx was in 1963, but it has only developed strongly in the last 15 years (annual quantity about 70% of heart transplant). In Vietnam, LTx was first performed in February 2017 (bi-lung transplant for children from 2 living donors). Up to now, there are a total of 8 LTx across the country, of which 5 have been performed in Viet Duc university hospital. This report aims to present some of the baseline results for these 5 LTx. Methods Retrospective descriptive study for all cases of LTx in Viet Duc hospital with the general results, since December 2018 to October 2020. Results The main disease of 5 recipients was following: lung Langerhans's; congenital bronchiectasis; Eisenmenger syndrome due to congenital heart disease; Progressive acute respiratory distress syndrome (ARDS) due to complications of influenza H1.N1; and interstitial lung disease. All LTx received multiple organs harvesting (≥ 5 organs) and all transplants then are doing at the same time in Viet Duc hospital according to a unified procedure, the donated lungs are protected and treated in accordance with the recipient in each case. Transplant time range from 10 to 16 hours, which depends heavily on the adhesion of diseased lungs to the chest wall. Two-lung transplant technique is done according to the procedure with the support of ECMO, through Clamshell opening, 2nd time of closure of the incision, and tracheostomy are the main technical characteristics of our LTx group. Postoperative care is complex, mainly related to airway problems, with the shortest hospital stay of 2 months, the longest 10 months in 4/5 patients living after the transplant. One case was death in third week after LTx (H1.N1) caused by very severe infection lasted 2 months before surgery. Life of patients after discharge, if there is no special sequelae (3 cases), it is very positive, the monitoring and treatment is not too complicated compared to heart transplant. Conclusion The initial success of LTx at Viet Duc Hospital in the past two years will make an important contribution to the development of LTx - which is classified as this complex, in the future in Vietnam.

Public Health and Economic Benefits of Influenza Vaccination of the Population Aged 50 to 59 Years without Risk Factors for Influenza Complications in Mexico: A Cross-Sectional Epidemiological Study.

The Mexican influenza vaccination program does not include a recommendation for people aged 50–59 years without risk factors for influenza complications, and there are limited data regarding the cost-effectiveness of vaccinating this population. To explore the clinical and economic effects of including this population in the vaccination schedule, we performed a cross-sectional epidemiological study using records (2009–2018) from Mexico’s Influenza Surveillance System (SISVEFLU), death records (2010–2015) from the National Mortality Epidemiological and Statistical System, and discharge and hospitalization records (2010–2015) from the Automated Hospital Discharge System databases. A 1-year decision-analytic model was used to assess cost-effectiveness through a decision-tree based on data from SISVEFLU. The primary outcome was influenza cases avoided; with associated influenza-related events as secondary outcomes. Including the population aged 50–59 years without risk factors in Mexico’s influenza immunization program would have resulted in 199,500 fewer cases; 67,008 fewer outpatient consultations; 33,024 fewer emergency room consultations; 33,091 fewer hospitalizations; 12 fewer deaths. These reductions equate to a substantial public health benefit as well as an economic benefit; yielding net savings of 49.8 million US dollars over a typical influenza season. Expansion of the current Mexican vaccination schedule to include these people would be a cost-saving and dominant strategy.

Identification of pathogens from the upper respiratory tract of adult emergency department patients at high risk for influenza complications in a pre-Sars-CoV-2 environment

The emergence of SARS-CoV-2 and subsequent COVID-19 pandemic highlights the morbidity and potential disease severity caused by respiratory viruses. To elucidate pathogen prevalence, etiology of coinfections and URIs from symptomatic adult Emergency department patients in a pre-SARS-CoV-2 environment, we evaluated specimens from four geographically diverse Emergency departments in the United States from 2013-2014 utilizing ePlex RP RUO cartridges (Genmark Diagnostics). The overall positivity was 30.1% (241/799), with 6.6% (16/241) coinfections. Noninfluenza pathogens from most to least common were rhinovirus/enterovirus, coronavirus, human metapneumovirus and RSV, respectively. Broad differences in disease prevalence and pathogen distributions were observed across geographic regions; the site with the highest detection rate (for both mono and coinfections) demonstrated the greatest pathogen diversity. A variety of respiratory pathogens and geographic variations in disease prevalence and copathogen type were observed. Further research is required to evaluate the clinical relevance of these findings, especially considering the SARS-CoV-2 pandemic and related questions regarding SARS-CoV-2 disease severity and the presence of co-infections.

Knowledge, attitudes, and practices of seasonal influenza vaccination among older adults in nursing homes and daycare centers, Honduras.

BackgroundOlder adults represent 70–90% of seasonal influenza-related deaths and 50–70% of influenza-related hospitalizations. Vaccination is the most efficient means of preventing influenza and reducing influenza-related illnesses. We aimed to describe knowledge, attitudes, and practices (KAP) of seasonal influenza vaccination among older adults in Honduras.MethodsFrom August 29–October 26, 2018, we conducted a cross-sectional KAP survey regarding seasonal influenza vaccinations to samples of older adults 1) admitted to nursing homes and 2) attending daycare centers. We used the Minimental State Examination (MMSE) psychometric tool to assess the cognitive status of older adults and included participants with scores of ≥23 points in the survey. We reported frequency distributions for demographics, KAP of influenza virus and vaccination, and vaccination coverage. We used logistic regression to analyze associations between demographics and verified influenza vaccination.ResultsOf 511 MMSE participants, 341 completed the survey (95 adults in 12 nursing homes and 246 older adults in ten daycare centers). Almost all participants knew that influenza causes severe illness and may be transmitted from person to person, vaccination is safe and protects against disease, and older adults have greater risk of complications. Of 284 participants with verified vaccinations, 81.3% were vaccinated for influenza: 87.9% attending daycare centers and 61.4% in nursing homes. Among all participants, verified current influenza vaccination was associated with self-reported influenza vaccination in previous year (aOR: 14.05; 95% CI: 5.36–36.81); no formal education (aOR: 4.83; 95% CI: 1.63–14.37) or primary school education (aOR: 4.51; 95% CI: 1.79–11.37) having ≥secondary as reference; and indigenous (aOR: 4.55; 95% CI: 1.18–17.49) having Mestizo as reference. Reasons for vaccination were perceived self-benefits, protection against influenza complications, favorable vaccination hours, and healthcare provider recommendations.ConclusionFour-fifths of older adults were vaccinated for seasonal influenza. Educational efforts provided in conjunction with vaccination campaigns resulted in high knowledge of influenza virus, transmission, and vaccination. Further outreach regarding disease risks and vaccine safety needs to be directed towards older adults in nursing homes who had lower knowledge and coverage than older adults in daycare centers.

The impact of obesity on seasonal influenza: a single-center, retrospective study conducted in Israel.

Obesity is associated with an increased susceptibility to infections. Several studies have reported adverse clinical outcomes of influenza among obese individuals. Our aim was to examine the association between obesity and the clinical outcomes of hospitalized adult patients ill with seasonal influenza. Consecutive hospitalized adult patients between 10/2017 and 4/2018 with laboratory confirmed influenza A and B were divided into an obese group (body mass index (BMI) ≥ 30 kg/m2) and controls. The primary outcome was a composite endpoint of 30-day all-cause mortality, vasopressor use, mechanical ventilation, ICU admission, and severe influenza complication (myocarditis and encephalitis). Secondary outcomes encompassed all the components of the primary outcome, 90-day all-cause mortality, occurrence of pneumonia, length of hospital stay, and 90-day readmission rates. The study comprised 512 hospitalized adults diagnosed with laboratory-confirmed influenza A (195/512) and B (317/512). Within this group, 17% (86/512) were classified obese; the remaining 83% (426/512) were controls. Results of the composite outcome (7/85, 8% vs. 45/422, 11%; p=0.5) and the crude 30-day all-cause mortality rate (5/86, 6% vs. 34/426, 8%, p=0.5) were similar between the two groups. The multivariate analysis demonstrated that obesity was not a significant risk factor for influenza adverse events (OR=1.3, CI 95% 0.3–3.3; p=0.5), whereas advanced age, chronic kidney disease, and hypoalbuminemia were significant risk factors (OR=1.03, OR=2.7, and OR=5.4, respectively). Obesity was not associated with influenza-related morbidity and mortality among the hospitalized adults during the 2017–2018 influenza season. Further studies researching different influenza seasons are essential.

Outcome predictors of influenza for hospitalization and mortality in children.

Severity of disease caused by influenza virus and the influencing factors that may be different. Moreover, the disease course actually may not be determined specifically in children because of lower seroprotection rates of children. Herein, the results clinic and outcome data of children with influenza from Turkey were reported. We present here the results from 2013 to 2017. Nasopharyngeal swab samples of the children with influenza were investigated via multiplex polymerase chain reaction. A total of 348 children were diagnosed with influenza; 143 (41.1%) were influenza A, 85 (24.4%) were influenza B, and 120 (34.5%) were mixt infection with other respiratory viruses. Fifty‐four percent of children admitted to intensive care unit (ICU) were under 2 years of age (p = .001). Having an underlying disease was detected as the main predictor for both hospitalization and ICU stay according to multiple logistic regression analysis (odds ratio [OR], 11.784: 95% confidence interval [CI], 5.212–26.643; p = .001 and OR, 4.972: 95% CI, 2.331–10.605; p = .001, respectively). Neurological symptoms most frequently seen in cases who died (44.4%; p = .02). Lymphopenia was relatively higher (55.6%) and thrombocytopenia was most frequently seen in cases who died (77.8%) with a significant ratio (p = .001). Underlying diseases was found a risk factor for influenza being hospitalized and being admitted to ICU. Children under 2 years of age and with underlying diseases should be vaccinated particularly in countries where the influenza vaccination is still not routinely implemented in the immunization schedule.Highlights Underlying diseases is a risk factor for influenza to be hospitalized and admitted to ICU. Influenza vaccination is of great importance to prevent life‐threatening complications of influenza, particularly in children require ICU admission. The possibility to reduce the outpatient visit number by vaccination has a great impact on disease burden in addition to the underestimated crucial social benefits, as well.

Prevention of influenza during mismatched seasons in older adults with an MF59-adjuvanted quadrivalent influenza vaccine: a randomised, controlled, multicentre, phase 3 efficacy study

The absolute degree of protection from influenza vaccines in older adults has not been studied since 2001. This study aimed to show the clinical efficacy of an MF59-adjuvanted quadrivalent influenza vaccine (aQIV) in adults 65 years or older compared with adults not vaccinated to prevent influenza. We did a randomised, stratified, observer-blind, controlled, multicentre, phase 3 study at 89 sites in 12 countries in 2016-17 northern hemisphere and 2017 southern hemisphere influenza seasons. We enrolled community-dwelling male and female adults aged 65 years and older who were healthy or had comorbidities that increased their risk of influenza complications. We stratified eligible participants by age (cohorts 65-74 years and ≥75 years) and risk of influenza complications (high and low) and randomly assigned them (1:1) via an interactive response technology to receive either aQIV or a non-influenza comparator vaccine. We masked participants and outcome assessors to the administered vaccine. Personnel administering the vaccines did not participate in endpoint assessment. The primary outcome was absolute vaccine efficacy assessed by RT-PCR-confirmed influenza due to any influenza strain in the overall study population (full analysis set) from day 21 to 180 or the end of the influenza season. Vaccine efficacy was calculated on the basis of a Cox proportional hazard regression model for time to first occurrence of RT-PCR-confirmed influenza due to any strain of influenza. Safety outcomes were assessed in the overall study population. This trial was registered with ClinicalTrials.gov, NCT02587221. Northern hemisphere enrolment occurred between Sept 30, 2016, and Feb 28, 2017, and southern hemisphere enrolment between May 26, 2017, and 30 June 30, 2017. aQIV was administered to 3381 participants, who subsequently had 122 (3·6%) RT-PCR-confirmed influenza cases, and the comparator was administered to 3380 participants, who subsequently had 151 (4·5%) influenza cases. The majority, 214 (78·4%) of 273, were caused by influenza A H3N2. Most antigenically characterised isolates were mismatched to the vaccine strain (118 [85%] of 139). Vaccine efficacy was 19·8% (multiplicity-adjusted 95% CI -5·3 to 38·9) against all influenza and 49·9% (-24·0 to 79·8) against antigenically matched strains, when the protocol definition of influenza-like illness was used. The most common local solicited adverse event was injection site pain, reported by 102 (16·3%) of 624 participants in the aQIV group and 71 (11·2%) of 632 of participants in the comparator group. Deaths were evenly distributed; none were considered related to study vaccines. The safety profile for aQIV was similar to previously reported trials. The prespecified criterion for showing the efficacy of aQIV in older adults was not met during the influenza seasons with high amounts of vaccine strain mismatch. Vaccine efficacy was higher against influenza cases associated with higher fever, which represent more clinically significant disease. Seqirus UK.

Risk Factors for Pneumonia and Death in Adult Patients With Seasonal Influenza and Establishment of Prediction Scores: A Population-Based Study.

BackgroundSeasonal influenza remains a global health problem; however, there are limited data on the specific relative risks for pneumonia and death among outpatients considered to be at high risk for influenza complications. This population-based study aimed to develop prediction models for determining the risk of influenza-related pneumonia and death.MethodsWe included patients diagnosed with laboratory-confirmed influenza between 2016 and 2017 (main cohort, n = 25 659), those diagnosed between 2015 and 2016 (validation cohort 1, n = 16 727), and those diagnosed between 2017 and 2018 (validation cohort 2, n = 34 219). Prediction scores were developed based on the incidence and independent predictors of pneumonia and death identified using multivariate analyses, and patients were categorized into low-, medium-, and high-risk groups based on total scores.ResultsIn the main cohort, age, gender, and certain comorbidities (dementia, congestive heart failure, diabetes, and others) were independent predictors of pneumonia and death. The 28-day pneumonia incidence was 0.5%, 4.1%, and 10.8% in the low-, medium-, and high-risk groups, respectively (c-index, 0.75); the 28-day mortality was 0.05%, 0.7%, and 3.3% in the low-, medium-, and high-risk groups, respectively (c-index, 0.85). In validation cohort 1, c-indices for the models for pneumonia and death were 0.75 and 0.87, respectively. In validation cohort 2, c-indices for the models were 0.74 and 0.87, respectively.ConclusionsWe successfully developed and validated simple-to-use risk prediction models, which would promptly provide useful information for treatment decisions in primary care settings.

220 Trends in racial disparities in adverse outcomes in influenza in pregnancy

Non-Hispanic Black (NHB) pregnant women experience higher rates of maternal morbidity compared to their non-Hispanic White (NHW) peers, regardless of influenza. Whether NHB experience worse outcomes with influenza remains to be defined. Our objective was to assess whether NHB women with influenza during pregnancy are at increased risk of severe maternal morbidity (SMM). An analysis of delivery hospitalizations with influenza during pregnancy was conducted using the 2000-2015 National Inpatient Sample. Maternal race was assessed for women of NHW, NHB, and Hispanic race. Outcomes were SMM excluding transfusion (defined by the Centers for Disease Control and Prevention), and complications of influenza, sepsis/shock, acute respiratory distress syndrome (ARDS), and mechanical ventilation/tracheostomy. Trend analysis was conducted presenting the average annual percent change (AAPC). The association between maternal race and outcomes were calculated using log linear models, adjusted for demographic, hospital, and clinical variables. Between 2000-2015, 182,228 (0.3%) deliveries were complicated by influenza and 15.7% of women were NHB. Overall, 2.1% had SMM, 4.8% sepsis/shock, 23.4% ARDS, and 4.2% mechanical ventilation/tracheostomy. The rate of SMM was higher among NHB compared to NHW patients with an AAPC 5.6% (95% CI: 0.7%, 10.7%) versus 5.1% (95% CI: 1.2%, 9.3%) (Figure). NHB women with influenza were at higher risk of SMM compared to their NHW peers (3.5% vs. 2.0%, aRR 1.64, 95% CI: 1.48, 1.81) and similarly elevated with mechanical ventilation and sepsis/shock (Table). Non-Hispanic Black women with influenza during pregnancy experience higher rates of maternal morbidity compared to their non-Hispanic White peers. Addressing racial disparities in adverse outcomes for pregnant women with influenza should be a public health priority, including improving influenza vaccination rates in minority populations.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

What do pregnant women think about influenza disease and vaccination practices in selected countries

ABSTRACT Introduction: We evaluated knowledge, attitudes, and practices (KAP) related to influenza and influenza vaccination among pregnant women in three selected countries. Methods: During 2017, pregnant women seeking antenatal care at hospitals at participating sites were enrolled. We described characteristics and responses to KAP questions. We also evaluated predictors associated with influenza vaccination during pregnancy at sites with substantial influenza vaccine uptake by multivariable logistic regression. Results: Overall, 4,648 pregnant women completed the survey. There were substantial differences among the three survey populations; only 8% of the women in Nagpur had heard of influenza, compared to 90% in Lima and 96% in Bangkok (p-value<0.01). Despite significant differences in sociodemographic characteristics in the three populations, most participants across sites who were aware of influenza prior to study enrollment believe they and their infants are at risk of influenza and related complications and believe influenza vaccination is safe and effective. Half of women in Lima had verified receipt of influenza vaccine compared to <5% in Bangkok and Nagpur (p < .05). For further analysis conducted among women in Lima only, household income above the poverty line (aOR: 1.38; 95%CI: 1.01, 1.88), having 8+ antenatal visits, compared to 0–4 (aOR: 2.41; 95%CI: 1.39, 2.87, respectively), having 0 children, compared to 2+ (aOR: 1.96; 95%CIs: 1.23, 3.12), and vaccination recommended by a health-care provider (aOR: 8.25; 95%CI: 6.11, 11.14) were strongly associated with receipt of influenza vaccine during pregnancy. Conclusions: Our findings identify opportunities for targeted interventions to improve influenza vaccine uptake among pregnant women in these settings.

Preventive effects of influenza and pneumococcal vaccination in the elderly – results from a population-based retrospective cohort study

ABSTRACT Influenza and pneumococcal vaccinations are recommended in the elderly to reduce life-threatening complications like sepsis. Protection may be reduced with increasing age. We aimed to assess the effectiveness of both vaccines in the elderly by performing a retrospective cohort study of 138,877 individuals aged ≥60 y in Germany, who were insured in a large statutory health insurance (AOK PLUS). We used longitudinal claims data to classify individuals according to vaccination status 2008–2014, and assessed vaccine effectiveness (VE) in 2015 and 2016. Inverse probability weighting based on generalized propensity scores was used to adjust for systematic between-group differences. Influenza vaccination was associated with a reduction of hospital treatment in laboratory-confirmed influenza in 2015 (VE = 41.32 [95%CI 0.85, 65.26]), but had no significant impact on the overall influenza incidence. Complications of influenza (pneumonia and sepsis) were reduced in 2016. We found a rise in influenza-like illness and acute respiratory infections in both years and an increased 90-d mortality after hospital-treated pneumonia in vaccinees in 2015. Pneumococcal vaccination was effective in preventing hospital-treated pneumonia within the first and second year after vaccination (VE = 52.45 [13.31, 73.92] and 46.04 [5.46, 69.21], respectively), but had no impact on sepsis incidence or pneumonia mortality. Influenza and pneumococcal vaccination can prevent severe complications from influenza and hospital-treated pneumonia in the elderly, respectively. Vaccine effects differ between years and seasons and are partly difficult to interpret. Despite extensive efforts to adjust for between-group differences, residual bias cannot be ruled out, possibly explaining signals like increased ILI or pneumonia mortality.

Antibody and Cell-Mediated Immune Responses Are Correlates of Protection against Influenza Infection in Vaccinated Older Adults.

Despite efforts to design better vaccines for older adults, the risk for serious complications of influenza remains disproportionately high. Identifying correlates of vaccine effectiveness and understanding the heterogeneity of health outcomes in older adults are key to the vaccine development pipeline. We sought correlates of protection against laboratory-confirmed influenza illness (LCII) in a 4-year randomized trial of standard versus high-dose influenza vaccination of adults 65 years and older. To this end, we quantified serum hemagglutination-inhibition (HAI) titers and interferon-gamma (IFNγ) and interleukin-10 (IL-10) secretion by virus-challenged peripheral blood mononuclear cells. Of the 608 participants included, 26 developed either A/H3N2-(n = 17) or B-LCII (n = 9) at 10–20 weeks post-vaccination. Antibody titres for A/H3N2 at 4-weeks post-vaccination were significantly associated with protection against LCII, where every 1-standard deviation increase reduced the odds of A/H3N2-LCII by 53%. Although B-titres did not correlate with protection against B-LCII, the fold-increase in IFNγ:IL-10 ratios from pre- to 4-weeks post-vaccination was significantly associated with protection against B-LCII, where every 1-standard deviation increase reduced the odds by 71%. Our results suggest that both antibody and cell-mediated immune measures are valuable and potentially complementary correlates of protection against LCII in vaccinated older adults, although this may depend on the viral type causing infection.