Periods Of Influenza Activity Research Articles

Influenza Activity and Preterm Birth in the Atlanta Metropolitan Area: A Time-Series Analysis from 2010 to 2017.

Annual influenza epidemics lead to substantial public health burden, and pregnant people are vulnerable to severe outcomes. Influenza during pregnancy is hypothesized to increase risk of adverse birth outcomes, but population-based epidemiologic evidence remains limited and inconsistent. We conducted a time-series analysis to estimate short-term associations between community-level seasonal influenza activity and daily counts of preterm births in Atlanta, United States from October 17th, 2010 to July 10th, 2017. We defined weekly influenza exposures four ways: (1) percent test-positive from virologic surveillance, (2) percent of patients with symptoms of influenza-like illness (ILI) in outpatient settings, (3) a composite measure of percent test-positive and ILI, and (4) influenza hospitalization rates. We used Poisson log-linear models to estimate associations, adjusting for time-varying confounders and ongoing at-risk pregnancies. We further examined associations by influenza type and exposure lags, and effect modification by maternal characteristics. We studied a total of 316,253 births. We found consistent positive associations between influenza activity and preterm birth across different exposure measures and exposure lags. An interquartile range increase in composite measure of ILI activity and percent test-positive was associated with a 1.014 (95% confidence interval: 1.001, 1.027) increase in preterm birth during the same week. In stratified analyses, associations were more pronounced among married, non-Black, and Hispanic pregnant people. Periods of high influenza activity were associated with increased risk of preterm birth.

Cell-based flu vaccine could be more effective in preventing the flu

A new retrospective analysis by Divino and colleagues published in the January 2022 issue of Open Forum Infectious Diseases found that cell-derived quadrivalent influenza vaccines (IIV4c) are significantly more effective than standard egg-derived quadrivalent influenza vaccines (IIV4e) at preventing influenza-related hospitalizations or ED visits, which is also associated with lower overall health care costs. Most influenza vaccines in the United States are manufactured using a traditional egg-based process, which is the standard of care and plays a critical role in influenza prevention. Based on the study’s initial sample of recipients, 79.3% (6,578,855 out of 8,300,292) of the study participants received IIV4e, while 20.7% (1,721,437 out of 8,300,292) received IIV4c during the study period of August 2019 to January 2020. “The IIV4e process can cause the influenza strain to mutate, which may lead to an antigenic mismatch between the circulating strains and the inactivated strains contained within the seasonal influenza vaccine,” said Victoria Divino, the study’s lead investigator. “This can result in reduced vaccine effectiveness, particularly for influenza A(H3N2) viruses.” The study used the IQVIA PharMetrics Plus administrative claims database to investigate influenza-related hospitalizations or ED visits and other clinical outcomes postvaccination classified by diagnosis codes during the 2019–2020 influenza season (beginning August 4, 2019, and ending March 7, 2020). Inverse probability of treatment weighting (IPTW)–weighted multivariate Poisson regression models were developed to estimate adjusted rate ratios (RRs) for IIV4c compared to IIV4e to estimate the adjusted average treatment effect, or the effect of treatment in the entire study population. Adjusted rVE was calculated as (1-RR)*100%. After applying eligibility criteria and IPTW adjustment, 1,150,134 and 3,924,819 participants aged 4 to 64 years received IIV4c and IIV4e, respectively. Comorbidities were evaluated at baseline, and vaccine cohorts were well-balanced on all measured confounders post-IPTW, including baseline comorbidity, said Divino, who is an associate principal at IQVIA, a data science company in Durham, NC. Clinical outcomes and all-cause costs were evaluated separately in this study post-IPTW. Divino and colleague’s study results demonstrate that IIV4c was significantly more effective than IIV4e in preventing influenza-related hospitalizations or ED visits, with an adjusted relative vaccine effectiveness (rVE) of 5.3% during a high influenza activity period between December 8, 2019, and March 7, 2020. Adjusted rVE was significantly higher for IIV4c in preventing hospitalizations/ED visits concerning any respiratory event (8.2%), pneumonia (6.7%), or asthma/COPD/bronchial events (7.6%), according to the study. IIV4c was also associated with significantly lower annualized all-cause costs postvaccination—with a difference of $467 per participant—than IIV4e, which Divino said is driven by lower costs for outpatient medical services and inpatient hospitalizations. Although IPTW was used to adjust for imbalances in measured confounders between the cohorts, which were well-balanced post-IPTW, it is possible that imbalances remained due to potential unmeasured confounding variables, according to Divino. “Unfortunately, the utilized database does not include information on socioeconomic status, race, or culture,” said Divino. “Also, the study sample was largely commercially insured or self-insured, so these findings may not be representative of the uninsured or Medicaid populations,” Divino noted, indicating that additional research is needed among uninsured and Medicaid populations. Given a choice between IIV4c and IIV4e influenza vaccine options, the findings demonstrate that the adjusted rVE of IIV4c is significantly better than that of IIV4e in preventing influenza-related hospitalizations/ED visits. IIV4c is also associated with significant cost savings.

96. Relative Vaccine Effectiveness Against Influenza-Related and Any Respiratory-Related Hospital Encounter During the 2019/20 High Influenza Activity Period: A Comprehensive Real-World Analysis to Compare Quadrivalent Cell-based and Egg-based Influenza Vaccines

Abstract Background Changes in the influenza hemagglutinin protein during replication of influenza in eggs during vaccine production may contribute to low vaccine effectiveness (VE). This phenomenon, egg adaptation, can explain VE differences between egg-based (QIVe-SD) and cell-based (QIVc) quadrivalent influenza vaccines. This research evaluated the relative vaccine effectiveness (rVE) of QIVc versus QIVe-SD in the reduction of influenza-related and any respiratory-related hospitalizations/emergency room (ER) visits among subjects 4-64 years old during the 2019/20 influenza season. Methods A retrospective cohort analysis was conducted among subjects 4-64 years old vaccinated with QIVc or QIVe-SD using administrative claims data in the U.S. (IQVIA PharMetrics® Plus). The adjusted number of events and rates of influenza-related hospitalizations/ER visits and respiratory-related hospitalizations/ER visits were assessed using inverse probability of treatment weighting (IPTW). Poisson regression was used to estimate relative vaccine effectiveness (rVE). In the main analysis, the study period was from Aug 4, 2019 to Mar 7, 2020 (ending early to avoid any influenza outcome misclassification with COVD-19 infection). In the assessment of the high influenza activity period (HIAP), the analysis period was restricted to Dec 8, 2019 to Mar 7, 2020. Results During the 2019/20 influenza season, 1,150,134 recipients of QIVc and 3,924,819, of QIVe-SD were identified following IPTW. In the main analysis, adjusted results show that QIVc was associated with a significantly higher rVE compared to QIVe-SD against influenza-related hospitalizations/ER visits (5.3% [95%CI: 0.5%-9.9%]) and respiratory-related hospitalizations/ER visits (8.2% [95%CI: 6.5%-9.8%]). Similarly, in the HIAP analysis, QIVc was associated with a significantly higher rVE compared to QIVe-SD for influenza-related hospitalizations/ER visits (5.7% [95%CI: 0.8%-10.4%]) and respiratory-related hospitalizations/ER visits (7.3% [95%CI: 5.4%-9.2%]). Conclusion QIVc was more effective in preventing influenza-related and respiratory-related hospitalizations/ER visits compared to QIVe-SD, using either a broad influenza season definition or restricting to the HIAP. Disclosures Victoria Divino, PhD, Seqirus (Consultant) Maarten Postma, Dr., Seqirus (Consultant) Stephen I. Pelton, MD, Seqirus (Consultant) Joaquin F. Mould-Quevedo, PhD, Seqirus (Employee) Ruthwik Anupindi, PhD, Seqirus (Consultant) Mitchell DeKoven, PhD, Seqirus (Consultant) myron J. levin, MD, GSK group of companies (Employee, Research Grant or Support)

14. A Comprehensive Real-World Analysis to Compare Adjuvanted Trivalent Influenza Vaccine and Trivalent High Dose Influenza Vaccine by Age and Period of High Influenza Activity for the 2018–19 Season among U.S. Elderly

BackgroundInfluenza vaccine effectiveness decreases with increasing age due to the senescence of immune function and a reduced immune response to antigens. There is also considerable vaccine effectiveness heterogeneity depending on the influenza activity time period, especially in seasons where two different circulating strains predominated, such as the 2018–19 season. This research aimed to assess the effect of age and high influenza activity period (HIAP) on the relative vaccine effectiveness (rVE) of adjuvanted trivalent influenza vaccine (aTIV) vs. trivalent high-dose influenza vaccine (HD-TIV) among elderly (≥65y) recipients in the U.S.MethodsDuring the 2018–19 influenza season, a retrospective cohort analysis was conducted using professional fee, prescription claims and hospital charge master data in the U.S. The first sub-analysis evaluated rVE for different age groups (65–74 years, 75–84 years, ≥85 years). The second sub-analysis evaluated rVE overall, restricting the observation period from to HAIP: Dec 2018-Mar 2019 (August 2018-July 2019 in the main analysis). Adjusted analyses were conducted through inverse probability of treatment weighting (IPTW) to control for selection bias. Poisson regression was used to estimate the adjusted pairwise rVE for influenza-related hospitalizations/emergency room (ER) visits and office visits.ResultsFollowing IPTW, 561,315 recipients of aTIV and 1,672,779 of TIV-HD were identified. Following IPTW adjustment and Poisson regression, aTIV was more effective in reducing influenza-related office visits compared to TIV-HD (7.0%; 95% CI: 2.6%-11.2%) in the HIAP sub-analysis. In the age sub-analysis, the rVE favoring aTIV ranged from 5.1% (95% CI: -0.17%-10.1%) for the youngest group (65–74) up to 11.4% (95% CI: 0.6%-21.1%) for the eldest group (≥85y) for influenza-related office visits. No statistically significant differences were found for aTIV compared to TIV-HD for prevention of influenza-related hospitalizations/ER visits in the sub-analyses evaluated.ConclusionIn adjusted analyses, aTIV reduced influenza-related office visits compared to TIV-HD within the two older age groups and HIAP sub-analysis. aTIV and TIV-HD demonstrated comparable reductions in influenza-related hospitalizations/ER visits.Disclosures Maarten Postma, Dr., IQVIA (Consultant) Stephen I. Pelton, MD, Merck vaccine (Consultant, Grant/Research Support)Pfizer (Consultant, Grant/Research Support)Sanofi Pasteur (Consultant, Other Financial or Material Support, DSMB)Seqirus Vaccine Ltd. (Consultant) Victoria Divino, PhD, Seiqrus Vaccines Ltd. (Consultant) Joaquin F. Mould-Quevedo, PhD, Seqirus Vaccines Ltd. (Employee, Shareholder) Drishti Shah, PhD, Seqirus Vaccines Ltd. (Consultant) Mitchell DeKoven, PhD, Seqirus Vaccines Ltd. (Consultant)

Multiplex Real-Time Reverse-Transcription Polymerase Chain Reaction Assays for Diagnostic Testing of Severe Acute Respiratory Syndrome Coronavirus 2 and Seasonal Influenza Viruses: A Challenge of the Phase 3 Pandemic Setting.

BackgroundPandemic coronavirus disease 2019 (COVID-19) disease represents a challenge for healthcare structures. The molecular confirmation of samples from infected individuals is crucial and therefore guides public health decision making. Clusters and possibly increased diffuse transmission could occur in the context of the next influenza season. For this reason, a diagnostic test able to discriminate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from influenza viruses is urgently needed.MethodsA multiplex real-time reverse-transcription polymerase chain reaction (PCR) assay was assessed using 1 laboratory protocol with different real-time PCR instruments. Overall, 1000 clinical samples (600 from samples SARS-CoV-2–infected patients, 200 samples from influenza-infected patients, and 200 negative samples) were analyzed.ResultsThe assay developed was able to detect and discriminate each virus target and to intercept coinfections. The limit of quantification of each assay ranged between 5 and 10 genomic copy numbers, with a cutoff value of 37.7 and 37.8 for influenza and SARS-CoV-2 viruses, respectively. Only 2 influenza coinfections were detected in COVID-19 samples.ConclusionsThis study suggests that multiplex assay is a rapid, valid, and accurate method for the detection of SARS-CoV-2 and influenza viruses in clinical samples. The test may be an important diagnostic tool for both diagnostic and surveillance purposes during the seasonal influenza activity period.

Abstract P113: Increased Incidence of Atrial Fibrillation During Periods of High Influenza Activity

Introduction: Influenza is an important inflammatory illness which results in 3 to 5 million cases of severe illness, and 290,000 to 650,000 deaths per year, worldwide. Influenza’s role in triggering acute coronary syndromes is well established, but influenza’s impact on cardiac arrhythmias has yet to be investigated. Hypothesis: We investigated the effect of influenza on triggering atrial fibrillation (AFib) episodes. Methods: This retrospective observational study included de-identified data from patients who had a Zio patch (iRhythm Technologies, San Francisco), a wearable continuous cardiac monitoring device. Data were available from October 2012 to September 2017. The “influenza activity” was defined as the percentage of positive respiratory specimens that tested for influenza virus during each influenza season reported by the Centers for Disease Control and Prevention (CDC). We included all cases with AFib burden <=90% from the weeks with the highest and lowest influenza activity up to two consecutive weeks after them. An independent-samples t-test was used to compare the burden of AFib in weeks with the highest and lowest influenza activity. Results: We reviewed the records of 825,869 patients (mean age= 61.1 ± 15.3 years; 48.8% male) who had a Zio patch from October 2012 to September 2017. Of these patients, 47,106 met the pre-defined inclusion criteria for our study. There was a significant difference in the AFib burden in high influenza activity (Mean=1.19, SD=0.69) and low influenza activity (Mean=1.03, SD=0.63) conditions; t (47104) = -2.6, p =0.009. The incidence of AFib was 15% higher in high influenzas activity weeks (OR=1.15, 95%CI, 1.03-1.19, p=0.009). The higher burden of AFib in high influenza activity weeks was significant for each influenza season and a similar trend was observed consistently in each individual influenza season. Conclusions: High seasonal influenza activity is associated with increased odds of AFib. Prospective studies are needed to determine the clinical implications of this finding.

1347The flu vaccine and mortality in hypertension. A Danish nationwide cohort study

Abstract Background Influenza infection is associated with an increased risk of acute myocardial infarction (AMI) and stroke. It is currently unknown whether influenza vaccination may reduce mortality in patients with hypertension. Purpose To determine whether influenza vaccination is associated with lower risks of death in hypertensive patients without significant cardiovascular or other chronic disease. Methods Using nationwide registers, we identified all patients with hypertension in Denmark during 9 consecutive influenza seasons in the period 2007–2016 who were treated with at least 2 different classes of antihypertensive medication (beta-blockers, diuretics, calcium antagonists or renin-angiotensin system inhibitors). Patients who were not 18–100 years old or had ischemic heart disease, heart failure, chronic obstructive lung disease, cancer or cerebrovascular disease were excluded. Prior to each influenza season we assessed the exposure to influenza vaccination. End-points were death from all causes, from AMI or stroke, or cardiovascular death. For each season, patients were followed from December 1 until April 1 the next year, spanning the period of high influenza activity in Denmark. Results A total of 608,452 Patients were followed for a median of 5 seasons (interquartile-range: 2–8 seasons), with total follow-up time of 975,902 person-years. The vaccine coverage during study seasons ranged from 26% to 36%. During follow-up, 21,571 patients died of all-causes (3.5%), 12,270 patients died of cardiovascular causes (2.0%) and 3,846 patients died of AMI/stroke (0.6%). Vaccination was associated with older age, Diabetes Mellitus, atrial fibrillation, lower educational level, lower income and higher medication use. In unadjusted analysis considering all seasons, vaccination was significantly associated with increased risk of all-cause death, cardiovascular death and death from AMI/stroke. However, following adjustment for season, age, sex, comorbidities, medications, income, education, and more, vaccination was significantly associated with reduced risks of all-cause death, cardiovascular death and death from AMI/stroke (Figure). PY, person-years. Conclusion In a nationwide study spanning 9 consecutive influenza seasons including more than 600,000 hypertensive patients without significant cardiovascular disease identified through medication use, influenza vaccination was significantly associated with a reduced risk of death from all-causes, cardiovascular causes and AMI/stroke. Influenza vaccination may improve patient outcome in hypertension. Acknowledgement/Funding Daniel Modin was supported by the Herlev & Gentofte University Hospital Internal Research Fund and by the Novo Nordisk Foundation.

Cold Weather Viruses.

1. Asif Noor, MD* 2. Theresa Fiorito, MD* 3. Leonard R. Krilov, MD*,† 1. *Department of Pediatrics, Children's Medical Center, NYU Winthrop Hospital, Mineola, NY 2. †Department of Pediatrics, State University of New York, Stony Brook School of Medicine, Stony Brook, NY * Abbreviations: AAP: : American Academy of Pediatrics Adv: : adenovirus CDC: : Centers for Disease Control and Prevention FDA: : Food and Drug Administration hMPV: : human metapneumovirus PCR: : polymerase chain reaction PIV: : parainfluenza virus RSV: : respiratory syncytial virus RV: : rhinovirus Clinicians must learn to identify viral infections in children during the winter months and must practice caution with the use of unnecessary medications in such cases. Recognition of the clinical pattern of viral infection (eg, bronchiolitis) in conjunction with judicious use of viral tests (either office-based immunoassays or newer molecular tests) may assist in epidemiological monitoring, cohorting patients in the hospital, withholding unnecessary therapies, and providing a definitive diagnosis. After completing this article, readers should be able to: 1. Review the epidemiological aspects and clinical signs and symptoms of common cold weather viruses. 2. Recognize situations in which viral testing is indicated. 3. Recognize situations in which treatment is indicated. In early November you are evaluating a 9-month-old boy born at 33 weeks of gestation. The infant presents with 2 days of fevers (101°F–102°F [38.3°C–38.8°C]), copious rhinorrhea, and 1 day of coughing with difficulty breathing. He is otherwise feeding well and has had adequate urination. His 4-year-older sister has an upper respiratory tract infection. On physical examination, the infant has a respiratory rate of 45 breaths/min without chest wall retractions. On auscultation there is good air entry with scattered rhonchi bilaterally. What is the most appropriate next step in management? 1. Obtain respiratory syncytial virus (RSV) and influenza antigen testing. 2. Obtain a chest radiograph to look for focal infiltrate. 3. Provide supportive care with nasal …

Measurement of birth outcomes in analyses of the impact of maternal influenza vaccination.

BackgroundThe estimated association of maternal influenza vaccination and birth outcomes may be sensitive to methods used to define preterm birth or small‐for‐gestational age (SGA).MethodsIn a cohort of pregnant women in Lao People's Democratic Republic, we estimated gestational age from: (a) date of last menstrual period (LMP), (b) any prenatal ultrasound, (c) first trimester ultrasound, (d) Ballard Score at delivery, and (e) an algorithm combining LMP and ultrasound. Infants were classified as SGA at birth using a Canadian, global, and equation‐based growth reference. We estimated the association of maternal influenza vaccination and birth outcomes, by influenza activity, using multivariable log‐binomial regression and Cox proportional hazards regression with vaccination as a time‐varying exposure.ResultsThe frequency of preterm birth in the cohort varied by method to estimate gestational age, from 5% using Ballard Score to 15% using any ultrasound. Using LMP, any ultrasound, or the algorithm, we found statistically significant reductions in preterm birth among vaccinated women during periods of high influenza activity and statistically significant increases in SGA, using a Canadian growth reference. We did not find statistically significant associations with SGA when using global or equation‐based growth references.ConclusionsThe association of maternal influenza vaccination and birth outcomes was most affected by the choice of a growth reference used to define SGA at birth. The association with pre‐term birth was present and consistent across multiple statistical approaches. Future studies of birth outcomes, specifically SGA, should carefully consider the potential for bias introduced by measurement choice.

Effectiveness of influenza vaccination on influenza-associated hospitalisations over time among children in Hong Kong: a test-negative case-control study

The protection conferred by influenza vaccination is generally thought to last less than a year, necessitating annual revaccination. However, the speed with which influenza vaccine effectiveness might decline during a year is unknown, which is of particular importance for locations with year-round influenza activity. We aimed to assess how influenza vaccine effectiveness changes by time intervals between vaccination and admission to hospital, taking advantage of almost year-round circulation of influenza in Hong Kong. In this test-negative case-control study, we analysed vaccine effectiveness in children (aged 6 months to 17 years) who were admitted to hospital in Hong Kong over 5 consecutive years (2012-17). We included those who were admitted to general wards in four public hospitals in Hong Kong with a fever (≥38°C) and any respiratory symptom, such as runny nose, cough, or sore throat. We used direct immunofluorescence assay and reverse transcription PCR to detect influenza virus infection, and recorded children's influenza immunisation history. We compared characteristics of positive cases and negative controls and examined how vaccine effectiveness changed by time between vaccination and admission to hospital with regression analyses. Between Sept 1, 2012, and Aug 31, 2017, we enrolled 15 695 children hospitalised for respiratory infections, including 2500 (15·9%) who tested positive for influenza A or B and 13 195 (84·1%) who tested negative. 159 (6·4%) influenza-positive cases and 1445 (11·0%) influenza-negative cases had been vaccinated. Most vaccinations were done by December of each influenza vaccination season. Influenza-related admissions to hospital occurred year-round, with peaks in January through March in most years and a large summer peak in 2016; pooled vaccine effectiveness for children of all ages was 79% (95% CI 42-92) for September to December, 67% (57-74) for January to April, and 43% (25-57) for May to August. Vaccine effectiveness against influenza A or B was estimated as 79% (95% CI 64-88) within 0·5-2 months of vaccination, 60% (46-71) within >2-4 months, 57% (39-70) within >4-6 months, and 45% (22-61) within >6-9 months. In separate analyses by type and subtype, we estimated that vaccine effectiveness declined by 2-5 percentage points per month. Influenza vaccine effectiveness decreased during the 9 months after vaccination in children in Hong Kong. Our findings confirm the importance of annual vaccination in children. Influenza vaccines that provide broader and longer-lasting protection are needed to provide year-round protection in regions with irregular influenza seasonality or lengthy periods of influenza activity. Health and Medical Research Fund, Hong Kong and the Research Grants Council, Hong Kong.

Primary care influenza-like illness surveillance in Ho Chi Minh City, Vietnam 2013-2015.

BackgroundYear‐round transmission of influenza has been detected in Vietnam through both national surveillance and other epidemiological studies. Understanding the demographic and clinical features of influenza‐like illness (ILI) presenting to primary care in urban Vietnam is vital to understand these transmission dynamics.MethodsAn observational study of patients with ILI in Ho Chi Minh City, Vietnam, was conducted between August 2013 and November 2015 in a mix of public and private primary care settings. Molecular testing for influenza A and influenza B and 12 other respiratory viruses was performed.ResultsA total of 1152 ILI patients were recruited. 322 and 136 subjects tested positive for influenza A and influenza B, respectively. 193 subjects tested positive for another respiratory virus; most commonly rhinovirus and parainfluenza virus 3. Influenza was detected in 81% of the 116 study weeks. Three peaks of influenza activity were detected; an H3N2 peak April‐June 2014, an influenza B peak July‐December 2014, and a mixed H3N2 and H1N1 peak March‐September 2015. Subjects recruited from private clinics were more likely to have higher income and to have reported previous influenza vaccination. Antibiotic use was common (50.3%) despite limited evidence of bacterial infection.ConclusionInfluenza in southern Vietnam has complex transmission dynamics including periods of intense influenza activity of alternating types and subtypes. Broadening surveillance from hospital to the community in tropical settings is feasible and a valuable for improving our understanding of the global spread and evolution of the virus.

The burden of influenza A and B in Mexico from the year 2010 to 2013: An observational, retrospective, database study, on records from the Directorate General of Epidemiology database

ABSTRACTDespite vaccination programs, influenza still represents a significant disease burden in Mexico. We conducted an observational, retrospective analysis to better understand the epidemiological situation of the influenza virus in Mexico. Analysis of the seasonal patterns of influenza A and B were based on the Directorate General of Epidemiology dataset of influenza-like illness(ILI), and severe acute respiratory infection(SARI) that were recorded between January 2010 and December 2013. Our objectives were 1) to describe influenza A and B activity, by age group, and subtype and, 2) to analyze the number of laboratory-confirmed cases presenting with ILI by influenza type, the regional distribution of influenza, and its clinical features. Three periods of influenza activity were captured: August 2010–January 2011, December 2011–March 2012, and October 2012–March 2013. Cases were reported throughout Mexico, with 50.3% (n = 10,320) of cases found in 18–49 year olds. Over the entire capture period, a total of 76,085 ILI/SARI episodes had swab samples analyzed for influenza, 27% were positive. During the same period, influenza A cases were higher in the 18–49 years old, and influenza B cases in both 5–17 and 18–49 age groups. Peak activity occurred in January 2012 (n = 4,159) and December 2012 (n = 348) for influenza A and B respectively. This analysis confirms that influenza is an important respiratory pathogen for children and adults in Mexico despite vaccination recommendations. School-age children and adolescents were more prone to influenza B infection; while younger adults were susceptible to both influenza A and B viruses. Over the seasons, influenza A and B co-circulated.

Does locally relevant, real-time infection epidemiological data improve clinician management and antimicrobial prescribing in primary care? A systematic review.

PurposeAntimicrobial resistance is a significant threat to public health. Diagnostic uncertainty is a key driver of antimicrobial prescribing. We sought to determine whether locally relevant, real-time syndromic or microbiological infection epidemiology can improve prescribing by reducing diagnostic uncertainty.MethodsEligible studies investigated effects on primary care prescribing for common infections in Organisation For Economic Co-Operation And Development countries. We searched Medline, Embase, Cumulative index to nursing and allied health literature, Web of Science, grey literature sources, thesis databases and trial registries.ResultsWe identified 9548 reports, of which 17 were eligible, reporting 12 studies, of which 3 reported relevant outcomes. The first (observational) showed antibacterial prescribing for upper respiratory infections reduced from 26.4% to 8.6% (P = 0.01). The second (observational) showed antibacterial prescribing reduced during influenza pandemic compared with seasonal influenza periods [odds ratio (OR) 0.72 (95% CI, 0.68 to 0.77), P < 0.001], while antiviral prescribing increased [OR 6.43 (95% CI, 5.02 to 8.25), P < 0.001]. The likelihood of prescribing also decreased as the number of infection cases a physician saw increased in the previous week [OR 0.57 (95% CI, 0.51 to 0.63), P < 0.001 for ≥12 versus ≤1 patient). The third (randomized-controlled trial) showed an absolute reduction in antibacterial prescribing of 5.1% during a period of moderate influenza activity (P < 0.05). We did not find measures of diagnostic certainty, harms or costs.ConclusionThere is promising evidence that epidemiological syndromic and microbiological data can reduce primary care antimicrobial prescribing. Future research should use randomized designs of behaviourally informed interventions, investigate costs and harms, and establish mechanisms of behaviour change.PROSPERO registrationCRD42016038871.

Global influenza seasonality to inform country-level vaccine programs: An analysis of WHO FluNet influenza surveillance data between 2011 and 2016.

By analyzing publicly available surveillance data from 2011–2016, we produced country-specific estimates of seasonal influenza activity for 118 countries in the six World Health Organization regions. Overall, the average country influenza activity period was 4.7 months. Our analysis characterized 100 countries (85%) with one influenza peak season, 13 (11%) with two influenza peak seasons, and five (4%) with year-round influenza activity. Surveillance data were limited for many countries. These data provide national estimates of influenza activity, which may guide planning for influenza vaccination implementation, program timing and duration, and policy development.

Influenza vaccine effectiveness in the tropics: moderate protection in a case test-negative analysis of a hospital-based surveillance population in Bangkok between August 2009 and January 2013.

Influenza in the tropics occurs year round with peaks that correspond variably to temperate regions. However, data on influenza vaccine effectiveness (VE) in the tropics is sparse. We report on the effectiveness of influenza vaccine to prevent medically attended laboratory confirmed influenza from sentinel surveillance conducted at a Thai military medical facility in Bangkok, Thailand from August 2009 to January 2013. Patients ≥6 months old presenting with influenza-like illness underwent combined nasal/throat swabs which were tested by influenza RT-PCR. A case test-negative study design was used to evaluate VE. Of 2999 samples available for analysis,1059 (35.3%) were PCR-positive (cases) and 1940 (64.6%) were PCR-negative (test-negative controls). Five hundred and seven (16.9%) of these patients reported being vaccinated within the previous 12 months. Periods of high and low influenza activity were defined based on publicly available Thai Ministry of Public Health data. Overall VE adjusted for age and epiweek was found to be 50.1% (95%CI: 35.0, 61.9%). The May to April adjusted VE for year 2010, 2011 and 2012 was 57.7% (95%CI: 33.7, 73.8%), 57.1% (95% CI: 35.2, 68.3%) and 37.6% (95% CI: 3.5, 62.9%).During high influenza activity in years with the same vaccine formulation, the adjusted VE was 54.9% (95%CI: 38.9, 66.9%). VE appeared to be much higher during high versus low influenza activity periods. The adjusted point estimate for VE was highest in the 18–49 year age group (76.6%) followed by 6–23 months (58.1%) and 2–17 years (52.5%). Adjusted estimates were not done for those ≥50 years of age due to small numbers. VE in patients with underlying disease was 75.5% compared to 48.0% in those without. Our findings demonstrate moderate protection by influenza vaccination and support the utility of influenza vaccination in the tropics including in very young children and those with underlying disease.

Triggering interventions for influenza: the ALERT algorithm.

Early, accurate predictions of the onset of influenza season enable targeted implementation of control efforts. Our objective was to develop a tool to assist public health practitioners, researchers, and clinicians in defining the community-level onset of seasonal influenza epidemics. Using recent surveillance data on virologically confirmed infections of influenza, we developed the Above Local Elevated Respiratory Illness Threshold (ALERT) algorithm, a method to identify the period of highest seasonal influenza activity. We used data from 2 large hospitals that serve Baltimore, Maryland and Denver, Colorado, and the surrounding geographic areas. The data used by ALERT are routinely collected surveillance data: weekly case counts of laboratory-confirmed influenza A virus. The main outcome is the percentage of prospective seasonal influenza cases identified by the ALERT algorithm. When ALERT thresholds designed to capture 90% of all cases were applied prospectively to the 2011-2012 and 2012-2013 influenza seasons in both hospitals, 71%-91% of all reported cases fell within the ALERT period. The ALERT algorithm provides a simple, robust, and accurate metric for determining the onset of elevated influenza activity at the community level. This new algorithm provides valuable information that can impact infection prevention recommendations, public health practice, and healthcare delivery.

Age- and Influenza Activity-Stratified Case Definitions of Influenza-Like Illness: Experience from Hospital-Based Influenza Surveillance in South Korea

ObjectivesThis study aims to identify clinical case definitions of influenza with higher accuracy in patients stratified by age group and influenza activity using hospital-based surveillance system.MethodsIn seven tertiary hospitals across South Korea during 2011–2012 influenza season, respiratory specimens were obtained from patients presenting an influenza-like illness (ILI), defined as having fever plus at least one of following symptoms: cough, sore throat or rhinorrhea. Influenza was confirmed by reverse transcriptase-polymerase chain reaction. We performed multivariate logistic regression analyses to identify clinical variables with better relation with laboratory-confirmed influenza, and compared the accuracy of combinations.ResultsOver the study period, we enrolled 1417 patients, of which 647 had laboratory-confirmed influenza. Patients with cough, rhinorrhea, sore throat or headache were more likely to have influenza (p<0.05). The most accurate criterion across the study population was the combination of cough, rhinorrhea, sore throat and headache (sensitivity 71.3%, specificity 60.1% and AUROC 0.66). The combination of rhinorrhea, sore throat and sputum during the peak influenza activity period in the young age group showed higher accuracy than that using the whole population (sensitivity 89.3%, specificity 72.1%, and AUROC 0.81).ConclusionsThe accuracy of clinical case definitions of influenza differed across age groups and influenza activity periods. Categorizing the entire population into subgroups would improve the detection of influenza patients in the hospital-based surveillance system.

Impact of maternal characteristics on the effect of maternal influenza vaccination on fetal outcomes

BackgroundMaternal infections during pregnancy have been associated with adverse fetal and infant health outcomes, and vaccination against influenza is the most effective tool to prevent morbidity and mortality due to seasonal and pandemic influenza. We evaluated the association between receipt of the inactivated seasonal influenza vaccine on preterm and small for gestational age (SGA) births, with the aim to assess racial and socioeconomic variations in vaccine effect. MethodsWe conducted a retrospective analysis of state-wide surveillance data from Georgia for the most recent four years available at the beginning of the study, a total of 8393 live births in Georgia from January 1, 2005 through December 31, 2008. We constructed multivariable logistic regression models and calculated odds ratios (OR) estimates with corresponding 95% confidence intervals (CI) to evaluate the effect of maternal influenza vaccination on SGA (birth weight <10th percentile for gestational age) and preterm (gestational age at birth <37 weeks) births while controlling for potential confounders. ResultsAmong all women, we found significant strong associations between maternal influenza vaccination and reduced odds of a preterm birth during the widespread influenza activity period [OR=0.39, 95% CI: 0.18, 0.83]. In this period, vaccination was protective against SGA births among women at higher risk for influenza related morbidity – women enrolled in the Women, Infant and Child (WIC) program [OR=0.20, 95% CI: 0.04, 0.98] and Black women [OR=0.15 95% CI: 0.02, 0.94]; maternal influenza vaccination was associated with reduced odds of a preterm birth among white women [OR=0.34, 95% CI: 0.12, 0.91] and women of higher socio-economic status [OR=0.30, 95% CI: 0.12, 0.74]. ConclusionInfluenza vaccination during pregnancy was significantly associated with reduced odds of small for gestational age and preterm births during the widespread influenza activity period. Vaccination effects varied by socio-demographic characteristics.

A Comparison of the Clinical and Epidemiological Characteristics of Adult Patients with Laboratory-Confirmed Influenza A or B during the 2011–2012 Influenza Season in Korea: A Multi-Center Study

BackgroundDuring the 2011/2012 winter influenza season in the Republic of Korea, influenza A (H3N2) was the predominant virus in the first peak period of influenza activity during the second half of January 2012. On the other hand, influenza B was the predominant virus in the second peak period of influenza activity during the second half of March 2012. The objectives of this study were to compare the clinical and epidemiological characteristics of patients with laboratory-confirmed influenza A or influenza B.Methodology/Principal FindingsWe analyzed data from 2,129 adult patients with influenza-like illnesses who visited the emergency rooms of seven university hospitals in Korea from October 2011 to May 2012. Of 850 patients with laboratory-confirmed influenza, 656 (77.2%) had influenza A (H3N2), and 194 (22.8%) influenza B. Age, and the frequencies of cardiovascular disorders, diabetes, hypertension were significantly higher in patients with influenza A (H3N2) (P<0.05). The frequencies of leukopenia or thrombocytopenia in patients with influenza B at initial presentation were statistically higher than those in patients with influenza A (H3N2) (P<0.05). The rate of hospitalization, and length of hospital stay were statistically higher in patients with influenza A (H3N2) (P<0.05), and of the 79 hospitalized patients, the frequency of diabetes, hypertension, cases having at least one of the comorbid conditions, and the proportion of elderly were significantly higher in patients with influenza A (H3N2) (P<0.05).ConclusionsThe proportion of males to females and elderly population were significantly higher for influenza A (H3N2) patients group compared with influenza B group. Hypertension, diabetes, chronic lung diseases, cardiovascular disorders, and neuromuscular diseases were independently associated with hospitalization due to influenza. Physicians should assess and treat the underlying comorbid conditions as well as influenza viral infections for the appropriate management of patients with influenza.

Impact of Seasonal and Pandemic Influenza on Emergency Department Visits, 2003–2010, Ontario, Canada

ObjectivesWeekly influenza-like illness (ILI) consultation rates are an integral part of influenza surveillance. However, in most health care settings, only a small proportion of true influenza cases are clinically diagnosed as influenza or ILI. The primary objective of this study was to estimate the number and rate of visits to the emergency department (ED) that are attributable to seasonal and pandemic influenza and to describe the effect of influenza on the ED by age, diagnostic categories, and visit disposition. A secondary objective was to assess the weekly “real-time” time series of ILI ED visits as an indicator of the full burden due to influenza.MethodsThe authors performed an ecologic analysis of ED records extracted from the National Ambulatory Care Reporting System (NARCS) database for the province of Ontario, Canada, from September 2003 to March 2010 and stratified by diagnostic characteristics (International Classification of Diseases, 10th Revision [ICD-10]), age, and visit disposition. A regression model was used to estimate the seasonal baseline. The weekly number of influenza-attributable ED visits was calculated as the difference between the weekly number of visits predicted by the statistical model and the estimated baseline.ResultsThe estimated rate of ED visits attributable to influenza was elevated during the H1N1/2009 pandemic period at 1,000 per 100,000 (95% confidence interval [CI] = 920 to 1,100) population compared to an average annual rate of 500 per 100,000 (95% CI = 450 to 550) for seasonal influenza. ILI or influenza was clinically diagnosed in one of 2.6 (38%) and one of 14 (7%) of these visits, respectively. While the ILI or clinical influenza diagnosis was the diagnosis most specific to influenza, only 87% and 58% of the clinically diagnosed ILI or influenza visits for pandemic and seasonal influenza, respectively, were likely directly due to an influenza infection. Rates for ILI ED visits were highest for younger age groups, while the likelihood of admission to hospital was highest in older persons. During periods of seasonal influenza activity, there was a significant increase in the number of persons who registered with nonrespiratory complaints, but left without being seen. This effect was more pronounced during the 2009 pandemic. The ratio of influenza-attributed respiratory visits to influenza-attributed ILI visits varied from 2.4:1 for the fall H1N1/2009 wave to 9:1 for the 2003/04 influenza A(H3N2) season and 28:1 for the 2007/08 H1N1 season.ConclusionsInfluenza appears to have had a much larger effect on ED visits than was captured by clinical diagnoses of influenza or ILI. Throughout the study period, ILI ED visits were strongly associated with excess respiratory complaints. However, the relationship between ILI ED visits and the estimated effect of influenza on ED visits was not consistent enough from year to year to predict the effect of influenza on the ED or downstream in-hospital resource requirements.