Pandemic Season Research Articles

Is weight associated with severity of acute respiratory illness?

Background/ObjectivesObesity was an independent risk factor for severe disease in hospitalized adults during the 2009 pandemic H1N1 influenza season. Few studies have investigated the association between weight and severity of acute respiratory illnesses in children or in adults seeking care in the emergency department (ED) during other winter respiratory seasons.Subjects/MethodsWe prospectively and systematically enrolled patients ≥2 years of age who presented to the ED or inpatient setting in a single geographic region with fever/acute respiratory illness over four consecutive winter respiratory seasons (2010–14). We collected demography, height and weight, and high risk co-morbid conditions. Multivariable logistic regression was used for prediction of hospital admission (primary outcome), length of stay and supplemental oxygen requirement among those hospitalized, and antibiotic prescription (secondary outcomes).ResultsWe enrolled 3560 patients (N=749 children, 2811 adults), 1405 (39%) with normal weight, 860 (24%) with overweight, and 1295 (36%) with obesity. Following multivariable logistic regression, very young or very old age (p<0.001) and high-risk conditions (p<0.001) predicted hospitalization. Risk of hospitalization was decreased for adults with overweight [aOR 0.8 (95% CI 0.6-1.0)], class 1 obesity [aOR 0.7 (95% CI 0.5-1.0)] and class 2 obesity [aOR 0.6 (95% CI 0.4-0.8)] compared to normal-weight. Class 3 obesity was associated with supplemental oxygen requirement in adults [aOR 1.6 (95% CI 1.1-2.5)]. No association was seen in children.ConclusionOverweight and obesity were not associated with increased risk of hospitalization during winter respiratory seasons in children or adults.

Viral Co-Infections Involving Influenza A: Changes Observed During the 2009 Pandemic Season

1. Abstract 1.1. Objectives: Our objective is to highlight and focus on the viral etiology of influenza-like-illness (ILI), to compare the viral co-infections during 2009 pandemics and other influenza seasons, and to evaluate if respiratory viruses had an effect on the spread. 1.2. Methods: <span lang=EN-GB style=font-size:10.0pt;font-family: times= new= roman,serif;mso-ansi-language:en-gb=>Between 15 July and 31 December 2009 upper respiratory tract specimens from ILI patients were prospectively examined by viral culture and/or A(H1N1)2009 PCR. On samples of 620 critically-ill patients,another 16 respiratory viruses were detected by combined monoplex/duplex PCR. This algorithm was also used during two preceding influenza seasons, while in later seasons multiparameter PCR on customized Taqman Array Cardswereused.Five influenza/winter seasons (October 1st March 31st) were evaluated. 1.3. <span lang=EN-GB style=font-size:10.0pt; font-family: times= new= roman,serif;mso-ansi-language:en-gb=>Results: From July to December 2009, 4,101 patients presented with ILI, 48.4% of them were hospitalized and 15.1% were admitted to ICU. In total, 4,895 samples of different episodes were analysed. A(H1N1)2009 was cultured from 781 samples (33.0%), of which 2.9% showed viral co-infections. More than 54% of the ICU patients had a viral infection; 13.1% of them were co-infected. Co-infections were found in 7% and 18.4% of A(H1N1)2009-positive samples, and A(H1N1)2009-negative samples respectively. Overall, rhinoviruses (hRV) were the most frequently involved viruses in co-infections, closely followed by Parainfluenza viruses (PIV). The opposite was noticed in the ICU patients, where PIV was followed by both hRV and adenoviruses in equal numbers. Comparing the same period in previous/later seasons (1 October to 31 March) reveals significant lower percentages (P<0.0001) of viral co-infections with and without the presence of circulating influenza A (IA) strain during the winter 2009-2010, both in culture and PCR. In season 2007-2008 (seasonal A/H1N1) and 2008-2009 (seasonal A/H3N2 predominantly), 34.2% and 36.7% of IA infected samples respectively, were co-infected, compared to 28.7% and 25.8% in 2012-2013 and 2013-2014 respectively, considering respiratory samples examined by multiparameter PCR. Looking at viral culture, a significant decrease of co-infections from 12.9% to 4% of IA infected samples frompre-pandemic to pandemic season was observed (P 1.4. <span lang=EN-GB style=font-size:10.0pt; font-family: times= new= roman,serif;mso-ansi-language:en-gb=>Conclusions: During the pandemic season of 2009, A(H1N1)2009 circulated in a dominant way, and patients with ILI were less co-infected than in surrounding flu seasons. This could partly be explained by the fact that the flu season started earlier than expected, when other respiratory viruses were less prevalent , but more decisive the new recombinant strain was less likely associated with other viruses. <span lang=EN-GB style=font-size:10.0pt; font-family: times= new= roman,serif;mso-ansi-language:en-gb=> A(H1N1)2009circulated preferentially isolated in its first season but lost its dominance in subsequent years.

Cerebral vein thrombosis complicating influenza A in a toddler

We describe a child who presented with a respiratory illness in the influenza pandemic season and was found to be positive for the influenza A, he developed neurological manifestations of cranial nerve palsies and was found to have radiological evidence of cerebral sinus thrombosis. He received treatment with oseltamivir and supportive therapy and was discharged home free of long-term neurological sequelae. This is a rare complication which might have associated with this infection and has not been reported in children before as far as we are aware. Children who develop focal neurological signs during the course of flu epidemic should be evaluated for the possibility of cerebral sinus thrombosis.

Estimated rates of influenza-associated outpatient visits during 2001-2010 in 6 US integrated healthcare delivery organizations.

BackgroundPopulation‐based estimates of influenza‐associated outpatient visits including both pandemic and interpandemic seasons are uncommon. Comparisons of such estimates with laboratory‐confirmed rates of outpatient influenza are rare.ObjectiveTo estimate influenza‐associated outpatient visits in 6 US integrated healthcare delivery organizations enrolling ~7.7 million persons.MethodsUsing negative binomial regression methods, we modeled rates of influenza‐associated visits with ICD‐9‐CM‐coded pneumonia or acute respiratory outpatient visits during 2001‐10. These estimated counts were added to visits coded specifically for influenza to derive estimated rates. We compared these rates with those observed in 2 contemporaneous studies recording RT‐PCR‐confirmed influenza outpatient visits.ResultsOutpatient rates estimated with pneumonia visits were 39 (95% confidence interval [CI], 30‐70) and 203 (95% CI, 180‐240) per 10 000 person‐years, respectively, for interpandemic and pandemic seasons. Corresponding rates estimated with respiratory visits were 185 (95% CI, 161‐255) and 542 (95% CI, 441‐823) per 10 000 person‐years. During the pandemic, children aged 2‐17 years had the largest increase in rates (when estimated with pneumonia visits, from 64 [95% CI, 50‐121] to 381 [95% CI, 366‐481]). Rates estimated with pneumonia visits were consistent with rates of RT‐PCR‐confirmed influenza visits during 4 of 5 seasons in 1 comparison study. In another, rates estimated with pneumonia visits during the pandemic for children and adults were consistent in timing, peak, and magnitude.ConclusionsEstimated rates of influenza‐associated outpatient visits were higher in children than adults during pre‐pandemic and pandemic seasons. Rates estimated with pneumonia visits plus influenza‐coded visits were similar to rates from studies using RT‐PCR‐confirmed influenza.

Influenza virus infections from 0 to 2 years of age: A birth cohort study.

Influenza vaccine has been recommended in Finland since 2007 for all children of 6-35 months of age and in 2009 for those ≥6 months against pandemic influenza. We investigated the incidence of influenza and vaccine effectiveness in a birth cohort of children in 2008-2011. We followed 923 children from birth to 2 years of age for respiratory tract infections. A nasal swab sample for PCR for influenza A and B viruses was taken at the onset of acute respiratory infections. Samples were collected either at the study clinic or at home by parents. Vaccination data was retrieved from the health registries. Vaccination coverage of children aged 6-23 months was 22-47% against seasonal influenza and 80% against the A(H1N1)pdm09 virus in the pandemic season 2009-2010. During 3 influenza seasons, 1607 nasal swab samples were collected. Influenza was confirmed in 56 (6.1%) of 923 children (16 A(H1N1), 14 A(H3N2), and 26B viruses). The incidence of influenza was 5.1% in 2008-2009, 2.7% in 2009-2010, and 5.0% in 2010-2011. Effectiveness of the adjuvanted vaccine against the pandemic influenza A(H1N1)pdm09 was 97% (95% confidence interval, 76-100%). Three children with influenza were hospitalized. The yearly incidence of seasonal influenza was 5% in this cohort of very young children with variable influenza vaccine coverage. Adjuvanted vaccine against the pandemic influenza was highly effective. Both seasonal and pandemic influenza cases were mostly non-severe.

Influenza Season Hospitalization Trends in Israel: A Multi-Year Comparative Analysis 2005/2006 Through 2012/2013.

Influenza-related morbidity impacts healthcare systems, including hospitals. To obtain a quantitative assessment of hospitalization burden in pediatric and internal medicine departments during influenza seasons compared with the summer months in Israel. Data on pediatric and internal medicine hospitalized patients in general hospitals in Israel during the influenza seasons between 2005 and 2013 were analyzed for rate of hospitalizations, rate of hospitalization days, hospital length of stay (LOS), and bed occupancy and compared with the summer months. Data were analyzed for hospitalizations for all diagnoses, diagnoses of respiratory or cardiovascular disease (ICD9 390-519), and influenza or pneumonia (ICD9480-487), with data stratified by age. The 2009-2010 pandemic influenza season was excluded. Rates of monthly hospitalizations and hospitalization days for all diagnoses were 4.8% and 8% higher, respectively, during influenza seasons as compared with the summers. The mean LOS per hospitalization for all diagnoses demonstrated a small increase during influenza seasons as compared with summer seasons. The excess hospitalizations and hospitalization days were especially noticed for the age groups under 1 year, 1-4 years, and 85 years and older. The differences were severalfold higher for patients with a diagnosis of respiratory or cardiovascular disease and influenza or pneumonia. Bed occupancy was higher during influenza seasons compared with the summer, particularly in pediatric departments. Hospital burden in pediatric and internal medicine departments during influenza seasons in Israel was associated with age and diagnosis. These results are important for optimal preparedness for influenza seasons.

Genetic analysis of the complete genome of influenza A (H1N1) pdm09 during the first wave of the pandemic season in Indonesia

Genetic analysis of the complete genome of influenza A (H1N1) pdm09 during the first wave of the pandemic season in Indonesia

Developing a system to estimate the severity of influenza infection in England: findings from a hospital-based surveillance system between 2010/2011 and 2014/2015.

The UK Severe Influenza Surveillance System (USISS) was established following the 2009 influenza pandemic to monitor severe seasonal influenza. This article describes the severity of influenza observed in five post-2009 pandemic seasons in England. Two key measures were used to assess severity: impact measured through the cumulative incidence of laboratory-confirmed hospitalised influenza and case severity through the proportion of confirmed hospitalised cases admitted into intensive care units (ICU)/high dependency units (HDU). The impact of influenza varied by subtype and age group across the five seasons with the highest crude cumulative hospitalisation incidence for influenza A/H1N1pdm09 cases in 2010/2011 and in 0-4 year olds each season for all-subtypes. Case severity also varied by subtype and season with a higher hospitalisation: ICU ratio for A/H1N1pdm09 and older age groups (older than 45 years). The USISS system provides a tool for measuring severity of influenza each year. Such seasonal surveillance can provide robust baseline estimates to allow for rapid assessment of the severity of seasonal and emerging influenza viruses.

Predictors of Hospitalization and Admission to Intensive Care Units of Influenza Patients in Serbia through Four Influenza Seasons from 2010/2011 to 2013/2014.

A retrospective analysis of the surveillance data on laboratory confirmed cases of influenza in 4 post pandemic seasons in Serbia was performed to evaluate predictors of hospitalization and admission to intensive care units (ICU). The specimens, including nasal and throat swabs were tested for influenza. Univariate and multivariate logistic regression analyses were performed. Data of a total of 777 confirmed influenza cases were analyzed. Age > 65 years, the presence of any co-morbidity or the presence of ≥ 2 comorbidities, infection with influenza virus subtype A (H1) pdm09, and an interval greater than 3 days between symptom onset and the first physician visit, were independently associated with hospital admission. These variables, as well as infection with non-subtype influenza virus A, were predictors for ICU admission. Obesity and chronic neurological disease were independent predictors for ICU admission but not hospitalization. Overall, 41.7% of patients with influenza had at least one co-morbidity, but only 3% of all patients were vaccinated against influenza. Identification of high risk groups and education of these groups regarding their increased susceptibility to severe forms of influenza, and in particular regarding the importance of influenza vaccination, is essential.

Influenza vaccination coverages among high risk subjects and health care workers in Spain. Results of two consecutive National Health Surveys (2011–2014)

ObjectivesWe aim to describe influenza vaccination coverage for the Spanish population using data from two consecutive nation-wide representative health surveys. The data was analysed by high risk groups, health care workers (HCWs) and immigrants. Also, coverage trends were analysed. Material and methodsThe 2011/12 Spanish National Health Survey (N=21,007) and the 2014 European Health Interview Survey for Spain (N=22,842) were analysed. Influenza vaccination status was self-reported. Time trends for were estimated by a multivariate logistic regression model. ResultsOverall vaccination uptake was similar in 2011/12 and 2014, 19.1% and 18.9%, respectively, (p>0.05). 47% of the subjects surveyed were in the groups for which vaccination was recommended with coverages of 41.1% in 2011/12 and 40% in 2014 (p>0.05).In both surveys, uptake among subjects with a chronic disease was three times higher than uptake in subjects who did not have these diseases.In 2011/12 and 2014, 20% and 27.6% of health workers were vaccinated. Subjects born outside Spain were vaccinated less frequently than Spanish-born subjects (9.3% vs 20.4% and 8.9% vs 20%).Within the diseases studied, the best uptake was for patients with heart disease (52.5% in 2011/12 and 51.1% in 2014) and patients with diabetes (50.5% and 51.8%).Multivariate analysis showed that older age, having a chronic disease or being a HCW increases the possibility of being vaccinated whereas being born outside Spain decreased it. ConclusionsSeasonal influenza vaccine uptake rates in the recommended target groups, patients with chronic conditions and health care workers, in Spain are unacceptably low and seem to be stable in the post pandemic seasons. This finding should alert health authorities to the need to work directly with health care providers on the indications for this vaccine and to study strategies that make it possible to increase vaccination uptake.

Adverse events following pandemic influenza A (H1N1) 2009 monovalent and seasonal influenza vaccinations during the 2009–2010 season in the active component U.S. military and civilians aged 17–44 years reported to the Vaccine Adverse Event Reporting System

BackgroundNo comparative review of Vaccine Adverse Event Reporting System (VAERS) submissions following pandemic influenza A (H1N1) 2009 and seasonal influenza vaccinations during the pandemic season among U.S. military personnel has been published. MethodsWe compared military vs. civilian adverse event reporting rates. Adverse events (AEs) following vaccination were identified from VAERS for adults aged 17–44years after pandemic (monovalent influenza [MIV], and seasonal (trivalent inactivated influenza [IIV3], live attenuated influenza [LAIV3]) vaccines. Military vaccination coverage was provided by the Department of Defense’s Defense Medical Surveillance System. Civilian vaccination coverage was estimated using data from the National 2009 H1N1 Flu Survey and the Behavioral Risk Factor Surveillance System survey. ResultsVaccination coverage was more than four times higher for MIV and more than twenty times higher for LAIV3 in the military than in the civilian population. The reporting rate of serious AE reports following MIV in service personnel (1.19 per 100,000) was about half that reported by the civilian population (2.45 per 100,000). Conversely, the rate of serious AE reports following LAIV3 among service personnel (1.32 per 100,000) was more than twice that of the civilian population. Although fewer military AEs following MIV were reported overall, the rate of Guillain–Barré Syndrome (GBS) (4.01 per million) was four times greater than that in the civilian population. (1.04 per million). ConclusionsDespite higher vaccination coverage in service personnel, the rate of serious AEs following MIV was about half that in civilians. The rate of GBS reported following MIV was higher in the military.

Severe maternal morbidity due to respiratory disease and impact of 2009 H1N1 influenza A pandemic in Brazil: results from a national multicenter cross-sectional study.

BackgroundThe aim of this study was to assess the burden of respiratory disease, considering the influenza A pandemic season (H1N1pdm09), within the Brazilian Network for Surveillance of Severe Maternal Morbidity, and factors associated with worse maternal outcome.MethodsA multicenter cross-sectional study, involving 27 referral maternity hospitals in five Brazilian regions. Cases were identified in a prospective surveillance by using the WHO standardized criteria for potentially life-threatening conditions (PLTC) and maternal near miss (MNM). Women with severe complications from respiratory disease identified as suspected or confirmed cases of H1N1 influenza or respiratory failure were compared to those with other causes of severe morbidity. A review of suspected H1N1 influenza cases classified women as non-tested, tested positive and tested negative, comparing their outcomes. Factors associated with severe maternal outcome (SMO = MNM + MD) were assessed in both groups, in comparison to PLTC, using PR and 95 % CI adjusted for design effect of cluster sampling.ResultsAmong 9555 cases of severe maternal morbidity, 485 (5 %) had respiratory disease. Respiratory disease occurred in one-quarter of MNM cases and two-thirds of MD. H1N1 virus was suspected in 206 cases with respiratory illness. Around 60 % of these women were tested, yielding 49 confirmed cases. Confirmed H1N1 influenza cases had worse adverse outcomes (MNM:MD ratio < 1 (0.9:1), compared to 12:1 in cases due to other causes), and a mortality index > 50 %, in comparison to 7.4 % in other causes of severe maternal morbidity. Delay in medical care was associated with SMO in all cases considered, with a two-fold increased risk among respiratory disease patients. Perinatal outcome was worse in cases complicated by respiratory disease, with increased prematurity, stillbirth, low birth weight and Apgar score < 7.ConclusionsRespiratory disease, especially considering the influenza season, is a very severe cause of maternal near miss and death. Increased awareness about this condition, preventive vaccination during pregnancy, early diagnosis and treatment are required to improve maternal health.

Revealing the True Incidence of Pandemic A(H1N1)pdm09 Influenza in Finland during the First Two Seasons - An Analysis Based on a Dynamic Transmission Model.

The threat of the new pandemic influenza A(H1N1)pdm09 imposed a heavy burden on the public health system in Finland in 2009-2010. An extensive vaccination campaign was set up in the middle of the first pandemic season. However, the true number of infected individuals remains uncertain as the surveillance missed a large portion of mild infections. We constructed a transmission model to simulate the spread of influenza in the Finnish population. We used the model to analyse the two first years (2009-2011) of A(H1N1)pdm09 in Finland. Using data from the national surveillance of influenza and data on close person-to-person (social) contacts in the population, we estimated that 6% (90% credible interval 5.1 – 6.7%) of the population was infected with A(H1N1)pdm09 in the first pandemic season (2009/2010) and an additional 3% (2.5 – 3.5%) in the second season (2010/2011). Vaccination had a substantial impact in mitigating the second season. The dynamic approach allowed us to discover how the proportion of detected cases changed over the course of the epidemic. The role of time-varying reproduction number, capturing the effects of weather and changes in behaviour, was important in shaping the epidemic.

Different features of influenza A H1N1pdm09 virus infection among adults in 2009/10 and 2010/11.

Influenza A H1N1pdm09 virus infection causes an epidemiologically and clinically severe disease mostly characterized by pneumonia, resulting in a high mortality rate. The purpose of this study was to investigate and compare epidemiological and clinical characteristics of influenza A H1N1pdm09 virus infection in patients hospitalized during the pandemic (2009/10) and post-pandemic seasons (2010/11). The data of patients with laboratory-confirmed influenza A H1N1pdm09 virus infection hospitalized and treated at the University Hospital for Infectious Diseases Dr. Fran Mihaljevic in Zagreb, Croatia in the first two seasons of appearance were analyzed. Compared to the pandemic season, in the post-pandemic season, patients were hospitalized longer, had higher values of inflammatory parameters, and were more often treated with antibiotics. The total number of risk factors in patients did not vary significantly between the two seasons. In the pandemic season, a significantly higher number of obese patients and patients with chronic lung disease was observed, whereas in the post-pandemic season, a statistically significant number of patients presented with symptoms of chronic cardiac and neuromuscular diseases. Primary viral pneumonia was frequently registered in younger adults during the pandemic season, whereas in the post-pandemic season, there were more cases of bacterial pneumonia. During the pandemic season, the influenza A H1N1pdm09 virus infection caused a severe disease with rare bacterial complications, especially in adult patients. The common characteristics of the influenza A H1N1pdm09 virus were lost in the post-pandemic season, assuming the shape and characteristics of the seasonal influenza A virus.

Evaluating the case-positive, control test-negative study design for influenza vaccine effectiveness for the frailty bias

IntroductionPrevious influenza vaccine effectiveness studies were criticized for their failure to control for frailty. This study was designed to see if the test-negative study design overcomes this bias. MethodsAdults≥50 years of age with respiratory symptoms were enrolled from November 2006 through May 2012 during the influenza season (excluding the 2009–2010 H1N1 pandemic season) to perform yearly test-negative control influenza vaccine effectiveness studies in Nashville, TN. At enrollment, both a nasal and throat swab sample were obtained and tested for influenza by RT-PCR. Frailty was calculated using a modified Rockwood Index that included 60 variables ascertained in a retrospective chart review giving a score of 0 to 1. Subjects were divided into three strata: non frail (≤0.08), pre-frail (>0.08 to <0.25), and frail (≥0.25). Vaccine effectiveness was calculated using the formula [1-adjusted odds ratio (OR)]×100%. Adjusted ORs for individual years and all years combined were estimated by penalized multivariable logistic regression. ResultsOf 1023 hospitalized adults enrolled, 866 (84.7%) participants had complete immunization status, molecular influenza testing and covariates to calculate frailty. There were 83 influenza-positive cases and 783 test-negative controls overall, who were 74% white, 25% black, and 59% female. The median frailty index was 0.167 (Interquartile: 0.117, 0.267). The frailty index was 0.167 (0.100, 0.233) for the influenza positive cases compared to 0.183 (0.133, 0.267) for influenza negative controls (p=0.07). Vaccine effectiveness estimates were 55.2% (95%CI: 30.5, 74.2), 60.4% (95%CI: 29.5, 74.4), and 54.3% (95%CI: 28.8, 74.0) without the frailty variable, including frailty as a continuous variable, and including frailty as a categorical variable, respectively. ConclusionsUsing the case positive test negative study design to assess vaccine effectiveness, our measure of frailty was not a significant confounder as inclusion of this measure did not significantly change vaccine effectiveness estimates.

Quercetin as an Antiviral Agent Inhibits Influenza A Virus (IAV) Entry.

Influenza A viruses (IAVs) cause seasonal pandemics and epidemics with high morbidity and mortality, which calls for effective anti-IAV agents. The glycoprotein hemagglutinin of influenza virus plays a crucial role in the initial stage of virus infection, making it a potential target for anti-influenza therapeutics development. Here we found that quercetin inhibited influenza infection with a wide spectrum of strains, including A/Puerto Rico/8/34 (H1N1), A/FM-1/47/1 (H1N1), and A/Aichi/2/68 (H3N2) with half maximal inhibitory concentration (IC50) of 7.756 ± 1.097, 6.225 ± 0.467, and 2.738 ± 1.931 μg/mL, respectively. Mechanism studies identified that quercetin showed interaction with the HA2 subunit. Moreover, quercetin could inhibit the entry of the H5N1 virus using the pseudovirus-based drug screening system. This study indicates that quercetin showing inhibitory activity in the early stage of influenza infection provides a future therapeutic option to develop effective, safe and affordable natural products for the treatment and prophylaxis of IAV infections.

ORBiT: Oak Ridge biosurveillance toolkit for public health dynamics.

BackgroundThe digitization of health-related information through electronic health records (EHR) and electronic healthcare reimbursement claims and the continued growth of self-reported health information through social media provides both tremendous opportunities and challenges in developing effective biosurveillance tools. With novel emerging infectious diseases being reported across different parts of the world, there is a need to build systems that can track, monitor and report such events in a timely manner. Further, it is also important to identify susceptible geographic regions and populations where emerging diseases may have a significant impact.MethodsIn this paper, we present an overview of Oak Ridge Biosurveillance Toolkit (ORBiT), which we have developed specifically to address data analytic challenges in the realm of public health surveillance. In particular, ORBiT provides an extensible environment to pull together diverse, large-scale datasets and analyze them to identify spatial and temporal patterns for various biosurveillance-related tasks.ResultsWe demonstrate the utility of ORBiT in automatically extracting a small number of spatial and temporal patterns during the 2009-2010 pandemic H1N1 flu season using claims data. These patterns provide quantitative insights into the dynamics of how the pandemic flu spread across different parts of the country. We discovered that the claims data exhibits multi-scale patterns from which we could identify a small number of states in the United States (US) that act as "bridge regions" contributing to one or more specific influenza spread patterns. Similar to previous studies, the patterns show that the south-eastern regions of the US were widely affected by the H1N1 flu pandemic. Several of these south-eastern states act as bridge regions, which connect the north-east and central US in terms of flu occurrences.ConclusionsThese quantitative insights show how the claims data combined with novel analytical techniques can provide important information to decision makers when an epidemic spreads throughout the country. Taken together ORBiT provides a scalable and extensible platform for public health surveillance.

The Association of H1N1 Pandemic Influenza with Congenital Anomaly Prevalence in Europe: An Ecological Time Series Study.

In the context of the European Surveillance of Congenital Anomalies (EUROCAT) surveillance response to the 2009 influenza pandemic, we sought to establish whether there was a detectable increase of congenital anomaly prevalence among pregnancies exposed to influenza seasons in general, and whether any increase was greater during the 2009 pandemic than during other seasons. We performed an ecologic time series analysis based on 26,967 pregnancies with nonchromosomal congenital anomaly conceived from January 2007 to March 2011, reported by 15 EUROCAT registries. Analysis was performed for EUROCAT-defined anomaly subgroups, divided by whether there was a prior hypothesis of association with influenza. Influenza season exposure was based on World Health Organization data. Prevalence rate ratios were calculated comparing pregnancies exposed to influenza season during the congenital anomaly-specific critical period for embryo-fetal development to nonexposed pregnancies. There was no evidence for an increased overall prevalence of congenital anomalies among pregnancies exposed to influenza season. We detected an increased prevalence of ventricular septal defect and tricuspid atresia and stenosis during pandemic influenza season 2009, but not during 2007-2011 influenza seasons. For congenital anomalies, where there was no prior hypothesis, the prevalence of tetralogy of Fallot was strongly reduced during influenza seasons. Our data do not suggest an overall association of pandemic or seasonal influenza with congenital anomaly prevalence. One interpretation is that apparent influenza effects found in previous individual-based studies were confounded by or interacting with other risk factors. The associations of heart anomalies with pandemic influenza could be strain specific.

Pregnancy-Related Mortality Resulting From Influenza in the United States During the 2009-2010 Pandemic.

To estimate the burden of pregnancy-related mortality resulting from influenza A (H1N1)pdm09 virus infection during the 2009-2010 pandemic influenza season. Data from the Centers for Disease Control and Prevention's Pregnancy Mortality Surveillance System were used to identify women whose death during or shortly after pregnancy was attributed or likely attributed to the influenza A (H1N1)pdm09 virus from April 15, 2009, through June 30, 2010. We report the characteristics of these women and enumerate cases resulting in death as the pandemic began, peaked, and resolved. During the pandemic season, we identified 915 pregnancy-related deaths and 4,911,297 live births. Seventy-five (8.2%) women died as a result of confirmed influenza A (H1N1)pdm09 infection deaths and 34 (3.7%) women as a result of possible influenza A (H1N1)pdm09 infection deaths. The pregnancy-related mortality ratio for confirmed and possible (combined) influenza A (H1N1)pdm09 infection deaths was 2.2 per 100,000 live births. Most deaths occurred during the 2009 calendar year with the peak of the distribution of deaths over time occurring in October 2009. Twelve percent of pregnancy-related deaths were attributed to confirmed or possible influenza A (H1N1)pdm09 infection during the 2009-2010 pandemic season. Because prediction of pandemics is difficult, planning for prevention of influenza and care for those women affected are critical for preventing associated severe maternal morbidity and mortality. III.

Incidence of medically attended influenza during pandemic and post-pandemic seasons through the Influenza Incidence Surveillance Project, 2009–13

Since the introduction of pandemic influenza A (H1N1) to the USA in 2009, the Influenza Incidence Surveillance Project has monitored the burden of influenza in the outpatient setting through population-based surveillance. From Oct 1, 2009, to July 31, 2013, outpatient clinics representing 13 health jurisdictions in the USA reported counts of influenza-like illness (fever including cough or sore throat) and all patient visits by age. During four years, staff at 104 unique clinics (range 35-64 per year) with a combined median population of 368,559 (IQR 352,595-428,286) attended 35,663 patients with influenza-like illness and collected 13,925 respiratory specimens. Clinical data and a respiratory specimen for influenza testing by RT-PCR were collected from the first ten patients presenting with influenza-like illness each week. We calculated the incidence of visits for influenza-like illness using the size of the patient population, and the incidence attributable to influenza was extrapolated from the proportion of patients with positive tests each week. The site-median peak percentage of specimens positive for influenza ranged from 58.3% to 77.8%. Children aged 2 to 17 years had the highest incidence of influenza-associated visits (range 4.2-28.0 per 1000 people by year), and adults older than 65 years had the lowest (range 0.5-3.5 per 1000 population). Influenza A H3N2, pandemic H1N1, and influenza B equally co-circulated in the first post-pandemic season, whereas H3N2 predominated for the next two seasons. Of patients for whom data was available, influenza vaccination was reported in 3289 (28.7%) of 11,459 patients with influenza-like illness, and antivirals were prescribed to 1644 (13.8%) of 11,953 patients. Influenza incidence varied with age groups and by season after the pandemic of 2009 influenza A H1N1. High levels of influenza virus circulation, especially in young children, emphasise the need for additional efforts to increase the uptake of influenza vaccines and antivirals. US Centers for Disease Control and Prevention.