Model estimates of the burden of outpatient visits attributable to influenza in the United States.

BACKGROUND: Although many studies have modelled the national burdens of hospitalizations and deaths due to influenza, few studies have considered the outpatient burden. To fill this gap for the United States (US), we applied traditional statistical modelling approaches to time series derived from large medical claims databases held in the private sector. METHODS: We accessed ICD-9-coded office visit data extracted from Truven Health Analytics' MarketScan Commercial database covering about one third of the US population <65 years during 2001-2009, and Medicare Supplemental data covering about one fifth of US seniors 65+ during 2006-2009. We extracted weekly time series of visits due to respiratory diagnoses, otitis media (OM), and urinary tract infections (UTI), a "negative control". We used multiple linear regression modelling to estimate age-specific influenza-related excess in office visits. RESULTS: In the <65 year age group, in the 8 pre-pandemic seasons studied and for the broadest defined respiratory outcome, the model attributed an average of ~14.5 M (Standard deviation [SD] across seasons 3.9 million) office visits to influenza (rate of 5,581/100,000 population). Of these, ~80 % of visits occurred in the 5-17 and 18-49 age group. In school children aged 5-17 year olds and adult 18-64 year age groups the majority of visits were due to influenza B, while A/H3N2 explained most visits in children <5 year olds. The model further attributed ~2.2 M OM visits (SD across seasons 790,000) annually to influenza, of which 86 % of these occurred in children <18 years; this indicates that 6.4 % of all infants <2 years and 4.9 % of all toddlers aged 2-4 years in the US have an influenza-attributable outpatient visit with an OM diagnosis. In seniors 65 years and older, our model attributed ~0.7 M (SD across seasons 351,000) respiratory visits to influenza (rate of 1,887/100,000 population). The model identified no significant excess UTI (negative control) visits in most seasons. CONCLUSIONS: This is to our knowledge a first study of the outpatient burden of influenza in the US in a large database. The model estimated that 10 % of all children <18 years and 4 % of the entire population <65 years seek outpatient care for respiratory illness attributable to influenza annually. TRIAL REGISTRATION: ClinicalTrial.gov, NCT02019732 .

Respiratory syncytial virus surveillance in the United States, 2007-2012: results from a national surveillance system.

BACKGROUND: Annual respiratory syncytial virus (RSV) outbreaks throughout the US exhibit variable patterns in onset, peak month of activity and duration of season. RSVAlert, a US surveillance system, collects and characterizes RSV test data at national, regional, state and local levels. METHODS: RSV test data from 296 to 666 laboratories from 50 states, the District of Columbia and Puerto Rico (as of 2010) were collected during the 2007-2008 to 2011-2012 RSV seasons. Data were collected in early August/September to the following August/September each season. Participating laboratories provided the total number and types of RSV tests performed each week and test results. RSV season onset and offset were defined as the first and last, respectively, of 2 consecutive weeks during which the mean percentage of specimens testing positive for RSV was ≥10%. RESULTS: Nationally, the RSV season onset occurred in October/November of each year with offset occurring in March/April of the following year. The RSV season averaged 20 weeks and typically occurred earliest in the South and latest in the West. The onset, offset and duration varied considerably within the U.S. Department of Health and Human Services regions. RSV activity in Puerto Rico was elevated throughout the 2-year period studied. Median onset in core-based statistical areas ranged from 2 weeks earlier to 5 weeks later than those in their corresponding states. CONCLUSIONS: Substantial variability existed in the timing of RSV activity at all geographic strata analyzed. RSV actively circulated (ie, ≥10%) in many areas outside the traditionally defined RSV epidemic period of November to March.

Laboratory testing trends for respiratory syncytial virus, 2007-2011.

BACKGROUND: Antigen detection tests have been the most common diagnostic assay used to detect and diagnose respiratory syncytial virus (RSV). The utility and increased sensitivity of polymerase chain reaction (PCR) tests have been reported; however, their use in US hospital laboratories is not well characterized. OBJECTIVE: To describe changes in RSV test types used by US hospital-affiliated laboratories, focusing on PCR testing prevalence. STUDY DESIGN: Data were collected from 480 to 666 laboratories each RSV season (2007-2008 through 2010-2011) across 50 states, the District of Columbia, and Puerto Rico. A descriptive analysis was conducted using this convenience sample of RSV tests conducted from November to April each season. Total numbers and types of RSV tests performed were reported weekly and weekly proportions by test type were calculated. Kendall τ rank correlation was used to quantify associations between time and proportions of each test type. RESULTS: PCR tests accounted for 2%, 3%, 16%, and 21% of weekly tests (total range, 381,068-481,654 over 4 seasons) conducted each season from 2007 to 2011, respectively. The proportion of laboratories reporting ≥1 PCR tests was 4%, 5%, 10%, and 16%, respectively. Decreases in antigen testing and viral culture were similarly observed. CONCLUSIONS: Although antigen detection was the predominant test type reported in the sample of US hospital laboratories for RSV testing, PCR use increased to >20% of tests reported. These results demonstrate the increasing contribution of PCR to RSV surveillance. RSV surveillance systems relying solely on antigen detection results will not capture an increasing proportion of RSV test results.

Insurance coverage of emergency care for young adults under health reform.

BACKGROUND: The Affordable Care Act (ACA) established nationwide eligibility for young adults 19 to 25 years of age to retain coverage under their parents' private health plans. We conducted a study to determine how the implementation of this provision changed rates of insurance coverage for young adults seeking medical care for major emergencies. METHODS: We evaluated more than 480,000 nondiscretionary visits made to emergency departments from 2009 through 2011, as recorded in a large, geographically diverse data set of hospital claims, to estimate how the ACA provision affected private insurance coverage of such visits by young adults (19 to 25 years of age). To adjust for underlying trends in insurance coverage, we compared changes in the target age group with changes among adults 26 to 31 years of age, who were unaffected by the provision (control group). RESULTS: After the ACA provision took effect, private coverage of nondiscretionary visits to emergency departments by young adults increased by 3.1 percentage points (95% confidence interval [CI], 2.3 to 3.9; relative increase, 5.2%; P<0.001), as compared with similar visits in the control group. The percentage of visits by uninsured young adults also fell significantly (-1.7 percentage points; 95% CI, -2.8 to -0.7; relative decrease, 9.1%; P<0.001). The rates of nondiscretionary visits that were covered by Medicaid or other nonprivate insurers remained relatively steady throughout the study period. The coverage expansion led to an estimated 22,072 visits to emergency departments by newly insured young adults and $147 million in associated costs that were covered by private insurance plans during a 1-year period. CONCLUSIONS: Enactment of the dependent-coverage provision was associated with a significant increase in the proportion of young adults who were protected from the financial consequences of a serious medical emergency. (Funded by the Office of the Assistant Secretary for Planning and Evaluation, Department of Health and Human Services.).

Impact of the 2009/2010 influenza A (H1N1) pandemic on trends in influenza hospitalization, diagnostic testing, and treatment.

Analysis of a US hospitalization database demonstrated that more influenza patients were hospitalized and the age distribution of hospitalizations was younger during the 2009 (H1N1) influenza A pandemic compared with the three previous influenza seasons. The duration of hospital stay remained stable in all four seasons. A higher proportion of patients was treated with antivirals (P < 0·0001), comprised almost entirely of neuraminidase inhibitors, and the proportion was highest in those with influenza confirmed by diagnostic testing (P < 0·0001). Approximately one-third remained untreated. Young children had the lowest rate of neuraminidase-inhibitor treatment during the 2009 pandemic (P < 0·05).

Trends in U.S. pediatric influenza vaccination from 2006 to 2010 among children with private insurance.

In the United States, recommendations for the annual influenza vaccination of children have expanded significantly in recent years. Additionally, to facilitate influenza vaccination delivery by providers, recent recommendations have encouraged vaccination as soon as vaccine is available and throughout the influenza season. However, until now, there have been limited data published describing pediatric providers' responses to these recent recommendations. De-identified, patient-level data from an electronic health care reimbursement claims database that contains more than 60% of all medical claims from outpatient settings in the US were analyzed. Only claims from privately insured children were available; administration of federally purchased vaccine (i.e., via the Vaccines for Children program) and vaccinations administered in settings where claims data are not generated were not captured. Weekly counts of influenza vaccinations administered to children 6 months through 18 years of age between August 1 and March 31 for the 2006-2007 through 2009-2010 seasons were projected to yield national estimates. Seasonal vaccination peaked in November for the 2006-2007 and 2007-2008 seasons, October for the 2008-2009 season, and September for the 2009-2010 season. The proportion of vaccinations administered before November 1 increased each season from 2006-2007 through 2009-2010. In all seasons, vaccination dramatically declined in December and continued at a steadily declining rate through the end of the season. Vaccine delivery to children 6-23 months of age was more dispersed over the vaccination season relative to older age groups. Among children 6-23 months and 2-18 years of age, use of preservative-free inactivated vaccine and live attenuated vaccine, respectively, increased significantly over the study period. While pediatric influenza vaccination occurred earlier each year, vaccination in later months has not increased in recent seasons, despite efforts to extend the vaccination season.

Phylogeography of the spring and fall waves of the H1N1/09 pandemic influenza virus in the United States.

Spatial variation in the epidemiological patterns of successive waves of pandemic influenza virus in humans has been documented throughout the 20th century but never understood at a molecular level. However, the unprecedented intensity of sampling and whole-genome sequencing of the H1N1/09 pandemic virus now makes such an approach possible. To determine whether the spring and fall waves of the H1N1/09 influenza pandemic were associated with different epidemiological patterns, we undertook a large-scale phylogeographic analysis of viruses sampled from three localities in the United States. Analysis of genomic and epidemiological data reveals distinct spatial heterogeneities associated with the first pandemic wave, March to July 2009, in Houston, TX, Milwaukee, WI, and New York State. In Houston, no specific H1N1/09 viral lineage dominated during the spring of 2009, a period when little epidemiological activity was observed in Texas. In contrast, major pandemic outbreaks occurred at this time in Milwaukee and New York State, each dominated by a different viral lineage and resulting from strong founder effects. During the second pandemic wave, beginning in August 2009, all three U.S. localities were dominated by a single viral lineage, that which had been dominant in New York during wave 1. Hence, during this second phase of the pandemic, extensive viral migration and mixing diffused the spatially defined population structure that had characterized wave 1, amplifying the one viral lineage that had dominated early on in one of the world's largest international travel centers.

Reduction in gastroenteritis in United States children and correlation with early rotavirus vaccine uptake from national medical claims databases.

BACKGROUND: We sought to estimate rotavirus disease reduction among children in hospital and office settings in the 4 US regions following rotavirus vaccine introduction and to estimate vaccine uptake. METHODS: Two national third-party payer medical claims databases were used to examine the number of visits for gastroenteritis per annual nongastroenteritis visits among children aged <5 years during July 2003 to June 2008 in hospital and office settings. The gastroenteritis burden attributable to rotavirus was computed as the excess of all gastroenteritis visits during rotavirus seasons above the baseline of visits during nonrotavirus periods. Rotavirus vaccine uptake was estimated by comparing claims for rotavirus vaccine with those for diphtheria-tetanus-acellular pertussis vaccines. RESULTS: In the South, Northeast, and Midwest, the typical winter-spring gastroenteritis peak due to rotavirus was markedly dampened in 2007-2008. Compared with the mean for 3 prevaccine seasons, the excess gastroenteritis visits that occurred during the 2007-2008 rotavirus season was reduced by >90% among infants in all care settings in 3 regions and by >70% among children aged 1 to 4 years. In the West, disease reductions were lower (53%-63% reduction among hospitalized infants). At the onset of the 2007-2008 season, coverage with > or =1 rotavirus vaccine dose was an estimated 57% among infants, 17% among children aged 1 year, and 0 among those aged 2 to 4 years. CONCLUSIONS: The rotavirus burden in 2007-2008 was markedly reduced in all US regions and exceeded that explained by only direct protection of the youngest vaccinated children.

Assessing the burden of paediatric influenza in Europe: the European Paediatric Influenza Analysis (EPIA) project.

The European Paediatric Influenza Analysis (EPIA) project is a multi-country project that was created to collect, analyse and present data regarding the paediatric influenza burden in European countries, with the purpose of providing the necessary information to make evidence-based decisions regarding influenza immunisation recommendations for children. The initial approach taken is based on existing weekly virological and age-specific influenza-like illness (ILI) data from surveillance networks across Europe. We use a multiple regression model guided by longitudinal weekly patterns of influenza virus to attribute the weekly ILI consultation incidence pattern to each influenza (sub)type, while controlling for the effect of respiratory syncytial virus (RSV) epidemics. Modelling the ILI consultation incidence during 2002/2003-2008 revealed that influenza infections that presented for medical attention as ILI affected between 0.3% and 9.8% of children aged 0-4 and 5-14 years in England, Italy, the Netherlands and Spain in an average season. With the exception of Spain, these rates were always higher in children aged 0-4 years. Across the six seasons analysed (five seasons were analysed from the Italian data), the model attributed 47-83% of the ILI burden in primary care to influenza virus infection in the various countries, with the A(H3N2) virus playing the most important role, followed by influenza viruses B and A(H1N1). National season averages from the four countries studied indicated that between 0.4% and 18% of children consulted a physician for ILI, with the percentage depending on the country and health care system. Influenza virus infections explained the majority of paediatric ILI consultations in all countries. The next step will be to apply the EPIA modelling approach to severe outcomes indicators (i.e. hospitalisations and mortality data) to generate a complete range of mild and severe influenza burden estimates needed for decision making concerning paediatric influenza vaccination.

A novel active respiratory syncytial virus surveillance system in the United States: variability in the local and regional incidence of infection.

BACKGROUND: To characterize the onset, peak, and duration of the RSV season in major metropolitan areas in the United States as determined from laboratory test data collected by a novel RSV surveillance program (RSV Alert), including regional and national trends. METHODS: We prospectively analyzed results of more than 600,000 tests collected weekly during 3 seasons (2004/2005-2006/2007) by the RSV Alert program. More than 200 institutions participated in the first 2 seasons of the program, and more than 600 sites in the third. Data were analyzed for trends in season onset, offset, and duration at the local, regional, and national levels. RESULTS: Considerable variability in season onset and duration was noted between metropolitan areas located geographically within the same region. Seasonal outbreaks of RSV consistently peaked first, concluded earliest, and were of longest duration in the Southern region. The onset of the RSV season occurred latest and peaked last in the Midwest region each season. CONCLUSIONS: The variable nature of outbreaks observed between metropolitan areas located geographically within the same regions of the country is highlighted through data collected for 3 consecutive seasons. The RSV Alert program is a valuable reporting system that provides real-time surveillance data at a city/local level nationwide and has potential to aid clinicians in decisions regarding RSV management.

Molecular epidemiology of A/H3N2 and A/H1N1 influenza virus during a single epidemic season in the United States.

To determine the spatial and temporal dynamics of influenza A virus during a single epidemic, we examined whole-genome sequences of 284 A/H1N1 and 69 A/H3N2 viruses collected across the continental United States during the 2006-2007 influenza season, representing the largest study of its kind undertaken to date. A phylogenetic analysis revealed that multiple clades of both A/H1N1 and A/H3N2 entered and co-circulated in the United States during this season, even in localities that are distant from major metropolitan areas, and with no clear pattern of spatial spread. In addition, co-circulating clades of the same subtype exchanged genome segments through reassortment, producing both a minor clade of A/H3N2 viruses that appears to have re-acquired sensitivity to the adamantane class of antiviral drugs, as well as a likely antigenically distinct A/H1N1 clade that became globally dominant following this season. Overall, the co-circulation of multiple viral clades during the 2006-2007 epidemic season revealed patterns of spatial spread that are far more complex than observed previously, and suggests a major role for both migration and reassortment in shaping the epidemiological dynamics of human influenza A virus.