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The BNT162b2 (Pfizer-BioNTech) mRNA COVID-19 vaccine has demonstrated high efficacy in preventing infection with SARS-CoV-2 (the virus that causes COVID-19) in randomized placebo-controlled Phase III trials in persons aged 12-17 years (referred to as adolescents in this report) (1); however, data on real-word vaccine effectiveness (VE) among adolescents are limited (1-3). As of December 2021, the Pfizer-BioNTech vaccine is approved by the Food and Drug Administration (FDA) for adolescents aged 16-17 years and under FDA emergency use authorization for those aged 12-15 years. In a prospective cohort in Arizona, 243 adolescents aged 12-17 years were tested for SARS-CoV-2 by reverse transcription-polymerase chain reaction (RT-PCR) each week, irrespective of symptoms, and upon onset of COVID-19-like illness during July 25-December 4, 2021; the SARS-CoV-2 B.1.617.2 (Delta) variant was the predominant strain during this study period. During the study, 190 adolescents contributed fully vaccinated person-time (≥14 days after receiving 2 doses of Pfizer-BioNTech vaccine), 30 contributed partially vaccinated person-time (receipt of 1 dose or receipt of 2 doses but with the second dose completed14 days earlier), and 66 contributed unvaccinated person-time. Using the Cox proportional-hazards model, the estimated VE of full Pfizer-BioNTech vaccination for preventing SARS-CoV-2 infection was 92% (95% CI = 79%-97%), adjusted for sociodemographic characteristics, health information, frequency of social contact, mask use, location, and local virus circulation. These findings from a real-world setting indicate that 2 doses of Pfizer-BioNTech vaccine are highly effective in preventing SARS-CoV-2 infection among Arizona adolescents. CDC recommends COVID-19 vaccination for all eligible persons in the United States, including persons aged 12-17 years.

Background. We sought to evaluate the impact of changes in estimates of COVID-19 vaccine effectiveness on the incidence of laboratory-confirmed infection among frontline workers at high risk for SARS-CoV-2. Methods. We analyzed data from a prospective frontline worker cohort to estimate the incidence of COVID-19 by month as well as the association of COVID-19 vaccination, occupation, demographics, physical distancing and mask use with infection risk. Participants completed baseline and quarterly surveys, and each week self-collected mid-turbinate nasal swabs and reported symptoms. Results. Among 1,018 unvaccinated and 3,531 fully vaccinated workers, the monthly incidence of laboratory-confirmed SARS-CoV-2 infection in January 2021 was 13.9 (95% confidence interval [CI]: 10.4-17.4), declining to 0.5 (95% CI -0.4-1.4) per 1000 person-weeks in June. By September 2021, when the Delta variant predominated, incidence had once again risen to 13.6 (95% CI 7.8-19.4) per 1000 person-weeks. In contrast, there was no reportable incidence among fully vaccinated participants at the end of January 2021, and incidence remained low until September 2021 when it rose modestly to 4.1 (95% CI 1.9-3.8) per 1000. Below average facemask use was associated with a higher risk of infection for unvaccinated participants during exposure to persons who may have COVID-19, and vaccinated participants during hours in the community. Conclusions. COVID-19 vaccination was significantly associated with a lower risk of SARS-CoV-2 infection despite Delta variant predominance. Our data demonstrate the added protective benefit of facemask use among both unvaccinated and vaccinated frontline workers.

Background Workers critical to emergency response and continuity of essential services during the COVID-19 pandemic are at a disproportionally high risk of SARS-CoV-2 infection. Prospective cohort studies are needed for enhancing the understanding of the incidence of symptomatic and asymptomatic SARS-CoV-2 infections, identifying risk factors, assessing clinical outcomes, and determining the effectiveness of vaccination. Objective The Research on the Epidemiology of SARS-CoV-2 in Essential Response Personnel (RECOVER) prospective cohort study was designed to estimate the incidence of symptomatic and asymptomatic SARS-CoV-2 infections, examine the risk factors for infection and clinical spectrum of illness, and assess the effectiveness of vaccination among essential workers. Methods The RECOVER multisite network was initiated in August 2020 and aims to enroll 3000 health care personnel (HCP), first responders, and other essential and frontline workers (EFWs) at 6 US locations. Data on participant demographics, medical history, and vaccination history are collected at baseline and throughout the study. Active surveillance for the symptoms of COVID-19–like illness (CLI), access of medical care, and symptom duration is performed by text messages, emails, and direct participant or medical record reports. Participants self-collect a mid-turbinate nasal swab weekly, regardless of symptoms, and 2 additional respiratory specimens at the onset of CLI. Blood is collected upon enrollment, every 3 months, approximately 28 days after a reverse transcription polymerase chain reaction (RT-PCR)–confirmed SARS-CoV-2 infection, and 14 to 28 days after a dose of any COVID-19 vaccine. From February 2021, household members of RT-PCR–confirmed participants are self-collecting mid-turbinate nasal swabs daily for 10 days. Results The study observation period began in August 2020 and is expected to continue through spring 2022. There are 2623 actively enrolled RECOVER participants, including 280 participants who have been found to be positive for SARS-CoV-2 by RT-PCR. Enrollment is ongoing at 3 of the 6 study sites. Conclusions Data collected through the cohort are expected to provide important public health information for essential workers at high risk for occupational exposure to SARS-CoV-2 and allow early evaluation of COVID-19 vaccine effectiveness. International Registered Report Identifier (IRRID) DERR1-10.2196/31574

BackgroundData on the development of neutralizing antibodies against SARS-CoV-2 after SARS-CoV-2 infection and after vaccination with messenger RNA (mRNA) COVID-19 vaccines are limited.MethodsFrom a prospective cohort of 3,975 adult essential and frontline workers tested weekly from August, 2020 to March, 2021 for SARS-CoV-2 infection by Reverse Transcription- Polymerase Chain Reaction (RT-PCR) assay irrespective of symptoms, 497 participants had sera drawn after infection (170), vaccination (327), and after both infection and vaccination (50 from the infection population). Serum was collected after infection and each vaccine dose. Serum- neutralizing antibody titers against USA-WA1/2020-spike pseudotype virus were determined by the 50% inhibitory dilution. Geometric mean titers (GMTs) and corresponding fold increases were calculated using t-tests and linear mixed effects models.ResultsAmong 170 unvaccinated participants with SARS-CoV-2 infection, 158 (93%) developed neutralizing antibodies (nAb) with a GMT of 1,003 (95% CI=766-1,315). Among 139 previously uninfected participants, 138 (99%) developed nAb after mRNA vaccine dose-2 with a GMT of 3,257 (95% CI = 2,596-4,052). GMT was higher among those receiving mRNA-1273 vaccine (GMT =4,698, 95%CI= 3,186-6,926) compared to BNT162b2 vaccine (GMT=2,309, 95%CI=1,825-2,919). Among 32 participants with prior SARS-CoV-2 infection, GMT was 21,655 (95%CI=14,766-31,756) after mRNA vaccine dose-1, without further increase after dose- 2.ConclusionsA single dose of mRNA vaccine after SARS-CoV-2 infection resulted in the highest observed nAb response. Two doses of mRNA vaccine in previously uninfected participants resulted in higher nAb to SARS-CoV-2 than after one dose of vaccine or SARS- CoV-2 infection alone. Neutralizing antibody response also differed by mRNA vaccine product.Main Point SummaryOne dose of mRNA COVID-19 vaccine after previous SARS-CoV-2 infection produced the highest neutralizing antibody titers; among those without history of infection, two doses of mRNA vaccine produced the most robust response.

Background Influenza viruses pose significant disease burdens through seasonal outbreaks and unpredictable pandemics. Existing surveillance programs rely heavily on reporting of medically attended influenza (MAI). Continuously monitoring cause-specific school absenteeism may identify local acceleration of seasonal influenza activity. The Oregon Child Absenteeism Due to Respiratory Disease Study (ORCHARDS; Oregon, WI) implements daily school-based monitoring of influenza-like illness-specific student absenteeism (a-ILI) in kindergarten through Grade 12 schools and assesses this approach for early detection of accelerated influenza and other respiratory pathogen transmission in schools and surrounding communities. Methods Starting in September 2014, ORCHARDS combines automated reporting of daily absenteeism within six schools and home visits to school children with acute respiratory infection (ARI). Demographic, epidemiological, and symptom data are collected along with respiratory specimens. Specimens are tested for influenza and other respiratory viruses. Household members can opt into a supplementary household transmission study. Community comparisons are possible using a pre-existing and highly effective influenza surveillance program, based on MAI at five family medicine clinics in the same geographical area. Results Over the first 5 years, a-ILI occurred on 6634 (0.20%) of 3,260,461 student school days. Viral pathogens were detected in 64.5% of 1728 children with ARI who received a home visit. Influenza was the most commonly detected virus, noted in 23.3% of ill students. Conclusion ORCHARDS uses a community-based design to detect influenza trends over multiple seasons and to evaluate the utility of absenteeism for early detection of accelerated influenza and other respiratory pathogen transmission in schools and surrounding communities.

BACKGROUNDInformation is limited on messenger RNA (mRNA) BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) COVID-19 vaccine effectiveness (VE) in preventing SARS-CoV-2 infection or attenuating disease when administered in real-world conditions.METHODSProspective cohorts of 3,975 healthcare personnel, first responders, and other essential and frontline workers completed weekly SARS-CoV-2 testing during December 14 2020—April 10 2021. Self-collected mid-turbinate nasal swabs were tested by qualitative and quantitative reverse-transcription–polymerase-chain-reaction (RT-PCR). VE was calculated as 100%×(1−hazard ratio); adjusted VE was calculated using vaccination propensity weights and adjustments for site, occupation, and local virus circulation.RESULTSSARS-CoV-2 was detected in 204 (5.1%) participants; 16 were partially (≥14 days post-dose-1 to 13 days after dose-2) or fully (≥14 days post-dose-2) vaccinated, and 156 were unvaccinated; 32 with indeterminate status (CONCLUSIONSAuthorized mRNA vaccines were highly effective among working-age adults in preventing SARS-CoV-2 infections when administered in real-world conditions and attenuated viral RNA load, febrile symptoms, and illness duration among those with breakthrough infection despite vaccination.

Background Population-based estimates of influenza-associated outpatient visits including both pandemic and inter-pandemic seasons are uncommon. Comparisons of such estimates with laboratory-confirmed rates of outpatient influenza are rare. Objective To estimate influenza-associated outpatient visits in six US integrated health care delivery organizations enrolling ~7.7 million persons. Methods Using 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 two contemporaneous studies recording RT-PCR-confirmed influenza outpatient visits. Results Outpatient 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 inter-pandemic 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 one comparison study. In another, rates estimated with pneumonia visits during the pandemic for children and adults were consistent in timing, peak, and magnitude. Conclusions Estimated 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. This article is protected by copyright. All rights reserved.

Background Early influenza antiviral treatment within 2 days of illness onset can reduce illness severity and duration. Reliance on low sensitivity rapid influenza diagnostic tests (RIDTs) to guide antiviral prescribing has been reported. We describe antiviral prescribing practices among primary care providers from a large surveillance network in the United States. Methods From 2009–2016, a network of 36 to 68 outpatient clinics per year collected respiratory specimens and clinical data for patients with influenza-like illness (ILI). Specimens were tested for influenza using polymerase chain reaction (PCR). We used multivariable logistic regression to assess factors influencing antiviral prescribing. Results Among 13 540 patients with ILI, 2766 (20%) were prescribed antivirals. In age groups recommended to receive empiric antiviral treatment for suspected influenza, 11% of children Conclusion Primary care providers were more likely to prescribe antivirals to patients with a positive RIDT, but antivirals were prescribed infrequently even to patients in high-risk age groups. Understanding patient and provider characteristics associated with antiviral prescribing is important for communicating treatment recommendations.

Supplemental Digital Content is available in the text., Background: Parainfluenza viruses (PIV) have been shown to contribute substantially to pediatric hospitalizations in the United States. However, to date, there has been no systematic surveillance to estimate the burden among pediatric outpatients. Methods: From August 2010 through July 2014, outpatient health care providers with enumerated patient populations in 13 states and jurisdictions participating in the Influenza Incidence Surveillance Project conducted surveillance of patients with influenza-like illness (ILI). Respiratory specimens were collected from the first 10 ILI patients each week with demographic and clinical data. Specimens were tested for multiple respiratory viruses, including PIV1–4, using reverse transcriptase–polymerase chain reaction assays. Cumulative incidence was calculated using provider patient population size as the denominator. Results: PIVs 1–3 were detected in 8.0% of 7716 ILI-related outpatient specimens: 30% were PIV1, 26% PIV2 and 44% PIV3. PIV circulation varied noticeably by year and type, with PIV3 predominating in 2010–2011 (incidence 110 per 100,000 children), PIV1 in 2011–2012 (89 per 100,000), dual predominance of PIV2 and PIV3 (88 and 131 per 100,000) in 2012–2013 and PIV3 (100 per 100,000) in 2013–2014. The highest incidence of PIV detections was among patients aged

Background The long-term antibody response to measles vaccine (MV) administered at age 6 months with or without subsequent doses is not well documented. Methods Measles serum antibody responses were evaluated after a supplemental dose of measles vaccine (sMV) administered at a median age of 20 months among Malawian children who had previously received 2 doses of measles vaccine (MV) at ages 6 and 9 months (HIV-infected and random sample of HIV-uninfected) or 1 dose at age 9 months (random sample of HIV-uninfected). We compared measles antibody seropositivity between groups by enzyme linked immunoassay and seroprotection by plaque reduction neutralization geometric mean concentrations. Results Of 1756 children enrolled, 887 (50.5%) received a sMV dose following MV at 9 months of age and had specimens available after sMV receipt, including 401 HIV-uninfected children who received one MV dose at 9 months, 464 HIV-uninfected and 22 HIV-infected children who received two doses of MV at ages 6 and 9 months. Among HIV-uninfected children, protective levels of antibody were found post sMV in 90–99% through ages 24–36 months and were not affected by MV schedule. Geometric mean concentration levels of measles antibody were significantly increased post-sMV among those HIV-uninfected children previously non-responsive to vaccination. Among HIV-infected children, the proportion seroprotected increased initially but by 9 months post-sMV was no higher than pre-sMV. Conclusions Our findings support early 2-dose MV to provide measles immunity for young infants without risk of interference with antibody responses to subsequent MV doses administered as part of SIAs.

BACKGROUND: Researchers in observational studies of vaccine effectiveness (VE) in which they compared quadrivalent live attenuated vaccine (LAIV4) and inactivated influenza vaccine (IIV) among children and adolescents have shown inconsistent results, and the studies have been limited by small samples. METHODS: We combined data from 5 US studies from 2013–2014 through 2015–2016 to compare the VE of LAIV4 and IIV against medically attended, laboratory-confirmed influenza among patients aged 2 to 17 years by influenza season, subtype, age group, and prior vaccination status. The VE of IIV or LAIV4 was calculated as 100% × (1 − odds ratio), comparing the odds of vaccination among patients who were influenza-positive to patients who were influenza-negative from adjusted logistic regression models. Relative effectiveness was defined as the odds of influenza comparingLAIV4 and IIV recipients. RESULTS: Of 17 173 patients aged 2 to 17 years, 4579 received IIV, 1979 received LAIV4, and 10 615 were unvaccinated. Against influenza A/H1N1pdm09, VE was 67% (95% confidence interval [CI]: 62% to 72%) for IIV and 20% (95% CI: −6% to 39%) for LAIV4. Results were similar when stratified by vaccination in the previous season. LAIV4 recipients had significantly higher odds of influenza A/H1N1pdm09 compared with IIV recipients (odds ratio 2.66; 95% CI: 2.06 to 3.44). LAIV4 and IIV had similar effectiveness against influenza A/H3N2 and B. Our overall findings were consistent when stratified by influenza season and age group. CONCLUSIONS: From this pooled individual patient–level data analysis, we found reduced effectiveness of LAIV4 against influenza A/H1N1pdm09 compared with IIV, which is consistent with published results from the individual studies included.

Objective The Oregon Child Absenteeism due to Respiratory Disease Study (ORCHARDS) was implemented to assess the relationships between cause-specific absenteeism within a school district and medically attended influenza visits within the same community. Introduction Transmission and amplification of influenza within schools has been purported as a driving mechanism for subsequent outbreaks in surrounding communities. However, the number of studies assessing the utility of monitoring school absenteeism as an indicator of influenza in the community is limited. ORCHARDS was initiated to evaluate the relationships between all-cause (a-Tot), illness-related (a-I), and influenza-like illness (ILI)-related absenteeism (a-ILI) within a school district and medically attended influenza A or B visits within the same community. Methods ORCHARDS was based at the Oregon School District (OSD), which enrolls 3,640 students at six schools in south-central Wisconsin. Parents reported influenza-like symptoms on an existing phone-based absenteeism reporting system. Attendance staff identified ILI using a simple case definition. Absenteeism was logged into the OSD’s existing electronic information system (Infinite Campus), and an automated process extracted counts of a-Tot, a-I, and a-ILI each school day from 9/02/14 through 6/08/17. Parents of students with acute respiratory infections (ARI) were invited to contact study staff who assessed the students’ eligibility for the study based on presence of ILI symptoms. From 1/05/15 through 6/08/17, data and nasal swabs were collected from eligible OSD students whose parents volunteered to have a study home visit within 7 days of ILI onset. Specimens were tested for influenza A and B at the Wisconsin State Laboratory of Hygiene using the CDC Human Influenza Virus Real-time RT-PCR Diagnostic Panel. For community influenza, we used data from the Wisconsin Influenza Incidence Surveillance Project (WIISP) that monitors medically attended influenza using RT-PCR at five primary care clinics surrounding the OSD. Data analysis: Over-dispersed Poisson generalized additive log-linear regression models were fit to the daily number of medically attended influenza cases and daily absenteeism counts from three sources (a-Tot, a-I, and a-ILI) with year and season (calendar day within year) as smooth functions (thin plate regression splines). Two subgroups of a-ILI representing kindergarten through 4th grade (K-4) and 5th-12th grade (5-12) were also evaluated. Results During the study period, 168,859 total absentee days (8.57% of student days), 36,104 illness days (1.83%), and 4,232 ILI days (0.21%) were recorded. Home visits were completed on 700 children [mean age = 10.0 ± 3.5 (sd) years]. Influenza RT-PCR results were available for 695 (99.3%) children: influenza A was identified in 54 (13.3%) and influenza B in 51 (12.6%) specimens. There were one large and early outbreak of influenza A (H3N2) followed by B in 2014/15, an extremely late combined outbreak of influenza A (H1N1) and B in 2015/16, and a combined outbreak of influenza A/(H3N2) and B in 2016/17. PCR detection of influenza A or B, as compared to no influenza, was strongly associated with a child with a-ILI-positive status (OR=4.74; 95% CI: 2.78-8.18; P

BACKGROUND: Existing literature suggests that influenza C typically causes mild respiratory tract disease. However, clinical and epidemiological data are limited. METHODS: Four outpatient clinics and three hospitals submitted clinical data and respiratory specimens through a surveillance network for acute respiratory infection (ARI) during May 2013 through December 2016. Specimens were tested using multi-target nucleic acid amplification tests (NAAT) for 19–22 respiratory pathogens, including influenza C. RESULTS: Influenza C virus was detected among 59 of 10,202 (0.58%) hospitalized SARI cases and 11 of 2,282 (0.48%) outpatients. Most detections occurred from December to March, with 73% during the 2014–2015 season. Influenza C detections occurred among patients of all ages, with similar rates between inpatients and outpatients. The highest rate of detection occurred among children aged 6 to 24 months (1.2%). Among hospitalized cases, seven required intensive care. Medical co-morbidities were reported in 58% of hospitalized cases and all who required intensive care. At least one other respiratory pathogen was detected in 40 (66%) cases, most commonly rhinovirus/enterovirus (25%) and respiratory syncytial virus (RSV) (20%). The hemagglutinin-esterase-fusion (HEF) gene was sequenced in 37 specimens, and both C/Kanagawa and C/Sao Paulo lineages were detected in inpatients and outpatients. CONCLUSIONS: We found seasonal circulation of influenza C with year-to-year variability. Detection was most frequent among young children, but occurred in all ages. Some cases positive for influenza C, particularly those with co-morbid conditions, had severe disease, suggesting a need for further study of the role of influenza C virus in the pathogenesis of respiratory disease.

Background Surveillance of influenza-like illness (ILI) in the United States is primarily conducted through medical settings despite a significant burden of non-medically attended ILI. Objectives To assess consistency between surveillance for respiratory viruses in outpatient and community settings using ILI surveillance from the Centers for Disease Control and Prevention Influenza Incidence Surveillance Project (IISP) and the Mobile Surveillance for Acute Respiratory Infections (ARI) and Influenza-Like Illness in the Community (MoSAIC) Study. Methods The Influenza Incidence Surveillance Project conducts ILI surveillance in 3 primary care clinics in New York City, and MoSAIC conducts community-based ILI/ARI surveillance through text messaging among a cohort of New York City residents. Both systems obtain respiratory specimens from participants with ILI/ARI and test for multiple pathogens. We conducted a retrospective review of ILI cases in IISP and MoSAIC from January 2013 to May 2015 with descriptive analyses of clinical and laboratory data. Results Five-hundred twelve MoSAIC and 669 IISP participants met an ILI criteria (fever with cough or sore throat) and were included. Forty percent of MoSAIC participants sought care; the majority primary care. Pathogens were detected in 63% of MoSAIC and 70% of IISP cases. The relative distribution of influenza and other respiratory viruses detected was similar; however, there were statistically significant differences in the frequency that were not explained by care seeking. Conclusions Outpatient and community-based surveillance in the one found similar timing and relative distribution of respiratory viruses, but community surveillance in a single neighborhood may not fully capture the variations in ILI etiology that occur more broadly.

IntroductionThe ICD-9 codes for acute respiratory illness (ARI) andpneumonia/influenza (P&I) are commonly used in ARI surveillance;however, few studies evaluate the accuracy of these codes or theimportance of ICD-9 position. We reviewed ICD-9 codes reportedamong patients identified through severe acute respiratory infection(SARI) surveillance to compare medical record documentation withmedical coding and evaluated ICD-9 codes assigned to patients withinfluenza detections.MethodsThe Minnesota Department of Health (MDH) conducted SARIsurveillance at three hospitals. All hospitalized patients withsubmission of a physician-ordered upper respiratory specimens(e.g., sputum, throat or nasopharyngeal swabs) were enrolled.A medical chart review was conducted to identify those meetingSARI criteria, defined as patients admitted to an inpatient ward withnew onset of respiratory symptoms or acute exacerbation of chronicrespiratory conditions. Enrolled patients who did not meet the SARIcriteria were categorized as non-SARI. Residual material from theupper respiratory specimens were submitted to MDH for influenzatesting by RT-PCR. Demographic and clinical data, including upto eight ICD-9 codes, were collected through the medical recordreview. Patients with an ICD-9 code indicating ARI (460 to 466)or P&I (480 to 488) were defined as having an ARI/P&I code. Wecompared the frequency of ARI/P&I codes by SARI clinical criteriaand influenza detection and evaluated the position of the reportedARI/P&I code.ResultsFrom May 2013 through August 2015, we enrolled 5,950patients, of which 4,449 (75%) met SARI criteria and 1501 did not(non-SARI). An ARI/P&I code in any position was found in 61%(2705) of SARI vs. 16% (241) of non-SARI patients (odds ratio [OR]8.1, 95% confidence interval [CI] 7.0-9.4); an ARI/P&I code in thefirst position was found in 40% of SARI vs 7% of non-SARI patients(OR=8.6, 95% CI 7.0-10.5). Among SARI patients with at least oneARI/P&I code, 66% had their first or only ARI/P&I code in the 1stposition, 25% in the 2ndposition, and 6% in the 3rdposition. Foridentification of SARI, sensitivity/specificity was 61%/84% for ARI/P&I codes in any position and 40%/93% for ARI/P&I codes in the 1stposition. Among SARI patients, codes for pneumonia (486) and acutebronchiolitis (466.11, 466.19) were commonly reported. The mostfrequent codes among SARI patients without an ARI/P&I code werefever (780.6), acute respiratory failure (518.81), and asthma (493.92)(Table). Influenza was detected among 8% (351) of SARI patients.An ARI/P&I code in any position was more common in influenza-positive vs. influenza-negative SARI patients (77% vs 59%, OR 2.4,95% CI 1.8-3.1). An ARI/P&I code in the 1stposition was slightlymore common in influenza-positive vs -negative patients though notsignificant (44% vs 40%).ConclusionsAmong patients from whom a respiratory specimen was collected,administrative data identified those meeting SARI with moderatesensitivity and high specificity, and with lower sensitivity but greaterspecificity when limited to the 1stICD-9 position. Pneumonia andacute bronchiolitis ICD-9 codes were frequent ARI/P&I codes amongSARI patients. Further investigation is needed to determine the valueof including additional ICD-9 codes, such as respiratory distress andacute asthma exacerbation, in identifying SARI.

Objective This session will provide an overview of the current systems for influenza surveillance; review the role of schools in influenza transmission; discuss relationships between school closures, school absenteeism, and influenza transmission; and explore the usefulness of school absenteeism and unplanned school closure monitoring for early detection of influenza in schools and broader communities. Introduction Influenza surveillance is conducted through a complex network of laboratory and epidemiologic systems essential for estimating population burden of disease, selecting influenza vaccine viruses, and detecting novel influenza viruses with pandemic potential (1). Influenza surveillance faces numerous challenges, such as constantly changing influenza viruses, substantial variability in the number of affected people and the severity of disease, nonspecific symptoms, and need for laboratory testing to confirm diagnosis. Exploring additional components that provide morbidity information may enhance current influenza surveillance. School-aged children have the highest influenza incidence rates among all age groups. Due to the close interaction of children in schools and subsequent introduction of influenza into households, it is recognized that schools can serve as amplification points of influenza transmission in communities. For this reason, pandemic preparedness recommendations include possible pre-emptive school closures, before transmission is widespread within a school system or broader community, to slow influenza transmission until appropriate vaccines become available. During seasonal influenza epidemics, school closures are usually reactive, implemented in response to high absenteeism of students and staff after the disease is already widespread in the community. Reactive closures are often too late to reduce influenza transmission and are ineffective. To enhance timely influenza detection, a variety of nontraditional data sources have been explored. School absenteeism was suggested by several research groups to improve school-based influenza surveillance. A study conducted in Japan demonstrated that influenza- associated absenteeism can predict influenza outbreaks with high sensitivity and specificity (2). Another study found the use of all- causes absenteeism to be too nonspecific for utility in influenza surveillance (3). Creation of school-based early warning systems for pandemic influenza remains an interest, and further studies are needed. The panel will discuss how school-based surveillance can complement existing influenza surveillance systems.

BACKGROUND The observational test-negative study design is used to estimate vaccine effectiveness against influenza virus infection. An important assumption of the test-negative design is that vaccination does not affect the risk of infection with another virus. If such virus interference occurred, detection of other respiratory viruses would be more common among influenza vaccine recipients and vaccine effectiveness estimates could differ. We evaluated the potential for virus interference using data from the Influenza Incidence Surveillance Project. METHODS From 2010 to 2013, outpatients presenting to clinics in 13 US jurisdictions with acute respiratory infections were tested for influenza and other respiratory viruses. We investigated whether virus interference might affect vaccine effectiveness estimates by first evaluating the sensitivity of estimates using alternative control groups that include or exclude patients with other respiratory virus detections by age group and early/middle/late stage of influenza seasons. Second, we evaluated the association between influenza vaccination receipt and other respiratory virus detection among influenza test-negative patients. RESULTS Influenza was detected in 3,743/10,650 patients (35%), and overall vaccine effectiveness was 47% (95% CI: 42%, 52%). Estimates using each control group were consistent overall or when stratified by age groups, and there were no differences among early, middle, or late phase during influenza season. We found no associations between detection of other respiratory viruses and receipt of influenza vaccination. CONCLUSIONS In this 3-year test-negative design study in an outpatient setting in the United States, we found no evidence of virus interference or impact on influenza vaccine effectiveness estimation.

Background Schools are purported to be primary venues of influenza transmission and amplification with secondary spread to communities. We assessed K—12 student absenteeism monitoring as a means for early detection of influenza activity in the community. Methods. We conducted a 3-year, prospective observational study of all-cause (a-TOT), illness-associated (a-I), and influenza-like illness-associated (a-ILI) absenteeism within the Oregon School District, Oregon, WI (OSD: enrollment = 3,900 students). Absenteeism reporting was facilitated by automated processes within OSD’s electronic student information system. Students were screened for ILI, and, if eligible, visited at home, where pharyngeal specimens were collected for influenza RT-PCR (IVD CDC Human Influenza Virus RT-PCR Diagnostic Panel) and multipathogen testing (Luminex NxTAG RPP). The study definition of a-ILI was validated for 700 children with acute respiratory infections using binomial logistic regression. Surveillance of medically attended laboratory-confirmed influenza (MAI) occurred in five primary care clinics in and adjoining OSD as part of the Wisconsin Influenza Incidence Surveillance Project using the same laboratory testing. Poisson general additive log linear regression models of daily counts of absenteeism and MAI were compared using correlation analysis. Results. Influenza A and B were detected in 54 and 51 of the 700 visited students, respectively. Influenza was significantly associated with a-ILI status (OR = 4.74; 95% CI: 2.78—8.18; P < 0.001). Of MAI patients, 371 had influenza A and 143 had influenza B. a-I was significantly correlated with MAI in the community (r = 0.472; P < 0.001) with a 15-day lead time. a-ILI was significantly correlated with MAI in the community (r = 0.480; P < 0.001) with a 1-day lead time. a-TOT performed poorly (r = 0.278; P < 0.001), following MAI by 9 days (Figure 1). Conclusion. Surveillance using cause-specific absenteeism was feasible to implement in OSD and performed well over a 3-year period marked by diverse presentations of seasonal influenza. Monitoring a-I and a-ILI can detect influenza outbreaks in the community, providing early warning in time for community mitigation efforts for seasonal and pandemic influenza. Disclosures All authors: No reported disclosures.

Background Acute respiratory infection (ARI) diagnoses encompass syndromes such as pneumonia and bronchiolitis, and are among the leading causes of hospitalization. While outpatient care could present an opportunity to prevent subsequent hospitalization, few studies have measured healthcare utilization preceding hospitalization. We characterized outpatient visits in the 2 weeks prior to ARI hospitalization using commercial insurance and Medicare claims in MarketScan from 2012 to 2014. Methods We included inpatients with an ICD9 discharge diagnosis for ARI (460–466), pneumonia (480–486), or influenza (487–488) and evaluated outpatient records ≤14 days prior to admission, excluding the day of admission. We defined an outpatient visit as health encounters with a reasonable potential for medical care receipt (e.g., medical device delivery). We used the previous 12 months of medical records to define patients’ Charlson Index and health care utilization, including any prior hospitalizations and preventive and ambulatory care sensitive condition (ACSC) visits. Severe outcomes were defined as intensive care unit admission or death. We used multivariable logistic regression stratified by age group to evaluate demographic, clinical, health utilization, and outcome factors associated with outpatient care prior to admission. Results We identified 407,096 ARI hospitalizations, among which 60% of patients had ≥1 outpatient visit prior to admission; 36% of visits occurred 1 day prior to admission. Children aged

Background Quadrivalent live attenuated influenza vaccine (LAIV4) was not recommended for use in the United States for the 2016–2017 and 2017–2018 influenza seasons based on US observational studies of vaccine effectiveness (VE) from 2013–2014 to 2015–2016. We pooled individual patient data on children aged 2–17 years enrolled in 5 US studies during these 3 influenza seasons to further investigate VE by vaccine type. Methods Analyses included 17,173 children enrolled in the US Department of Defense Global Laboratory-based Influenza Surveillance Program, US Influenza Vaccine Effectiveness Network, Influenza Incidence Surveillance Project, Influenza Clinical Investigation for Children, and a Louisiana State University study. Participants’ specimens were tested for influenza by reverse transcription-polymerase chain reaction (RT-PCR), culture, or a combination of rapid antigen testing and RT-PCR. VE was calculated by comparing odds of vaccination with either inactivated influenza vaccine (IIV) or LAIV4 among influenza-positive cases to test-negative controls and calculated as 100 × (1 − odds ratio) in logistic regression models with age, calendar time, influenza season, and study site (random effect). Patients were stratified by prior season vaccination status in a subanalysis. Results Overall, 38% of patients (N = 6,558) were vaccinated in the current season, of whom 30% (N = 1,979) received LAIV4. Pooled VE of IIV against any influenza virus was 51% (95% CI: 47, 54) versus 26% (95% CI: 15, 36) for LAIV4. Point estimates for pooled VE against any influenza by age group ranged from 45% to 58% for IIV and 19% to 34% for LAIV4 during the 3 seasons (Figures 1 and 2). Pooled VE against influenza A(H1N1)pdm09 was 67% (95% CI: 62, 72) for IIV versus 20% (95% CI: −6, 39) for LAIV4. Pooled VE against influenza A(H3N2) was 29% (95% CI: 14, 42) for IIV versus 7% (95% CI: −11, 23) for LAIV4, and VE against influenza B was 52% (95% CI: 42, 60) for IIV and 66% (95% CI: 47, 77) for LAIV4. VE against influenza A(H1N1)pdm09 was lower for LAIV4 versus IIV across all strata of prior season vaccination (Figure 3). Conclusion Consistent with individual studies, our pooled analyses found that LAIV4 effectiveness was reduced for all age groups against influenza A(H1N1)pdm09 compared with IIV. This result did not vary based on prior vaccination status. Disclosures H. Caspard, AstraZeneca: Employee, Salary.

BACKGROUND: Human metapneumovirus (HMPV) infection causes respiratory illness, including bronchiolitis and pneumonia. However, national HMPV seasonality, as it compares with respiratory syncytial virus (RSV) and influenza seasonality patterns, has not been well described. METHODS: Hospital and clinical laboratories reported weekly aggregates of specimens tested and positive detections for HMPV, RSV, and influenza to the National Respiratory and Enteric Virus Surveillance System from 2008 to 2014. A season was defined as consecutive weeks with ≥3% positivity for HMPV and ≥10% positivity for RSV and influenza during a surveillance year (June through July). For each virus, the season, onset, offset, duration, peak, and 6-season medians were calculated. RESULTS: Among consistently reporting laboratories, 33 583 (3.6%) specimens were positive for HMPV, 281 581 (15.3%) for RSV, and 401 342 (18.2%) for influenza. Annually, 6 distinct HMPV seasons occurred from 2008 to 2014, with onsets ranging from November to February and offsets from April to July. Based on the 6-season medians, RSV, influenza, and HMPV onsets occurred sequentially and season durations were similar at 21 to 22 weeks. HMPV demonstrated a unique biennial pattern of early and late seasonal onsets. RSV seasons (onset, offset, peak) were most consistent and occurred before HMPV seasons. There were no consistent patterns between HMPV and influenza circulations. CONCLUSIONS: HMPV circulation begins in winter and lasts until spring and demonstrates distinct seasons each year, with the onset beginning after that of RSV. HMPV, RSV, and influenza can circulate simultaneously during the respiratory season.

Please cite this paper as: Regan et al. (2012) Epidemiology of influenza A (H1N1)pdm09-associated deaths in the United States, September–October 2009. Influenza and Other Respiratory Viruses 6(601), e169–e177. Background From April to July 2009, the United States experienced a wave of influenza A (H1N1)pdm09 virus (H1N1pdm09) infection. The majority of the deaths during that period occurred in persons

Background Influenza vaccines are now widely used to reduce the burden of annual epidemics of influenza virus infections. Influenza vaccine effectiveness (VE) is monitored annually to determine VE against each season's circulating influenza strains in different groups such as children, adults and the elderly. Few prospective surveillance programs are available to evaluate influenza VE against medically attended illness for patients of all ages in the United States. Methods We conducted surveillance of patients with acute respiratory illnesses in 101 clinics across the US during three consecutive influenza seasons. We analyzed laboratory testing results for influenza virus, self-reported vaccine history, and patient characteristics, defining cases as patients who tested positive for influenza virus and controls as patients who tested negative for influenza virus. Comparison of influenza vaccination coverage among cases versus controls, adjusted for potential confounders, was used to estimate VE as one minus the adjusted odds ratio multiplied by 100%. Results We included 10,650 patients during three influenza seasons from August 2010 through December 2013, and estimated influenza VE in children 6m–5y of age (58%; 95% CI: 49%–66%), children 6–17y (45%; 95% CI: 34%–53%), adults 18–49y (36%; 95% CI: 24%, 46%), and adults ≥50y (34%, 95% CI: 13%, 51%). VE was higher against influenza A(H1N1) compared to A(H3N2) and B. Conclusions Our estimates of moderate influenza VE confirm the important role of vaccination in protecting against medically attended influenza virus infection.

Background Hospital testing for respiratory pathogens is nonsystematic, leading to potential missed detection of clinically relevant pathogens. The Minnesota Severe Acute Respiratory Illness (SARI) surveillance program monitors hospitalizations due to acute respiratory illness and conducts systematic testing for several respiratory pathogens. We assessed viruses detected by the hospital and additional detections identified by expanded testing. Methods Residual upper respiratory specimens collected from patients hospitalized for suspected respiratory illness for routine diagnostic testing at three hospitals, including one children’s hospital, were submitted to the Minnesota Department of Health (MDH). Specimens were tested for 18 respiratory viruses by RT-PCR. Clinical and hospital test data were collected through medical record review. Results From September 2015 to August 2016, 2,351 hospitalized SARI patients were reported, with the following age distribution: 57% Conclusion Systematic, expanded testing at MDH identified a higher proportion of respiratory pathogens among SARI patients compared with clinical laboratory testing. Additional testing for clinically relevant respiratory pathogens may inform medical decision-making. Disclosures All authors: No reported disclosures.

Please cite this paper as: Jhung et al. (2011) Preliminary results of 2009 pandemic influenza surveillance in the United States using the Aggregate Hospitalization and Death Reporting Activity. Influenza and Other Respiratory Viruses 5(5), 321–327. Background To augment established influenza surveillance systems in the United States, the Centers for Disease Control and Prevention and the Council of State and Territorial Epidemiologists implemented the Aggregate Hospitalization and Death Reporting Activity (AHDRA) in August 2009. The AHDRA was designed to meet increased demands for timely and detailed information describing illness severity during the 2009 H1N1 influenza A (pH1N1) pandemic response. Objectives We describe the implementation of AHDRA and provide preliminary results from this new surveillance activity. Methods All 50 US states were asked to report influenza-associated hospitalizations and deaths to AHDRA each week using either a laboratory-confirmed or syndromic surveillance definition. Aggregate counts were used to calculate age-specific weekly and cumulative rates per 100 000, and laboratory-confirmed reports were used to estimate the age distribution of pH1N1 influenza-associated hospitalizations and deaths. Results From August 30, 2009, through April 6, 2010, AHDRA identified 41 689 laboratory-confirmed influenza-associated hospitalizations and 2096 laboratory-confirmed influenza-associated deaths. Aggregate Hospitalization and Death Reporting Activity rates peaked earlier than hospitalization and death rates seen in previous influenza seasons with other surveillance systems, and the age distribution of cases revealed a tendency for hospitalizations and deaths to occur in persons

During the spring of 2009, pandemic influenza A (H1N1) virus (pH1N1) was recognized and rapidly spread worldwide. To describe the geographic distribution and patient characteristics of pH1N1-associated deaths in the United States, the Centers for Disease Control and Prevention requested information from health departments on all laboratory-confirmed pH1N1 deaths reported from 17 April through 23 July 2009. Data were collected using medical charts, medical examiner reports, and death certificates. A total of 377 pH1N1-associated deaths were identified, for a mortality rate of .12 deaths per 100,000 population. Activity was geographically localized, with the highest mortality rates in Hawaii, New York, and Utah. Seventy-six percent of deaths occurred in persons aged 18-65 years, and 9% occurred in persons aged ≥ 65 years. Underlying medical conditions were reported for 78% of deaths: chronic lung disease among adults (39%) and neurologic disease among children (54%). Overall mortality associated with pH1N1 was low; however, the majority of deaths occurred in persons aged

There has recently been a surge of research efforts aimed at very early detection of disease outbreaks. An important strategy for improving the timeliness of outbreak detection is to identify signals that occur early in the epidemic process. We have developed a novel algorithm to identify aggregates of ''similar'' over-the-counter products that have strong association with a given disease. This paper discusses the proposed algorithm and reports the results of an evaluation experiment. The experimental results show that this algorithm holds promise for discovering product aggregates with outbreak detection performance that is superior to that of predefined categories. We also found that the products extracted by the proposed algorithm were more strongly correlated with the disease data than the standard predefined product categories, while also being more strongly correlated with each other than the products in any predefined category.

Respiratory syncytial virus (RSV) is the leading cause of pneumonia and bronchiolitis in infants and children. Immune prophylaxis can reduce the risk of severe RSV disease among some high-risk infants. A summary and update of analyses using National Respiratory and Enteric Virus Surveillance System (NREVSS) data is provided to explore using surveillance data to better define the timing of RSV activity and RSV immune prophylaxis. The methodology used was that outlined in a study by Mullins et al (Pediatr Infect Dis J. 2003;22:857-862), which analyzed weekly antigen detection data reported by laboratories to NREVSS. Data reported to NREVSS between 1990 and 2006 were used to assess seasonality among regional, state, and local areas. Season onset, offset, and duration were calculated for each year and each laboratory, and compared with the U.S. Census region and national median measurements. Results demonstrated a distinct winter peak of RSV activity each year. The extent of variation in the timing of RSV activity in a community from year to year makes it difficult to predict the timing of RSV outbreaks. In addition, the onset timing can vary between communities, even those in close proximity, during the same year. There are, however, regional community patterns that may help guide timing of immune prophylaxis. For example, the South region exhibited an earlier median season onset and longer duration than the other regions, with median onset week 47 and duration 16 weeks. In contrast, the Midwest exhibited a significantly later median onset and shorter duration than the other regions, with median onset week 1 of the following year and duration 13 weeks. Therefore, analyses of NREVSS data show that using surveillance data to tailor the timing of immune prophylaxis precisely will be difficult. Surveillance data can, however, be used to determine how well national patterns represent local patterns. Further analyses are needed to determine how local surveillance data can be used to guide timing of immune prophylaxis.

Summary Background 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. Methods 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. Findings 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. Interpretation 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. Funding US Centers for Disease Control and Prevention.

Hannah Friedlander, MPH1; Kathryn Como-Sabetti, MPH1; Sarah Bistodeau1; Anna Strain, PhD1; Dave Boxrud, MS1; Ashley Fowlkes, MPH2; Andrea Steffens, MPH2; Sandra S. Chaves, MD, MSc2; Stephen Lindstrom PhD2; Ruth Lynfield, MD1 1 Minnesota Department of Health, Saint Paul, MN; 2 U.S. Centers for Disease Control, Influenza Division, Atlanta, GA Hannah Friedlander Minnesota Department of Health PO Box 64975, St. Paul, MN 55164 651-201-5414, www.health.state.mn.us hannah.friedlander@state.mn.us

BACKGROUND Whether human herpesvirus 8 (HHV-8) is transmissible by blood transfusion remains undetermined. We evaluated the risk of HHV-8 transmission by blood transfusion in Uganda, where HHV-8 is endemic. METHODS We enrolled patients in Kampala, Uganda, who had received blood transfusions between December 2000 and October 2001. Pretransfusion and multiple post-transfusion blood specimens from up to nine visits over a 6-month period were tested for HHV-8 antibody. We calculated the excess risk of seroconversion over time among recipients of HHV-8-seropositive blood as compared with recipients of seronegative blood. RESULTS Of the 1811 transfusion recipients enrolled, 991 were HHV-8-seronegative before transfusion and completed the requisite follow-up, 43% of whom received HHV-8-seropositive blood and 57% of whom received seronegative blood. HHV-8 seroconversion occurred in 41 of the 991 recipients. The risk of seroconversion was significantly higher among recipients of HHV-8-seropositive blood than among recipients of seronegative blood (excess risk, 2.8%; P

Background Due to marked variability in circulating influenza viruses each year, annual evaluation of the vaccine’s effectiveness against severe outcomes is essential. We used the Minnesota Department of Health’s (MDH) Severe Acute Respiratory Illness (SARI) surveillance to evaluate vaccine effectiveness (VE) against influenza-associated hospitalization over three influenza seasons. Methods Residual respiratory specimens from patients admitted with SARI were sent to the MDH laboratory for influenza RT-PCR testing. Medical records were reviewed to collect patient data. Vaccination history was verified using the state immunization registry. We included patients aged ≥6 months to < 13 years, after which immunization reporting is not required, hospitalized from the earliest influenza detection after July through April each year. We defined vaccinated patients as those ≥1 dose of influenza vaccine in the current season. Children aged < 9 years with no history of vaccination were considered vaccinated if 2 were doses given a month apart. Partially vaccinated children were excluded. We estimated VE as 1 minus the adjusted odds ratio (x100%) of influenza vaccination among influenza cases vs. negative controls, controlling for age, race, days from onset to admission, comorbidities, and admission month. Results Among 2198 SARI patients, 763 (35%) were vaccinated for influenza, 180 (8.2%) were partially vaccinated, and 1255 (57%) were unvaccinated. Influenza was detected among 202 (9.2%) children, and significantly more frequently among children aged ≥5 years (17%) compared with younger children (7.4%). The adjusted VE in 2013–14 was 68% (95% Confidence Interval: 34, 85), but was non-significant during the 2014–15 and 2015–16 seasons (Figure). Estimates of VE by influenza A subtypes varied substantially by year; VE against influenza B viruses was significant, but could not be stratified by year. VE was impacted when live attenuated influenza vaccine recipients were excluded. Conclusion We report moderately high influenza VE in 2013–14 and a point estimate higher than other published estimates from outpatient data in 2014–15. These results, underscore the importance of influenza vaccination to prevent severe outcomes such as hospitalization. Disclosures All authors: No reported disclosures.

Please cite this paper as: Jhung et al. (2011) Preliminary results of 2009 pandemic influenza surveillance in the United States using the Aggregate Hospitalization and Death Reporting Activity. Influenza and Other Respiratory Viruses 5(5), 321–327. Background To augment established influenza surveillance systems in the United States, the Centers for Disease Control and Prevention and the Council of State and Territorial Epidemiologists implemented the Aggregate Hospitalization and Death Reporting Activity (AHDRA) in August 2009. The AHDRA was designed to meet increased demands for timely and detailed information describing illness severity during the 2009 H1N1 influenza A (pH1N1) pandemic response. Objectives We describe the implementation of AHDRA and provide preliminary results from this new surveillance activity. Methods All 50 US states were asked to report influenza‐associated hospitalizations and deaths to AHDRA each week using either a laboratory‐confirmed or syndromic surveillance definition. Aggregate counts were used to calculate age‐specific weekly and cumulative rates per 100 000, and laboratory‐confirmed reports were used to estimate the age distribution of pH1N1 influenza‐associated hospitalizations and deaths. Results From August 30, 2009, through April 6, 2010, AHDRA identified 41 689 laboratory‐confirmed influenza‐associated hospitalizations and 2096 laboratory‐confirmed influenza‐associated deaths. Aggregate Hospitalization and Death Reporting Activity rates peaked earlier than hospitalization and death rates seen in previous influenza seasons with other surveillance systems, and the age distribution of cases revealed a tendency for hospitalizations and deaths to occur in persons

BackgroundGoogle Flu Trends (GFT) uses anonymized, aggregated internet search activity to provide near-real time estimates of influenza activity. GFT estimates have shown a strong correlation with official influenza surveillance data. The 2009 influenza virus A (H1N1) pandemic [pH1N1] provided the first opportunity to evaluate GFT during a non-seasonal influenza outbreak. In September 2009, an updated United States GFT model was developed using data from the beginning of pH1N1.Methodology/principal findingsWe evaluated the accuracy of each U.S. GFT model by comparing weekly estimates of ILI (influenza-like illness) activity with the U.S. Outpatient Influenza-like Illness Surveillance Network (ILINet). For each GFT model we calculated the correlation and RMSE (root mean square error) between model estimates and ILINet for four time periods: pre-H1N1, Summer H1N1, Winter H1N1, and H1N1 overall (Mar 2009-Dec 2009). We also compared the number of queries, query volume, and types of queries (e.g., influenza symptoms, influenza complications) in each model. Both models' estimates were highly correlated with ILINet pre-H1N1 and over the entire surveillance period, although the original model underestimated the magnitude of ILI activity during pH1N1. The updated model was more correlated with ILINet than the original model during Summer H1N1 (r = 0.95 and 0.29, respectively). The updated model included more search query terms than the original model, with more queries directly related to influenza infection, whereas the original model contained more queries related to influenza complications.ConclusionsInternet search behavior changed during pH1N1, particularly in the categories "influenza complications" and "term for influenza." The complications associated with pH1N1, the fact that pH1N1 began in the summer rather than winter, and changes in health-seeking behavior each may have played a part. Both GFT models performed well prior to and during pH1N1, although the updated model performed better during pH1N1, especially during the summer months.

PURPOSE: Concerns have been raised regarding possible racial-ethnic disparities in 2009 pandemic influenza A (H1N1) (pH1N1) illness severity and health consequences for U.S. minority populations. METHODS: Using data from the Centers for Disease Control and Prevention's Behavioral Risk Factor Surveillance System, Emerging Infections Program Influenza-Associated Hospitalization Surveillance, and Influenza-Associated Pediatric Mortality Surveillance, we calculated race-ethnicity-specific, age-adjusted rates of self-reported influenza-like illness (ILI) and pH1N1-associated hospitalizations. We used χ(2) tests to evaluate racial-ethnic disparities in ILI-associated health care-seeking behavior and pH1N1 hospitalization. To evaluate pediatric deaths, we compared racial-ethnic proportions of deaths against U.S. population distributions. RESULTS: Prevalence of self-reported ILI was lower among Hispanics (6.5%), higher among American Indians/Alaska Natives (16.2%), and similar among non-Hispanic blacks (7.7%) compared with non-Hispanic whites (8.5%). No racial-ethnic differences were identified in ILI-associated health care-seeking behavior. Age-adjusted pH1N1-associated Emerging Infections Program hospitalization rates were higher among all minority populations (range: 8.1-10.9/100,000 population) compared with non-Hispanic whites (3.0/100,000). The proportion of pH1N1-associated pediatric deaths was higher than expected among Hispanics (31%) and lower than expected among non-Hispanic whites (45%) given the proportions of the U.S. population they comprise (22% and 58%, respectively). CONCLUSIONS: Racial-ethnic disparities in pH1N1-associated hospitalizations and pediatric deaths were identified. Vaccination remains the primary intervention for preventing influenza.

Background Enterovirus infections are very common and typically cause mild illness, although neonates are at higher risk for severe illness. In 2007, the Centers for Disease Control and Prevention (CDC) received multiple reports of severe neonatal illness and death associated with coxsackievirus B1 (CVB1), a less common enterovirus serotype not previously associated with death in surveillance reports to the CDC. Methods This report includes clinical, epidemiologic, and virologic data from cases of severe neonatal illness associated with CVB1 reported during the period from 2007 through 2008 to the National Enterovirus Surveillance System (NESS), a voluntary, passive surveillance system. Also included are data on additional cases reported to the CDC outside of the NESS. Virus isolates or original specimens obtained from patients from 25 states were referred to the CDC picornavirus laboratory for molecular typing or characterization. Results During 2007-2008, the NESS received 1079 reports of enterovirus infection. CVB1 accounted for 176 (23%) of 775 reported cases with known serotype, making it the most commonly reported serotype for the first time ever in the NESS. Six neonatal deaths due to CVB1 infection were also reported to the CDC during that time. Phylogenetic analysis of the 2007 and 2008 CVB1 strains indicated that the increase in cases resulted from widespread circulation of a single genetic lineage that had been present in the United States since at least 2001. Conclusions Healthcare providers and public health departments should be vigilant to the possibility of continuing CVB1-associated neonatal illness, and testing and continued reporting of enterovirus infections should be encouraged.

BACKGROUND: In 2006, routine immunization of US infants against rotavirus was initiated. We assessed national, regional, and local trends in rotavirus testing and detection before and after vaccine introduction. METHODS: We examined data for July 2000 through June 2008 from a national network of ∼70 US laboratories to compare geographical and temporal aspects of rotavirus season timing and peak activity. To assess trends in rotavirus testing and detection, we restricted the analyses to 33 laboratories that reported for ≥26 weeks per season from 2000 to 2008. RESULTS: Nationally, the onset and peak of the 2007–2008 rotavirus season were delayed 15 and 8 weeks, respectively, compared with prevaccine seasons from 2000–2006. Delays were observed in each region. The 2007–2008 rotavirus season lasted 14 weeks compared with a median of 26 weeks during the prevaccine era. Of 33 laboratories, 32 reported fewer positive results and a lower proportion of positive test results in 2007–2008 compared with the median in 2000–2006, with a 67% decline in the number and a 69% decline in the proportion of rotavirus-positive test results. The proportion of positive test results in 2007–2008 compared with the median in 2000–2006 declined >50% in 79% of the laboratories and >75% in 39% of the laboratories. CONCLUSIONS: The 2007–2008 US rotavirus season seems substantially delayed, shorter, and diminished in magnitude compared with seasons before vaccine implementation. The extent of change seems greater than expected on the basis of estimated vaccine coverage, suggesting indirect benefits to unvaccinated individuals. Monitoring in future seasons is needed to confirm these trends.

BACKGROUND: Human herpesvirus 8 (HHV-8) is endemic in Uganda where seroprevalence is approximately 40%. In a previous study, Ugandan patients receiving blood transfusions had multiple serum specimens collected for 6 months after transfusion to monitor for HHV-8 infection. It was observed that several HHV-8–seronegative patients were unexpectedly HHV-8 seropositive after blood transfusion. STUDY DESIGN AND METHODS: This study measured HHV-8 antibody in serially collected serum specimens from 542 patients who received transfusions and evaluated the risk of HHV-8 infection as a function of HHV-8 antibody levels in the donors. RESULTS: HHV-8 antibody was observed in 52% of patients transfused with HHV-8–seropositive blood in amounts that corresponded with their donor's antibody titer and waned within 40 days. Higher levels of passive HHV-8 antibody in patients who received transfusions appeared to be associated with a lower risk of HHV-8 infection. CONCLUSION: The source of transient antibody in patients who received transfusions was determined to be the transfused blood. Donors with higher HHV-8 antibody titers may have been less likely to have infectious virus in the blood.

Background. Encephalitis is a relatively rare presentation of enterovirus (EV) infections. Clinical and epidemiologic characteristics of EV encephalitis (EVE) have not been well characterized. Methods. Patients with encephalitis enrolled in the California Encephalitis Project from 1998 to 2005 were tested for a range of pathogens, including EV, using a standardized diagnostic algorithm. EVE was categorized as “confirmed” (EV detected in cerebrospinal fluid [CSF] or brain tissue) or “possible” (EV found in respiratory or fecal specimens or serum EV immunoglobulin [Ig] M detected). We compared clinical and epidemiologic characteristics of EVE with those of other infectious encephalitis cases. Results. EVE was diagnosed in 73 (4.6%) of 1571 patients (45 confirmed cases, 28 possible cases); 11.1% of cases had other infectious causes. Patients with confirmed EVE were younger, although 27% were adults, who presented with significantly less severe symptoms. Serotypes identified in EVE cases correlated with the predominant serotype for the given year reported to the National Enterovirus Surveillance System at the Centers for Disease Control and Prevention. Two of 4 fatal EVE cases were associated with EV71. Conclusion. EVs are an important cause of encephalitis cases requiring hospitalization, in both children and adults. Our data suggest that EVE severity varies by serotype, confirm the importance of CSF/brain tissue polymerase chain reaction, and demonstrate that serum IgM findings are of little value in diagnosing EVE. In the United States, encephalitis causes an estimated 19,000 hospitalizations and up to 1400 deaths each year