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COVID-19 vaccine breakthrough infection surveillance helps monitor trends in disease incidence and severe outcomes in fully vaccinated persons, including the impact of the highly transmissible B.1.617.2 (Delta) variant of SARS-CoV-2, the virus that causes COVID-19. Reported COVID-19 cases, hospitalizations, and deaths occurring among persons aged ≥18 years during April 4-July 17, 2021, were analyzed by vaccination status across 13 U.S. jurisdictions that routinely linked case surveillance and immunization registry data. Averaged weekly, age-standardized incidence rate ratios (IRRs) for cases among persons who were not fully vaccinated compared with those among fully vaccinated persons decreased from 11.1 (95% confidence interval [CI] = 7.8-15.8) to 4.6 (95% CI = 2.5-8.5) between two periods when prevalence of the Delta variant was lower (

On May 5, 2021, the Colorado Department of Public Health and Environment (CDPHE) identified the first five COVID-19 cases caused by the SARS-CoV-2 B.1.617.2 (Delta) variant in Mesa County in western Colorado (population 154,933

To improve recognition of coronavirus disease (COVID-19) and inform clinical and public health guidance, we randomly selected 600 COVID-19 case-patients in Colorado. A telephone questionnaire captured symptoms experienced, when symptoms occurred, and how long each lasted. Among 128 hospitalized patients, commonly reported symptoms included fever (84%), fatigue (83%), cough (73%), and dyspnea (72%). Among 236 nonhospitalized patients, commonly reported symptoms included fatigue (90%), fever (83%), cough (83%), and myalgia (74%). The most commonly reported initial symptoms were cough (21%–25%) and fever (20%–25%). In multivariable analysis, vomiting, dyspnea, altered mental status, dehydration, and wheezing were significantly associated with hospitalization, whereas rhinorrhea, headache, sore throat, and anosmia or ageusia were significantly associated with nonhospitalization. General symptoms and upper respiratory symptoms occurred earlier in disease, and anosmia, ageusia, lower respiratory symptoms, and gastrointestinal symptoms occurred later. Symptoms should be considered alongside other epidemiologic factors in clinical and public health decisions regarding potential COVID-19 cases.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic necessitated rapid local public health response, but studies examining the impact of social distancing policies on SARS-CoV-2 transmission have struggled to capture regional-level dynamics. We developed a susceptible-exposed-infected-recovered transmission model, parameterized to Colorado, USA‒specific data, to estimate the impact of coronavirus disease‒related policy measures on mobility and SARS-CoV-2 transmission in real time. During March‒June 2020, we estimated unknown parameter values and generated scenario-based projections of future clinical care needs. Early coronavirus disease policy measures, including a stay-at-home order, were accompanied by substantial decreases in mobility and reduced the effective reproductive number well below 1. When some restrictions were eased in late April, mobility increased to near baseline levels, but transmission remained low (effective reproductive number

Summary Background In May, 2018, Children's Hospital Colorado noted an outbreak of enterovirus A71 (EV-A71) neurological disease. We aimed to characterise the clinical features of EV-A71 neurological disease during this outbreak. Methods In this retrospective observational cohort study, children (younger than 18 years) who presented to Children's Hospital Colorado (Aurora, CO, USA) between March 1 and November 30, 2018, with neurological disease (defined by non-mutually exclusive criteria, including meningitis, encephalitis, acute flaccid myelitis, and seizures) and enterovirus detected from any biological specimen were eligible for study inclusion. The clinical characteristics of children with neurological disease associated with EV-A71 were compared with those of children with neurological disease associated with other enteroviruses during the same period. To explore the differences in clinical presentation of acute flaccid myelitis, we also used a subgroup analysis to compare clinical findings in children with EV-A71-associated acute flaccid myelitis during the study period with these findings in those with enterovirus D68 (EV-D68)-associated acute flaccid myelitis at the same hospital between 2013 and 2018. Findings Between March 10 and Nov 10, 2018, 74 children presenting to Children's Hospital Colorado were found to have enterovirus neurological disease; EV-A71 was identified in 43 (58%) of these children. The median age of the children with EV-A71 neurological disease was 22·7 months (IQR 4·0–31·9), and most of these children were male (34 [79%] children). 40 (93%) children with EV-A71 neurological disease had findings suggestive of meningitis, 31 (72%) children showed evidence of encephalitis, and ten (23%) children met our case definition of acute flaccid myelitis. All children with EV-A71 disease had fever and 18 (42%) children had hand, foot, or mouth lesions at or before neurological onset. Children with EV-A71 disease were best differentiated from those with other enteroviruses (n=31) by the neurological findings of myoclonus, ataxia, weakness, and autonomic instability. Of the specimens collected from children with EV-A71, this enterovirus was detected in 94% of rectal, 79% of oropharyngeal, 56% of nasopharyngeal, and 20% of cerebrospinal fluid specimens. 39 (93%) of 42 children with EV-A71 neurological disease who could be followed up showed complete recovery by 1–2 months. Compared with children with EV-D68-associated acute flaccid myelitis, children with EV-A71-associated acute flaccid myelitis were younger, showed neurological onset earlier after prodromal symptom onset, had milder weakness, showed more rapid improvement, and were more likely to completely recover. Interpretation This outbreak of EV-A71 neurological disease, the largest reported in the Americas, was characterised by fever, myoclonus, ataxia, weakness, autonomic instability, and full recovery in most patients. Because EV-A71 epidemiology outside of Asia remains difficult to predict, identification of future outbreaks will be aided by prompt recognition of these distinct clinical findings, testing of non-sterile and sterile site specimens, and enhanced enterovirus surveillance. Funding None.

We evaluated whether Denver neighborhoods with elevated rates of adult hospitalizations for laboratory-confirmed influenza had lower adult coverage with influenza vaccine. Overall vaccine coverage was low. Hospitalization rates were associated with demographic and socioeconomic characteristics. Active immunization of at-risk neighborhoods may be necessary to address disparities in influenza hospitalization rates.

BackgroundThe COVID-19 pandemic has caused substantial morbidity and mortality.ObjectiveTo describe monthly clinical trends among adults hospitalized with COVID-19.DesignPooled cross-sectional study.Setting99 counties in 14 states participating in the Coronavirus Disease 2019-Associated Hospitalization Surveillance Network (COVID-NET).PatientsU.S. adults (aged ≥18 years) hospitalized with laboratory-confirmed COVID-19 during 1 March to 31 December 2020.MeasurementsMonthly hospitalizations, intensive care unit (ICU) admissions, and in-hospital death rates per 100000 persons in the population; monthly trends in weighted percentages of interventions, including ICU admission, mechanical ventilation, and vasopressor use, among an age- and site-stratified random sample of hospitalized case patients.ResultsAmong 116743 hospitalized adults with COVID-19, the median age was 62 years, 50.7% were male, and 40.8% were non-Hispanic White. Monthly rates of hospitalization (105.3 per 100000 persons), ICU admission (20.2 per 100000 persons), and death (11.7 per 100000 persons) peaked during December 2020. Rates of all 3 outcomes were highest among adults aged 65 years or older, males, and Hispanic or non-Hispanic Black persons. Among 18508 sampled hospitalized adults, use of remdesivir and systemic corticosteroids increased from 1.7% and 18.9%, respectively, in March to 53.8% and 74.2%, respectively, in December. Frequency of ICU admission, mechanical ventilation, and vasopressor use decreased from March (37.8%, 27.8%, and 22.7%, respectively) to December (20.5%, 12.3%, and 12.8%, respectively); use of noninvasive respiratory support increased from March to December.LimitationCOVID-NET covers approximately 10% of the U.S. population; findings may not be generalizable to the entire country.ConclusionRates of COVID-19-associated hospitalization, ICU admission, and death were highest in December 2020, corresponding with the third peak of the U.S. pandemic. The frequency of intensive interventions for management of hospitalized patients decreased over time. These data provide a longitudinal assessment of clinical trends among adults hospitalized with COVID-19 before widespread implementation of COVID-19 vaccines.Primary funding sourceCenters for Disease Control and Prevention.

Background Hospitalized immunocompromised (IC) adults with influenza may have worse outcomes than hospitalized non-IC adults. Methods We identified adults hospitalized with laboratory-confirmed influenza during 2011–2015 seasons through CDC’s Influenza Hospitalization Surveillance Network. IC patients had human immunodefiency virus (HIV)/AIDS, cancer, stem cell or organ transplantation, nonsteroid immunosuppressive therapy, immunoglobulin deficiency, asplenia, and/or other rare conditions. We compared demographic and clinical characteristics of IC and non-IC adults using descriptive statistics. Multivariable logistic regression and Cox proportional hazards models controlled for confounding by patient demographic characteristics, pre-existing medical conditions, influenza vaccination, and other factors. Results Among 35 348 adults, 3633 (10%) were IC; cancer (44%), nonsteroid immunosuppressive therapy (44%), and HIV (18%) were most common. IC patients were more likely than non-IC patients to have received influenza vaccination (53% vs 46%; P < .001), and ~85% of both groups received antivirals. In multivariable analysis, IC adults had higher mortality (adjusted odds ratio [aOR], 1.46; 95% confidence interval [CI], 1.20–1.76). Intensive care was more likely among IC patients 65–79 years (aOR, 1.25; 95% CI, 1.06–1.48) and those >80 years (aOR, 1.35; 95% CI, 1.06–1.73) compared with non-IC patients in those age groups. IC patients were hospitalized longer (adjusted hazard ratio of discharge, 0.86; 95% CI, .83–.88) and more likely to require mechanical ventilation (aOR, 1.19; 95% CI, 1.05–1.36). Conclusions Substantial morbidity and mortality occurred among IC adults hospitalized with influenza. Influenza vaccination and antiviral administration could be increased in both IC and non-IC adults.

The B.1.427 and B.1.429 variants of SARS-CoV-2, the virus that causes COVID-19, were first described in Southern California on January 20, 2021 (1); on March 16 they were designated variants of concern* (2). Data on these variants are limited, but initial reports suggest that, compared with other lineages, they might be more infectious (1,2), cause more severe illness (2), and be less susceptible to neutralizing monoclonal antibody products such as bamlanivimab, an investigational treatment for mild-to-moderate COVID-19 (1-3). On January 24, the Colorado Department of Public Health and Environment (CDPHE) identified the first Colorado case of COVID-19 attributed to these variants. B.1.427 and B.1.429 were considered a single variant described as CAL.20C or B.1.427/B.1.429 in the 20C clade (1,3); in this report "B.1.427/B.1.429" refers to B.1.427 or B.1.429 lineage, including those reported as B.1.427/B.1.429 without further differentiation.

Background Most current evidence on risk factors for hospitalization because of coronavirus disease 2019 (COVID-19) comes from studies using data abstracted primarily from electronic health records, limited to specific populations, or that fail to capture over-the-counter medications and adjust for potential confounding factors. Properly understanding risk factors for hospitalization will help improve clinical management and facilitate targeted prevention messaging and forecasting and prioritization of clinical and public health resource needs. Objectives To identify risk factors for hospitalization using patient questionnaires and chart abstraction. Methods We randomly selected 600 of 1,738 laboratory-confirmed Colorado COVID-19 cases with known hospitalization status and illness onset during March 9–31, 2020. In April 2020, we collected demographics, social history, and medications taken in the 30 days before illness onset via telephone questionnaire and collected underlying medical conditions in patient questionnaires and medical record abstraction. Results Overall, 364 patients participated; 128 were hospitalized and 236 were non-hospitalized. In multivariable analysis, chronic hypoxemic respiratory failure with oxygen requirement (adjusted odds ratio [aOR] 14.64; 95% confidence interval [CI] 1.45–147.93), taking opioids (aOR 8.05; CI 1.16–55.77), metabolic syndrome (aOR 5.71; CI 1.18–27.54), obesity (aOR 3.35; CI 1.58–7.09), age ≥65 years (aOR 3.22; CI 1.20–7.97), hypertension (aOR 3.14; CI 1.47–6.71), arrhythmia (aOR 2.95; CI 1.00–8.68), and male sex (aOR 2.65; CI 1.44–4.88), were significantly associated with hospitalization. Conclusion We identified patient characteristics, medications, and medical conditions, including some novel ones, associated with hospitalization. These data can be used to inform clinical and public health resource needs.

Background Influenza may contribute to the burden of acute cardiovascular events during annual influenza epidemics. Objective To examine acute cardiovascular events and determine risk factors for acute heart failure (aHF) and acute ischemic heart disease (aIHD) in adults with a hospitalization associated with laboratory-confirmed influenza. Design Cross-sectional study. Setting U.S. Influenza Hospitalization Surveillance Network during the 2010-to-2011 through 2017-to-2018 influenza seasons. Participants Adults hospitalized with laboratory-confirmed influenza and identified through influenza testing ordered by a practitioner. Measurements Acute cardiovascular events were ascertained using discharge codes from the International Classification of Diseases (ICD), Ninth Revision, Clinical Modification, and ICD, 10th Revision. Age, sex, race/ethnicity, tobacco use, chronic conditions, influenza vaccination, influenza antiviral medication, and influenza type or subtype were included as exposures in logistic regression models, and marginal adjusted risk ratios and 95% CIs were estimated to describe factors associated with aHF or aIHD. Results Among 89 999 adults with laboratory-confirmed influenza, 80 261 had complete medical record abstractions and available ICD codes (median age, 69 years [interquartile range, 54 to 81 years]) and 11.7% had an acute cardiovascular event. The most common such events (non-mutually exclusive) were aHF (6.2%) and aIHD (5.7%). Older age, tobacco use, underlying cardiovascular disease, diabetes, and renal disease were significantly associated with higher risk for aHF and aIHD in adults hospitalized with laboratory-confirmed influenza. Limitation Underdetection of cases was likely because influenza testing was based on practitioner orders. Acute cardiovascular events were identified by ICD discharge codes and may be subject to misclassification bias. Conclusion In this population-based study of adults hospitalized with influenza, almost 12% of patients had an acute cardiovascular event. Clinicians should ensure high rates of influenza vaccination, especially in those with underlying chronic conditions, to protect against acute cardiovascular events associated with influenza. Primary funding source Centers for Disease Control and Prevention.

During January 1, 2020-May 18, 2020, approximately 1.3 million cases of coronavirus disease 2019 (COVID-19) and 83,000 COVID-19-associated deaths were reported in the United States (1). Understanding the demographic and clinical characteristics of decedents could inform medical and public health interventions focused on preventing COVID-19-associated mortality. This report describes decedents with laboratory-confirmed infection with SARS-CoV-2, the virus that causes COVID-19, using data from 1) the standardized CDC case-report form (case-based surveillance) (https://www.cdc.gov/coronavirus/2019-ncov/php/reporting-pui.html) and 2) supplementary data (supplemental surveillance), such as underlying medical conditions and location of death, obtained through collaboration between CDC and 16 public health jurisdictions (15 states and New York City).

Congregate work and residential locations are at increased risk for infectious disease transmission including respiratory illness outbreaks. SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), is primarily spread person to person through respiratory droplets. Nationwide, the meat and poultry processing industry, an essential component of the U.S. food infrastructure, employs approximately 500,000 persons, many of whom work in proximity to other workers (1). Because of reports of initial cases of COVID-19, in some meat processing facilities, states were asked to provide aggregated data concerning the number of meat and poultry processing facilities affected by COVID-19 and the number of workers with COVID-19 in these facilities, including COVID-19-related deaths. Qualitative data gathered by CDC during on-site and remote assessments were analyzed and summarized. During April 9-27, aggregate data on COVID-19 cases among 115 meat or poultry processing facilities in 19 states were reported to CDC. Among these facilities, COVID-19 was diagnosed in 4,913 (approximately 3%) workers, and 20 COVID-19-related deaths were reported. Facility barriers to effective prevention and control of COVID-19 included difficulty distancing workers at least 6 feet (2 meters) from one another (2) and in implementing COVID-19-specific disinfection guidelines.* Among workers, socioeconomic challenges might contribute to working while feeling ill, particularly if there are management practices such as bonuses that incentivize attendance. Methods to decrease transmission within the facility include worker symptom screening programs, policies to discourage working while experiencing symptoms compatible with COVID-19, and social distancing by workers. Source control measures (e.g., the use of cloth face covers) as well as increased disinfection of high-touch surfaces are also important means of preventing SARS-CoV-2 exposure. Mitigation efforts to reduce transmission in the community should also be considered. Many of these measures might also reduce asymptomatic and presymptomatic transmission (3). Implementation of these public health strategies will help protect workers from COVID-19 in this industry and assist in preserving the critical meat and poultry production infrastructure (4).

The burden of influenza in rural areas is largely unstudied. Rural populations may be vulnerable yet isolated from circulating virus. Laboratory-confirmed influenza hospitalizations in rural Colorado census tracts over eight influenza seasons were inconsistently distributed across seasons. Rural rates were, on average, lower than urban rates. Race, ethnicity, poverty, health insurance coverage, and distance from a hospital accounted for rate differences. Our interpretation is: 1) influenza regularly circulates in urban areas and inconsistently spreads to rural areas, 2) demographic and socioeconomic factors drive morbidity in exposed populations, and 3) public health interventions targeting high-risk urban census tracts may be beneficial.

Objective Despite relatively high national vaccination coverage for measles, geographic vaccination variation exists resulting in clusters of susceptibility. A portion of this geographic variation can be explained by differences in state policies related to nonmedical vaccine exemptions. The objective of this analysis was to determine the magnitude, likelihood, and cost of a measles outbreak under different nonmedical vaccine exemption policies. Methods An agent-based transmission model simulated the likelihood and magnitude of a measles outbreak under different nonmedical vaccine exemption policies, previously categorized as easy, medium, or difficult. The model accounted for measles herd immunity, infectiousness of the pathogen, vaccine efficacy, duration of incubation and communicable periods, acquired natural immunity, and the rate of recovery. Public health contact tracing was also modeled. Model outcomes, including the number of secondary cases, hospitalizations, and deaths, were monetized to determine the economic burden of the simulated outbreaks. Results A state with easy nonmedical vaccine exemption policies is 140% and 190% more likely to experience a measles outbreak compared with states with medium or difficult policies, respectively. The magnitude of these outbreaks can be reduced by half by strengthening exemption policies. These declines are associated with significant cost reductions to public health, the health care system, and the individual. Conclusions Strengthening nonmedical vaccine exemption policies is 1 mechanism to increase vaccination coverage to reduce the health and economic effect of a measles outbreak. States exploring options for decreasing their vulnerability to outbreaks of vaccine-preventable diseases should consider more stringent requirements for nonmedical vaccine exemptions.

Background Significant changes in influenza vaccination coverage and antiviral treatment guidance occurred following the 2009 influenza pandemic in children. However, data are limited describing recent epidemiology, clinical characteristics, antiviral use, vaccine coverage, and outcomes of influenza-related hospitalizations in children. Methods Children < 18 years hospitalized with influenza during seasons 2010–2011 through 2018–2019 were included through the US Influenza Hospitalization Surveillance Network (FluSurv-NET). Age-stratified hospitalization rates were calculated using the number of catchment-area residents with laboratory-confirmed influenza within 14 days prior to or ≤3 days after hospital admission during October 1-April 30 of each influenza season. Data on underlying medical history, influenza vaccination, antiviral use, and outcomes were abstracted from medical records using standard case report forms by trained surveillance officers. Results Over 9 seasons, 13,235 children were identified. Stepwise decreases in unadjusted hospitalization rates with age occurred, with the highest rates in infants < 6 months (ranging 56–184 per 100,000 persons) (Fig.1). Among these children, 56% were male, 34% were non-Hispanic White, 55% had a preexisting medical condition, and 8% were immunocompromised (Table 1). Use of antiviral treatment substantially increased from 56% to 85%, and influenza vaccination rates among hospitalized children increased from 34% to 43% over time. Regarding severe outcomes, 2,676 (20%) were admitted to ICU, 2,262 (17%) had pneumonia, 690 (5%) required mechanical ventilation, and 72 (0.5%) died. In univariable analysis, compared to hospitalized infants < 6 months, children >13 years had higher odds of ICU admission (odds ratio (OR), 2.0; 95% CI, 1.7–2.4), mechanical ventilation (OR, 1.7; 95% CI, 1.2–2.3), and pneumonia (OR, 2.6; 95% CI, 2.1–3.3) (Table 2). Figure 1 Table 1 Table 2 Conclusion Although influenza-related hospitalization rates decreased with increasing age, severe outcomes were more common among hospitalized older children. Room for improvement exists in influenza vaccination coverage and antiviral use. While 20% of children were admitted to ICU, death was uncommon. Disclosures Sue Kim, MPH, Council of State and Territorial Epidemiologists (CSTE) (Grant/Research Support) Melissa Sutton, MD, MPH, CDC funding (Emerging Infections Program) (Grant/Research Support) Evan J. Anderson, MD, Sanofi Pasteur (Scientific Research Study Investigator)

Background Pregnant women are at high-risk for influenza-associated hospitalization. We used data from the U.S. Influenza Hospitalization Surveillance Network (FluSurv-NET) to characterize pregnant women hospitalized with influenza. Methods We included pregnant women (15–44 years) residing within a FluSurv-NET catchment area and hospitalized with laboratory-confirmed influenza between October 1 and April 30, during the 2010–19 influenza seasons. Clinical data were obtained on cases through medical chart abstraction. We examined trends in vaccination coverage and antiviral treatment using the Cochran-Armitage test for trend and characterized maternal interventions and maternal and fetal outcomes during hospitalization. Results Of 9,652 women aged 15–44 years hospitalized with influenza, 2,697 (28%) were pregnant. Median maternal age was 28 years and median gestational age was 32 weeks; 36% were non-Hispanic white, 29% non-Hispanic black, and 20% Hispanic. Underlying conditions were present in 35% (n=931), with asthma (n=613; 22.7%) and chronic metabolic disease (n=204; 7.6%) as the most common; 12% (n=299) were current smokers. Vaccination coverage and antiviral receipt varied by season and age [Figures 1 and 2]. Overall, 31% (n=846) were vaccinated and 89% (n=2,408) received antivirals. Five percent (n=132) had intensive care unit admission, 2% (n=52) required mechanical ventilation, 6% (n=165) developed pneumonia and 0.3% (n=9) died; median length of hospital stay was 2 days (IQR 1–3). The most common symptoms at admission included cough (68%) and fever (66%) [Figure 3]. At discharge, most women (70%; n=1865) were still pregnant while 28% (n=758) were no longer pregnant and 2% (n=44) had unknown pregnancy status. Among women who were no longer pregnant at discharge, 96% (n=726) had pregnancies resulting in live births, 3% (n=25) had pregnancies resulting in loss of the fetus or neonate, and 1.0% (n=7) had unknown birth outcome. Figure 1. Vaccination coverage among pregnant women hospitalized with laboratory-confirmed influenza by season and by age group, FluSurv-NET 2010–2019 Figure 2. Antiviral treatment among pregnant women hospitalized with laboratory-confirmed influenza by season and by age group, FluSurv-NET 2010–2019 Figure 3. Symptoms at admission among pregnant women hospitalized with laboratory-confirmed influenza by age group, FluSurv-NET 2010–2019 Conclusion Over 9 influenza seasons, nearly one-third of women aged 15–44 years and hospitalized with influenza were pregnant. Severe maternal and fetal outcomes were rare. While most women received antivirals, fewer than one-third received current season influenza vaccine. Disclosures Sue Kim, MPH, Council of State and Territorial Epidemiologists (CSTE) (Grant/Research Support) Melissa Sutton, MD, MPH, CDC funding (Emerging Infections Program) (Grant/Research Support)

Background PCVs have been recommended for U.S. children since 2000. A 7-valent vaccine (PCV7) was introduced in 2000. This was replaced by a 13-valent vaccine (PCV13) in 2010. PCV13 was also recommended for adults aged ≥ 65 years in August 2014. We evaluated PCV impact on IPD. Methods IPD cases (isolation of pneumococcus from sterile sites) were identified through CDC’s Active Bacterial Core surveillance during 1998-2018. Isolates were serotyped by Quellung or whole genome sequencing and classified as PCV13-type and non-vaccine-type (NVT). Incidence rates (cases/100,000) were calculated using U.S. Census Bureau population denominators. Results From 1998 through 2018, overall IPD rates among children aged < 5 years decreased by 93% (from 95 to 7 cases/100,000). PCV13-type IPD decreased by 98% (from 88 to 2 cases/100,000). Among adults aged ≥ 65 years, overall IPD rates decreased by 60% (from 61 to 25 cases/100,000). PCV13-type IPD rates declined 86% (from 46 to 7 cases/100,000). Declines were most dramatic in the years following PCV7 introduction, with additional declines after PCV13 introduction in children (Figures 1 and 2). Serotypes 3, 19A, and 19F caused most of the remaining PCV13-type IPD. NVT IPD rates did not change significantly among children. Among adults aged 50-64 years, NVT IPD increased by 83% (from 6 to 12 cases/100,000) (p< 0.01). Among adults aged ≥ 65 years, NVT IPD increased by 22% (from 15 to 18 cases/100,000) (p< 0.01). The most common NVTs in 2018 were 22F (10% of all IPD), 9N (7%) and 15A (5%). Among children, the proportion of cases with meningitis increased from 5% to 14% (p< 0.01), and the proportion with pneumonia/empyema increased from 17% to 31% (p< 0.01). Among adults, the proportion of cases with meningitis did not change (3%), while the proportion with pneumonia/empyema increased from 72% to 76% (p=0.01). Figure 1: Incidence of invasive pneumococcal disease among children aged < 5 years, 1998-2018 Figure 2: Incidence of invasive pneumococcal disease among adults aged ≥ 65 years, 1998-2018 Conclusion Overall IPD incidence among children and adults decreased following PCV introduction for children, driven primarily by reductions in PCV-type IPD. NVT IPD increased in older adults, but these increases did not eliminate reductions from PCV13-type IPD. Disclosures Lee Harrison, MD, GSK (Consultant)Merck (Consultant)Pfizer (Consultant)Sanofi Pasteur (Consultant)

Background Multivalent influenza vaccine products provide protection against influenza A(H1N1)pdm09, A(H3N2), and B lineage viruses. The 2018–2019 influenza season in the United States included prolonged circulation of A(H1N1)pdm09 viruses well-matched to the vaccine strain and A(H3N2) viruses, the majority of which were mismatched to the vaccine. We estimated the number of vaccine-prevented influenza-associated illnesses, medical visits, hospitalizations, and deaths for the season. Methods We used a mathematical model and Monte Carlo algorithm to estimate numbers and 95% uncertainty intervals (UIs) of influenza-associated outcomes prevented by vaccination in the United States. The model incorporated age-specific estimates of national 2018–2019 influenza vaccine coverage, influenza virus–specific vaccine effectiveness from the US Influenza Vaccine Effectiveness Network, and disease burden estimated from population-based rates of influenza-associated hospitalizations through the Influenza Hospitalization Surveillance Network. Results Influenza vaccination prevented an estimated 4.4 million (95%UI, 3.4 million–7.1 million) illnesses, 2.3 million (95%UI, 1.8 million–3.8 million) medical visits, 58 000 (95%UI, 30 000–156 000) hospitalizations, and 3500 (95%UI, 1000–13 000) deaths due to influenza viruses during the US 2018–2019 influenza season. Vaccination prevented 14% of projected hospitalizations associated with A(H1N1)pdm09 overall and 43% among children aged 6 months–4 years. Conclusions Influenza vaccination averted substantial influenza-associated disease including hospitalizations and deaths in the United States, primarily due to effectiveness against A(H1N1)pdm09. Our findings underscore the value of influenza vaccination, highlighting that vaccines measurably decrease illness and associated healthcare utilization even in a season in which a vaccine component does not match to a circulating virus.

BackgroundRates of influenza hospitalizations differ by age, but few data are available regarding differences in laboratory-confirmed rates among adults aged ≥65 years.MethodsWe evaluated age-related differences in influenza-associated hospitalization rates, clinical presentation, and outcomes among 19 760 older adults with laboratory-confirmed influenza at 14 FluSurv-NET sites during the 2011–2012 through 2014–2015 influenza seasons using 10-year age groups.ResultsThere were large stepwise increases in the population rates of influenza hospitalization with each 10-year increase in age. Rates ranged from 101–417, 209–1264, and 562–2651 per 100 000 persons over 4 influenza seasons in patients aged 65–74 years, 75–84 years, and ≥85 years, respectively. Hospitalization rates among adults aged 75–84 years and ≥85 years were 1.4–3.0 and 2.2–6.4 times greater, respectively, than rates for adults aged 65–74 years. Among patients hospitalized with laboratory-confirmed influenza, there were age-related differences in demographics, medical histories, and symptoms and signs at presentation. Compared to hospitalized patients aged 65–74 years, patients aged ≥85 years had higher odds of pneumonia (aOR, 1.2; 95% CI, 1.0–1.3; P = .01) and in-hospital death or transfer to hospice (aOR, 2.1; 95% CI, 1.7–2.6; P < .01).ConclusionsAge-related differences in the incidence and severity of influenza hospitalizations among adults aged ≥65 years can inform prevention and treatment efforts, and data should be analyzed and reported using additional age strata.

Background National estimates of influenza burden may not reflect state‐level influenza activity, and local surveillance may not capture the full burden of influenza. Methods To provide state‐level information about influenza burden, we estimated excess pneumonia and influenza (P&I) and respiratory and circulatory (R&C) hospitalizations and deaths in Colorado from local hospital discharge records, death certificates, and influenza virus surveillance using negative binomial models. Results From July 2007 to June 2016, influenza was associated with an excess of 17 911 P&I hospitalizations (95%CI: 15 227, 20 354), 30 811 R&C hospitalizations (95%CI: 24 344, 37 176), 1,064 P&I deaths (95%CI: 757, 1298), and 3828 R&C deaths (95%CI: 2060, 5433). There was a large burden of influenza A(H1N1) among persons aged 0‐64 years, with high median seasonal rates of excess hospitalization among persons aged 0‐4 years. Persons aged ≥65 years experienced the largest numbers and highest median seasonal rates of excess hospitalization and death associated with influenza A (H3N2). The burden of influenza B was generally lower, with elevated median seasonal rates of excess hospitalization among persons aged 0‐4 years and ≥65 years. Conclusions These findings complement existing influenza surveillance. Periodic state‐level estimates of influenza disease burden may be useful for setting state public health priorities and planning prevention and control initiatives.

Background: In May 2018, Children's Hospital Colorado (CHCO) noted an outbreak of enterovirus (EV) A71-associated neurologic disease. Methods: A case of EV-associated neurologic disease was defined as any child presenting to CHCO with meningitis, encephalitis, acute flaccid myelitis (AFM), and/or seizures between March 1 and November 30, 2018 with an EV detected from a biologic specimen. EV-A71 cases were compared to other EV cases during the same period. EV-A71-associated AFM cases were also compared to EV-D68-associated AFM cases from 2013-2018. Findings: Of seventy-four children with EV-associated neurologic disease, forty-three (58%) were EV-A71-associated. Median age of EV-A71 cases was 22.7 months (IQR: 4-31.9 months); 34 (79%) were male. Neurologic involvement in EV-A71 cases included meningitis (93%), encephalitis (72%), and AFM (23%). All EV-A71 cases had fever; eighteen (42%) had hand, foot, or mouth (HFM) lesions. Neurologic findings distinguishing EV-A71-associated cases from other EV-associated cases (n=31) included myoclonus (60% vs. 16%, p

In August 2018, CDC noted an increased number of reports of patients having symptoms clinically compatible with acute flaccid myelitis (AFM), a rare condition characterized by rapid onset of flaccid weakness in one or more limbs and spinal cord gray matter lesions, compared with August 2017. Since 2014, CDC has conducted surveillance for AFM using a standardized case definition (1,2). An Epi-X* notice was issued on August 23, 2018, to increase clinician awareness and provide guidance for case reporting.

Background Existing data on the clinical features and outcomes of immunocompromised children with influenza are limited. Methods Data from the 2011–2012 through 2014–2015 influenza seasons were collected as part of the Centers for Disease Control and Prevention (CDC) Influenza Hospitalization Surveillance Network (FluSurv-NET). We compared clinical features and outcomes between immunocompromised and nonimmunocompromised children ( Results Among 5262 hospitalized children, 242 (4.6%) were immunocompromised; receipt of nonsteroidal immunosuppressive therapy (60%), cancer (39%), and solid organ transplantation (14%) were most common. Immunocompromised children were older than the nonimmunocompromised children (median, 8.8 vs 2.8 years, respectively; P < .001), more likely to have another comorbidity (58% vs 49%, respectively; P = .007), and more likely to have received an influenza vaccination (58% vs 39%, respectively; P < .001) and early antiviral treatment (35% vs 27%, respectively; P = .013). In multivariable analyses, immunocompromised children were less likely to receive intensive care (adjusted odds ratio [95% confidence interval], 0.31 [0.20–0.49]) and had a slightly longer duration of hospitalization (adjusted hazard ratio of hospital discharge [95% confidence interval], 0.89 [0.80–0.99]). Death was uncommon in both groups. Conclusions Immunocompromised children hospitalized with influenza received intensive care less frequently but had a longer hospitalization duration than nonimmunocompromised children. Vaccination and early antiviral use could be improved substantially. Data are needed to determine whether immunocompromised children are more commonly admitted with milder influenza severity than are nonimmunocompromised children.

Background The 2018–19 influenza season was characterized by prolonged co-circulation of Influenza A H3N2 (H3) and H1N1pdm09 (H1) viruses. We used data from the Influenza Hospitalization Surveillance Network (FluSurv-NET) to describe age-related differences in the distribution of influenza A subtypes. Methods We included all cases residing within a FluSurv-NET catchment area and hospitalized with laboratory-confirmed influenza during October 1, 2018–April 30, 2019. We multiply imputed influenza A subtype for 63% of cases with unknown subtype and based imputation on factors that could be associated with missing subtype including surveillance site, 10-year age groups and month of hospital admission. We calculated influenza hospitalization rates and 95% confidence intervals (95% CI) by type and subtype per 100,000 population. We compared the proportion of cases with H1 by year of age in FluSurv-NET to the distribution obtained from US public health laboratories participating in virologic surveillance and providing specimen-level influenza Results. Results Based on available data, 18,669 hospitalizations were reported; 41% received influenza vaccination ≥2 weeks prior to hospitalization and 90% received antivirals. Cumulative hospitalization rates per 100,000 population were as follows: H1 32.5 (95% CI 31.7–33.3), H3 29.3 (95% CI 28.5–30.1) and B 2.5 (95% CI 2.3–2.7). Based on weekly rates, H1 hospitalizations peaked during February (week 8) and H3 hospitalizations during March (week 11) (Figure A). FluSurv-NET data showed distinct patterns of subtype distribution by age, with H1 predominating among cases 0–9 and 24–70 years, and H3 predominating among cases 10–23 and ≥71 years. Data on the proportion of H1 results by age correlated well between FluSurv-NET and US virologic surveillance (Figure B). Conclusion Influenza A H1 and H3 virus circulation patterns varied by age group during the 2018–2019 season. The proportion of cases with H1 relative to H3 was low among those born between 1996 and 2009 and those born before 1948. These findings may indicate protection against H1 viruses in age groups with exposure to H1N1pdm09 during the 2009 pandemic or to older antigenically similar H1N1 viruses as young children. Disclosures Evan J. Anderson, MD, AbbVie (Consultant), GSK (Grant/Research Support), Merck (Grant/Research Support), Micron (Grant/Research Support), PaxVax (Grant/Research Support), Pfizer (Consultant, Grant/Research Support), sanofi pasteur (Grant/Research Support), Keipp Talbot, MD, MPH, Sequirus (Other Financial or Material Support, On Data Safety Monitoring Board).

Background Older adults residing in nursing homes (NH) are at increased risk for invasive group A Streptococcus (GAS) infections due to advanced age, presence of wounds, and comorbidities; approximately one-third of infected patients die. Beginning in 2015, increasing numbers of GAS infections in NH residents and several NH clusters were reported from the Denver metropolitan area. Colorado Department of Public Health and Environment (CDPHE) and CDC investigated to characterize cases and assess if outbreaks resulted from interfacility transmission. Methods We reviewed data from Active Bacterial Core surveillance (ABCs) in the 5-county Denver area from January 2017 to June 2018. We defined a case as isolation of GAS from a normally sterile site in an NH resident. GAS isolates underwent whole-genome sequencing (WGS) at CDC’s Streptococcus Laboratory to determine emm types for genotyping. Among isolates with the same emm type, pairwise single-nucleotide polymorphism (SNP) distances were calculated using Nucmer software. In October 2018, a CDPHE-CDC team assessed infection control at NHs with cases of the most common emm type. Results Over 18 months, among >100 NHs in the Denver area, ≥1 GAS case was identified in 29 NHs, with 6 having ≥3 cases. During this period, 68 cases in NH residents were identified. WGS identified 17 emm types among isolates from these cases; most common was emm11.10 (34%, n = 22), a rare subtype in ABCs. All emm11.10 isolates had nearly identical genomes (average pairwise SNP distance: 3.2), and were isolated from 10 NHs, with 2 NHs having ≥ 4 cases. Multiple infection control lapses were noted during site visits to 8 NHs. Conclusion Multiple outbreaks due to GAS were noted in 5-county Denver area NHs in 2017–2018. WGS of surveillance isolates identified a rarely seen emm subtype 11.10 from multiple facilities with temporal and genomic clustering suggesting interfacility GAS transmission. Disclosures All Authors: No reported Disclosures.

Background Influenza is most commonly associated with respiratory complications; however, nonrespiratory complications occur frequently among patients hospitalized with influenza. We used data from the Influenza Hospitalization Surveillance Network (FluSurv-NET) to describe complications recorded on discharge summaries of patients hospitalized with influenza. Methods We included children (0–17 years) and adults (≥18 years), who resided within a FluSurv-NET catchment area and were hospitalized with laboratory-confirmed influenza during 2016–2017. We abstracted data on underlying conditions and discharge diagnoses from medical charts. We calculated the frequency of respiratory and nonrespiratory complications in all age groups and used univariate and multivariable logistic regression to examine factors associated with select complications among adults. Results Among 17,489 patients, the most common respiratory complications were pneumonia (26%) and acute respiratory failure (23%) and the most common nonrespiratory complications were sepsis (16%) and acute renal failure (ARF) (12%). Complications varied by age group (figure). Pneumonia was the most common respiratory complication in all age groups except 0–4 years; among children aged 0–4 years bronchiolitis was most common (104/712; 15%). Among 97 children aged 0–4 years with bronchiolitis who underwent testing for respiratory syncytial virus (RSV), 37% had RSV. The most common nonrespiratory complication was seizures in children aged 0–17 years (17% had a history of prior seizures) and sepsis in adults. Among adults (n = 16,057), factors most strongly associated with ARF included chronic renal disease (adjusted odds ratio (AOR) 2.5; 95% confidence interval (95% CI) 2.2–2.8), male sex (AOR 1.5 95% CI 1.4–1.7) and age ≥65 years (AOR 1.4 95% CI 1.2–1.7); the factor most strongly associated with sepsis was chronic neuromuscular disease (AOR 1.5 95% CI 1.3–1.8). Conclusion Influenza hospitalizations are associated with a broad spectrum of complications including pneumonia, respiratory failure, sepsis, ARF and seizures. During the influenza season, astute clinicians should keep influenza in the differential diagnosis for patients with a wide range of presentations. :Disclosures. H. K. Talbot, sanofi pasteur: Investigator, Research grant. Gilead: Investigator, Research grant. MedImmune: Investigator, Research grant. Vaxinnate: Safety Board, none. Seqirus: Safety Board, none. E. J. Anderson, NovaVax: Grant Investigator, Research grant. Pfizer: Grant Investigator, Research grant. AbbVie: Consultant, Consulting fee. MedImmune: Investigator, Research support. PaxVax: Investigator, Research support. Micron: Investigator, Research support.

Objective We compared the effectiveness and cost-effectiveness of: 1) centralized reminder/recall (C-R/R) using the Colorado Immunization Information System (CIIS) versus practice-based reminder/recall (PB-R/R) approaches to increase immunization rates; 2) different levels of C-R/R intensity; and 3) C-R/R with versus without the name of the child's provider. Methods We conducted 3 sequential cluster-randomized trials involving children aged 19 to 25 months in 15 Colorado counties in March 2013 (trial 1), October 2013 (trial 2), and May 2014 (trial 3). In C-R/R counties, the intensity of the intervention decreased sequentially in trials 1 through 3, from 3 to 1 recall messages. In PB-R/R counties, practices were offered training using CIIS and financial support. The percentage of children with up-to-date (UTD) vaccinations was compared 6 months after recall. A mixed-effects model assessed the association between C-R/R versus PB-R/R and UTD rates. Results C-R/R was more effective in trials 1 to 3 (relative risk = 1.11; 95% confidence interval 1.01–1.20; P = .009). Effectiveness did not decrease with decreasing intervention intensity ( P = .59). Costs decreased with decreasing intensity in the C-R/R arm, from $18.72 per child brought UTD in trial 1 to $10.11 in trial 3. Costs were higher and more variable in the PB-R/R arm, ranging from $20.63 to $237.81 per child brought UTD. C-R/R was significantly more effective if the child's practice name was included ( P Conclusions C-R/R was more effective and cost-effective than PB-R/R for increasing UTD rates in young children and was most effective if messages included the child's provider name. Three reminders were not more effective than one, which may be explained by the increasing accuracy of contact information in CIIS over the course of the trials.

Background In May 2018, an outbreak of enterovirus A71 (EV-A71) neurologic disease was detected at Children’s Hospital Colorado (CHCO) prompting a public health investigation. We characterized clinical, laboratory, and radiologic findings during this outbreak. Methods A case was defined as meningitis, encephalitis, or acute flaccid myelitis with EV-A71 identified from a biologic specimen in a child examined at CHCO after March 1, 2018. Biologic specimens from children with neurologic disease and EV identified by clinical reverse-transcription polymerase chain reaction (RT-PCR) were typed by VP1 sequencing at CDC. Results As of July 20, 2018, 28 cases of EV-A71 neurologic disease were identified. This report describes the clinical, laboratory, and radiologic findings for the first 13 children identified with EV-A71 neurologic disease, for whom complete information is available. The median age was 13 months (range = 10 days–35 months) and 11 (85%) were male. Neurologic presentations included 12 (92%) with meningitis, 9 (69%) with encephalitis, and 3 (23%) with acute flaccid myelitis (AFM). All 13 children had fever and irritability; 3 (23%) had hand, foot, and mouth disease. Neurologic signs included encephalopathy (n = 7, 54%), ataxia (n = 7, 54%), myoclonus (n = 6, 46%), limb weakness (n = 4, 31%), cranial nerve deficits (n = 2, 15%), and seizures (n = 1, 8%). Nine (90%) of 10 children with cerebrospinal fluid (CSF) specimen analyzed had a pleocytosis (>5 white blood cells/uL); 6 of 8 (75%) children who had brain imaging showed abnormalities, with 5 (63%) in the brainstem, 3 (38%) in the cerebellum, and 3 (38%) in the spinal cord. All 13 children had EV-A71 identified in nasopharyngeal, pharyngeal, or fecal specimens; only 2 of 11 (18%) tested had EV identified in CSF. All 13 children were hospitalized and 4 (31%) required intensive care. The 3 (23%) children with AFM had residual limb weakness at time of discharge. All children survived. Conclusion EV-A71 should be considered when children present with myoclonus, ataxia, or limb weakness in the setting of a febrile illness. Testing of nonsterile sites (respiratory, pharyngeal, or fecal) should be considered when CNS disease associated with EV is suspected and initial CSF testing is negative. Disclosures All authors: No reported disclosures.

Background Few data describe the epidemiology of influenza among adults ≥65 years old according to age strata. We evaluated age-related differences in influenza-associated hospitalization rates, clinical presentation, and outcomes among older adults at 14 FluSurv-NET sites during the 2011–2012 through 2014-2015 influenza seasons. Methods Study patients were hospitalized ≤14 days after and ≤3 days before a positive influenza test. Age strata were 65–74, 75–84, and ≥85 years old. We adjusted hospitalization rates for under detection and assessed for age-related trends in risk factors and symptoms. We used logistic regression to calculate odds ratios (OR) for pneumonia and in-hospital death adjusted for season, sex, nursing home residence, smoking, medical comorbidities, influenza vaccination, and study site. Results There were 19,760 patients, including 5,956 aged 65–74 years, 6,998 aged 75–84 years, and 6,806 aged ≥85 years. There was a stepwise increase in hospitalization rates with age (figure). Increasing age was positively associated with female sex, nursing home residence, neurologic disorder, cardiovascular and renal disease, and vaccination, and inversely associated with morbid obesity, smoking, asthma, chronic metabolic disease, and immunosuppression (P < 0.01). Among 10,548 (53.3%) patients with symptom data from 2014 to 2015, increasing age was associated with a higher prevalence of altered mental status and lower prevalence of fever, myalgias, respiratory or gastrointestinal symptoms, and headache (P ≤ 0.01). Compared with 65–74 year olds, older patients had a higher risk of pneumonia (≥85 year-olds: OR 1.2, 95% CI 1.0, 1.3, P = 0.01) and death (75–84 year olds: OR 1.4, 95% CI 1.2, 1.7, P < 0.01; ≥85 year-olds: OR 2.1, 95% CI 1.7, 2.6, P < 0.01). Conclusion There are age-related differences in the epidemiology, clinical presentation, and outcomes of older adults hospitalized with influenza. These may reflect differences in health status and healthcare provider practice patterns. Public health epidemiologists should consider using additional age strata in ≥65 year-olds when analyzing influenza surveillance data. Clinicians should be aware that influenza among the oldest adults may present atypically and that mortality is increased. Disclosures E. J. Anderson, NovaVax: Grant Investigator, Research grant. Pfizer: Grant Investigator, Research grant. AbbVie: Consultant, Consulting fee. MedImmune: Investigator, Research support. PaxVax: Investigator, Research support. Micron: Investigator, Research support. W. Schaffner, Merck: Member, Data Safety Monitoring Board, Consulting fee. Pfizer: Member, Data Safety Monitoring Board, Consulting fee. Dynavax: Consultant, Consulting fee. Seqirus: Consultant, Consulting fee. SutroVax: Consultant, Consulting fee. Shionogi: Consultant, Consulting fee.

Reminder/recall notifications used by primary care practices increase the rates of childhood immunizations, but fewer than 20% of primary care practitioners nationally deliver such reminders. A reminder/recall notification conducted centrally by health departments in collaboration with primary care practices may reduce practice burden, reach children without a primary care practitioner, and decrease the cost of reminders/recalls.To assess the effectiveness and cost-effectiveness of collaborative centralized (CC) vs practice-based (PB) reminder/recall approaches using the Colorado Immunization Information System (CIIS).We performed a randomized pragmatic trial from September 7, 2012, through March 17, 2013, including 18,235 children aged 19 to 35 months in 15 Colorado counties.In CC counties, children who needed at least 1 immunization were sent as many as 4 reminders/recalls by mail or autodialed telephone calls by the CIIS. Primary care practices in these counties were given the option of endorsing the reminder/recall notification by adding the practice name to the message. In PB counties, primary care practices were invited to web-based reminder/recall training and offered financial support for sending notifications.Documentation of any new immunization within 6 months constituted the primary outcome; achieving up-to-date (UTD) immunization status was secondary. We assessed the cost and cost-effectiveness of each approach and used a generalized linear mixed-effects model to assess the effect of the intervention on outcomes.In PB counties, 24 of 308 primary care practices (7.8%) attended reminder/recall training and 2 primary care practices (0.6%) endorsed reminder/recall notifications. Within CC counties, 129 of 229 practices (56.3%) endorsed the reminder/recall letter. Documentation rates for at least 1 immunization were 26.9% for CC vs 21.7% for PB counties (P .001); 12.8% vs 9.3% of patients, respectively, achieved UTD status (P .001). The effect of CC counties on children's UTD status was greater when the reminder/recall notification was endorsed by the primary care practice (19.2% vs 9.8%; P .001). The total cost of the CC reminder/recall was $28 620 or $11.75 per child for any new immunization and $24.72 per child achieving UTD status; the total cost to the 2 practices that conducted PB reminders/recalls was $74.00 per child for any immunization and $124.45 per child achieving UTD status. The modeling resulted in an adjusted odds ratio of 1.31 (95% CI, 1.16-1.48) for any new immunization in CC vs PB counties.A CC reminder/recall notification was more effective and more cost-effective than a PB system, although the effect size was modest. Endorsement by practices may further increase the effectiveness of CC reminder/recall.clinicaltrials.gov Identifier: NCT01557621.