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Background: Pneumonia is common in adults hospitalized with laboratory-confirmed influenza, but the association between timeliness of influenza antiviral treatment and severe clinical outcomes in patients with influenza-associated pneumonia is not well characterized., Methods: We included adults aged ≥18 years hospitalized with laboratory-confirmed influenza and a discharge diagnosis of pneumonia over 7 influenza seasons (2012-2019) sampled from a multistate population-based surveillance network. We evaluated 3 treatment groups based on timing of influenza antiviral initiation relative to admission date (day 0, day 1, days 2-5). Baseline characteristics and clinical outcomes were compared across groups using unweighted counts and weighted percentages accounting for the complex survey design. Logistic regression models were generated to evaluate the association between delayed treatment and 30-day all-cause mortality., Results: A total of 26 233 adults were sampled in the analysis. Median age was 71 years and most (92.2%) had ≥1 non-immunocompromising condition. Overall, 60.9% started antiviral treatment on day 0, 29.5% on day 1, and 9.7% on days 2-5 (median, 2 days). Baseline characteristics were similar across groups. Thirty-day mortality occurred in 7.5%, 8.5%, and 10.2% of patients who started treatment on day 0, day 1, and days 2-5, respectively. Compared to those treated on day 0, adjusted odds ratio for death was 1.14 (95% confidence interval [CI], 1.01-1.27) in those starting treatment on day 1 and 1.40 (95% CI, 1.17-1.66) in those starting on days 2-5., Conclusions: Delayed initiation of antiviral treatment in patients hospitalized with influenza-associated pneumonia was associated with higher risk of death, highlighting the importance of timely initiation of antiviral treatment at admission., Competing Interests: Potential conflicts of interest. K. Y.-H., J. M., I. A., and W. S. report grants from the CDC, during the conduct of the study. A. F. and L. R. report grants from the Michigan Department of Health and Human Services, during the conduct of the study. M. L. M. reports grants from the CDC Emerging Infections Program, during the conduct of the study. R. L. reports grants from the CDC Emerging Infections Program cooperative agreement, during the conduct of the study, and fee for work as Associate Editor for the American Academy of Pediatrics Report of the Committee on Infectious Diseases (Red Book), which donated to the Minnesota Department of Health. H. K. T. reports funding from CDC for this work and other areas of research. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2024.)

Asymptomatic influenza virus infection occurs but may vary by factors such as age, vaccination status, or season. We examined the frequency of influenza virus infection and symptoms using data from two case-ascertained household transmission studies (2017-2023) with prospective, systematic collection of respiratory specimens and symptoms. From the 426 influenza virus infected household contacts that met our inclusion criteria, 8% were asymptomatic, 6% had non-respiratory symptoms, 23% had acute respiratory symptoms, and 62% had influenza-like illness symptoms. Understanding the prevalence of asymptomatic and mildly symptomatic influenza cases is important for implementing effective influenza prevention strategies and enhancing symptom-based surveillance systems., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2024.)

Background: While the estimated number of U.S. influenza-associated deaths is reported annually, detailed data on the epidemiology of influenza-associated deaths, including the burden of in-hospital versus post-hospital discharge deaths are limited., Methods: Using data from the 2010-11 through 2018-19 seasons from the Influenza Hospitalization Surveillance Network, we linked cases to death certificates to identify patients who died from any cause during their influenza hospital stay or within 30 days post discharge. We described demographic and clinical characteristics of patients who died in hospital versus post discharge and characterized locations and causes of death (COD)., Results: Among 121,390 cases hospitalized with laboratory-confirmed influenza over 9 seasons, 5.5% died; 76% of deaths were in patients ≥65 years, 71% were non-Hispanic White, and 34% had ≥4 underlying medical conditions. Among all patients with an influenza-associated hospitalization who died, 48% of deaths occurred after hospital discharge; the median days from discharge to death was 9 days (IQR 3-19 days). Post-discharge deaths more often occurred in older patients and among those with underlying medical conditions. Only 37% of patients who died had "influenza" as a COD on their death certificate. Influenza was more frequently listed as a COD among persons who died in-hospital compared with cardiovascular disease among those who died after discharge., Conclusions: All-cause mortality burden is substantial among patients hospitalized with influenza, with almost 50% of deaths occurring within 30 days after hospital discharge. Surveillance systems should consider capture of post-discharge outcomes to better characterize the impact of influenza on all-cause mortality., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2024.)

Background: With aging of the population and improvements in diagnosis, treatment, and supportive care, the number of cancer survivors in the United States has increased; updated prevalence estimates are needed., Methods: Cancer prevalence on January 1, 2022, was estimated using the Prevalence Incidence Approach Model, utilizing incidence, survival, and mortality. Prevalence by age decade, sex, and time from diagnosis was calculated. The percentage of cancer survivors in the projected US population by age and sex was calculated as the ratio of the sex-specific projected prevalence to the sex-specific projected US population., Results: There were an estimated 18.1 million US cancer survivors as of January 1, 2022. From 2022 to 2030, the number of US cancer survivors is projected to increase to 21.6 million; by 2040, the number is projected to be 26 million. Long-term survivors are highly prevalent; in 2022, 70% of cancer survivors had lived 5 years or more after diagnosis, and 11% of cancer survivors had lived 25 years or more after diagnosis. Among all US females aged 40-54 years, 3.6% were cancer survivors; among females aged 65-74 years, 14.5% were cancer survivors; among females aged 85 years and older, 36.4% were cancer survivors. Among all US males aged 40-54 years, 2.1% were cancer survivors; among males aged 65-74 years, 16% were cancer survivors; and among those aged 85 years and older, 48.3% were cancer survivors., Conclusions: Cancer survivors are growing in number. In the United States, most cancer survivors are long-term and very long-term survivors, representing a substantial proportion of the US population., (Published by Oxford University Press 2024.)

Understanding whether influenza vaccine promotion strategies produce community-wide indirect effects is important for establishing vaccine coverage targets and optimizing vaccine delivery. Empirical epidemiologic studies and mathematical models have been used to estimate indirect effects of vaccines but rarely for the same estimand in the same dataset. Using these approaches together could be a powerful tool for triangulation in infectious disease epidemiology because each approach is subject to distinct sources of bias. We triangulated evidence about indirect effects from a school-located influenza vaccination program using two approaches: a difference-in-difference (DID) analysis, and an age-structured, deterministic, compartmental model. The estimated indirect effect was substantially lower in the mathematical model than in the DID analysis (2.1% (95% Bayesian credible intervals 0.4 - 4.4%) vs. 22.3% (95% CI 7.6% - 37.1%)). To explore reasons for differing estimates, we used sensitivity analyses and probabilistic bias analyses. When we constrained model parameters such that projections matched the DID analysis, results only aligned with the DID analysis with substantially lower pre-existing immunity among school-age children and older adults. Conversely, DID estimates corrected for potential bias only aligned with mathematical model estimates under differential outcome misclassification. We discuss how triangulation using empirical and mathematical modelling approaches could strengthen future studies., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.)

Food insecurity (FI) is a modifiable social determinant of health that impacts approximately 10 percent of the U.S. population. FI has been linked to poorer health outcomes and higher healthcare costs. Given the prevalence of chronic health conditions in the United States, including serious mental illness (SMI), the current study aims to better understand the relationship between FI and chronic conditions, including SMI, in a nationally representative sample. Authors analyzed data from the 2016 Medical Expenditure Panel Survey household component and food security supplement. Findings indicate the prevalence of FI among those with diabetes, lung disease, stroke, and SMI is higher than among the general population, with the prevalence for those with SMI being particularly high (43 percent of the sample). Logistic regression models indicate strong, statistically significant relationships between FI and chronic conditions, including SMI, as well as FI and two or more chronic illnesses, even when controlling for sociodemographic and health factors. There are likely bidirectional relationships between FI and chronic conditions. Findings have implications for social workers, in relation to prevention and treatment of SMI and FI through direct care, advocacy, and integrated services in health, mental health, and social services., (© 2024 National Association of Social Workers.)

Background: Communities and researchers have called for a paradigm shift from describing health disparities to a health equity research agenda that addresses structural drivers. Therefore, we examined whether the cancer survivorship research portfolio has made this shift., Methods: We identified grants focused on populations experiencing health disparities from the National Institutes of Health (NIH) Cancer Survivorship Research Portfolio (N = 724), Fiscal Years 2017-2022. Grant characteristics were abstracted, drivers of health disparities were mapped onto the levels and domains of influence, and opportunities for future research were identified., Results: A total of 147 survivorship grants focused on health disparities were identified, of which 73.5% of grants focused on survivors from racial and ethnic minoritized groups, 25.9% living in rural areas, 24.5% socioeconomically disadvantaged, and 2.7% sexual and gender minority groups. Study designs were 51.0% observational; 82.3% of grants measured or intervened on at least 1 individual-level of influence compared to higher levels of influence (32.7% interpersonal, 41.5% institutional and community, and 12.2% societal). Behavioral and health care system domains of influence were commonly represented, especially at the individual level (47.6% and 36.1%, respectively). Less frequently represented was the physical and built environment (12.2%)., Conclusions: NIH-funded cancer survivorship research on health disparities is still focused on individual level of influence. However, the proportion of grants examining structural and social drivers as well as the mechanisms that drive disparities in health care and health outcomes among cancer survivors have increased over time. Gaps in funded research on specific populations, cancer types, and focus areas of survivorship science were identified and warrant priority., (Published by Oxford University Press 2024.)

From 2 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) household transmission studies (enrolling April 2020 to January 2022) with rapid enrollment and specimen collection for 14 days, 61% (43/70) of primary cases had culturable virus detected ≥6 days post-onset. Risk of secondary infection among household contacts tended to be greater when primary cases had culturable virus detected after onset. Regardless of duration of culturable virus, most secondary infections (70%, 28/40) had serial intervals <6 days, suggesting early transmission. These data examine viral culture as a proxy for infectiousness, reaffirm the need for rapid control measures after infection, and highlight the potential for prolonged infectiousness (≥6 days) in many individuals., Competing Interests: Potential conflicts of interest. C. G. G. reports grants from Campbell Alliance/Syneos, the National Institutes of Health, the Food and Drug Administration, the Agency for Health Care Research and Quality, and Sanofi-Pasteur; and consultation fees from Pfizer, Merck, and Sanofi-Pasteur. J. R. S. reports support from Roche Diagnostics. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2023.)

Given renewed attention to racial equity in the social work profession, the authors suggest the use of counternarratives, an established tool of critical race theory, as an accessible method to challenge racism and examine privilege in social work education, practice, and research. Counternarratives use the technique of storytelling to elevate the lived experiences of marginalized individuals and communities and invite the listener into critical reflection about dominant, privileged discourses. The ultimate goal of counternarratives is the achievement of racial equity. The authors provide context about how counternarratives can align with social work education, practice, and research, and then use specific, illustrative examples from their own work to bring this method and its application to life. The authors also share their own processes of reflection and dialogue across disciplines and social locations in the use of counternarratives. The reflections of an experienced social justice educator provide additional insights on the use of counternarratives in the field of social work., (© 2023 National Association of Social Workers.)

Background: Influenza virus and SARS-CoV-2 are significant causes of respiratory illness in children., Methods: Influenza- and COVID-19-associated hospitalizations among children <18 years old were analyzed from FluSurv-NET and COVID-NET, 2 population-based surveillance systems with similar catchment areas and methodology. The annual COVID-19-associated hospitalization rate per 100 000 during the ongoing COVID-19 pandemic (1 October 2020-30 September 2021) was compared with influenza-associated hospitalization rates during the 2017-2018 through 2019-2020 influenza seasons. In-hospital outcomes, including intensive care unit (ICU) admission and death, were compared., Results: Among children <18 years, the COVID-19-associated hospitalization rate (48.2) was higher than influenza-associated hospitalization rates: 2017-2018 (33.5), 2018-2019 (33.8), and 2019-2020 (41.7). The COVID-19-associated hospitalization rate was higher among adolescents 12-17 years old (COVID-19: 59.9; influenza range: 12.2-14.1), but similar or lower among children 5-11 (COVID-19: 25.0; influenza range: 24.3-31.7) and 0-4 (COVID-19: 66.8; influenza range: 70.9-91.5) years old. Among children <18 years, a higher proportion with COVID-19 required ICU admission compared with influenza (26.4% vs 21.6%; P < .01). Pediatric deaths were uncommon during both COVID-19- and influenza-associated hospitalizations (0.7% vs 0.5%; P = .28)., Conclusions: In the setting of extensive mitigation measures during the COVID-19 pandemic, the annual COVID-19-associated hospitalization rate during 2020-2021 was higher among adolescents and similar or lower among children <12 years compared with influenza during the 3 seasons before the COVID-19 pandemic. COVID-19 adds substantially to the existing burden of pediatric hospitalizations and severe outcomes caused by influenza and other respiratory viruses., Competing Interests: Potential conflicts of interest. E. J. A. reports grants from Pfizer, Merck, PaxVax, Micron, Sanofi-Pasteur, Janssen, MedImmune, and GlaxoSmithKline (all for clinical trials); personal fees from Sanofi-Pasteur, Pfizer, Medscape, Kentucky Bioprocessing, Inc, Sanofi-Pasteur, and Janssen (all for consulting); and participation on a personal fees for participating on a Data Safety Monitoring Board for Kentucky Bioprocessing, Inc, and Sanofi-Pasteur outside the submitted work. His institution has also received funding from the National Institute of Health to conduct clinical trials of Moderna and Janssen COVID-19 vaccines, unrelated to this work. W. S. reports personal fees from VBI Vaccines, outside the submitted work. N. B. A. reports an Emerging Infections Program cooperative agreement from the Centers for Disease Control and Prevention (CDC) outside the submitted work. K. T. reports grants from CDC/CSTE related to flu surveillance activities unrelated to this work. A. W. reports multiple grants from CDC/CSTE for flu surveillance (eg, Youth in Agriculture, Enhancing Laboratory Capacity) outside the submitted work. R. L. reports a position as an associate editor of Red Book (American Academy of Pediatrics Report of the Committee on Infectious Diseases). L. M. B. reports receipt of Epidemiology and Laboratory Capacity (ELC) and Immunizations and Vaccines for Children (VFC) grant funding from CDC to support vaccine-preventable disease epidemiology staffing, outside the submitted work. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

We used daily real-time reverse-transcription polymerase chain reaction (RT-PCR) results from 67 cases of SARS-CoV-2 infection in a household transmission study, conducted April 2020-May 2021, to examine the trajectory of cycle threshold (Ct) values, an inverse correlate of viral RNA concentration. Ct values varied across RT-PCR platforms and by participant age. Specimens collected from children and adolescents had higher Ct values and adults aged ≥50 years showed lower Ct values than adults aged 18-49 years. Ct values were lower on days when participants reported experiencing symptoms, with the lowest Ct value occurring 2-6 days after symptom onset., Competing Interests: Potential conflicts of interest. C. G. G. reports grants from Campbell Alliance/Syneos, the National Institutes of Health, the Food and Drug Administration, the Agency for Health Care Research and Quality, and Sanofi-Pasteur; and consultation fees from Pfizer, Merck, and Sanofi-Pasteur. N. B. H. reports grant support from Sanofi-Pasteur and Quidel. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2022.)

Protein fusions are frequently used for fluorescence imaging of individual molecules, both in vivo and in vitro. The SNAP, CLIP, HALO (aka HaloTag7), and DHFR protein tags can be linked to small molecule dyes that provide brightness and photo-stability superior to fluorescent proteins. To facilitate fluorescent dye tagging of proteins in the yeast Saccharomyces cerevisiae, we constructed a modular set of vectors with various combinations of labeling protein tags and selectable markers. These vectors can be used in combination to create strains where multiple proteins labeled with different colored dyes can be simultaneously observed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Genetics Society of America.)

Background: Acute respiratory infections (ARI) are the most common infectious diseases globally. Community surveillance may provide a more comprehensive picture of disease burden than medically attended illness alone., Methods: In this longitudinal study conducted from 2012 to 2017 in the Washington Heights/Inwood area of New York City, we enrolled 405 households with 1915 individuals. Households were sent research text messages twice weekly inquiring about ARI symptoms. Research staff confirmed symptoms by follow-up call. If ≥2 criteria for ARI were met (fever/feverish, cough, congestion, pharyngitis, myalgias), staff obtained a mid-turbinate nasal swab in participants' homes. Swabs were tested using the FilmArray reverse transcription polymerase chain reaction (RT-PCR) respiratory panel., Results: Among participants, 43.9% were children, and 12.8% had a chronic respiratory condition. During the 5 years, 114 724 text messages were sent; the average response rate was 78.8% ± 6.8%. Swabs were collected for 91.4% (2756/3016) of confirmed ARI; 58.7% had a pathogen detected. Rhino/enteroviruses (51.9%), human coronaviruses (13.9%), and influenza (13.2%) were most commonly detected. The overall incidence was 0.62 ARI/person-year, highest (1.73) in <2 year-olds and lowest (0.46) in 18-49 year-olds. Approximately one-fourth of those with ARI sought healthcare; percents differed by pathogen, demographic factors, and presence of a chronic respiratory condition., Conclusions: Text messaging is a novel method for community-based surveillance that could be used both seasonally as well as during outbreaks, epidemics and pandemics. The importance of community surveillance to accurately estimate disease burden is underscored by the findings of low rates of care-seeking that varied by demographic factors and pathogens., Competing Interests: Potential conflicts of interest. M. S. reports several grants and subcontracts from the National Institutes of Health (NIH), CDC, to trustees of Columbia University outside of the submitted work; received honoraria for speaking at the Kentucky Infectious Diseases Coronavirus Disease 2019 (COVID-19) Task Force Forum and the 23rd Annual Frontiers in Pediatrics Conference Charleston, South Carolina; Associate Director of American Academy of Pediatrics Pediatric Research in Office Settings (PROS) to Trustees of Columbia University; and BioFire Diagnostics, Inc, loaned machines for this study, and provided kits at a reduced rate for research. L. S. reports grants or contracts from Merck Co, Inc, National Institute of Allergy and Infectious Diseases (NIAID), Bill and Melinda Gates Foundation, and Cystic Fibrosis Foundation outside of the submitted work; consulting fees from Cystic Fibrosis Foundation and Matrix Inc; and participation on a Data Safety Monitoring Board or Advisory Board for Merck Co, Inc, and Armata. P. L. reports grants or contracts from Merck Co, Inc, outside of the submitted work and unrestricted gift from Pfizer for vaccine education to Trustees of Columbia University, used for salary, and conference. L. S., E. L., and P. L. received funding from Merck for a project related to RSV. The work detailed in this manuscript pre-dates that funding. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Flu Near You (FNY) is an online participatory syndromic surveillance system that collects health-related information. In this article, we summarized the healthcare-seeking behavior of FNY participants who reported influenza-like illness (ILI) symptoms., Methods: We applied inverse probability weighting to calculate age-adjusted estimates of the percentage of FNY participants in the United States who sought health care for ILI symptoms during the 2015-2016 through 2018-2019 influenza season and compared seasonal trends across different demographic and regional subgroups, including age group, sex, census region, and place of care using adjusted χ 2 tests., Results: The overall age-adjusted percentage of FNY participants who sought healthcare for ILI symptoms varied by season and ranged from 22.8% to 35.6%. Across all seasons, healthcare seeking was highest for the <18 and 65+ years age groups, women had a greater percentage compared with men, and the South census region had the largest percentage while the West census region had the smallest percentage., Conclusions: The percentage of FNY participants who sought healthcare for ILI symptoms varied by season, geographical region, age group, and sex. FNY compliments existing surveillance systems and informs estimates of influenza-associated illness by adding important real-time insights into healthcare-seeking behavior., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: Monitoring of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody prevalence can complement case reporting to inform more accurate estimates of SARS-CoV-2 infection burden, but few studies have undertaken repeated sampling over time on a broad geographic scale., Methods: We performed serologic testing on a convenience sample of residual serum obtained from persons of all ages, at 10 sites in the United States from 23 March through 14 August 2020, from routine clinical testing at commercial laboratories. We standardized our seroprevalence rates by age and sex, using census population projections and adjusted for laboratory assay performance. Confidence intervals were generated with a 2-stage bootstrap. We used bayesian modeling to test whether seroprevalence changes over time were statistically significant., Results: Seroprevalence remained below 10% at all sites except New York and Florida, where it reached 23.2% and 13.3%, respectively. Statistically significant increases in seroprevalence followed peaks in reported cases in New York, South Florida, Utah, Missouri, and Louisiana. In the absence of such peaks, some significant decreases were observed over time in New York, Missouri, Utah, and Western Washington. The estimated cumulative number of infections with detectable antibody response continued to exceed reported cases in all sites., Conclusions: Estimated seroprevalence was low in most sites, indicating that most people in the United States had not been infected with SARS-CoV-2 as of July 2020. The majority of infections are likely not reported. Decreases in seroprevalence may be related to changes in healthcare-seeking behavior, or evidence of waning of detectable anti-SARS-CoV-2 antibody levels at the population level. Thus, seroprevalence estimates may underestimate the cumulative incidence of infection., (Published by Oxford University Press for the Infectious Diseases Society of America 2021.)

Background: In the United States, laboratory-confirmed coronavirus disease 2019 (COVID-19) is nationally notifiable. However, reported case counts are recognized to be less than the true number of cases because detection and reporting are incomplete and can vary by disease severity, geography, and over time., Methods: To estimate the cumulative incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, symptomatic illnesses, and hospitalizations, we adapted a simple probabilistic multiplier model. Laboratory-confirmed case counts that were reported nationally were adjusted for sources of underdetection based on testing practices in inpatient and outpatient settings and assay sensitivity., Results: We estimated that through the end of September, 1 of every 2.5 (95% uncertainty interval [UI]: 2.0-3.1) hospitalized infections and 1 of every 7.1 (95% UI: 5.8-9.0) nonhospitalized illnesses may have been nationally reported. Applying these multipliers to reported SARS-CoV-2 cases along with data on the prevalence of asymptomatic infection from published systematic reviews, we estimate that 2.4 million hospitalizations, 44.8 million symptomatic illnesses, and 52.9 million total infections may have occurred in the US population from 27 February-30 September 2020., Conclusions: These preliminary estimates help demonstrate the societal and healthcare burdens of the COVID-19 pandemic and can help inform resource allocation and mitigation planning., (Published by Oxford University Press for the Infectious Diseases Society of America 2020.)

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), was first identified in Wuhan, China, in December 2019, with subsequent worldwide spread. The first US cases were identified in January 2020., Methods: To determine if SARS-CoV-2-reactive antibodies were present in sera prior to the first identified case in the United States on 19 January 2020, residual archived samples from 7389 routine blood donations collected by the American Red Cross from 13 December 2019 to 17 January 2020 from donors resident in 9 states (California, Connecticut, Iowa, Massachusetts, Michigan, Oregon, Rhode Island, Washington, and Wisconsin) were tested at the Centers for Disease Control and Prevention for anti-SARS-CoV-2 antibodies. Specimens reactive by pan-immunoglobulin (pan-Ig) enzyme-linked immunosorbent assay (ELISA) against the full spike protein were tested by IgG and IgM ELISAs, microneutralization test, Ortho total Ig S1 ELISA, and receptor-binding domain/ACE2 blocking activity assay., Results: Of the 7389 samples, 106 were reactive by pan-Ig. Of these 106 specimens, 90 were available for further testing. Eighty-four of 90 had neutralizing activity, 1 had S1 binding activity, and 1 had receptor-binding domain/ACE2 blocking activity >50%, suggesting the presence of anti-SARS-CoV-2-reactive antibodies. Donations with reactivity occurred in all 9 states., Conclusions: These findings suggest that SARS-CoV-2 may have been introduced into the United States prior to 19 January 2020., (Published by Oxford University Press for the Infectious Diseases Society of America 2020.)

Background: Several observational studies have shown decreases in measured influenza vaccine effectiveness (mVE) during influenza seasons. One study found decreases of 6-11%/month during the 2011-2012 to 2014-2015 seasons. These findings could indicate waning immunity but could also occur if vaccine effectiveness is stable and vaccine provides partial protection in all vaccinees ("leaky") rather than complete protection in a subset of vaccinees. Since it is unknown whether influenza vaccine is leaky, we simulated the 2011-2012 to 2014-2015 influenza seasons to estimate the potential contribution of leaky vaccine effect to the observed decline in mVE., Methods: We used available data to estimate daily numbers of vaccinations and infections with A/H1N1, A/H3N2, and B viruses. We assumed that vaccine effect was leaky, calculated mVE as 1 minus the Mantel-Haenszel relative risk of vaccine on incident cases, and determined the mean mVE change per 30 days since vaccination. Because change in mVE was highly dependent on infection rates, we performed simulations using low (15%) and high (31%) total (including symptomatic and asymptomatic) seasonal infection rates., Results: For the low infection rate, decreases (absolute) in mVE per 30 days after vaccination were 2% for A/H1N1 and 1% for A/H3N2and B viruses. For the high infection rate, decreases were 5% for A/H1N1, 4% for A/H3, and 3% for B viruses., Conclusions: The leaky vaccine bias could account for some, but probably not all, of the observed intraseasonal decreases in mVE. These results underscore the need for strategies to deal with intraseasonal vaccine effectiveness decline., (Published by Oxford University Press for the Infectious Diseases Society of America 2020.)

Background: Respiratory syncytial virus (RSV) is a major cause of hospitalizations in young children. We estimated the burden of community-onset RSV-associated hospitalizations among US children aged <2 years by extrapolating rates of RSV-confirmed hospitalizations in 4 surveillance states and using probabilistic multipliers to adjust for ascertainment biases., Methods: From October 2014 through April 2015, clinician-ordered RSV tests identified laboratory-confirmed RSV hospitalizations among children aged <2 years at 4 influenza hospitalization surveillance network sites. Surveillance populations were used to estimate age-specific rates of RSV-associated hospitalization, after adjusting for detection probabilities. We extrapolated these rates using US census data., Results: We identified 1554 RSV-associated hospitalizations in children aged <2 years. Of these, 27% were admitted to an intensive care unit, 6% needed mechanical ventilation, and 5 died. Most cases (1047/1554; 67%) had no underlying condition. Adjusted age-specific RSV hospitalization rates per 100 000 population were 1970 (95% confidence interval [CI],1787 to 2177), 897 (95% CI, 761 to 1073), 531 (95% CI, 459 to 624), and 358 (95% CI, 317 to 405) for ages 0-2, 3-5, 6-11, and 12-23 months, respectively. Extrapolating to the US population, an estimated 49 509-59 867 community-onset RSV-associated hospitalizations among children aged <2 years occurred during the 2014-2015 season., Conclusions: Our findings highlight the importance of RSV as a cause of hospitalization, especially among children aged <2 months. Our approach to estimating RSV-related hospitalizations could be used to provide a US baseline for assessing the impact of future interventions., (Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society 2019.)

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., (Published by Oxford University Press for the Infectious Diseases Society of America 2020.)

Background: Vaccination is the best way to prevent influenza; however, greater benefits could be achieved. To help guide research and policy agendas, we aimed to quantify the magnitude of influenza disease that would be prevented through targeted increases in vaccine effectiveness (VE) or vaccine coverage (VC)., Methods: For 3 influenza seasons (2011-12, 2015-16, and 2017-18), we used a mathematical model to estimate the number of prevented influenza-associated illnesses, medically attended illnesses, and hospitalizations across 5 age groups. Compared with estimates of prevented illness during each season, given observed VE and VC, we explored the number of additional outcomes that would have been prevented from a 5% absolute increase in VE or VC or from achieving 60% VE or 70% VC., Results: During the 2017-18 season, compared with the burden already prevented by influenza vaccination, a 5% absolute VE increase would have prevented an additional 1 050 000 illnesses and 25 000 hospitalizations (76% among those aged ≥65 years), while achieving 60% VE would have prevented an additional 190 000 hospitalizations. A 5% VC increase would have resulted in 785 000 fewer illnesses (56% among those aged 18-64 years) and 11 000 fewer hospitalizations; reaching 70% would have prevented an additional 39 000 hospitalizations., Conclusions: Small, attainable improvements in effectiveness or VC of the influenza vaccine could lead to substantial additional reductions in the influenza burden in the United States. Improvements in VE would have the greatest impact in reducing hospitalizations in adults aged ≥65 years, and VC improvements would have the largest benefit in reducing illnesses in adults aged 18-49 years., (Published by Oxford University Press for the Infectious Diseases Society of America 2019.)

Background: In recent studies of influenza vaccine effectiveness (VE), lower effectiveness with increasing time since vaccination was observed, raising the question of optimal vaccination timing. We sought to evaluate the estimated number of influenza-associated hospitalizations among older adults due to potential changes in vaccination timing., Methods: Using empirical data and a health state transition model, we estimated change in influenza-associated hospitalizations predicted to occur among the US population aged ≥65 years if vaccination were delayed until October 1. We assumed the vaccination timing, coverage, and effectiveness observed in 2012-2013 as a prototypical influenza season, approximately 7% monthly waning of VE, and that between 0% and 50% of individuals who usually get vaccinated earlier than October failed to get vaccinated. We also assessed change in influenza-associated hospitalizations if vaccination uptake shifted substantially toward August and September., Results: In a typical season, delaying vaccination until October increased influenza hospitalizations if more than 14% of older adults usually vaccinated in August and September failed to get vaccinated. The consequences of delayed vaccination depended heavily on influenza season timing, rate of waning, and overall VE. A shift toward vaccination in August and September led to, on average, an increase in influenza-associated hospitalizations, but this result was also sensitive to influenza season timing., Conclusions: Consequences of delayed vaccination varied widely. Uncertainties about vaccine waning and effects of a delay on vaccine coverage suggest it is premature to change current vaccine recommendations, although it may be prudent to prevent a substantial shift toward early vaccination., (Published by Oxford University Press for the Infectious Diseases Society of America 2019.)

Background: The severity of the 2017-2018 influenza season in the United States was high, with influenza A(H3N2) viruses predominating. Here, we report influenza vaccine effectiveness (VE) and estimate the number of vaccine-prevented influenza-associated illnesses, medical visits, hospitalizations, and deaths for the 2017-2018 influenza season., Methods: We used national age-specific estimates of 2017-2018 influenza vaccine coverage and disease burden. We estimated VE against medically attended reverse-transcription polymerase chain reaction-confirmed influenza virus infection in the ambulatory setting using a test-negative design. We used a compartmental model to estimate numbers of influenza-associated outcomes prevented by vaccination., Results: The VE against outpatient, medically attended, laboratory-confirmed influenza was 38% (95% confidence interval [CI], 31%-43%), including 22% (95% CI, 12%-31%) against influenza A(H3N2), 62% (95% CI, 50%-71%) against influenza A(H1N1)pdm09, and 50% (95% CI, 41%-57%) against influenza B. We estimated that influenza vaccination prevented 7.1 million (95% CrI, 5.4 million-9.3 million) illnesses, 3.7 million (95% CrI, 2.8 million-4.9 million) medical visits, 109 000 (95% CrI, 39 000-231 000) hospitalizations, and 8000 (95% credible interval [CrI], 1100-21 000) deaths. Vaccination prevented 10% of expected hospitalizations overall and 41% among young children (6 months-4 years)., Conclusions: Despite 38% VE, influenza vaccination reduced a substantial burden of influenza-associated illness, medical visits, hospitalizations, and deaths in the United States during the 2017-2018 season. Our results demonstrate the benefit of current influenza vaccination and the need for improved vaccines., (Published by Oxford University Press for the Infectious Diseases Society of America 2019.)

Background: The evolution of influenza A viruses results in birth cohorts that have different initial influenza virus exposures. Historically, A/H3 predominant seasons have been associated with more severe influenza-associated disease; however, since the 2009 pandemic, there are suggestions that some birth cohorts experience more severe illness in A/H1 predominant seasons., Methods: United States influenza virologic, hospitalization, and mortality surveillance data during 2000-2017 were analyzed for cohorts born between 1918 and 1989 that likely had different initial influenza virus exposures based on viruses circulating during early childhood. Relative risk/rate during H3 compared with H1 predominant seasons during prepandemic versus pandemic and later periods were calculated for each cohort., Results: During the prepandemic period, all cohorts had more influenza-associated disease during H3 predominant seasons than H1 predominant seasons. During the pandemic and later period, 4 cohorts had higher hospitalization and mortality rates during H1 predominant seasons than H3 predominant seasons., Conclusions: Birth cohort differences in risk of influenza-associated disease by influenza A virus subtype can be seen in US influenza surveillance data and differ between prepandemic and pandemic and later periods. As the population ages, the amount of influenza-associated disease may be greater in future H1 predominant seasons than H3 predominant seasons., (Published by Oxford University Press for the Infectious Diseases Society of America 2019.)

Background: The epidemiology and clinical features of human coronaviruses (HCoVs) in children are not fully characterized., Methods: A retrospective study of children with HCoV detected by reverse-transcriptase polymerase chain reaction (RT-PCR) was performed for a community cohort and a children's hospital in the same community from January 2013 to December 2014. The RT-PCR assay detected HCoV 229E, HKU1, NL63, and OC43 in nasal swabs from symptomatic children ≤18 years. Factors associated with increased severity of illness in hospitalized children were assessed by multivariable logistic regression., Results: Human coronavirus was detected in 261 children, 49 and 212 from the community and hospital, respectively. The distribution of HCoV types and seasonal trends were similar in the community and hospital. Community cases were older than hospitalized cases (median age, 4.4 versus 1.7 years, respectively; P < .01), and a minority of community cases (26.5%) sought medical attention. Among the hospitalized children with HCoV detected, 39 (18.4%) received respiratory support and 24 (11.3%) were admitted to the pediatric intensive care unit (PICU). Age <2 years (odds ratio [OR] = 5.0; 95% confidence interval [CI], 1.9-13.1) and cardiovascular (OR = 3.9; 95% CI, 1.6-9.5), genetic/congenital (OR = 2.8; 95% CI, 1.1-7.0), and respiratory chronic complex conditions ([CCCs] OR = 4.5; 95% CI, 1.7-12.0) were associated with receiving respiratory support. Genetic/congenital (OR = 2.8; 95% CI, 1.1-7.4) CCCs were associated with PICU admission. Severity of illness was similar among hospitalized children with different HCoV types., Conclusions: Children in the community with HCoV detected generally had mild illness as demonstrated by few medically attended cases. In hospitalized children, young age and CCCs, but not HCoV type, were associated with increased severity of illness.

Background: The seasonal incidence of influenza is often approximated as 5%-20%., Methods: We used 2 methods to estimate the seasonal incidence of symptomatic influenza in the United States. First, we made a statistical estimate extrapolated from influenza-associated hospitalization rates for 2010-2011 to 2015-2016, collected as part of national surveillance, covering approximately 9% of the United States, and including the existing mix of vaccinated and unvaccinated persons. Second, we performed a literature search and meta-analysis of published manuscripts that followed cohorts of subjects during 1996-2016 to detect laboratory-confirmed symptomatic influenza among unvaccinated persons; we adjusted this result to the US median vaccination coverage and effectiveness during 2010-2016., Results: The statistical estimate of influenza incidence among all ages ranged from 3.0%-11.3% among seasons, with median values of 8.3% (95% confidence interval [CI], 7.3%-9.7%) for all ages, 9.3% (95% CI, 8.2%-11.1%) for children <18 years, and 8.9% (95% CI, 8.2%-9.9%) for adults 18-64 years. Corresponding values for the meta-analysis were 7.1% (95% CI, 6.1%-8.1%) for all ages, 8.7% (95% CI, 6.6%-10.5%) for children, and 5.1% (95% CI, 3.6%-6.6%) for adults., Conclusions: The 2 approaches produced comparable results for children and persons of all ages. The statistical estimates are more versatile and permit estimation of season-to-season variation. During 2010-2016, the incidence of symptomatic influenza among vaccinated and unvaccinated US residents, including both medically attended and nonattended infections, was approximately 8% and varied from 3% to 11% among seasons.

Assessments of influenza season severity can guide public health action. We used the moving epidemic method to develop intensity thresholds (ITs) for 3 US surveillance indicators from the 2003-2004 through 2014-2015 influenza seasons (excluding the 2009 pandemic). The indicators were: 1) outpatient visits for influenza-like illness; 2) influenza-related hospitalizations; and 3) influenza- and pneumonia-related deaths. ITs were developed for the population overall and separately for children, adults, and older adults, and they were set at the upper limit of the 50% (IT50), 90% (IT90), and 98% (IT98) 1-sided confidence intervals of the geometric mean of each season's 3 highest values. Severity was classified as low if ≥2 systems peaked below IT50, moderate if ≥2 peaked between IT50 and IT90, high if ≥2 peaked between IT90 and IT98, and very high if ≥2 peaked above IT98. We pilot-tested this method with the 2015-2016 season and the 2009 pandemic. Overall, 4 seasons were classified as low severity, 7 as moderate, 2 as high, and none as very high. Among the age groups, older adults had the most seasons (n = 3) classified as high, and children were the only group to have seasons (n = 2) classified as very high. We will apply this method to classify the severity of future seasons and inform pandemic response.

Background: The effect of body mass index (BMI) on community-acquired pneumonia (CAP) severity is unclear., Methods: We investigated the relationship between BMI and CAP outcomes (hospital length of stay [LOS], intensive care unit [ICU] admission, and invasive mechanical ventilation) in hospitalized CAP patients from the Centers for Disease Control and Prevention Etiology of Pneumonia in the Community (EPIC) study, adjusting for age, demographics, underlying conditions, and smoking status (adults only)., Results: Compared with normal-weight children, odds of ICU admission were higher in children who were overweight (adjusted odds ratio [aOR], 1.7; 95% confidence interval [CI], 1.1-2.8) or obese (aOR, 2.1; 95% CI, 1.4-3.2), and odds of mechanical ventilation were higher in children with obesity (aOR, 2.7; 95% CI, 1.3-5.6). When stratified by asthma (presence/absence), these findings remained significant only in children with asthma. Compared with normal-weight adults, odds of LOS >3 days were higher in adults who were underweight (aOR, 1.6; 95% CI, 1.1-2.4), and odds of mechanical ventilation were lowest in adults who were overweight (aOR, 0.5; 95% CI, .3-.9)., Conclusions: Children who were overweight or obese, particularly those with asthma, had higher odds of ICU admission or mechanical ventilation. In contrast, adults who were underweight had longer LOS. These results underscore the complex relationship between BMI and CAP outcomes., (Published by Oxford University Press for the Infectious Diseases Society of America 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Background: We describe the impact of early initiation of influenza antiviral treatment among pregnant women hospitalized with laboratory-confirmed influenza during the 2010-2014 influenza seasons., Methods: Severe influenza was defined as illness with ≥1 of the following: intensive care unit admission, need for mechanical ventilation, respiratory failure, pulmonary embolism, sepsis, or death. Within severity stratum, we used parametric survival analysis to compare length of stay by timing of antiviral treatment, adjusting for underlying conditions, influenza vaccination, and pregnancy trimester., Results: Among 865 pregnant women, the median age was 27 years (interquartile range [IQR], 23-31 years). Most (68%) were healthy, and 85% received antiviral treatment. Sixty-three women (7%) had severe influenza, and 4 died. Severity was associated with preterm delivery and fetal loss. Women with severe influenza were less likely to be vaccinated than those without severe influenza (14% vs 26%; P = .03). Among women treated with antivirals ≤2 days versus those treated >2 days from illness onset, the median length of stay was 2.2 days (interquartile range [IQR], 0.9-5.8 days; n = 8) versus 7.8 days (IQR, 3.0-20.6 days; n = 7), respectively, for severe influenza (P = .03) and 2.4 days (IQR, 2.3-2.5 days; n = 153) versus 3.1 days (IQR, 2.8-3.5 days; n = 62), respectively, for nonsevere influenza (P < .01)., Conclusions: Early initiation of influenza antiviral treatment to pregnant women hospitalized with influenza may reduce the length of stay, especially among those with severe influenza. Influenza during pregnancy is associated with maternal and infant morbidity, and annual influenza vaccination is warranted., (Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Background: Prior retrospective studies suggest that statins may benefit patients with community-acquired pneumonia (CAP) due to antiinflammatory and immunomodulatory effects. However, prospective studies of the impact of statins on CAP outcomes are needed. We determined whether statin use was associated with improved outcomes in adults hospitalized with CAP., Methods: Adults aged ≥18 years hospitalized with CAP were prospectively enrolled at 3 hospitals in Chicago, Illinois, and 2 hospitals in Nashville, Tennessee, from January 2010-June 2012. Adults receiving statins before and throughout hospitalization (statin users) were compared with those who did not receive statins (nonusers). Proportional subdistribution hazards models were used to examine the association between statin use and hospital length of stay (LOS). In-hospital mortality was a secondary outcome. We also compared groups matched on propensity score., Results: Of 2016 adults enrolled, 483 (24%) were statin users; 1533 (76%) were nonusers. Statin users were significantly older, had more comorbidities, had more years of education, and were more likely to have health insurance than nonusers. Multivariable regression demonstrated that statin users and nonusers had similar LOS (adjusted hazard ratio [HR], 0.99; 95% confidence interval [CI], .88-1.12), as did those in the propensity-matched groups (HR, 1.03; 95% CI, .88-1.21). No significant associations were found between statin use and LOS or in-hospital mortality, even when stratified by pneumonia severity., Conclusions: In a large prospective study of adults hospitalized with CAP, we found no evidence to suggest that statin use before and during hospitalization improved LOS or in-hospital mortality., (Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Conservation and environmental management are principal countermeasures to the degradation of marine ecosystems and their services. However, in many cases, current practices are insufficient to reverse ecosystem declines. We suggest that restoration ecology , the science underlying the concepts and tools needed to restore ecosystems, must be recognized as an integral element for marine conservation and environmental management. Marine restoration ecology is a young scientific discipline, often with gaps between its application and the supporting science. Bridging these gaps is essential to using restoration as an effective management tool and reversing the decline of marine ecosystems and their services. Ecological restoration should address objectives that include improved ecosystem services, and it therefore should encompass social-ecological elements rather than focusing solely on ecological parameters. We recommend using existing management frameworks to identify clear restoration targets, to apply quantitative tools for assessment, and to make the re-establishment of ecosystem services a criterion for success.

In this community-based cohort study of 275 primarily low-income, urban households in New York City, overall 2013-2014 influenza vaccine effectiveness (VE) was 62.5% (95% confidence interval, 21.7%-82.0%). VE point estimates were highest against 2009 H1N1 and for those who were vaccinated in 2013-2014 but not in 2012-2013., (© The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

Background: In 2012, one third of cases in a multistate outbreak of variant influenza A(H3N2) virus ([H3N2]v) infection occurred in Ohio. We conducted an investigation of (H3N2)v cases associated with agricultural Fair A in Ohio., Methods: We surveyed Fair A swine exhibitors and their household members. Confirmed cases had influenza-like illness (ILI) and a positive laboratory test for (H3N2)v, and probable cases had ILI. We calculated attack rates. We determined risk factors for infection, using multivariable log-binomial regression., Results: We identified 20 confirmed and 94 probable cases associated with Fair A. Among 114 cases, the median age was 10 years, there were no hospitalizations or deaths, and 82% had swine exposure. In the exhibitor household cohort of 359 persons (83 households), we identified 6 confirmed cases (2%) and 40 probable cases (11%). An age of <10 years was a significant risk factor (P < .01) for illness. One instance of likely human-to-human transmission was identified., Conclusions: In this (H3N2)v outbreak, no evidence of sustained human-to-human (H3N2)v transmission was found. Our risk factor analysis contributed to the development of the recommendation that people at increased risk of influenza-associated complications, including children aged <5 years, avoid swine barns at fairs during the 2012 fair season., (Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Background: Human illness from influenza A(H7N9) was identified in March 2013, and candidate vaccine viruses were soon developed. To understand factors that may impact influenza vaccination programs, we developed a model to evaluate hospitalizations and deaths averted considering various scenarios., Methods: We utilized a model incorporating epidemic curves with clinical attack rates of 20% or 30% in a single wave of illness, case hospitalization ratios of 0.5% or 4.2%, and case fatality ratios of 0.08% or 0.53%. We considered scenarios that achieved 80% vaccination coverage, various starts of vaccination programs (16 or 8 weeks before, the same week of, or 8 or 16 weeks after start of pandemic), an administration rate of 10 or 30 million doses per week (the latter rate is an untested assumption), and 2 levels of vaccine effectiveness (2 doses of vaccine required; either 62% or 80% effective for persons aged <60 years, and either 43% or 60% effective for persons aged ≥ 60 years)., Results: The start date of vaccination campaigns most influenced impact; 141,000-2,200,000 hospitalizations and 11,000-281,000 deaths were averted when campaigns started before a pandemic, and <100-1 300,000 hospitalizations and 0-165,000 deaths were averted for programs beginning the same time as or after the introduction of the pandemic virus. The rate of vaccine administration and vaccine effectiveness did not influence campaign impact as much as timing of the start of campaign., Conclusions: Our findings suggest that efforts to improve the timeliness of vaccine production will provide the greatest impacts for future pandemic vaccination programs., (Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Surveillance for acute respiratory infection (ARI) and influenza-like illness (ILI) relies primarily on reports of medically attended illness. Community surveillance could mitigate delays in reporting, allow for timely collection of respiratory tract samples, and characterize cases of non–medically attended ILI representing substantial personal and economic burden. Text messaging could be utilized to perform longitudinal ILI surveillance in a community-based sample but has not been assessed. We recruited 161 households (789 people) in New York City for a study of mobile ARI/ILI surveillance, and selected reporters received text messages twice weekly inquiring whether anyone in the household was ill. Home visits were conducted to obtain nasal swabs from persons with ARI/ILI. Participants were primarily female, Latino, and publicly insured. During the 44-week period from December 2012 through September 2013, 11,282 text messages were sent. In responses to 8,250 (73.1%) messages, a household reported either that someone was ill or no one was ill; 88.9% of responses were received within 4 hours. Swabs were obtained for 361 of 363 reported ARI/ILI episodes. The median time from symptom onset to nasal swab was 2 days; 65.4% of samples were positive for a respiratory pathogen by reverse-transcriptase polymerase chain reaction. In summary, text messaging promoted rapid ARI/ILI reporting and specimen collection and could represent a promising approach to timely, community-based surveillance.

In the management of emerging infectious disease epidemics, precise and accurate estimation of severity indices, such as the probability of death after developing symptoms-the symptomatic case fatality ratio (sCFR)-is essential. Estimation of the sCFR may require merging data gathered through different surveillance systems and surveys. Since different surveillance strategies provide different levels of precision and accuracy, there is need for a theory to help investigators select the strategy that maximizes these properties. Here, we study the precision of sCFR estimators that combine data from several levels of the severity pyramid. We derive a formula for the standard error, which helps us find the estimator with the best precision given fixed resources. We further propose rules of thumb for guiding the choice of strategy: For example, should surveillance of a particular severity level be started? Which level should be preferred? We derive a formula for the optimal allocation of resources between chosen surveillance levels and provide a simple approximation that can be used in thinking more heuristically about planning surveillance. We illustrate these concepts with numerical examples corresponding to 3 influenza pandemic scenarios. Finally, we review the equally important issue of accuracy., (© The Author 2014. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.)

Background: Few data exist describing healthcare-seeking behaviors among persons with influenza-like illness (ILI) or adherence to influenza antiviral treatment recommendations., Methods: We analyzed adult responses to the Behavioral Risk Factor Surveillance System in 31 states and the District of Columbia (DC) and pediatric responses in 25 states and DC for January-April 2011 by demographics and underlying health conditions., Results: Among 75 088 adult and 15 649 child respondents, 8.9% and 33.9%, respectively, reported ILI. ILI was more frequent among adults with asthma (16%), chronic obstruction pulmonary disease (COPD; 26%), diabetes (12%), heart disease (19%), kidney disease (16%), or obesity (11%). Forty-five percent of adults and 57% of children sought healthcare for ILI. Thirty-five percent of adults sought care ≤ 2 days after ILI onset. Seeking care ≤ 2 days was more frequent among adults with COPD (48%) or heart disease (55%). Among adults with a self-reported physician diagnosis of influenza, 34% received treatment with antiviral medications. The only underlying health condition with a higher rate of treatment was diabetes (46%)., Conclusions: Adults with underlying health conditions were more likely to report ILI, but the majority did not seek care promptly, missing opportunities for early influenza antiviral treatment., (Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

We compared influenza vaccine-prevented hospitalizations in adults aged ≥65 years for a range of hypothetical effectiveness estimates. During 2012-2013, a vaccine with 10% effectiveness (66% coverage) would have averted approximately 13 000 hospitalizations, and a vaccine with 40% effectiveness would have averted approximately 60 000 hospitalizations. Annual vaccination is merited in this vulnerable population., (Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Background: Persons with influenza can develop complications that result in hospitalization and death. These are most commonly respiratory related, but cardiovascular or neurologic complications or exacerbations of underlying chronic medical conditions may also occur. Patterns of complications observed during pandemics may differ from typical influenza seasons, and characterizing variations in influenza-related complications can provide a better understanding of the impact of pandemics and guide appropriate clinical management and planning for the future., Methods: Using a population-based surveillance system, we compared clinical complications using International Classification of Diseases, Ninth Revision (ICD-9) discharge diagnosis codes in adults hospitalized with seasonal influenza (n = 5270) or 2009 pandemic influenza A(H1N1) (H1N1pdm09; n = 4962)., Results: Adults hospitalized with H1N1pdm09 were younger (median age, 47 years) than those with seasonal influenza (median age, 68 years; P < .01), and differed in the frequency of certain underlying medical conditions. Whereas there was similar risk for many influenza-associated complications, after controlling for age and type of underlying medical condition, adults hospitalized with H1N1pdm09 were more likely to have lower respiratory tract complications, shock/sepsis, and organ failure than those with seasonal influenza. They were also more likely to be admitted to the intensive care unit, require mechanical ventilation, or die. Young adults, in particular, had 2-4 times the risk of severe outcomes from H1N1pdm09 than persons of the same ages with seasonal influenza., Conclusions: Although H1N1pdm09 was thought of as a relatively mild pandemic, these data highlight the impact of the 2009 pandemic on the risk of severe influenza, especially among younger adults, and the impact this virus may continue to have., (Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Natural infection-induced humoral immunity to matrix protein 2 (M2) of influenza A viruses in humans is not fully understood. Evidence suggests that anti-M2 antibody responses following influenza A virus infection are weak and/or transient. We show that the seroprevalence of anti-M2 antibodies increased with age in 317 serum samples from healthy individuals in the United States in 2007-2008. Infection with 2009 pandemic H1N1 influenza A virus (A[H1N1]pdm09) elicited a recall serum antibody response to M2 protein of A(H1N1)pdm09 in 47% of the affected 118 individuals tested. Anti-M2 antibody responses were more robust among individuals with preexisting antibodies to M2 protein. Moreover, the antibodies induced as a result of infection with A(H1N1)pdm09 were cross-reactive with M2 protein of seasonal influenza A viruses. These results emphasize the need to further investigate the possible roles of anti-M2 antibodies in human influenza A virus infection.

Background: Variant influenza virus infections are rare but may have pandemic potential if person-to-person transmission is efficient. We describe the epidemiology of a multistate outbreak of an influenza A(H3N2) variant virus (H3N2v) first identified in 2011., Methods: We identified laboratory-confirmed cases of H3N2v and used a standard case report form to characterize illness and exposures. We considered illness to result from person-to-person H3N2v transmission if swine contact was not identified within 4 days prior to illness onset., Results: From 9 July to 7 September 2012, we identified 306 cases of H3N2v in 10 states. The median age of all patients was 7 years. Commonly reported signs and symptoms included fever (98%), cough (85%), and fatigue (83%). Sixteen patients (5.2%) were hospitalized, and 1 fatal case was identified. The majority of those infected reported agricultural fair attendance (93%) and/or contact with swine (95%) prior to illness. We identified 15 cases of possible person-to-person transmission of H3N2v. Viruses recovered from patients were 93%-100% identical and similar to viruses recovered from previous cases of H3N2v. All H3N2v viruses examined were susceptible to oseltamivir and zanamivir and resistant to adamantane antiviral medications., Conclusions: In a large outbreak of variant influenza, the majority of infected persons reported exposures, suggesting that swine contact at an agricultural fair was a risk for H3N2v infection. We identified limited person-to-person H3N2v virus transmission, but found no evidence of efficient or sustained person-to-person transmission. Fair managers and attendees should be aware of the risk of swine-to-human transmission of influenza viruses in these settings.