BACKGROUND: Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infection in children less than 5 years of age worldwide. In the United States, RSV commonly causes hospitalization in young children and is the leading cause of hospitalizations in infants. As new RSV immunizations become available, burden estimates are critical to guide the implementation of recommendations and quantify impact. METHODS: We estimated RSV-associated hospitalization rates at a large US pediatric medical center during an 8-year period using five approaches, namely, estimation directly from active and passive surveillance systems, both a crude and stratified capture-recapture analysis of data from both systems, and estimation based on discharge diagnosis codes. The stratified analysis was performed to ensure adherence with the capture-recapture methodology assumption that samples are independent and participants have an equal probability of being observed within each system. RESULTS: Overall, estimated RSV-associated hospitalization rates per 1000 children were 4.0 (2.5, 6.1) based on adjusted estimates from active surveillance, 1.7 (2.1, 4.4) from passive surveillance, 7.9 (5.7, 13.0) from crude capture-recapture analysis, 5.0 (3.8, 7.2) from the stratified capture-recapture, and 4.4 (4.0, 4.9) from discharge diagnosis codes. CONCLUSIONS: Each method has limitations and inherent biases that may impact the estimation of the burden of RSV. Capture-recapture analysis may be a useful tool to estimate the burden of RSV, but needs to be adjusted to account for possible violation of the assumptions of independence and equal probability of capture to ensure accurate approximation of disease burden and avoid over estimation.

BACKGROUND: The 2023-2024 influenza season included sustained elevated activity from December 2023-February 2024 and continued activity through May 2024. Influenza A(H1N1), A(H3N2), and B viruses circulated during the season. METHODS: During September 1, 2023-May 31, 2024, a multistate sentinel surveillance network of 24 medical centers in 20 U.S. states enrolled adults aged ≥18 years hospitalized with acute respiratory illness (ARI). Consistent with a test-negative design, cases tested positive for influenza viruses by molecular or antigen test, and controls tested negative for influenza viruses and SARS-CoV-2. Vaccine effectiveness (VE) against influenza-associated hospitalization was calculated as (1 - adjusted odds ratio for vaccination) × 100%. RESULTS: Among 7690 patients, including 1170 influenza cases (33% vaccinated) and 6520 controls, VE was 40% (95% CI: 31%-48%) with varying estimates by age (18-49 years: 53% [34%-67%]; 50-64 years: 47% [31%-60%]; ≥65 years: 31% [16%-43%]). Protection was similar among immunocompetent patients (40% [30%-49%]) and immunocompromised patients (32% [7-50%]). VE was statistically significant against influenza B (67% [35%-84%]) and A(H1N1) (36% [21%-48%]) and crossed the null against A(H3N2) (19% [-8%-39%]). VE was higher for patients 14-60 days from vaccination (54% [40%-65%]) than >120 days (18% [-1%-33%]). CONCLUSIONS: During 2023-2024, influenza vaccination reduced the risk of influenza A(H1N1)- and influenza B-associated hospitalizations among adults; effectiveness was lower in patients vaccinated >120 days prior to illness onset compared with those vaccinated 14-60 days prior.

BACKGROUND: clinical guidelines recommend initiation of antiviral therapy as soon as possible for patients hospitalized with confirmed or suspected influenza. METHODS: A multicenter US observational sentinel surveillance network prospectively enrolled adults (aged ≥18 years) hospitalized with laboratory-confirmed influenza at 24 hospitals during October 1, 2022-July 21, 2023. A multivariable proportional odds model was used to compare peak pulmonary disease severity (no oxygen support, standard supplemental oxygen, high-flow oxygen/non-invasive ventilation, invasive mechanical ventilation, or death) after the day of hospital admission among patients starting oseltamivir treatment on the day of admission (early) versus those who did not (late or not treated), adjusting for baseline (admission day) severity, age, sex, site, and vaccination status. Multivariable logistic regression models were used to evaluate the odds of intensive care unit (ICU) admission, acute kidney replacement therapy or vasopressor use, and in-hospital death. RESULTS: A total of 840 influenza-positive patients were analyzed, including 415 (49%) who started oseltamivir treatment on the day of admission, and 425 (51%) who did not. Compared with late or not treated patients, those treated early had lower peak pulmonary disease severity (proportional aOR: 0.60, 95% CI: 0.49-0.72), and lower odds of intensive care unit admission (aOR: 0.24, 95% CI: 0.13-0.47), acute kidney replacement therapy or vasopressor use (aOR: 0.40, 95% CI: 0.22-0.67), and in-hospital death (aOR: 0.36, 95% CI: 0.18-0.72). CONCLUSION: Among adults hospitalized with influenza, treatment with oseltamivir on day of hospital admission was associated reduced risk of disease progression, including pulmonary and extrapulmonary organ failure and death.

BACKGROUND: In test-negative studies of vaccine effectiveness (VE), including patients with co-circulating, vaccine-preventable, respiratory pathogens in the control group for the pathogen of interest can introduce a downward bias on VE estimates. METHODS: A multicenter sentinel surveillance network in the US prospectively enrolled adults hospitalized with acute respiratory illness from September 1, 2022-March 31, 2023. We evaluated bias in estimates of VE against influenza-associated and COVID-19-associated hospitalization based on: inclusion vs exclusion of patients with a co-circulating virus among VE controls; observance of VE against the co-circulating virus (rather than the virus of interest), unadjusted and adjusted for vaccination against the virus of interest; and observance of influenza or COVID-19 against a sham outcome of respiratory syncytial virus (RSV). RESULTS: Overall VE against influenza-associated hospitalizations was 6 percentage points lower when patients with COVID-19 were included in the control group, and overall VE against COVID-19-associated hospitalizations was 2 percentage points lower when patients with influenza were included in the control group. Analyses of VE against the co-circulating virus and against the sham outcome of RSV showed that downward bias was largely attributable the correlation of vaccination status across pathogens, but also potentially attributable to other sources of residual confounding in VE models. CONCLUSION: Excluding cases of confounding respiratory pathogens from the control group in VE analysis for a pathogen of interest can reduce downward bias. This real-world analysis demonstrates that such exclusion is a helpful bias mitigation strategy, especially for measuring influenza VE, which included a high proportion of COVID-19 cases among controls.

SARS-CoV-2 infection in young children is often mild or asymptomatic; however, some children are at risk for severe disease. Data describing the protective effectiveness of COVID-19 mRNA vaccines against COVID-19-associated emergency department (ED) visits and hospitalization in this population are limited. Data from the New Vaccine Surveillance Network, a prospective population-based surveillance system, were used to estimate vaccine effectiveness using a test-negative, case-control design and describe the epidemiology of SARS-CoV-2 in infants and children aged 6 months-4 years during July 1, 2022-September 30, 2023. Among 7,434 children included, 5% received a positive SARS-CoV-2 test result, and 95% received a negative test result; 86% were unvaccinated, 4% had received 1 dose of any vaccine product, and 10% had received ≥2 doses. When compared with receipt of no vaccines among children, receipt of ≥2 COVID-19 mRNA vaccine doses was 40% effective (95% CI = 8%-60%) in preventing ED visits and hospitalization. These findings support existing recommendations for COVID-19 vaccination of young children to reduce COVID-19-associated ED visits and hospitalization.

IMPORTANCE: Human prion disease surveillance is critical to detect possible cases of variant Creutzfeldt-Jakob disease and other acquired forms of prion disease in the United States. Results are presented here that describe 12 years of surveillance in Washington, the only US state that has reported the presence of classic bovine spongiform encephalopathy, an animal prion disease that has been shown to transmit to humans. OBJECTIVE: To describe the current prion disease surveillance system in Washington and the epidemiological and clinical results of surveillance from 2006 through 2017. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study reports findings from the human prion disease surveillance system in place in Washington state from January 1, 2006, through December 31, 2017. Participants included Washington residents with a clinical suspicion of human prion disease or suggestive test results from the National Prion Disease Pathology Surveillance Center or with prion disease listed as a cause of death on the death certificate. Data for this report were analyzed from June 1, 2016, to July 1, 2020. EXPOSURE: Human prion disease diagnosis. MAIN OUTCOMES AND MEASURES: The main outcome was incidence of human prion disease cases, including identification of variant Creutzfeldt-Jakob disease. RESULTS: A total of 143 human prion disease cases were detected during the study period, none of which met criteria for a variant Creutzfeldt-Jakob disease diagnosis. Among 137 definite or probable cases, 123 (89.8%) occurred in persons aged 55 years or older, with a median age at death of 66 years (range, 38-84 years). Most patients were White (124 [92.5%] among 134 with reported race), and slightly over half were male (70 [51.1%]). The average annual age-adjusted prion disease incidence was 1.5 per million population per year, slightly higher than the national rate of 1.2 per million. A total of 99 cases (69.2%) were confirmed by neuropathology. Sporadic prion disease was the most common diagnosis, in 134 cases (93.7%), followed by familial prion disease in 8 cases (5.6%). One iatrogenic prion disease case (0.7%) was also reported. CONCLUSIONS AND RELEVANCE: The findings of this cross-sectional study suggest that demographic characteristics of patients with prion disease in Washington are consistent with national findings. The slightly higher incidence rate may be due to the state's enhanced surveillance activities, including close collaboration with key partners and educational efforts targeted toward health care providers. Results indicate that surveillance will continue to be beneficial for monitoring epidemiological trends, facilitating accurate diagnoses, and detecting variant Creutzfeldt-Jakob disease or other emerging human prion disease cases.