BACKGROUND: Seasonal influenza causes an estimated 120 000 to 710 000 hospitalizations annually in the United States. Treatment with antiviral medications, such as oseltamivir, can reduce risks of hospitalization among people with influenza-associated illness. The US Centers for Disease Control and Prevention recommends initiating antiviral treatment as soon as possible for outpatients with suspected or confirmed influenza who have severe or progressive illness or are at higher risk of influenza complications. METHODS: We developed a probabilistic model to estimate the impact of antiviral treatment in reducing hospitalizations among US outpatients with influenza. Parameters were informed by seasonal influenza surveillance platforms and stratified by age group and whether individuals had a condition associated with higher risk of influenza complications. We modeled different scenarios for influenza antiviral effectiveness and outpatient testing and prescribing practices, then compared our results with a baseline scenario in which antivirals were not used. RESULTS: Across the modeled scenarios, antiviral treatment resulted in 1215 to 14 184 fewer influenza-associated hospitalizations on average when compared with the baseline scenario (0.2%-2.7% reduction). The greatest effects occurred among adults aged ≥65 years and individuals with conditions associated with higher risk of influenza complications. Modeling 50% improvements in access to care, testing, prescribing, and treatment resulted in greater potential impacts, with over 71 000 (13.3%) influenza-associated hospitalizations averted on average compared to baseline. CONCLUSIONS: Our results support recommendations to prioritize outpatient antiviral treatment among older adults and others at higher risk of influenza complications. Improving access to prompt testing and treatment among outpatients with suspected influenza could reduce hospitalizations substantially.

BACKGROUND: Various underlying medical conditions (UMCs) elevate the risk of influenza-associated hospitalization. We evaluated how these rates changed by type and number of UMCs. METHODS: Retrospective cohorts were constructed among adult members of two health systems aged ≥18 years with prior healthcare utilization. Across the 2016-17 to 2019-20 seasons, we estimated influenza-associated hospitalization rates by type and number of UMCs. Hospitalizations were defined using discharge diagnoses or laboratory confirmation. We calculated adjusted rate ratios (aRR) using Poisson regression controlling for site, season, and demographic characteristics. We used causal mediation to estimate the effect of UMCs on influenza-associated hospitalization accounting for influenza vaccination status. RESULTS: Among 870,888 cohort members, 1,403 were hospitalized with influenza at least once within a season across four seasons. Compared to those without, the aRR for influenza-associated hospitalization was highest for individuals with congestive heart failure (4.2, 95% CI: 3.6-4.9). The aRRs also increased with each additional UMCs compared to those with no UMCs. The effect of UMCs on influenza-associated hospitalizations was higher when not mediated by vaccination status; for those with ≥4 UMCs compared to no UMCs, rates were about 60% higher. CONCLUSION: The burden of baseline medical conditions is associated with higher rates of influenza-associated hospitalization. Among those with varying types and number of UMCs, if vaccination prevalence had been lower than observed, influenza-associated hospitalization rates would have been higher. These findings highlight the importance of preventive medical care and annual influenza vaccination in reducing influenza-associated hospitalizations, particularly for individuals at high-risk.

BACKGROUND: Coronavirus disease 2019 (COVID-19) burden is difficult to quantify with cases missed by surveillance systems. During COVID-19 Delta and Omicron BA.1-5 periods, we assessed the COVID-19 burden in New South Wales (NSW), Australia, from May 2021-July 2022 using a participatory surveillance system of self-reported respiratory disease and a database of people seeking healthcare. METHODS: To estimate community illness burden, we adjusted the NSW age-stratified non-case population by reported severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) percent positive and acute respiratory illness (ARI) rates. Hospitalization and death burden were estimated by adjusting reported rates to the NSW population and by the proportion of COVID-19 admissions attributable to COVID-19 illness. Burden estimates were compared to reported case counts. RESULTS: From May 2021-July 2022, an estimated 3,450,516 (95%CI: 2,847,355-4,119,472) symptomatic community ARI illnesses, 24,684 (95%CI: 20,714-29,144) hospitalizations, and 4,638 (95% CI: 3,263-6,049) deaths were attributable to COVID-19 in NSW. Reported cases (3,039,239) were 14% lower than the estimated symptomatic community illness burden but within the estimate's 95% confidence interval. Overall, 0.7% of symptomatic community illnesses resulted in hospitalization and 0.1% resulted in death. CONCLUSIONS: Estimated symptomatic case hospitalization and fatality risk could be used for COVID-19 modelling and forecasting.

BACKGROUND: While the estimated number of US influenza-associated deaths is reported annually, detailed data on the epidemiology of influenza-associated deaths, including the burden of in-hospital vs post-hospital discharge deaths, are limited. METHODS: Using data from the 2010-2011 through 2018-2019 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 the hospital vs post discharge and characterized locations and causes of death (CODs). RESULTS: Among 121 390 cases hospitalized with laboratory-confirmed influenza over 9 seasons, 5.5% died; 76% of deaths were in patients aged ≥65 years, 71% were non-Hispanic White, and 34% had 4 or more underlying medical conditions. Among all patients with an influenza-associated hospitalization who died, 48% of deaths occurred after hospital discharge; the median number of days from discharge to death was 9 (interquartile range, 3-19). 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 the 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.

Emergency department (ED) visits during influenza seasons represent a critical yet less examined indicator of the acute burden of influenza. This study investigates the burden of influenza-associated ED visits in six U.S. cities during influenza seasons from 2005-06 to 2016-17. Using a time-series design, we estimated associations between daily ED visits and weekly influenza activity data from the Influenza Hospitalization Surveillance Network (FluSurv-NET). A counterfactual approach was then used to calculate attributable expected ED. Highest influenza-associated rates were observed among the youngest (0-4 years) and oldest (65+ years) age groups. Combining estimates across seasons, the influenza-associated ED visit rate for respiratory diseases was almost six times larger compared to the subset of ED visits that resulted in hospitalization: 364 per 100,000 population (95% CI: 294-435) for total ED visits versus 58 per 100,000 population (95% CI: 45-71) for hospitalization. This difference was particularly large for the 0-4 year age group: 911 per 100,000 population (95% CI: 558-1,263) for total ED visits versus 43 per 100,000 population (95% CI: 15-71) for hospitalization. This study highlights the substantial burden of influenza on emergency healthcare services and the importance of integrating such data into public health planning and influenza management strategies.

In late January 2025, CDC received anecdotal reports of children with influenza-associated acute necrotizing encephalopathy (ANE), a severe form of influenza-associated encephalopathy or encephalitis (IAE), including several fatal cases. In response, CDC examined trends in the proportions of cases with IAE among influenza-associated pediatric deaths reported during the 2010-11 through 2024-25 influenza seasons, including demographic and clinical characteristics of identified cases. CDC contacted state health departments to ascertain whether any pediatric influenza-associated deaths with IAE reported this season also had a diagnosis of ANE. Among 1,840 pediatric influenza-associated deaths during the 2010-11 through 2024-25 influenza seasons, 166 (9%) had IAE, ranging from 0% (2020-21 season) to 14% (2011-12 season); preliminary data for the 2024-25 season (through February 8, 2025) indicate that nine of 68 (13%) had IAE. Across seasons, the median age of patients with fatal IAE was 6 years; 54% had no underlying medical conditions, and only 20% had received influenza vaccination. Because no dedicated national surveillance for IAE or ANE exists, it is unknown if the numbers of cases this season vary from expected numbers. Health care providers should consider IAE in children with acute febrile illness and neurologic signs or symptoms lasting >24 hours. Evaluation should include testing for influenza and other viruses and neuroimaging; clinical management should include early antiviral treatment for suspected or confirmed influenza and supportive critical care management as needed. Influenza vaccination is recommended for all eligible persons aged ≥6 months as long as influenza viruses are circulating.

Annual influenza vaccination is recommended for all persons aged ≥6 months in the United States. Interim influenza vaccine effectiveness (VE) was calculated among patients with acute respiratory illness-associated outpatient visits and hospitalizations from four VE networks during the 2024-25 influenza season (October 2024-February 2025). Among children and adolescents aged <18 years, VE against any influenza was 32%, 59%, and 60% in the outpatient setting in three networks, and against influenza-associated hospitalization was 63% and 78% in two networks. Among adults aged ≥18 years, VE in the outpatient setting was 36% and 54% in two networks and was 41% and 55% against hospitalization in two networks. Preliminary estimates indicate that receipt of the 2024-2025 influenza vaccine reduced the likelihood of medically attended influenza and influenza-associated hospitalization. CDC recommends annual receipt of an age-appropriate influenza vaccine by all eligible persons aged ≥6 months as long as influenza viruses continue to circulate locally.

BACKGROUND: Limited data are available regarding the development and durability of immune responses following COVID-19 infection or vaccination in pediatric solid-organ transplant (SOT) recipients. METHODS: Renal, liver, or intestinal transplant recipients < 21 years of age followed at Seattle Children's Hospital were enrolled from August 2020 to May 2021. Blood samples were collected at ~6-month intervals for up to 3 years and tested for antinucleocapsid (N) antibodies. COVID-19 vaccination data were collected from the Washington State Immunization Information System and/or the medical record. Semi-quantitative anti-S IgG testing was performed on all postvaccine samples using the Abbott Architect platform. We further evaluated a subset of postvaccine samples using variant-specific quantitative binding (Meso Scale Discovery, MSD) immunoassays and pseudovirus-neutralization assays. Antibody levels were compared over time and by vaccine category. RESULTS: We followed 83 SOT recipients for a median of 12.5 months (IQR 7.0, 28.3). Overall, 16 (19.3%) participants had evidence of SARS-CoV-2 infection based on anti-N antibody detection. Forty-six (55%) participants had a blood sample collected > 14 days after receipt of a vaccination. Serum IgG to spike antigens (anti-S antibody) increased following vaccination and increased with the number of vaccine doses received as assessed by both the Abbott and MSD assays. Neutralizing activity was significantly lower against the Omicron subvariants compared to the ancestral strain. CONCLUSION: Pediatric SOT recipients demonstrated strong antibody responses following SARS-CoV-2 vaccination, with higher anti-S antibody responses following > 2 doses of vaccine. Our study offers unique longitudinal immune response data in this vulnerable patient population.

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.

BACKGROUND: To improve understanding of influenza and rurality, we investigated differences in influenza testing and anti-viral treatment rates between micropolitan (muSAs) and metropolitan statistical areas (MSAs) using national medical claims data over multiple influenza seasons. METHODS: Using billing data from the Centers for Medicare and Medicaid Services for those aged 65 years and older, we estimated weekly rates of ordered rapid influenza diagnostic tests (RIDT) and antivirals (AV) among Medicare enrollees by core-based statistical areas (CBSAs) during 2010-2016. We used Negative Binomial generalized mixed models to estimate adjusted rate ratios (aRR) between MSAs and muSAs, adjusting for clustering by CBSA plus explanatory variables. We ran models for all weeks and only high influenza activity weeks. RESULTS: For all weeks, the unadjusted rate of RIDTs was 1.97 per 10,000 people in MSAs compared with 2.69 in muSAs (Rate ratio (RR) = 0.73, 95% Confidence Interval (CI): 0.73-0.74) and of AVs was 1.85 in MSAs compared with 1.40 in muSAs (RR = 1.32, CI: 1.31-1.32). From the multivariate model, aRR for RIDTs was 0.82 (0.73-0.94) and for AVs was 1.12 (1.04-1.22) in MSAs versus muSAs. For high influenza activity weeks, aRR for RIDTs was 0.82 (0.73-0.92) and for AVs was 1.15 (1.06-1.24). All models found influenza testing rates higher in muSAs and treatment rates higher in MSAs. CONCLUSIONS: Our study found lower testing and higher treatment in U.S. metropolitan versus micropolitan areas from 2010 to 2016 for those aged 65 years and older in our population. Identifying differences in influenza rates by rurality may improve public health response. Further research into the relationship of rurality and health disparities is needed.

BACKGROUND: Understanding how symptoms are associated with SARS-CoV-2 culture positivity is important for isolation and transmission control guidelines. METHODS: Individuals acutely infected with SARS-CoV-2 in Tennessee and their household contacts were recruited into a prospective study. All participants self-collected nasal swabs daily for 14 days and completed symptom diaries from the day of illness onset through day 14 postenrollment. Nasal specimens were tested for SARS-CoV-2 using RT-qPCR. Positive specimens with cycle threshold values < 40 were sent to the Centers for Disease Control and Prevention (CDC) for viral culture. First, we modeled the association between symptoms and the risk of culture positivity using an age-adjusted generalized additive model (GAM) accounting for repeated measurements within participants and a symptom-day spline. Next, we investigated how timing of symptom resolution was associated with the timing of culture resolution. RESULTS: In a GAM restricted to follow-up days after symptoms began, the odds of a specimen being culture positive was significantly increased on days when wheezing, loss of taste or smell, runny nose, nasal congestion, sore throat, fever, or any symptom were reported. For all symptoms except sore throat, it was more common for participants to have culture resolution before symptom resolution than for culture to resolve after or on the same day as symptom resolution. CONCLUSIONS: Overall, symptomatic individuals were more likely to be SARS-CoV-2 viral culture positive. For most symptoms, culture positivity was more likely to end before symptoms resolved. However, a proportion of individuals remained culture positive after symptom resolved, across all symptoms.

BACKGROUND: Highly pathogenic avian influenza A(H5N1) viruses have caused widespread infections in dairy cows and poultry in the United States, with sporadic human cases. We describe characteristics of human A(H5N1) cases identified from March through October 2024 in the United States. METHODS: We analyzed data from persons with laboratory-confirmed A(H5N1) virus infection using a standardized case-report form linked to laboratory results from the Centers for Disease Control and Prevention influenza A/H5 subtyping kit. RESULTS: Of 46 case patients, 20 were exposed to infected poultry, 25 were exposed to infected or presumably infected dairy cows, and 1 had no identified exposure; that patient was hospitalized with nonrespiratory symptoms, and A(H5N1) virus infection was detected through routine surveillance. Among the 45 case patients with animal exposures, the median age was 34 years, and all had mild A(H5N1) illness; none were hospitalized, and none died. A total of 42 patients (93%) had conjunctivitis, 22 (49%) had fever, and 16 (36%) had respiratory symptoms; 15 (33%) had conjunctivitis only. The median duration of illness among 16 patients with available data was 4 days (range, 1 to 8). Most patients (87%) received oseltamivir; oseltamivir was started a median of 2 days after symptom onset. No additional cases were identified among the 97 household contacts of case patients with animal exposures. The types of personal protective equipment (PPE) that were most commonly used by workers exposed to infected animals were gloves (71%), eye protection (60%), and face masks (47%). CONCLUSIONS: In the cases identified to date, A(H5N1) viruses generally caused mild illness, mostly conjunctivitis, of short duration, predominantly in U.S. adults exposed to infected animals; most patients received prompt antiviral treatment. No evidence of human-to-human A(H5N1) transmission was identified. PPE use among occupationally exposed persons was suboptimal, which suggests that additional strategies are needed to reduce exposure risk. (Funded by the Centers for Disease Control and Prevention.).

We compared the number of Aedes aegypti females per trap and the number of detections of this mosquito species per week during 8 wk in 3 types of autocidal gravid traps, the Centers for Disease Control and Prevention (CDC) Autocidal Gravid Ovitrap (AGO), Biogents Gravid Aedes Trap (GAT), and Singapore Gravitrap (SGT), in central Puerto Rico. These traps use the same principles for attracting gravid Ae. aegypti females as traditional ovitraps, such as dark colors, standing water, and decomposing plant materials. The traps differ in size, AGO being the biggest and SGT the smallest. Average captures of female Ae. aegypti per trap per week were 11.1, 7.2, and 1.7 in AGO, GAT, and SGT traps, respectively, a pattern consistent with the sizes of the traps. These results indicated that GAT traps and SGT traps captured 35.5% and 84.7% fewer females of Ae. aegypti, respectively, than AGO traps. Although Ae. aegypti was present in all 20 sites during the 8 wk of observations, AGO, GAT, and SGT traps did not catch specimens in 1, 9, and 58 out of 160 observations per trap type (trap-wk), respectively. Trap failures were 1, 6, and 1 for the AGO, GAT, and SGT traps, respectively. Despite the absence of females of Ae. aegypti at some sites and weeks in each of the traps, all 3 traps were able to detect the presence of this mosquito at each of the 20 sites during the 8 wk of observations and could be used for Ae. aegypti surveillance.

IMPORTANCE: Influenza vaccine effectiveness (VE) is commonly assessed against prevention of illness that requires medical attention. Few studies have evaluated VE against secondary influenza infections. OBJECTIVE: To determine the estimated effectiveness of influenza vaccines in preventing secondary infections after influenza was introduced into households. DESIGN, SETTINGS, AND PARTICIPANTS: During 3 consecutive influenza seasons (2017-2020), primary cases (the first household members with laboratory-confirmed influenza) and their household contacts in Tennessee and Wisconsin were enrolled into a prospective case-ascertained household transmission cohort study. Participants collected daily symptom diaries and nasal swabs for up to 7 days. Data were analyzed from September 2022 to February 2024. EXPOSURES: Vaccination history, self-reported and verified through review of medical and registry records. MAIN OUTCOMES AND MEASURES: Specimens were tested using reverse transcription-polymerase chain reaction to determine influenza infection. Longitudinal chain binomial models were used to estimate secondary infection risk and the effectiveness of influenza vaccines in preventing infection among household contacts overall and by virus type and subtype and/or lineage. RESULTS: The analysis included 699 primary cases and 1581 household contacts. The median (IQR) age of the primary cases was 13 (7-38) years, 381 (54.5%) were female, 60 (8.6%) were Hispanic, 46 (6.6%) were non-Hispanic Black, 553 (79.1%) were Non-Hispanic White, and 343 (49.1%) were vaccinated. Among household contacts, the median age was 31 (10-41) years, 833 (52.7%) were female, 116 (7.3%) were Hispanic, 78 (4.9%) were non-Hispanic Black, 1283 (81.2%) were non-Hispanic White, 792 (50.1%) were vaccinated, and 356 (22.5%) had laboratory-confirmed influenza during follow-up. The overall secondary infection risk of influenza among household contacts was 18.8% (95% CI, 15.9% to 22.0%). The risk was highest among children and was 20.3% (95% CI, 16.4% to 24.9%) for influenza A and 15.9% (95% CI, 11.8% to 21.0%) for influenza B. The overall estimated VE for preventing secondary infections among unvaccinated household contacts was 21.0% (95% CI, 1.4% to 36.7%) and varied by type; estimated VE against influenza A was 5.0% (95% CI, -22.3% to 26.3%) and 56.4% (95% CI, 30.1% to 72.8%) against influenza B. CONCLUSIONS AND RELEVANCE: After influenza was introduced into households, the risk of secondary influenza among unvaccinated household contacts was approximately 15% to 20%, and highest among children. Estimated VE varied by influenza type, with demonstrated protection against influenza B virus infection.

The risk for transmission of highly pathogenic avian influenza A(H5N1) virus from dairy cows to humans is currently low; however, personal protective equipment (PPE) use during work activities on dairy farms has not been well described. PPE use can protect farmworkers when they are working with highly pathogenic avian influenza A(H5N1)-infected cows. The Colorado Department of Public Health and Environment (CDPHE) and the Colorado Department of Agriculture (CDA) offered PPE to all Colorado farms before or during an A(H5N1) outbreak in cows in 2024. CDPHE surveyed 83 dairy workers from three farms with a confirmed bovine A(H5N1) outbreak. Frequently reported farm worker activities included milking cows or working in the milking parlor (51%), cleaning cow manure (49%), and transporting cows (46%). Frequently reported PPE items available to workers before A(H5N1) outbreaks included gloves (88%), eye protection (e.g., safety glasses or goggles) (76%), rubber boots or boot covers (71%), and head covers (69%). N95 respirator use was low among workers who were exposed to ill cows after detection of A(H5N1) virus (26%). PPE use while working with ill cows increased a mean of 28% after detection of A(H5N1) virus on surveyed farms; use of eye protection while milking cows increased the most (40%). Public health PPE distribution, education, and collaboration with CDA might have increased PPE use on dairy farms with A(H5N1) virus-infected cows and mitigated risk for farmworkers acquiring A(H5N1) virus.

Since April 2024, sporadic infections with highly pathogenic avian influenza (HPAI) A(H5) viruses have been detected among dairy farm workers in the United States. To date, infections have mostly been detected through worker monitoring, and have been mild despite the possibility of more severe illness. During June-August 2024, CDC collaborated with the Michigan Department of Health and Human Services and the Colorado Department of Public Health and Environment to implement cross-sectional serologic surveys to ascertain the prevalence of recent infection with HPAI A(H5) virus among dairy workers. In both states, a convenience sample of persons who work in dairies was interviewed, and blood specimens were collected. Among 115 persons, eight (7%; 95% CI = 3.6%-13.1%) had serologic evidence of recent infection with A(H5) virus; all reported milking cows or cleaning the milking parlor. Among persons with serologic evidence of infection, four recalled being ill around the time cows were ill; symptoms began before or within a few days of A(H5) virus detections among cows. This finding supports the need to identify and implement strategies to prevent transmission among dairy cattle to reduce worker exposures and for education and outreach to dairy workers concerning prevention, symptoms, and where to seek medical care if the workers develop symptoms. Timely identification of infected herds can support rapid initiation of monitoring, testing, and treatment for human illness, including mild illness, among exposed dairy workers.

PROBLEM/CONDITION: Seasonal influenza accounts for 9.3 million-41 million illnesses, 100,000-710,000 hospitalizations, and 4,900-51,000 deaths annually in the United States. Since 2003, the Influenza Hospitalization Surveillance Network (FluSurv-NET) has been conducting population-based surveillance for laboratory-confirmed influenza-associated hospitalizations in the United States, including weekly rate estimations and descriptions of clinical characteristics and outcomes for hospitalized patients. However, a comprehensive summary of trends in hospitalization rates and clinical data collected from the surveillance platform has not been available. REPORTING PERIOD: 2010-11 through 2022-23 influenza seasons. DESCRIPTION OF SYSTEM: FluSurv-NET conducts population-based surveillance for laboratory-confirmed influenza-associated hospitalizations among children and adults. During the reporting period, the surveillance network included 13-16 participating sites each influenza season, with prespecified geographic catchment areas that covered 27 million-29 million persons and included an estimated 8.8%-9.5% of the U.S. population. A case was defined as a person residing in the catchment area within one of the participating states who had a positive influenza laboratory test result within 14 days before or at any time during their hospitalization. Each site abstracted case data from hospital medical records into a standardized case report form, with selected variables submitted to CDC on a weekly basis for rate estimations. Weekly and cumulative laboratory-confirmed influenza-associated hospitalization rates per 100,000 population were calculated for each season from 2010-11 through 2022-23 and stratified by patient age (0-4 years, 5-17 years, 18-49 years, 50-64 years, and ≥65 years), sex, race and ethnicity, influenza type, and influenza A subtype. During the 2020-21 season, only the overall influenza hospitalization rate was reported because case counts were insufficient to estimate stratified rates. RESULTS: During the 2010-11 to 2022-23 influenza seasons, laboratory-confirmed influenza-associated hospitalization rates varied significantly across seasons. Before the COVID-19 pandemic, hospitalization rates per 100,000 population ranged from 8.7 (2011-12) to 102.9 (2017-18) and had consistent seasonality. After SARS-CoV-2 emerged, the hospitalization rate for 2020-21 was 0.8, and the rate did not return to recent prepandemic levels until 2022-23. Inconsistent seasonality also was observed during 2020-21 through 2022-23, with influenza activity being very low during 2020-21, extending later than usual during 2021-22, and occurring early during 2022-23. Molecular assays, particularly multiplex standard molecular assays, were the most common influenza test type in recent seasons, increasing from 12% during 2017-18 for both pediatric and adult cases to 43% and 55% during 2022-23 for pediatric and adult cases, respectively. During each season, adults aged ≥65 years consistently had the highest influenza-associated hospitalization rate across all age groups, followed in most seasons by children aged 0-4 years. Black or African American and American Indian or Alaska Native persons had the highest age-adjusted influenza-associated hospitalization rates across these seasons. Among patients hospitalized with influenza, the prevalence of at least one underlying medical condition increased with increasing age, ranging from 36.9% among children aged 0-4 years to 95.4% among adults aged ≥65 years. Consistently across each season, the most common underlying medical conditions among children and adolescents were asthma, neurologic disorders, and obesity. The most common underlying medical conditions among adults were hypertension, obesity, chronic metabolic disease, chronic lung disease, and cardiovascular disease. The proportion of FluSurv-NET patients with acute respiratory signs and symptoms at hospital admission decreased from 90.6% during 2018-19 to 83.2% during 2022-23. Although influenza antiviral use increased during the 2010-11 through the 2017-18 influenza seasons, it decreased from 90.2% during 2018-19 to 79.1% during 2022-23, particularly among children and adolescents. Admission to the intensive care unit, need for invasive mechanical ventilation, and in-hospital death ranged from 14.1% to 22.3%, 4.9% to 11.1%, and 2.2% to 3.5% of patients hospitalized with influenza, respectively, during the reported surveillance period. INTERPRETATIONS: Influenza continues to cause severe morbidity and mortality, particularly in older adults, and disparities have persisted in racial and ethnic minority groups. Persons with underlying medical conditions represented a large proportion of patients hospitalized with influenza. Increased use of multiplex tests and other potential changes in facility-level influenza testing practices (e.g., influenza screening at all hospital admissions) could have implications for the detection of influenza infections among hospitalized patients. Antiviral use decreased in recent seasons, and explanations for the decrease should be further evaluated. PUBLIC HEALTH ACTION: Continued robust influenza surveillance is critical to monitor progress in efforts to encourage antiviral treatment and improve clinical outcomes for persons hospitalized with influenza. In addition, robust influenza surveillance can potentially reduce disparities by informing efforts to increase access to preventive measures for influenza and monitoring any subsequent changes in hospitalization rates.

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.

Isolation of symptomatic infectious persons can reduce influenza transmission. However, virus shedding that occurs without symptoms will be unaffected by such measures. Identifying effective isolation strategies for influenza requires understanding the interplay between individual virus shedding and symptom presentation. From 2017 to 2020, we conducted a case-ascertained household transmission study using influenza real-time RT-qPCR testing of nasal swabs and daily symptom diary reporting for up to 7 days after enrolment (≤14 days after index onset). We assumed real-time RT-qPCR cycle threshold (Ct) values were indicators of quantitative virus shedding and used symptom diaries to create a score that tracked influenza-like illness (ILI) symptoms (fever, cough, or sore throat). We fit phenomenological nonlinear mixed-effects models stratified by age and vaccination status and estimated two quantities influencing isolation effectiveness: shedding before symptom onset and shedding that might occur once isolation ends. We considered different isolation end points (including 24 h after fever resolution or 5 days after symptom onset) and assumptions about the infectiousness of Ct shedding trajectories. Of the 116 household contacts with ≥2 positive tests for longitudinal analyses, 105 (91%) experienced ≥1 ILI symptom. On average, children <5 years experienced greater peak shedding, longer durations of shedding, and elevated ILI symptom scores compared with other age groups. Most individuals (63/105) shed <10% of their total shed virus before symptom onset, and shedding after isolation varied substantially across individuals, isolation end points, and infectiousness assumptions. Our results can inform strategies to reduce transmission from symptomatic individuals infected with influenza.

Persons who work in close contact with dairy cattle and poultry that are infected with highly pathogenic avian influenza (HPAI) A(H5N1) virus are at increased risk for infection. In July 2024, the Colorado Department of Public Health & Environment responded to two poultry facilities with HPAI A(H5N1) virus detections in poultry. Across the two facilities, 663 workers assisting with poultry depopulation (i.e., euthanasia) received screening for illness; 109 (16.4%) reported symptoms and consented to testing. Among those who received testing, nine (8.3%) received a positive influenza A(H5) virus test result, and 19 (17.4%) received a positive SARS-CoV-2 test result. All nine workers who received positive influenza A(H5) test results had conjunctivitis, experienced mild illness, and received oseltamivir. This poultry exposure-associated cluster of human cases of influenza A(H5) is the first reported in the United States. The identification of these cases highlights the ongoing risk to persons who work in close contact with infected animals. Early response to each facility using multidisciplinary, multilingual teams facilitated case-finding, worker screening, and treatment. As the prevalence of HPAI A(H5N1) virus clade 2.3.4.4b genotype B3.13 increases, U.S. public health agencies should prepare to rapidly investigate and respond to illness in agricultural workers, including workers with limited access to health care.

Asymptomatic influenza virus infection occurs but may vary by factors such as age, influenza vaccination status, or influenza season. We examined the frequency of influenza virus infection and associated symptoms using data from two case-ascertained household transmission studies (conducted from 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 the effectiveness of symptom-based surveillance systems.

Accurate forecasts can enable more effective public health responses during seasonal influenza epidemics. For the 2021-22 and 2022-23 influenza seasons, 26 forecasting teams provided national and jurisdiction-specific probabilistic predictions of weekly confirmed influenza hospital admissions for one-to-four weeks ahead. Forecast skill is evaluated using the Weighted Interval Score (WIS), relative WIS, and coverage. Six out of 23 models outperform the baseline model across forecast weeks and locations in 2021-22 and 12 out of 18 models in 2022-23. Averaging across all forecast targets, the FluSight ensemble is the 2(nd) most accurate model measured by WIS in 2021-22 and the 5(th) most accurate in the 2022-23 season. Forecast skill and 95% coverage for the FluSight ensemble and most component models degrade over longer forecast horizons. In this work we demonstrate that while the FluSight ensemble was a robust predictor, even ensembles face challenges during periods of rapid change.

Direct-on-Filter (DoF) analysis of respirable crystalline silica (RCS) by Fourier Transform Infrared (FTIR) spectroscopy is a useful tool for assessing exposure risks. With the RCS exposure limits becoming lower, it is important to characterize and reduce measurement uncertainties. This study systematically evaluated two filter types (i.e., polyvinyl chloride [PVC] and polytetrafluoroethylene [PTFE]) for RCS measurements by DoF FTIR spectroscopy, including the filter-to-filter and day-to-day variability of blank filter FTIR reference spectra, particle deposition patterns, filtration efficiencies, and pressure drops. For PVC filters sampled at a flow rate of 2.5 L/min for 8 h, the RCS limit of detection (LOD) was 7.4 μg/m(3) when a designated laboratory reference filter was used to correct the absorption by the filter media. When the spectrum of the pre-sample filter (blank filter before dust sampling) was used for correction, the LOD could be up to 5.9 μg/m(3). The PVC absorption increased linearly with reference filter mass, providing a means to correct the absorption differences between the pre-sample and reference filters. For PTFE, the LODs were 12 and 1.2 μg/m(3) when a designated laboratory blank or the pre-sample filter spectrum was used for blank correction, respectively, indicating that using the pre-sample blank spectrum will reduce RCS quantification uncertainty. Both filter types exhibited a consistent radially symmetric deposition pattern when particles were collected using 3-piece cassettes, indicating that RCS can be quantified from a single measurement at the filter center. The most penetrating aerodynamic diameters were around 0.1 µm with filtration efficiencies ≥ 98.8% across the measured particle size range with low-pressure drops (0.2-0.3 kPa) at a flow rate of 2.5 L/min. This study concludes that either the PVC or the PTFE filters are suitable for RCS analysis by DoF FTIR, but proper methods are needed to account for the variability of blank absorption among different filters.

Background: Understanding how symptoms are associated with SARS-CoV-2 culture positivity is important for isolation and transmission control guidelines. Methods: Individuals acutely infected with SARS-CoV-2 in Tennessee and their household contacts were recruited into a prospective study. All participants self-collected nasal swabs daily for 14 days and completed symptom diaries from the day of illness onset through day 14 postenrollment. Nasal specimens were tested for SARS-CoV-2 using RT-qPCR. Positive specimens with cycle threshold values < 40 were sent to the Centers for Disease Control and Prevention (CDC) for viral culture. First, we modeled the association between symptoms and the risk of culture positivity using an age-adjusted generalized additive model (GAM) accounting for repeated measurements within participants and a symptom-day spline. Next, we investigated how timing of symptom resolution was associated with the timing of culture resolution. Results: In a GAM restricted to follow-up days after symptoms began, the odds of a specimen being culture positive was significantly increased on days when wheezing, loss of taste or smell, runny nose, nasal congestion, sore throat, fever, or any symptom were reported. For all symptoms except sore throat, it was more common for participants to have culture resolution before symptom resolution than for culture to resolve after or on the same day as symptom resolution. Conclusions: Overall, symptomatic individuals were more likely to be SARS-CoV-2 viral culture positive. For most symptoms, culture positivity was more likely to end before symptoms resolved. However, a proportion of individuals remained culture positive after symptom resolved, across all symptoms. © 2024 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

We present a novel small molecule antiviral chemotype that was identified by an unconventional cell-free protein synthesis and assembly-based phenotypic screen for modulation of viral capsid assembly. Activity of PAV-431, a representative compound from the series, has been validated against infectious viruses in multiple cell culture models for all six families of viruses causing most respiratory diseases in humans. In animals, this chemotype has been demonstrated efficacious for porcine epidemic diarrhoea virus (a coronavirus) and respiratory syncytial virus (a paramyxovirus). PAV-431 is shown to bind to the protein 14-3-3, a known allosteric modulator. However, it only appears to target the small subset of 14-3-3 which is present in a dynamic multi-protein complex whose components include proteins implicated in viral life cycles and in innate immunity. The composition of this target multi-protein complex appears to be modified upon viral infection and largely restored by PAV-431 treatment. An advanced analog, PAV-104, is shown to be selective for the virally modified target, thereby avoiding host toxicity. Our findings suggest a new paradigm for understanding, and drugging, the host-virus interface, which leads to a new clinical therapeutic strategy for treatment of respiratory viral disease.

BACKGROUND: Novel influenza viruses pose a potential pandemic risk, and rapid detection of infections in humans is critical to characterizing the virus and facilitating the implementation of public health response measures. METHODS: We use a probabilistic framework to estimate the likelihood that novel influenza virus cases would be detected through testing in different community and healthcare settings (urgent care, emergency department, hospital, and intensive care unit [ICU]) while at low frequencies in the United States. Parameters were informed by data on seasonal influenza virus activity and existing testing practices. RESULTS: In a baseline scenario reflecting the presence of 100 novel virus infections with similar severity to seasonal influenza viruses, the median probability of detecting at least one infection per month was highest in urgent care settings (72%) and when community testing was conducted at random among the general population (77%). However, urgent care testing was over 15 times more efficient (estimated as the number of cases detected per 100,000 tests) due to the larger number of tests required for community testing. In scenarios that assumed increased clinical severity of novel virus infection, median detection probabilities increased across all healthcare settings, particularly in hospitals and ICUs (up to 100%) where testing also became more efficient. CONCLUSIONS: Our results suggest that novel influenza virus circulation is likely to be detected through existing healthcare surveillance, with the most efficient testing setting impacted by the disease severity profile. These analyses can help inform future testing strategies to maximize the likelihood of novel influenza detection.

Control of dust in underground coal mines is critical for mitigating both safety and health hazards. For decades, the National Institute of Occupational Safety and Health (NIOSH) has led research to evaluate the effectiveness of various dust control technologies in coal mines. Recent studies have included the evaluation of auxiliary scrubbers to reduce respirable dust downstream of active mining and the use of canopy air curtains (CACs) to reduce respirable dust in key operator positions. While detailed dust characterization was not a focus of such studies, this is a growing area of interest. Using preserved filter samples from three previous NIOSH studies, the current work aims to explore the effect of two different scrubbers (one wet and one dry) and a roof bolter CAC on respirable dust composition and particle size distribution. For this, the preserved filter samples were analyzed by thermogravimetric analysis and/or scanning electron microscopy with energy dispersive X-ray. Results indicate that dust composition was not appreciably affected by either scrubber or the CAC. However, the wet scrubber and CAC appeared to decrease the overall particle size distribution. Such an effect of the dry scrubber was not consistently observed, but this is probably related to the particular sampling location downstream of the scrubber which allowed for significant mixing of the scrubber exhaust and other return air. Aside from the insights gained with respect to the three specific dust control case studies revisited here, this work demonstrates the value of preserved dust samples for follow-up investigation more broadly. © The Author(s) 2024.