PROBLEM/CONDITION: An estimated 450,000 enteric illnesses, 5,000 hospitalizations, and 76 deaths associated with animal contact occur each year in the United States. Enteric illnesses are diseases that affect the stomach or intestines and cause symptoms, such as diarrhea, nausea, or vomiting, and are typically transmitted from animals to humans through the fecal-oral route. Humans might encounter animal feces or bodily fluids through contact with the animal itself, the animal's environment, or the animal's food or water. Although outbreak-associated illnesses account for a small subset of all enteric illnesses linked to animal contact, data obtained from outbreak surveillance offer insights into the underlying epidemiologic factors contributing to illnesses, including the pathogens, animals, pathogen-animal category pairs, and settings of outbreaks associated with animal contact. PERIOD COVERED: 2009-2021. DESCRIPTION OF SYSTEM: The Animal Contact Outbreak Surveillance System (ACOSS) was launched in 2009 in conjunction with the National Outbreak Reporting System (NORS), a web-based platform that includes reports of foodborne and waterborne outbreaks as well as enteric disease outbreaks transmitted by contact with environmental sources, infected persons or animals, or unknown modes. ACOSS encompasses animal contact outbreaks that are reported to CDC through NORS. Local, state, and territorial health departments voluntarily report animal contact outbreaks, which are defined as two or more enteric illnesses associated with a common animal source. Outbreaks can involve single or multiple states; CDC staff typically report multistate outbreaks on behalf of state and territorial health departments. ACOSS defines an animal source as an animal (including domestic and wild animals); an animal's feces or bodily fluids (except milk and other fluids consumed as food, which are defined as foodborne sources); an animal's fur, hair, feathers, scales, or skin; an animal's food; or an animal's environment, which includes places in which it lives and roams. RESULTS: During 2009-2021, a total of 557 animal contact outbreaks of enteric disease were reported in the United States through ACOSS, accounting for 14,377 illnesses, 2,656 hospitalizations, and 22 deaths. Exposures were reported in all 50 states, Washington, DC, and Puerto Rico. During the period there were 393 single-state outbreaks and 164 multistate outbreaks. Although multistate outbreaks comprised 29% of all outbreaks reported through ACOSS, they accounted for 80% of illnesses, 88% of hospitalizations, and 82% of deaths. Among 474 outbreaks with a confirmed single etiology, Salmonella was the most common cause of outbreaks (248 outbreaks [52%]); these outbreaks accounted for the most outbreak-associated illnesses (11,822 [85%]), hospitalizations (2,393 [91%]), and deaths (17 [77%]). Cryptosporidium (108 outbreaks [23%]) was the second leading cause of confirmed, single etiology outbreaks, followed by Escherichia coli (63 [13%]) and Campylobacter (52 [11%]). The most common exposure locations among outbreaks with a single location reported were private home (168 [40%]) and farm or dairy (89 [21%]). Among 467 outbreaks for which an animal source could be attributed to a single animal category, ruminants (171 [37%]) were the most implicated animal category (with 75% of ruminant outbreaks attributed to cattle), followed by poultry (155 [33%]) and turtles (39 [12%]). Poultry were associated with the most outbreak-associated illnesses (9,095 [66% of illnesses resulting from outbreaks attributed to a single animal category]), hospitalizations (1,804 [70%]), and deaths (15 [83%]). Most outbreaks (130 [84% of all poultry outbreaks]) attributed to poultry had private home reported as at least one of the exposure locations (i.e., backyard poultry) and were responsible for nearly all poultry-associated illnesses (8,897 [98%]). The most common confirmed pathogen-animal pair was Salmonella and poultry (132 outbreaks), followed by Cryptosporidium and ruminants (88), and Salmonella and turtles (37). Salmonella and poultry accounted for the highest number of outbreak-associated illnesses (8,965), hospitalizations (1,790), and deaths (15). INTERPRETATION: Animal contact outbreaks of enteric disease reported through ACOSS provide insights into the animals and etiologies causing outbreak-associated enteric illnesses as well as other outbreak characteristics, such as settings in which outbreaks occur. These findings can guide public health actions, developed in collaboration with specific populations (e.g., backyard poultry owners) and including interventions tailored to settings, such as private homes and farms or dairies, that are more commonly associated with animal contact outbreaks. The high proportion of outbreaks occurring in private homes identifies a potential gap in proper hygiene and enteric disease prevention knowledge among animal owners, including owners of backyard poultry, which might be considered by owners to be pets rather than livestock. Settings and populations linked to ruminants, poultry, and turtles (particularly cattle, backyard poultry, and small turtles, respectively) are important targets for public health interventions because of the high number of outbreaks and outbreak-associated illnesses associated with these animal sources. Furthermore, the disproportionate impact of multistate outbreaks reiterates the importance of a collaborative national response but also might reflect limited resources to investigate or report animal contact outbreaks at state and local levels. PUBLIC HEALTH ACTION: Public health partners should continue to report animal contact outbreaks through ACOSS to inform evidence-based interventions tailored to specific animals, pathogens, populations, and settings. Strengthening the capacity of local, state, and territorial health departments to investigate and report animal contact outbreaks is critical to improving surveillance of animal contact outbreaks. Close collaboration between state, local, and Federal public health and agricultural partners nationwide is also key in investigating and responding to multistate outbreaks. An integrated One Health approach that leverages the expertise of animal, environmental, and public health partners can facilitate successful public health interventions aimed at preventing animal contact outbreaks.

BACKGROUND: Risk factors for severe respiratory syncytial virus (RSV) illness include early infancy, premature birth, and underlying medical conditions. However, the clinical significance of respiratory viral co-detection is unclear. We compared the clinical outcomes of young children with RSV-only detection and those with RSV viral co-detection. METHODS: We conducted active, population-based surveillance of children with medically attended fever or respiratory symptoms at 7 US medical centers (1 December 2016-31 March 2020). Demographic and clinical data were collected through parental interviews and chart abstractions. Nasal swabs, with or without throat swabs, were systematically tested for RSV and 6 other common respiratory virus groups. We compared clinical outcomes, including hospitalization, and among those hospitalized, length of stay, intensive care unit admission, supplemental oxygen use, and intubation, between children aged <2 years with RSV-only detection and those with RSV co-detection. RESULTS: We enrolled 18 008 children aged <2 years. Of 17 841 (99.1%) tested for RSV, 5099 (28.6%) were positive. RSV was singly detected in 3927 children (77.0%) and co-detected in 1172 (23.0%). RSV co-detection with parainfluenza virus or adenovirus was associated with significantly lower odds of hospitalization (adjusted odds ratio, 0.56; 95% confidence interval [CI]: .33-.95; P = .031) and supplemental oxygen use (adjusted odds ratio, 0.66; 95% CI: .46-.95; P = .026), respectively, than RSV-only detection. For all other comparisons, we did not identify a significant association between RSV co-detection and worse clinical outcomes. CONCLUSIONS: Co-detection of RSV with another respiratory virus was not significantly associated with worse clinical outcomes compared with RSV-only detection.

IMPORTANCE: Enterovirus D68 (EV-D68) typically causes mild to severe acute respiratory illness (ARI). Testing and surveillance for EV-D68 in the US are limited, and important epidemiologic gaps remain. OBJECTIVE: To characterize the epidemiology and clinical severity of EV-D68 among US children seeking care for ARI from 2017 to 2022, using a multisite, active, systematic surveillance network. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study collected data from the New Vaccine Surveillance Network, an active, prospective, population-based surveillance system of emergency departments (EDs) and hospitals at 7 US academic medical centers. Children with ARI and EV-D68-positive results were enrolled during platform-wide EV-D68 testing periods (July to October 2017, July to November 2018, July to November 2020, and July 2021 to December 2022). Included children were aged younger than 18 years, reported 1 or more qualifying ARI symptoms, with a symptom duration less than 14 days at enrollment. Data were analyzed from in October 2024. EXPOSURES: Laboratory-confirmed EV-D68 infection, including overall infections or those without viral codetection. MAIN OUTCOMES AND MEASURES: Trends and characteristics of EV-D68, including demographics, underlying conditions, and clinical severity by health care setting, were explored. Among hospitalized children with EV-D68-positive results without viral codetection, multivariable logistic regression was used to examine factors associated with receipt of (1) supplemental oxygen or (2) intensive care. RESULTS: From 2017 to 2022, 976 children with EV-D68-positive results were identified (median [IQR] age, 47 [18-63] months; 391 [40.1%] female); most were enrolled in 2018 (382 children) and 2022 (533 children). Among these, 856 had no viral codetection, of which 320 were discharged home from the ED (median [IQR] age, 33 [16-59] months; 180 male [56.3%]; 237 [74.1%] with no reported underlying conditions) and 536 were hospitalized (median [IQR] age, 40 [19-69] months; 330 male [61.6%]; 268 [50.0%] with no reported underlying conditions). Among those hospitalized, 199 (37.1%) reported a history of asthma or reactive airway disease (RAD) and 77 (14.4%) reported a condition other than asthma or RAD. Having an underlying condition other than asthma or RAD was associated with increased odds of receiving supplemental oxygen (adjusted odds ratio, 2.72; 95% CI, 1.43-5.18) or intensive care admission (adjusted odds ratio, 3.09; 95% CI, 1.72-5.56); neither age group nor history of asthma or RAD were associated with oxygen receipt or intensive care admission. CONCLUSIONS AND RELEVANCE: In this cross-sectional study of children with medically attended EV-D68 infections, EV-D68 was associated with severe disease in otherwise healthy children of all ages, and children with nonasthma or RAD comorbidities were at higher risk for severe outcomes when hospitalized.

Maternal respiratory syncytial virus (RSV) vaccine and nirsevimab, a long-acting monoclonal antibody for infants aged 0-7 months and children aged 8-19 months who are at increased risk for severe RSV disease, became widely available for prevention of severe RSV disease among infants and young children during the 2024-25 RSV season. To evaluate the association between availability of these products and infant and child RSV-associated hospitalization rates, the rates among children aged <5 years were compared for the 2024-25 and 2018-20 RSV seasons using data from the RSV-Associated Hospitalization Surveillance Network (RSV-NET) and New Vaccine Surveillance Network (NVSN). Among infants aged 0-7 months (eligible for protection with maternal vaccination or nirsevimab), 2024-25 RSV-associated hospitalization rates were lower compared with 2018-20 pooled rates (estimated relative rate reductions of 43% [RSV-NET: 95% CI = 40%-46%] and 28% [NVSN: 95% CI = 18%-36%]). The largest estimated rate reduction was observed among infants aged 0-2 months (RSV-NET: 52%, 95% CI = 49%-56%; NVSN: 45%, 95% CI = 32%-57%) and during peak hospitalization periods (December-February). These findings support Advisory Committee on Immunization Practices' recommendations for maternal vaccination or nirsevimab to protect against severe RSV disease in infants and highlight the importance of implementing the recommendations to protect infants as early in the RSV season as possible, before peak transmission, and for infants born during the RSV season, within the first week of life, ideally during the birth hospitalization.

BACKGROUND: Human parainfluenza viruses (PIV) are a major cause of acute respiratory infection (ARI) leading to hospitalization in young children. In order to quantify the burden of PIV hospitalizations and to evaluate the characteristics of children hospitalized with PIV by virus type, we used data from the New Vaccine Surveillance Network (NVSN), a multicenter, active, prospective population-based surveillance network, enrolling children hospitalized for ARI (defined as fever and/or respiratory symptoms) at 7 U.S. children's hospitals. METHODS: The study period included December 1, 2016 through March 31, 2020. Data captured included demographic characteristics, clinical presentation, underlying medical conditions, discharge diagnoses, and virus detection by RT-PCR. Linear and logistic regression were used to compare descriptive and clinical characteristics among children. Population-based PIV-associated hospitalization rates were calculated by age group and PIV-type. RESULTS: Of the 16,791 enrolled children with PIV virologic testing, 10,488 had only one respiratory virus detected, among whom 702 (7%) had positive testing for PIV without a co-detected virus (mean age [SD], 2.2 [3.2] years). Of these 702 children, 340 (48%) had underlying comorbidities, 139 (20%) had a history of prematurity, 121 (17%) were admitted to the ICU, and 23 (3%) required intubation. Overall, PIV hospitalization rates were highest in children aged 0-5 months (1.91 hospitalizations per 1,000 children per year [95% CI, 1.61-2.23], with PIV-3 contributing to the highest rates in that age group, followed by PIV-1 and PIV-4: 1.08 [0.84-1.21], 0.42 [0.28-0.58] and 0.25 [0.15-0.37] per 1,000 children per year, respectively. Seasonal distribution of PIV-associated hospitalizations varied by type. CONCLUSIONS: PIV infection was associated with a substantial number of ARI hospitalizations in children aged 0-5 months. Results suggest that future PIV prevention strategies in the US that focus on younger children and protection against PIV-3, PIV-1, and PIV-4 might have the greatest impact on reducing PIV hospitalization burden.

IMPORTANCE: During the 2023-2024 respiratory syncytial virus (RSV) season in the United States, 2 new RSV prevention products were recommended to protect infants in their first RSV season: nirsevimab and Pfizer's maternal RSV vaccine. Postlicensure studies are needed to assess prevention product impact and effectiveness. OBJECTIVE: To compare the epidemiology and disease burden of medically attended RSV-associated acute respiratory illness (ARI) among children younger than 5 years during the 2023-2024 RSV season with 3 prepandemic RSV seasons (2017-2020), estimate nirsevimab effectiveness against medically attended RSV-associated ARI, and compare nirsevimab binding site mutations among circulating RSV in infants with and without nirsevimab receipt. DESIGN, SETTING, AND PARTICIPANTS: This study included a prospective population-based surveillance for medically attended ARI with systematic molecular testing for RSV and whole-genome sequencing of RSV positive samples, as well as a test-negative case-control design to estimate nirsevimab effectiveness. The study was conducted in 7 academic pediatric medical centers in the United States with data from RSV seasons (September 1 through April 30) in 2017 through 2024. Participants were children younger than 5 years with medically attended ARI. EXPOSURE: For the nirsevimab effectiveness analyses, nirsevimab receipt among infants younger than 8 months as of or born after October 1, 2023. MAIN OUTCOME AND MEASURE: Medically attended RSV-associated ARI. RESULTS: Overall, 28 689 children younger than 5 years with medically attended ARI were enrolled, including 9536 during September 1, 2023, through April 30, 2024, and 19 153 during the same calendar period of 2017-2020. Of these children, 16 196 (57%) were male, and 12 444 (43.4) were female; the median (IQR) age was 15 (6-29) months. During 2023-2024, the proportion of children with RSV was 23% (2199/9490) among all medically attended episodes, similar to 2017-2020. RSV-associated hospitalization rates in 2023-2024 were similar to average 2017-2020 seasonal rates with 5.0 (95% CI, 4.6-5.3) per 1000 among children younger than 5 years; the highest rates were among children aged 0 to 2 months (26.6; 95% CI, 23.0-30.2). Low maternal RSV vaccine uptake precluded assessment of effectiveness. Overall, 10 of 765 case patients (1%) who were RSV positive and 126 of 851 control patients (15%) who were RSV negative received nirsevimab. Nirsevimab effectiveness was 89% (95% CI, 79%-94%) against medically attended RSV-associated ARI and 93% (95% CI, 82%-97%) against RSV-associated hospitalization. Among 229 sequenced specimens, there were no differences in nirsevimab binding site mutations by infant nirsevimab receipt status. CONCLUSIONS AND RELEVANCE: This analysis documented the continued high burden of medically attended RSV-associated ARI among young children in the US. There is a potential for substantial public health impact with increased and equitable prevention product coverage in future seasons.

Annually, tens of thousands of U.S. children and adolescents are hospitalized with seasonal influenza virus infection. Both influenza vaccination and early initiation of antiviral treatment can reduce complications of influenza. Using data from two U.S. influenza surveillance networks for children and adolescents aged <18 years with medically attended, laboratory-confirmed influenza for whom antiviral treatment is recommended, the percentage who received treatment was calculated. Trends in antiviral treatment of children and adolescents hospitalized with influenza from the 2017-18 to the 2023-2024 influenza seasons were also examined. Since 2017-18, when 70%-86% of hospitalized children and adolescents with influenza received antiviral treatment, the proportion receiving treatment notably declined. Among children and adolescents with influenza during the 2023-24 season, 52%-59% of those hospitalized received antiviral treatment. During the 2023-24 season, 31% of those at higher risk for influenza complications seen in the outpatient setting in one network were prescribed antiviral treatment. These findings demonstrate that influenza antiviral treatment is underutilized among children and adolescents who could benefit from treatment. All hospitalized children and adolescents, and those at higher risk for influenza complications in the outpatient setting, should receive antiviral treatment as soon as possible for suspected or confirmed influenza.

BACKGROUND: The coronavirus disease 2019 pandemic disrupted respiratory syncytial virus (RSV) seasonality resulting in early, atypical RSV seasons in 2021 and 2022, with an intense 2022 peak overwhelming many pediatric healthcare facilities. METHODS: We conducted prospective surveillance for acute respiratory illness during 2016-2022 at 7 pediatric hospitals. We interviewed parents, reviewed medical records, and tested respiratory specimens for RSV and other respiratory viruses. We estimated annual RSV-associated hospitalization rates in children aged <5 years and compared hospitalization rates and characteristics of RSV-positive hospitalized children over 4 prepandemic seasons (2016-2020) to those hospitalized in 2021 or 2022. RESULTS: There was no difference in median age or age distribution between prepandemic and 2021 seasons. Median age of children hospitalized with RSV was higher in 2022 (9.6 months vs 6.0 months, P < .001). RSV-associated hospitalization rates were higher in 2021 and 2022 than the prepandemic average across age groups. Comparing 2021 to 2022, RSV-associated hospitalization rates were similar among children <2 years of age; however, children aged 24 to 59 months had significantly higher rates of RSV-associated hospitalization in 2022 (rate ratio 1.68 [95% confidence interval 1.37-2.00]). More RSV-positive hospitalized children received supplemental oxygen and there were more respiratory virus codetections in 2022 than in prepandemic seasons (P < .001 and P = .003, respectively), but there was no difference in the proportion hypoxemic, mechanically ventilated, or admitted to intensive care. CONCLUSIONS: The atypical 2021 and 2022 RSV seasons resulted in higher hospitalization rates with similar disease severity to prepandemic seasons.

BACKGROUND: Respiratory syncytial virus (RSV) is a leading cause of acute respiratory illnesses in children. RSV can be broadly categorized into 2 major subtypes: A and B. RSV subtypes have been known to cocirculate with variability in different regions of the world. Clinical associations with viral subtype have been studied among children with conflicting findings such that no conclusive relationships between RSV subtype and severity have been established. METHODS: During 2016-2020, children aged <5 years were enrolled in prospective surveillance in the emergency department or inpatient settings at 7 US pediatric medical centers. Surveillance data collection included parent/guardian interviews, chart reviews, and collection of midturbinate nasal plus/minus throat swabs for RSV (RSV-A, RSV-B, and untyped) using reverse transcription polymerase chain reaction. RESULTS: Among 6398 RSV-positive children aged <5 years, 3424 (54%) had subtype RSV-A infections, 2602 (41%) had subtype RSV-B infections, and 272 (5%) were not typed, inconclusive, or mixed infections. In both adjusted and unadjusted analyses, RSV-A-positive children were more likely to be hospitalized, as well as when restricted to <1 year. By season, RSV-A and RSV-B cocirculated in varying levels, with 1 subtype dominating proportionally. CONCLUSIONS: Findings indicate that RSV-A and RSV-B may only be marginally clinically distinguishable, but both subtypes are associated with medically attended illness in children aged <5 years. Furthermore, circulation of RSV subtypes varies substantially each year, seasonally and geographically. With introduction of new RSV prevention products, this highlights the importance of continued monitoring of RSV-A and RSV-B subtypes.

Respiratory syncytial virus (RSV) is the leading cause of hospitalization among infants in the United States. In August 2023, CDC's Advisory Committee on Immunization Practices recommended nirsevimab, a long-acting monoclonal antibody, for infants aged <8 months to protect against RSV-associated lower respiratory tract infection during their first RSV season and for children aged 8-19 months at increased risk for severe RSV disease. In phase 3 clinical trials, nirsevimab efficacy against RSV-associated lower respiratory tract infection with hospitalization was 81% (95% CI = 62%-90%) through 150 days after receipt; post-introduction effectiveness has not been assessed in the United States. In this analysis, the New Vaccine Surveillance Network evaluated nirsevimab effectiveness against RSV-associated hospitalization among infants in their first RSV season during October 1, 2023-February 29, 2024. Among 699 infants hospitalized with acute respiratory illness, 59 (8%) received nirsevimab ≥7 days before symptom onset. Nirsevimab effectiveness was 90% (95% CI = 75%-96%) against RSV-associated hospitalization with a median time from receipt to symptom onset of 45 days (IQR = 19-76 days). The number of infants who received nirsevimab was too low to stratify by duration from receipt; however, nirsevimab effectiveness is expected to decrease with increasing time after receipt because of antibody decay. Although nirsevimab uptake and the interval from receipt of nirsevimab were limited in this analysis, this early estimate supports the current nirsevimab recommendation for the prevention of severe RSV disease in infants. Infants should be protected by maternal RSV vaccination or infant receipt of nirsevimab.

In the United States, annual influenza vaccination is recommended for all persons aged ≥6 months. Using data from four vaccine effectiveness (VE) networks during the 2023-24 influenza season, interim influenza VE was estimated among patients aged ≥6 months with acute respiratory illness-associated medical encounters using a test-negative case-control study design. Among children and adolescents aged 6 months-17 years, VE against influenza-associated outpatient visits ranged from 59% to 67% and against influenza-associated hospitalization ranged from 52% to 61%. Among adults aged ≥18 years, VE against influenza-associated outpatient visits ranged from 33% to 49% and against hospitalization from 41% to 44%. VE against influenza A ranged from 46% to 59% for children and adolescents and from 27% to 46% for adults across settings. VE against influenza B ranged from 64% to 89% for pediatric patients in outpatient settings and from 60% to 78% for all adults across settings. These findings demonstrate that the 2023-24 seasonal influenza vaccine is effective at reducing the risk for medically attended influenza virus infection. CDC recommends that all persons aged ≥6 months who have not yet been vaccinated this season get vaccinated while influenza circulates locally.