Estimating the Burden of Influenza Hospitalizations Across Multiple Seasons Using Capture-Recapture.

INTRODUCTION: Influenza remains an important cause of hospitalizations in the United States. Estimating the number of influenza hospitalizations is vital for public health decision making. Combining existing surveillance systems through capture-recapture methods allows for more comprehensive burden estimations. METHODS: Data from independent surveillance systems were combined using capture-recapture methods to estimate influenza hospitalization rates for children and adults in Middle Tennessee during consecutive influenza seasons from 2016-17 through 2019-20. EIP identified cases through surveillance of laboratory results for hospitalized children and adults. HAIVEN and NVSN recruited hospitalized patients with respiratory symptoms or fever. Population-based influenza rates and the proportion of cases detected by each surveillance system were calculated. RESULTS: Estimated overall influenza hospitalization rates ranged from 23 influenza-related hospitalizations per 10,000 persons in 2016-17 to 40 per 10,000 persons in 2017-18. Adults age ≥65 years had the highest hospitalization rates across seasons and experienced a rate of 170 hospitalizations per 10,000 persons during the 2017-18 season. EIP consistently identified a higher proportion of influenza cases for adults and children compared with HAIVEN and NVSN, respectively. CONCLUSION: Current surveillance systems underestimate the influenza burden. Capture-recapture provides an alternative approach to use data from independent surveillance systems and complement population-based burden estimates.

Vaccine Effectiveness Against Acute Respiratory Illness Hospitalizations for Influenza-Associated Pneumonia During the 2015-2016 to 2017-2018 Seasons: US Hospitalized Adult Influenza Vaccine Effectiveness Network (HAIVEN).

BACKGROUND: Evidence for vaccine effectiveness (VE) against influenza-associated pneumonia has varied by season, location, and strain. We estimate VE against hospitalization for radiographically identified influenza-associated pneumonia during 2015-2016 to 2017-2018 seasons in the US Hospitalized Adult Influenza Vaccine Effectiveness Network (HAIVEN). METHODS: Among adults aged ≥18 years admitted to 10 US hospitals for acute respiratory illness (ARI), clinician-investigators used keywords from reports of chest imaging performed during 3 days around hospital admission to assign a diagnosis of "definite/probable pneumonia." We used a test-negative design to estimate VE against hospitalization for radiographically identified laboratory-confirmed influenza-associated pneumonia, comparing reverse transcriptase-polymerase chain reaction-confirmed influenza cases with test-negative subjects. Influenza vaccination status was documented in immunization records or self-reported, including date and location. Multivariable logistic regression models were used to adjust for age, site, season, calendar-time, and other factors. RESULTS: Of 4843 adults hospitalized with ARI included in the primary analysis, 266 (5.5%) had "definite/probable pneumonia" and confirmed influenza. Adjusted VE against hospitalization for any radiographically confirmed influenza-associated pneumonia was 38% (95% confidence interval [CI], 17-53%); by type/subtype, it was 74% (95% CI, 52-87%) influenza A (H1N1)pdm09, 25% (95% CI, -15% to 50%) A (H3N2), and 23% (95% CI, -32% to 54%) influenza B. Adjusted VE against intensive care for any influenza was 57% (95% CI, 19-77%). CONCLUSIONS: Influenza vaccination was modestly effective among adults in preventing hospitalizations and the need for intensive care associated with influenza pneumonia. VE was significantly higher against A (H1N1)pdm09 and was low against A (H3N2) and B.

Influenza Vaccine Failure Associated With Age and Immunosuppression.

BACKGROUND: The influenza vaccine is one of the best ways to prevent influenza infection, but little is known about influenza vaccine failure. METHODS: This study evaluated patients admitted for acute respiratory illness during 2015-2019 influenza seasons to compare vaccinated influenza-negative to vaccinated influenza-positive patients. Statistical analyses were performed with STATA and R using Pearson χ 2, Kruskal-Wallis, Wilcoxon rank-sum tests, and multivariate logistic regression. RESULTS: Of 1236 enrolled patients vaccinated for influenza, 235 (19%) tested positive for influenza. Demographics, vaccines, and comorbidities were similar between groups except for morbid obesity (13% influenza negative vs 8%, P = .04), and immunosuppression (63% influenza positive vs 54%, P = .01). Logistic regression analysis demonstrated older patients (odds ratio [OR], 1.47; 95% confidence interval [CI], 1.03-2.10) and immunosuppressed patients (OR, 1.56; 95% CI, 1.15-2.12) were at increased risk for influenza despite immunization. When evaluated by influenza subtype, immunosuppression increased the risk for influenza A/H3N2 (OR, 1.86; 95% CI, 1.25-2.75). CONCLUSIONS: Our study demonstrated increased risk of influenza vaccine failure in older patients and immunosuppressed patients. These groups are also at increased risk for influenza complications. To improve protection of patients against influenza illnesses, more effective vaccines and strategies are needed.

Effectiveness of Pfizer-BioNTech and Moderna Vaccines Against COVID-19 Among Hospitalized Adults Aged ≥65 Years - United States, January-March 2021.

Adults aged ≥65 years are at increased risk for severe outcomes from COVID-19 and were identified as a priority group to receive the first COVID-19 vaccines approved for use under an Emergency Use Authorization (EUA) in the United States (1-3). In an evaluation at 24 hospitals in 14 states,* the effectiveness of partial or full vaccination† with Pfizer-BioNTech or Moderna vaccines against COVID-19-associated hospitalization was assessed among adults aged ≥65 years. Among 417 hospitalized adults aged ≥65 years (including 187 case-patients and 230 controls), the median age was 73 years, 48% were female, 73% were non-Hispanic White, 17% were non-Hispanic Black, 6% were Hispanic, and 4% lived in a long-term care facility. Adjusted vaccine effectiveness (VE) against COVID-19-associated hospitalization among adults aged ≥65 years was estimated to be 94% (95% confidence interval [CI] = 49%-99%) for full vaccination and 64% (95% CI = 28%-82%) for partial vaccination. These findings are consistent with efficacy determined from clinical trials in the subgroup of adults aged ≥65 years (4,5). This multisite U.S. evaluation under real-world conditions suggests that vaccination provided protection against COVID-19-associated hospitalization among adults aged ≥65 years. Vaccination is a critical tool for reducing severe COVID-19 in groups at high risk.

Risk Factors for Outpatient Use of Antibiotics in Children with Acute Respiratory Illnesses.

OBJECTIVES: Antibiotics for acute respiratory illness (ARI) constitute most pediatric medication use and contribute to the emergence of antimicrobial resistance. We investigated antibiotic prescription risk factors for ARI in pediatric clinics and clinical follow-up in individuals prescribed and not prescribed antibiotics. METHODS: In this observational study, we enrolled children ages 2 to 17 years old presenting with ARI with fever to two academic pediatric primary care outpatient clinics during influenza season 2013-2014. We collected information on demographics, initial symptoms, medical conditions, laboratory tests, discharge diagnoses, treatments, and 30 days of follow-up medical encounters. Factors associated with antibiotic prescription receipt were evaluated using logistic regression. RESULTS: Of 206 consented and enrolled children, 59 (29%) were prescribed antibiotics, 51 of 59 (86%) for indicated diagnoses: 34 for streptococcal pharyngitis, 15 for acute otitis media (AOM), and 2 for pneumonia. Discharge diagnoses were the only factors independently associated with an antibiotic prescription. Of children prescribed/not prescribed an antibiotic, 17%/17% received follow-up telephone calls and 27%/17% had follow-up visits related to ARI within 30 days. Two children with AOM were prescribed a second antibiotic during follow-up, and one developed Clostridium difficile colitis. Eighteen of 206 (9%) additional children were prescribed antibiotics within 30 days for ARI symptoms, 17 for streptococcal pharyngitis, AOM, pneumonia, or sinusitis; one was prescribed antibiotics for influenza-like illness. CONCLUSIONS: Among study children 2 to 17 years old with outpatient ARI, 29% were prescribed antibiotics at the initial visit and another 9% were prescribed antibiotics during the 30-day follow-up (most were for appropriate indications). Further decreasing antibiotic use in similar settings will likely require wider implementation of watchful waiting for AOM, a change in guidelines for pharyngitis management, and/or reductions in these diseases.

Estimating the Undetected Burden of Respiratory Syncytial Virus Hospitalizations in Adults Through Capture-Recapture Methods.

INTRODUCTION: Traditional surveillance systems may underestimate the burden caused by respiratory syncytial virus (RSV). Capture-recapture methods provide alternatives for estimating the number of RSV-related hospitalizations in a population. METHODS: Capture-recapture methods were used to estimate the number of RSV-related hospitalizations in adults in Middle Tennessee from two independent hospitalization surveillance systems during consecutive respiratory seasons from 2016-2017 to 2019-2020. Data from the Hospitalized Adult Influenza Vaccine Effectiveness Network (HAIVEN) and the Emerging Infections Program (EIP) were used. Annual RSV hospitalization rates were calculated using the capture-recapture estimates weighted by hospitals' market share divided by the corresponding census population. RESULTS: Using capture-recapture methods, the estimated overall adult hospitalization rates varied from 8.3 (95% CI: 5.9-15.4) RSV-related hospitalizations per 10,000 persons during the 2016-2017 season to 28.4 (95% CI: 18.2-59.0) hospitalizations per 10,000 persons in the 2019-2020 season. The proportion of hospitalizations that HAIVEN determined ranged from 8.7% to 36.7% of the total capture-recapture estimated hospitalization, whereas EIP detected 23.5% to 52.7% of the total capture-recapture estimated hospitalizations. CONCLUSION: Capture-recapture estimates showed that individual traditional surveillance systems underestimated the hospitalization burden in adults. Using capture-recapture allows for a more comprehensive estimate of RSV hospitalizations.

Comparison of a frailty short interview to a validated frailty index in adults hospitalized for acute respiratory illness.

BACKGROUND: Frailty is an important physiologic factor in studies of influenza and influenza vaccines carried out in older adults and hospitalized populations. Unfortunately, comprehensive assessments of frailty requiring physical assessments and extensive medical record review are not often feasible in time- and resource-limited settings common to studies of influenza and influenza vaccines. METHODS: We developed a 5-question frailty short interview, and implemented it in a multicenter, hospital-based study of influenza over two years. Frailty status defined by the frailty short interview was compared to a validated frailty index based on medical record review of 59 parameters. Agreement between the two frailty measures was assessed, and multivariable linear regression models were used to explore differences between the measures. The association between each frailty measure and likelihood of influenza vaccination was also assessed. RESULTS: During the 2015-2016 and 2016-2017 influenza seasons, 2070 adult patients hospitalized with acute respiratory illness were enrolled and included in analyses. Frailty was frequently identified in the study population; 43% of participants were defined as frail by the frailty short interview and 32% by frailty index. Responses to the frailty short interview were only moderately correlated with the frailty index, and agreement between the two frailty measures was low. Women were more likely to be defined as frail by the frailty short interview than men. White individuals were more likely than other races to be defined as frail by the frailty index. Increasing frailty index was associated with increased likelihood of influenza vaccination, but the frailty short interview was not associated with vaccination. CONCLUSIONS: The frailty short interview provided a feasible and consistent measure of frailty across study hospitals and study years. However, its modest correlation with the frailty index and differential association with likelihood of influenza vaccination highlight differences in the conceptualization of frailty.