Sara Y. Tartof

Introduction Respiratory syncytial virus (RSV) protein subunit vaccines reduce the risk of severe outcomes such as hospitalization and emergency department (ED) visits for at least two RSV seasons following vaccination. No data have been published on real-world RSV vaccine effectiveness (VE) beyond the second season after vaccination. This study evaluates bivalent RSVpreF VE against RSV-related respiratory disease hospitalizations/ED visits throughout three seasons after vaccination. Methods This retrospective test-negative case–control study evaluates bivalent RSVpreF VE among adults aged ≥60 years at Kaiser Permanente Southern California, USA, with lower respiratory tract disease (LRTD) or acute respiratory illness (ARI) over three RSV seasons (11/24/2023–4/18/2026). Cases were RSV-positive without coinfection. Controls were negative for RSV, hMPV, influenza, SARS-CoV-2, and positive for a non-vaccine preventable disease pathogen. Exposure was bivalent RSVpreF (Abrysvo) receipt ≥ 21 days before LRTD/ARI. Adjusted VE was estimated using odds ratios from multivariable logistic regression or generalized estimating equations. Results Overall adjusted VE against RSV-related LRTD hospitalization/ED visits was 80% (95% CI 68–87), 70% (95% CI 53–81), and 51% (95% CI —12–78) in the first, second, and third season after vaccination, respectively. Overall adjusted VE against RSV-related ARI hospitalization/ED visits was 81% (71–87), 64% (48–75), and 60% (15–81), respectively. Adjusted VE among non-immunocompromised individuals trended 4–7% higher than corresponding overall estimates. Overall adjusted VE across the three combined seasons was 73% (95% CI 64–80) and 73% (95% CI 65–79) against RSV-related LRTD and ARI, respectively. Conclusion Bivalent RSVpreF provides protection against RSV-related respiratory hospitalization/ED visits for at least three seasons after vaccination in this population of older adults with a high prevalence of comorbidities. Estimates in the third season for ARI were more definitive, while those for LRTD were imprecise due to limited event numbers. This suggests bivalent RSVpreF vaccination results in substantial individual and public health benefit. Trial Registration ClinicalTrials.gov ID: NCT06077968

Background: Consensus definitions for clinical identification of invasive aspergillosis (IA) are lacking, likely owing to difficulties in diagnosis. While the European Organisation for Research and Treatment of Cancer–Mycoses Study Group (EORTC/MSG) has provided benchmark guidelines to define IA, the criteria are highly restrictive. In this study, we constructed alternative definitions of IA using structured data from electronic health records (EHRs). Methods: From October 1, 2015, to March 31, 2022, we identified patients with IA from EHRs at Kaiser Permanente Southern California using definitions comprised of combinations of diagnosis codes, antifungal prescriptions, and/or positive mycological findings. Here, we report patient characteristics, including demographic information, underlying comorbidities, and immunosuppression, diagnostic measures, and morbidity and mortality after diagnosis for the population comprising each IA definition. Results: Between 86 and 4580 individuals were identified as possible IA cases across 7 definitions. All IA definitions that except for that only required positive mycology had similar patient characteristics and outcomes to those meeting 2008 EORTC/MSG criteria. The largest of these cohorts was comprised of 1067 patients, compared with the 86 that met EORTC/MSG criteria. Across IA definitions, all-cause mortality ranged from 11.7% to 33.1% within 6 months following diagnosis. The number of IA cases began trending upward between 2019 and 2020 and continued steadily through the coronavirus disease 2019 pandemic. Conclusions: IA definitions based on structured data can increase efficiency and identify clinically significant IA cases that might otherwise go unrepresented. Variability in the number of patients identified between definitions further highlights critical deficits in current IA diagnostics.

Background: The 2024–2025 influenza season was the most severe in the United States (US) since 2017–2018, with co-circulation of both influenza A virus subtypes (H1N1 and H3N2). Influenza vaccine effectiveness (VE) has varied by season, setting, and patient characteristics. Methods: Using electronic healthcare encounter data from 7 VISION sites in 8 US states, we evaluated influenza VE against influenza-associated hospitalizations and emergency department or urgent care (ED/UC) encounters from October 2024 to April 2025 among children aged 6 months–17 years and adults aged ≥18 years. Using a test-negative, case-control design, we compared the odds of influenza vaccination between acute respiratory illness encounters with a positive (cases) versus negative (controls) test for influenza by molecular assay, adjusting for confounders. Results: Analyses included 108 618 encounters (5764 hospitalizations and 102 854 ED/UC encounters) among children and 309 483 encounters (76 072 hospitalizations and 233 411 ED/UC encounters) among adults. Among children across care settings, 17.0% (6097/35 765) of cases versus 29.4% (21 449/72 853) of controls were vaccinated. Among adults, 28.2% (21 832/77 477) of cases versus 44.2% (102 560/232 006) of controls were vaccinated. VE was 51% (95% confidence interval [95% CI]: 41%–60%) against influenza-associated hospitalizations and 54% (95% CI: 52%–55%) against influenza-associated ED/UC encounters among children. VE was 43% (95% CI: 41%–46%) against influenza-associated hospitalizations and 49% (95% CI: 47%–50%) against influenza-associated ED/UC encounters among adults. Conclusions: Influenza vaccination provided protection against influenza-associated hospitalizations and ED/UC encounters among children and adults in the US during the severe 2024–2025 influenza season. These findings support influenza vaccination as an important tool to reduce influenza.

Epidemiological theory holds that core groups of high-risk individuals sustain pathogen transmission. However, the scale at which these dynamics operate is poorly understood. We leveraged doxycycline post-exposure prophylaxis (doxyPEP) implementation among at-risk men who have sex with men (MSM) and transgender women (TGW) as a natural experiment to probe bacterial sexually transmitted infection (STI) dynamics within and across sexual networks. DoxyPEP uptake by 9% of at-risk MSM and TGW was associated with pronounced indirect protection within their sexual networks, substantiating the notion that core groups of individuals wield outsize influence on transmission. Risk of chlamydia and syphilis declined by 80% (95% confidence interval: 71-86%) and 65% (30-82%), respectively, among doxyPEP recipients, and by 41% (32-48%) and 29% (13-42%), respectively, among MSM and TGW who did not receive doxyPEP. However, this substantial reduction in disease among at-risk MSM and TGW did not impact incidence among females and other males. Our findings substantiate core group dynamics of STIs among MSM and TGW but call into question the "bisexual bridge" hypothesis positioning this population as a core group impacting STI dynamics among heterosexuals. These findings should inform rational expectations for the impacts of doxyPEP in settings implementing this intervention.

Introduction: RSV vaccines reduce the risk of severe outcomes such as hospitalization and emergency department (ED) visits for at least 2 RSV seasons following vaccination. No data have been published on real-world RSV vaccine effectiveness (VE) beyond the second season after vaccination. This study evaluates bivalent RSVpreF VE against RSV-related lower respiratory tract disease (LRTD) hospitalizations/ED visits throughout 3 seasons after vaccination. Methods: This retrospective test-negative case-control evaluates bivalent RSVpreF VE among adults aged ≥60 years at Kaiser Permanente Southern California with LRTD over 3 RSV seasons (11/24/2023–4/18/2026). Cases were RSV-positive without coinfection. Controls were negative for RSV, hMPV, influenza, SARS-CoV-2, and positive for a non-vaccine preventable disease pathogen. Exposure was bivalent RSVpreF (Abrysvo) receipt ≥21 days before LRTD. Adjusted VE was estimated using odds ratios from multivariable logistic regression or generalized estimating equations. Results: Overall, adjusted VE against RSV-related LRTD hospitalization/ED visits was 80% (95% CI:68–87), 70% (95% CI:53–81), and 51% (95% CI:-12–78) in the first, second, and third season after vaccination, respectively. Among non-immunocompromised individuals, adjusted VE against RSV-related LRTD was 87% (95% CI:75–94), 76% (95% CI:55–87), and 58% (95% CI:-21–86) in the first, second, and third season after vaccination, respectively. Adjusted VE across the 3 combined seasons was 73% (95% CI: 64-80) overall and 80% (95% CI: 69-87) among non-immunocompromised individuals. Conclusion: These results suggest Bivalent RSVpreF provides protection against RSV-related LRTD outcomes for at least three seasons after vaccination in this population of older adults with a prevalence of comorbidities. This suggests RSV vaccination results in substantial individual and public health benefit. Key Summary Points: Why carry out this study?: RSV vaccines reduce the risk of severe outcomes such as hospitalization and emergency department (ED) visits for at least 2 RSV seasons after vaccination Real-world RSV vaccine effectiveness (VE) beyond the second season after vaccination is currently unknown This study evaluates bivalent RSVpreF VE against RSV-related lower respiratory tract disease (LRTD) hospitalizations/ED visits throughout 3 seasons after vaccination. What was learned from this study?: Overall, VE against RSV-related LRTD hospitalization/ED visits was 80% (95% CI:68–87), 70% (95% CI:53–81), and 51% (95% CI:-12–78) in the first, second, and third season after vaccination, respectively, and 73% (95% CI: 64-80) across the 3 combined seasons. These results suggest Bivalent RSVpreF provides protection against RSV-related LRTD outcomes for at least three seasons after vaccination in this population of older adults with a prevalence of comorbidities. RSV vaccination results in substantial individual and public health benefit.