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Background: In 2014, the Advisory Committee on Immunization Practices recommended routine use of the 13-valent pneumococcal conjugate vaccine (PCV13) in adults age ≥ 65 years. Incidence of most PCV13-serotype cases declined, however serotype 3 cases have persisted. We estimated PCV13 vaccine effectiveness (VE) against PCV13-serotypes and serotype 3 invasive pneumococcal disease (IPD) among Kaiser Permanente Northern California (KPNC) adults., Methods: This observational study included adults ≥65 years between September 1, 2014-December 31, 2020. We used active laboratory-based surveillance to identify and serotype all Streptococcus pneumoniae isolates obtained from normally-sterile sites. We estimated the odds ratio (OR) of vaccine-type IPD using conditional logistic regression stratified by age and calendar day, adjusting for sex, age, race, ethnicity, influenza vaccine receipt, 23-valent pneumococcal polysaccharide vaccine receipt since age 65, pneumonia risk factors, healthcare utilization, and KPNC service area. We estimated VE Adjusted as (1-OR Adjusted ) × 100 %., Results: There were 610,576 adults ≥65 years in the study population. By the end of the study period, PCV13 coverage was nearly 80 %. There were 307 IPD cases during the study period, of which 98 (31.9 %) were serotype 3. PCV13 was associated with a VE Adjusted of 61.5 % (95 % CI: 36.2, 76.7; p < 0.001) against PCV13-serotype IPD and 46.3 % (95 % CI: -2.4, 77.9; p = 0.06) against serotype 3 IPD., Conclusions: PCV13 vaccination protected adults ≥65 years against IPD due to PCV13 serotypes. Continued surveillance will be critical in the ≥65-year-old population to assess the impact of higher valent PCVs on IPD serotype distribution, including individual serotypes such as serotype 3., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Klein reported receiving grants from Sanofi Pasteur, GlaxoSmithKline, Merck, Pfizer, Seqirus, and the US Centers for Disease and Control outside of the submitted work. Dr. Suaya, Ms. Alexander-Parrish, Dr. Grant, and Dr. Gessner reported being employed by Pfizer at the time of this study and have or had ownership interests in Pfizer. No other conflicts were reported., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The 2023-2024 influenza season had predominant influenza A(H1N1)pdm09 virus activity, but A(H3N2) and B viruses co-circulated. Seasonal influenza vaccine strains were well-matched to these viruses., Methods: Using health care encounters data from health systems in 8 states, we evaluated influenza vaccine effectiveness (VE) against influenza-associated medical encounters from October 2023-April 2024. Using a test-negative design, we compared the odds of vaccination between patients with an acute respiratory illness (ARI) who tested positive (cases) versus negative (controls) for influenza by molecular assay, adjusting for confounders. VE was stratified by age group, influenza type (overall, influenza A, influenza B), and care setting (hospitalization, emergency department or urgent care [ED/UC] encounter)., Results: Overall, 74,000 encounters in children and adolescents aged 6 months - 17 years (3,479 hospitalizations, 70,521 ED/UC encounters) and 267,606 in adults aged ≥18 years (66,828 hospitalizations, 200,778 ED/UC encounters) were included. Across care settings, among children and adolescents 15% (2,758/17,833) of cases versus 32% (18,240/56,167) of controls had received vaccination. Among adults, 25% (11,632/46,614) of cases versus 44% (97,811/220,992) of controls across care settings had received vaccination. VE was 58% (95% confidence interval [95% CI]: 44-69%) against hospitalization and 58% (95% CI: 56-60%) against ED/UC encounters for children and adolescents, and 39% (95% CI: 35-43) against hospitalization and 47% (95% CI: 46-49%) against ED/UC encounters for adults. Across age groups, VE was higher against influenza B than influenza A., Conclusions: Influenza vaccines provided protection against influenza-associated illness across health care settings and age groups during the 2023-2024 influenza season., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2024.)

Background: Respiratory syncytial virus vaccines first recommended for use during 2023 were efficacious against lower respiratory tract disease in clinical trials. Limited real-world data regarding respiratory syncytial virus vaccine effectiveness are available. To inform vaccine policy and address gaps in evidence from the clinical trials, we aimed to assess the effectiveness against respiratory syncytial virus-associated hospitalisations and emergency department encounters among adults aged at least 60 years., Methods: We conducted a test-negative design analysis in an electronic health records-based network in eight states in the USA, including hospitalisations and emergency department encounters with respiratory syncytial virus-like illness among adults aged at least 60 years who underwent respiratory syncytial virus testing from Oct 1, 2023, to March 31, 2024. Respiratory syncytial virus vaccination status at the time of the encounter was derived from electronic health record documentation, state and city immunisation registries, and, for some sites, medical claims. Vaccine effectiveness was estimated by immunocompromise status, comparing the odds of vaccination among respiratory syncytial virus-positive case patients and respiratory syncytial virus-negative control patients, and adjusting for age, race and ethnicity, sex, calendar day, social vulnerability index, number of underlying non-respiratory medical conditions, presence of respiratory underlying medical conditions, and geographical region., Findings: Among 28 271 hospitalisations for respiratory syncytial virus-like illness among adults aged at least 60 years without immunocompromising conditions, vaccine effectiveness was 80% (95% CI 71-85) against respiratory syncytial virus-associated hospitalisations, and vaccine effectiveness was 81% (52-92) against respiratory syncytial virus-associated critical illness (ICU admission or death, or both). Among 8435 hospitalisations for respiratory syncytial virus-like illness among adults with immunocompromising conditions, vaccine effectiveness was 73% (48-85) against associated hospitalisation. Among 36 521 emergency department encounters for respiratory syncytial virus-like illness among adults aged at least 60 years without an immunocompromising condition, vaccine effectiveness was 77% (70-83) against respiratory syncytial virus-associated emergency department encounters. Vaccine effectiveness estimates were similar by age group and product type., Interpretation: Respiratory syncytial virus vaccination was effective in preventing respiratory syncytial virus-associated hospitalisations and emergency department encounters among adults aged at least 60 years in the USA during the 2023-24 respiratory syncytial virus season, which was the first season after respiratory syncytial virus vaccine was approved., Funding: The Centers for Disease Control and Prevention., Competing Interests: Declaration of interests NPK reports support for other work from Sanofi Pasteur, Merck, Pfizer, Seqirus, and GSK, unpaid expert panel membership for a planned hepatitis E phase 2 vaccine clinical trial among pregnant women in Pakistan, and unpaid membership on the Western States COVID-19 Scientific Safety Review Workgroup, Board on Population Health and Public Health Practice, National Academies of Science, Engineering, and Medicine, and National Vaccine Advisory Committee Safety Subcommittee. SJG reports funding from the National Institutes of Health's National Center for Advancing Translation Sciences and National Institute of Mental Health. TCO reports consulting fees from Regenstrief Institute as a domain expert in patient matching in global health informatics, travel support from Regenstrief Institute and Patient-Centered Outcomes Research institute, and holds a patent (patent number PCT/US2018/047961). MBD, BED, and WFF report an additional CDC contract for the Vaccine Safety Datalink. TS reports unpaid participation as a member of the Advisory Committee on the Immunization Practices Influenza Vaccine Work Group, is chief of the Utah Adult Immunization Coalition, and is a member of the Utah Department of Health and Human Services Scientific Advisory Committee on Vaccines. OZ reports funding from the National Institute of Allergy and Infectious Diseases (grant number R01AI168373). NPK, JT, and KG report a CDC contract for VISION (contract number 75D30123C17595). SR reports funding from Biofire and GSK. MB reports speaker bureau participation for Innoviva Specialty Therapeutics. CEM reports funding from AstraZeneca, GSK, National Institutes of Health, US Department of Defense, and Patient-Centered Outcomes Research Institute, payment or honoraria for a lecture from Pri-Med, and leadership on the American Lung Association of Minnesota board, the Minnesota Department of Health Long COVID Advisory Committee, and on the Minnesota Department of Health Asthma Care Advisory Committee. JAW, PKM, SWB, SER, and EAKR report a CDC contract for VISION (contract number 75D30121D12779). KD, SAI, SJG, TCO, MBD, KN, BED, WFF, CR, KSA, and CEM report payments made to their institution by CDC via Westat. All other authors declare no competing interests., (Copyright © 2024 Published by Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Objectives: The aim of this study is to determine the incidence and risk factors associated with COVID-19 hospitalization among unvaccinated children., Methods: Children aged 0- < 18 years, members of Kaiser Permanente Northern California (KPNC), were followed from March 1, 2020, until the earliest occurrence of: chart-confirmed COVID-19 hospitalization, disenrollment from KPNC, age 18 years, receipt of COVID-19 vaccine, death, or study end (December 31, 2022). We calculated the incidence rate of hospitalization by SARS-CoV-2 variant period and by age group. We determined risk factors for hospitalization using Poisson regression. We also conducted descriptive analyses of hospitalized cases., Results: Among 1,107,799 children, 423 were hospitalized for COVID-19 during follow-up. The incidence of hospitalization increased with each new SARS-CoV-2 variant and was highest among children aged < 6 months. Among the < 6-month-olds, the incidence rate per 100,000 person-months was 7 during predelta, 13.3 during delta, and 22.4 during omicron. Black (RR = 2.05, 95% CI: 1.33-3.16) and Hispanic children (RR = 1.82, 95% CI: 1.34-2.46) and children with any comorbidities were at high risk of hospitalization (RR = 3.81, 95% CI: 2.94-4.95). Overall, 20.3% of hospitalized children were admitted to an intensive care unit (ICU), but ICU admission was 36.1% among 12- < 18-year-olds. The majority of ICU admits (91.8%) had no comorbidities., Conclusion: Children too young to be vaccinated had the highest incidence of COVID-19 hospitalization, while adolescents had the highest proportion of ICU admissions. To prevent severe disease in children and adolescents, everyone eligible should be vaccinated., (© 2024 The Author(s). Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

Background: The 2022-2023 United States influenza season had unusually early influenza activity with high hospitalization rates. Vaccine-matched A(H3N2) viruses predominated, with lower levels of A(H1N1)pdm09 activity also observed., Methods: Using the test-negative design, we evaluated influenza vaccine effectiveness (VE) during the 2022-2023 season against influenza A-associated emergency department/urgent care (ED/UC) visits and hospitalizations from October 2022 to March 2023 among adults (aged ≥18 years) with acute respiratory illness (ARI). VE was estimated by comparing odds of seasonal influenza vaccination among case-patients (influenza A test positive by molecular assay) and controls (influenza test negative), applying inverse-propensity-to-be-vaccinated weights., Results: The analysis included 85 389 ED/UC ARI encounters (17.0% influenza A positive; 37.8% vaccinated overall) and 19 751 hospitalizations (9.5% influenza A positive; 52.8% vaccinated overall). VE against influenza A-associated ED/UC encounters was 44% (95% confidence interval [CI], 40%-47%) overall and 45% and 41% among adults aged 18-64 and ≥65 years, respectively. VE against influenza A-associated hospitalizations was 35% (95% CI, 27%-43%) overall and 23% and 41% among adults aged 18-64 and ≥65 years, respectively., Conclusions: VE was moderate during the 2022-2023 influenza season, a season characterized with increased burden of influenza and co-circulation with other respiratory viruses. Vaccination is likely to substantially reduce morbidity, mortality, and strain on healthcare resources., Competing Interests: Potential conflicts of interest. During the conduct of the study, all Westat- and Kaiser Permanente Northern California Division of Research–affiliated authors reported receiving contractual support from the CDC via payments made to their respective institutions. Additionally, all authors affiliated with Baylor Scott & White Health, Children's Minnesota, Columbia University Irving Medical Center, HealthPartners Institute, Intermountain Healthcare, Kaiser Permanente Center for Health Research, Regenstrief Institute, University of Colorado Anschutz Medical Campus, and Vanderbilt University Medical Center reported receiving contractual support from the CDC during the conduct of the study, via subcontracts from Westat, Inc, with payments made to their respective institutions. Unrelated to the submitted work, the following disclosures were reported from the past 36 months: A. L. N. received grants from Pfizer and Vir Biotechnology; M. N. received grants directly from CDC and from CDC via subcontracts from Abt Associates and Vanderbilt University Medical Center to her institution; C. E. M. received grants AstraZeneca; S. R. received grants from GSK; and N. P. K. received research support from Pfizer, Merck, GlaxoSmithKline, Sanofi Pasteur, and Seqirus. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2023.)

Background: During the 2022-2023 influenza season, the United States experienced the highest influenza-associated pediatric hospitalization rate since 2010-2011. Influenza A/H3N2 infections were predominant., Methods: We analyzed acute respiratory illness (ARI)-associated emergency department or urgent care (ED/UC) encounters or hospitalizations at 3 health systems among children and adolescents aged 6 months-17 years who had influenza molecular testing during October 2022-March 2023. We estimated influenza A vaccine effectiveness (VE) using a test-negative approach. The odds of vaccination among influenza-A-positive cases and influenza-negative controls were compared after adjusting for confounders and applying inverse-propensity-to-be-vaccinated weights. We developed overall and age-stratified VE models., Results: Overall, 13 547 of 44 787 (30.2%) eligible ED/UC encounters and 263 of 1862 (14.1%) hospitalizations were influenza-A-positive cases. Among ED/UC patients, 15.2% of influenza-positive versus 27.1% of influenza-negative patients were vaccinated; VE was 48% (95% confidence interval [CI], 44-52%) overall, 53% (95% CI, 47-58%) among children aged 6 months-4 years, and 38% (95% CI, 30-45%) among those aged 9-17 years. Among hospitalizations, 17.5% of influenza-positive versus 33.4% of influenza-negative patients were vaccinated; VE was 40% (95% CI, 6-61%) overall, 56% (95% CI, 23-75%) among children ages 6 months-4 years, and 46% (95% CI, 2-70%) among those 5-17 years., Conclusions: During the 2022-2023 influenza season, vaccination reduced the risk of influenza-associated ED/UC encounters and hospitalizations by almost half (overall VE, 40-48%). Influenza vaccination is a critical tool to prevent moderate-to-severe influenza illness in children and adolescents., Competing Interests: Potential conflicts of interest . N. P. K. reports research support from Sanofi Pasteur and Seqirus for unrelated adult influenza vaccine effectiveness studies, and from Pfizer, Merck, and GlaxoSmithKline for unrelated studies. S. R. received funds from GlaxoSmithKline. M. G. reports a research grant and contract for the CDC Ambulatory US Flu/COVID VE Network, a grant for HAIVEN Adult Inpatient Flu/COVID VE, a contract for SYNERGY FLU/COVID study, and subcontracts for the IVY COVID/FLU VE PHS project and RECOVER-PROTECT COVID Cohort studies. D.-H. Y., L. K., M. M. D., S. W. B., and Z. A. W. report payments made to Westat via CDC contract number 200-2019-F-06819. A. B. K., A. L. N., J. A., K. D., K. N., M. B. D., M. G., N. G., P. J. E., S. A. I, S. J. G., S. R., and T. C. O. report payments made to their institution by CDC via Westat. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2023.)

On June 19, 2022, the original monovalent mRNA COVID-19 vaccines were approved as a primary series for children aged 6 months-4 years (Pfizer-BioNTech) and 6 months-5 years (Moderna) based on safety, immunobridging, and limited efficacy data from clinical trials. On December 9, 2022, CDC expanded recommendations for use of updated bivalent vaccines to children aged ≥6 months. mRNA COVID-19 vaccine effectiveness (VE) against emergency department or urgent care (ED/UC) encounters was evaluated within the VISION Network during July 4, 2022-June 17, 2023, among children with COVID-19-like illness aged 6 months-5 years. Among children aged 6 months-5 years who received molecular SARS-CoV-2 testing during August 1, 2022-June 17, 2023, VE of 2 monovalent Moderna doses against ED/UC encounters was 29% (95% CI = 12%-42%) ≥14 days after dose 2 (median = 100 days after dose 2; IQR = 63-155 days). Among children aged 6 months-4 years with a COVID-19-like illness who received molecular testing during September 19, 2022-June 17, 2023, VE of 3 monovalent Pfizer-BioNTech doses was 43% (95% CI = 17%-61%) ≥14 days after dose 3 (median = 75 days after dose 3; IQR = 40-139 days). Effectiveness of ≥1 bivalent dose, comparing children with at least a complete primary series and ≥1 bivalent dose to unvaccinated children, irrespective of vaccine manufacturer, was 80% (95% CI = 42%-96%) among children aged 6 months-5 years a median of 58 days (IQR = 32-83 days) after the dose. All children should stay up to date with recommended COVID-19 vaccines, including initiation of COVID-19 vaccination immediately when they are eligible., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Nicola P. Klein reports institutional support from Pfizer, Merck, GSK, Sanofi Pasteur, and Protein Sciences (now Sanofi Pasteur). Allison L. Naleway reports institutional support from Pfizer for an unrelated study of meningococcal B vaccine safety during pregnancy study and from Vir Biotechnology for an unrelated influenza study. Suchitra Rao reports grant support from GSK. No other potential conflicts of interest were disclosed.

Background: Following historically low influenza activity during the 2020-2021 season, the United States saw an increase in influenza circulating during the 2021-2022 season. Most viruses belonged to the influenza A(H3N2) 3C.2a1b 2a.2 subclade., Methods: We conducted a test-negative case-control analysis among adults ≥18 years of age at 3 sites within the VISION Network. Encounters included emergency department/urgent care (ED/UC) visits or hospitalizations with ≥1 acute respiratory illness (ARI) discharge diagnosis codes and molecular testing for influenza. Vaccine effectiveness (VE) was calculated by comparing the odds of influenza vaccination ≥14 days before the encounter date between influenza-positive cases (type A) and influenza-negative and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-negative controls, applying inverse probability-to-be-vaccinated weights, and adjusting for confounders., Results: In total, 86 732 ED/UC ARI-associated encounters (7696 [9%] cases) and 16 805 hospitalized ARI-associated encounters (649 [4%] cases) were included. VE against influenza-associated ED/UC encounters was 25% (95% confidence interval (CI), 20%-29%) and 25% (95% CI, 11%-37%) against influenza-associated hospitalizations. VE against ED/UC encounters was lower in adults ≥65 years of age (7%; 95% CI, -5% to 17%) or with immunocompromising conditions (4%; 95% CI, -45% to 36%)., Conclusions: During an influenza A(H3N2)-predominant influenza season, modest VE was observed. These findings highlight the need for improved vaccines, particularly for A(H3N2) viruses that are historically associated with lower VE., Competing Interests: Potential conflicts of interest. S. R. received grants from GlaxoSmithKline. A. L. N. received grants from Pfizer and Vir Biotechnology. C. M. received grants from AstraZeneca. N. P. K. received grants from Pfizer, Merck, GlaxoSmithKline, and Sanofi Pasteur. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2023.)

During June-October 2022, the SARS-CoV-2 Omicron BA.5 sublineage accounted for most of the sequenced viral genomes in the United States, with further Omicron sublineage diversification through November 2022.* Bivalent mRNA vaccines contain an ancestral SARS-CoV-2 strain component plus an updated component of the Omicron BA.4/BA.5 sublineages. On September 1, 2022, a single bivalent booster dose was recommended for adults who had completed a primary vaccination series (with or without subsequent booster doses), with the last dose administered ≥2 months earlier (1). During September 13-November 18, the VISION Network evaluated vaccine effectiveness (VE) of a bivalent mRNA booster dose (after 2, 3, or 4 monovalent doses) compared with 1) no previous vaccination and 2) previous receipt of 2, 3, or 4 monovalent-only mRNA vaccine doses, among immunocompetent adults aged ≥18 years with an emergency department/urgent care (ED/UC) encounter or hospitalization for a COVID-19-like illness. † VE of a bivalent booster dose (after 2, 3, or 4 monovalent doses) against COVID-19-associated ED/UC encounters was 56% compared with no vaccination, 32% compared with monovalent vaccination only with last dose 2-4 months earlier, and 50% compared with monovalent vaccination only with last dose ≥11 months earlier. VE of a bivalent booster dose (after 2, 3, or 4 monovalent doses) against COVID-19-associated hospitalizations was 59% compared with no vaccination, 42% compared with monovalent vaccination only with last dose 5-7 months earlier, and 48% compared with monovalent vaccination only with last dose ≥11 months earlier. Bivalent vaccines administered after 2, 3, or 4 monovalent doses were effective in preventing medically attended COVID-19 compared with no vaccination and provided additional protection compared with past monovalent vaccination only, with relative protection increasing with time since receipt of the last monovalent dose. All eligible persons should stay up to date with recommended COVID-19 vaccinations, including receiving a bivalent booster dose. Persons should also consider taking additional precautions to avoid respiratory illness this winter season, such as masking in public indoor spaces, especially in areas where COVID-19 community levels are high., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Nicola P. Klein received grants from Pfizer, Merck, GlaxoSmithKline, and Sanofi Pasteur. Allison L. Naleway received grants from Pfizer and Vir Biotechnology. Suchitra Rao received grants from GlaxoSmithKline. Charlene McEvoy received grants from AztraZeneca. No other potential conflicts of interest were disclosed.

During June-October 2022, the SARS-CoV-2 Omicron BA.5 sublineage accounted for most of the sequenced viral genomes in the United States, with further Omicron sublineage diversification through November 2022.* Bivalent mRNA vaccines contain an ancestral SARS-CoV-2 strain component plus an updated component of the Omicron BA.4/BA.5 sublineages. On September 1, 2022, a single bivalent booster dose was recommended for adults who had completed a primary vaccination series (with or without subsequent booster doses), with the last dose administered ≥2 months earlier (1). During September 13-November 18, the VISION Network evaluated vaccine effectiveness (VE) of a bivalent mRNA booster dose (after 2, 3, or 4 monovalent doses) compared with 1) no previous vaccination and 2) previous receipt of 2, 3, or 4 monovalent-only mRNA vaccine doses, among immunocompetent adults aged ≥18 years with an emergency department/urgent care (ED/UC) encounter or hospitalization for a COVID-19-like illness. † VE of a bivalent booster dose (after 2, 3, or 4 monovalent doses) against COVID-19-associated ED/UC encounters was 56% compared with no vaccination, 31% compared with monovalent vaccination only with last dose 2-4 months earlier, and 50% compared with monovalent vaccination only with last dose ≥11 months earlier. VE of a bivalent booster dose (after 2, 3, or 4 monovalent doses) against COVID-19-associated hospitalizations was 57% compared with no vaccination, 38% compared with monovalent vaccination only with last dose 5-7 months earlier, and 45% compared with monovalent vaccination only with last dose ≥11 months earlier. Bivalent vaccines administered after 2, 3, or 4 monovalent doses were effective in preventing medically attended COVID-19 compared with no vaccination and provided additional protection compared with past monovalent vaccination only, with relative protection increasing with time since receipt of the last monovalent dose. All eligible persons should stay up to date with recommended COVID-19 vaccinations, including receiving a bivalent booster dose. Persons should also consider taking additional precautions to avoid respiratory illness this winter season, such as masking in public indoor spaces, especially in areas where COVID-19 community levels are high., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Nicola P. Klein received grants from Pfizer, Merck, GlaxoSmithKline, and Sanofi Pasteur. Allison L. Naleway received grants from Pfizer and Vir Biotechnology. Suchitra Rao received grants from GlaxoSmithKline. Charlene McEvoy received grants from AztraZeneca. No other potential conflicts of interest were disclosed.

Objectives: Since 2006, the US human papillomavirus (HPV) vaccination program has led to decreases in HPV infections caused by high-risk vaccine-targeted HPV types (HPV 16/18). We assessed differences in high-risk HPV prevalence by cervical cytology result among 20- to 24-year-old persons participating in routine cervical cancer screening in 2015-2017 compared with 2007., Materials and Methods: Residual routine cervical cancer screening specimens were collected from 20- to 24-year-old members of 2 integrated healthcare delivery systems as part of a cross-sectional study and were tested for 37 HPV types. Cytology results and vaccination status (≥1 dose) were extracted from medical records. Cytology categories were normal, atypical squamous cells of undefined significance, low-grade squamous intraepithelial lesions (SIL), or high-grade SIL/atypical squamous cells cannot exclude high-grade SIL. Prevalences of HPV categories (HPV 16/18, HPV 31/33/45/52/58, HPV 35/39/51/56/59/66/68) were estimated by cytology result for 2007 and 2015-2017., Results: Specimens from 2007 (n = 4046) were from unvaccinated participants; 4574 of 8442 specimens (54.2%) from 2015-2017 were from vaccinated participants. Overall, HPV 16/18 positivity was lower in 2015-2017 compared with 2007 in all groups: high-grade SIL/atypical squamous cells cannot exclude high-grade SIL, 16.0% vs 69.2%; low-grade SIL, 5.4% vs 40.1%; atypical squamous cells of undefined significance, 5.0% vs 25.6%; and normal, 1.3% vs 8.1%. Human papillomavirus 31/33/45/52/58 prevalence was stable for all cytology groups; HPV 35/39/51/56/59/66/68 prevalence increased among low-grade SIL specimens (53.9% to 65.2%) but remained stable in other groups., Conclusions: Prevalence of vaccine-targeted high-risk HPV types 16/18 was dramatically lower in 2015-2017 than 2007 across all cytology result groups while prevalence of other high-risk HPV types was mainly stable, supporting vaccine impact with no evidence of type replacement., Competing Interests: A.L.N. has received research funding from Pfizer, Takeda, MedImmune, and Merck for unrelated studies. N.P.K. has received research funding from Merck, GlaxoSmithKline, Sanofi Pasteur, Novartis, MedImmune, Pfizer, and Protein Sciences (now Sanofi Pasteur) for unrelated studies. S.W. has received research funding from GlaxoSmithKline for an unrelated study. The other authors have declared they have no conflicts of interest., (Copyright © 2022, ASCCP.)

Importance: Following routine use of 13-valent pneumococcal conjugate vaccine (PCV13) in children in 2010, invasive pneumococcal disease rates have decreased substantially in children and adults. In 2014, the Advisory Committee for Immunization Practices recommended routine use of PCV13 among adults aged 65 years or older; previously only 23-valent pneumococcal polysaccharide vaccine (PPV23) was recommended., Objective: To estimate the association between the incidence of hospitalized all-cause pneumonia and lower respiratory tract infections (LRTI) and PCV13 vaccination among older adults at Kaiser Permanente Northern California (KPNC)., Design, Setting, and Participants: This retrospective cohort study included adults at KPNC aged 65 years or older between July 1, 2015, and June 30, 2018, born after 1936 with no known history of PPV23 or PCV13 receipt before age 65. The study took place at an integrated health care system with an annual membership more than 4 million individuals, approximately 15% of whom are 65 years or older and broadly representative of the region. Data analysis took place from July 2018 to December 2021, and data collection took place from November 2016 to June 2018., Exposures: PCV13 vaccination status was ascertained from the electronic medical record (EMR). Individuals were considered vaccinated 14 days following immunization., Main Outcomes and Measures: First hospitalized all-cause pneumonia was identified in the EMR using primary/secondary discharge diagnosis International Classification of Diseases, Ninth Revision and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes. First hospitalized LRTI was identified using pneumonia codes and acute bronchitis codes. Relative risk (RR) of first pneumonia or LRTI hospitalization of individuals who were PCV13 vaccinated vs PCV13 unvaccinated was estimated using Poisson regressions adjusted for sex, race, ethnicity, age, influenza vaccine receipt, PPV23 receipt since age 65, pneumonia risk factors, health care use, and season. Vaccine effectiveness (VE) was estimated as (1-RR) × 100%., Results: Of 192 061 adults, 107 957 (56%) were female and 139 024 (72%) were White individuals. PCV13 coverage increased from 0 in 2014 to 135 608 (76.9%) by 2018. There were 3488 individuals with 3766 pneumonia hospitalizations and 3846 individuals with 4173 LRTI hospitalizations. PCV13 was associated with an adjusted VE of 10.0% (95% CI, 2.4-17.0; P = .01) against hospitalized pneumonia and 9.4% (95% CI, 2.1-16.1; P = .01) against hospitalized LRTI., Conclusions and Relevance: In the context of a robust pediatric PCV13 immunization program, PCV13 vaccination of adults aged 65 years or older was associated with significant reductions in hospitalizations for all-cause pneumonia and LRTI. Vaccinating older adults with PCVs may provide broader public health benefit against pneumonia hospitalizations.

Background: Clostridioides difficile infection (CDI) is a major cause of severe diarrhea. In this retrospective study, we identified CDI risk factors by comparing demographic and clinical characteristics for Kaiser Permanente Northern California members ≥18 years old with and without laboratory-confirmed incident CDI., Methods: We included these risk factors in logistic regression models to develop 2 risk scores that predict future CDI after an Index Date for Risk Score Assessment (IDRSA), marking the beginning of a period for which we estimated CDI risk., Results: During May 2011 to July 2014, we included 9986 CDI cases and 2 230 354 members without CDI. The CDI cases tended to be older, female, white race, and have more hospitalizations, emergency department and office visits, skilled nursing facility stays, antibiotic and proton pump inhibitor use, and specific comorbidities. Using hospital discharge as the IDRSA, our risk score model yielded excellent performance in predicting the likelihood of developing CDI in the subsequent 31-365 days (C-statistic of 0.848). Using a random date as the IDRSA, our model also predicted CDI risk in the subsequent 31-365 days reasonably well (C-statistic 0.722)., Conclusions: These results can be used to identify high-risk populations for enrollment in C difficile vaccine trials and facilitate study feasibility regarding sample size and time to completion., (© The Author(s) 2021. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Recombinant trivalent influenza vaccine (RIV3) was initially licensed in 2013 and approved for all adults ≥18 in 2014. This study evaluated the safety of RIV3 compared with trivalent standard-dose, inactivated influenza vaccine (IIV3) in Kaiser Permanente Northern California (KPNC)., Methods: This Phase 4 observational, postmarketing safety study included persons ≥18 years vaccinated with RIV3 or IIV3 in KPNC during the 2015-2016 influenza season. We compared (1) the rates of prespecified diagnoses of interest (Guillain-Barré Syndrome, pericarditis, pleural effusion, narcolepsy/cataplexy, asthma, acute hypersensitivity reactions, and fever) during various postvaccination risk intervals as well as (2) all-cause hospitalization and mortality 0-180 days after vaccination. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) using logistic regression analyses adjusted for age, sex, race/ethnicity, month of vaccination, and concomitant receipt of other vaccinations., Results: Comparing the 21 976 persons who received RIV3 with the 283 683 who received IIV3, there were statistically significant differences in the prespecified diagnoses of interest between the 2 groups. Specifically, RIV3 vaccination was associated with fewer fever diagnoses during the 0-41 days postvaccination (OR, 0.38; 95% CI, 0.14-0.86). Also, RIV3 was associated with fewer all-cause hospitalizations during the 0-180 days postvaccination (OR, 0.66; 95% CI, 0.61-0.73), which was mostly related to pregnancy-related hospitalizations in IIV3 recipients. There were no serious adverse events or deaths related to RIV3., Conclusions: This study did not identify any safety concerns regarding the use of RIV3 in adults., (© The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Highly effective human papillomavirus (HPV) vaccines are used in many national programs in 3- or 2-dose schedules. We examined HPV vaccine effectiveness against HPV prevalence by number of doses., Methods: We collected residual liquid-based cytology samples from US women aged 20-29 years who were screened for cervical cancer. Women continuously enrolled from 2006 through the specimen collection date were analyzed. Specimens were tested using the Linear Array assay. We analyzed prevalence of quadrivalent HPV vaccine (4vHPV) types (HPV 6,11,16,18) and other HPV-type categories and determined prevalence ratios (PRs) and 95% confidence intervals (CIs) for 1, 2, and 3 compared with no vaccine doses., Results: Among 4269 women, 1052 (24.6%) were unvaccinated, 2610 (61.1%) received 3 doses, 304 (7.1%) received 2 doses, and 303 (7.1%) received 1 dose. The 4vHPV-type prevalence was 7.4% among unvaccinated women compared with 1.7%, 1.0%, and 1.0% among 1-, 2-, and 3-dose recipients. Among women vaccinated at ≤18 years, adjusted PRs for 1, 2, and 3 doses were 0.06 (95% CI, 0.01-0.42), 0.05 (95% CI, 0.01-0.39), and 0.06 (95% CI, 0.04-0.12)., Conclusions: Among women who received their first dose at age ≤18, estimated HPV vaccine effectiveness was high regardless of number of doses., (Published by Oxford University Press for the Infectious Diseases Society of America 2019.)

An observational post-licensure (Phase IV) retrospective large-database safety study was conducted at Kaiser Permanente, a US integrated medical care organization, to assess the safety of Tetanus Toxoid, Reduced Diphtheria Toxoid and 5-Component Acellular Pertussis Vaccine (Tdap5) administered as part of routine healthcare among adolescents and adults. We evaluated incidence rates of various clinical events resulting in outpatient clinic, emergency department (ED), and hospital visits during various time intervals (windows) following Tdap5 vaccination using 2 pharmacoepidemiological methods (risk interval and historic cohort) and several screening thresholds. Plausible outcomes of interest with elevated incidence rate ratios (IRRs) were further evaluated by reviewing individual patient records to confirm the diagnosis, timing (temporal relationship), alternative etiology, and other health record details to discern possible relatedness of the health events to vaccination. Overall, 124,139 people received Tdap5 vaccine from September 2005 through mid-October 2006, and 203,154 in the comparison cohort received a tetanus and diphtheria toxoid adsorbed vaccine (and no live virus vaccine) during the year prior to initiation of this study. In the outpatient, ED and hospital databases, respectively, we identified 11/26, 179/700 and 187/700 unique health outcomes with IRRs significantly >1.0. Among the same unique health outcomes in the outpatient, ED, and hospital databases, 9, 146, and 385, respectively, had IRRs significantly <1.0. Further scrutiny of the outcomes with elevated IRRs did not reveal unexpected signals of adverse outcomes related to vaccination. In conclusion, Tdap5 vaccine was found to be safe among this large population of adolescents and adults.

Background: The combination DTaP-IPV/Hib vaccine was licensed in the United States in 2008 for children ages 6weeks through 4years with doses administered at 2, 4, 6, and 15-18months of age. The aim of this study was to assess the safety of DTaP-IPV/Hib vaccine routinely administered as part of clinical care to infants at Kaiser Permanente Northern California., Methods: This was an observational, retrospective study that included all 2-month-old infants vaccinated with either DTaP-IPV/Hib or another DTaP-containing vaccine. We monitored all subjects for non-elective hospitalizations, emergency department visits and selected outpatient outcomes (seizures, Guillain-Barré Syndrome, encephalopathy, encephalitis, alteration of consciousness, meningitis, hypersensitivity reactions, immune thrombocytopenic purpura, hemolytic anemia, type 1 diabetes, and Kawasaki disease) beginning with their first dose through 6months after a 4th dose or until 24months of age. We calculated incidence rate ratios (IRRs) in the primary analysis by comparing rates of outcomes during the post-vaccination risk interval with rates during a comparison interval more remote from vaccination. Secondary analyses compared outcomes after DTaP-IPV/Hib with those after other DTaP-containing vaccines. We reviewed the medical records of selected outcomes., Results: From October 1, 2008 through July 31, 2010, 14,042 subjects received a first dose of DTaP-IPV/Hib, 13,194 received 2 doses, 12,548 received 3 doses and 6702 received 4 doses. Overall, there were 166 comparisons with significantly elevated IRRs and 165 comparisons with significantly reduced IRRs. Medical record review of outcomes with significantly elevated IRRs in both the primary and secondary analyses did not suggest any relationship with DTaP-IPV/Hib., Conclusions: This study did not detect any safety concerns following DTaP-IPV/Hib and provides reassurance that DTaP-IPV/Hib administered as part of routine care was not associated with unexpected safety risks. ClinicalTrials.gov Identifier: NCT00804284., (Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.)