Association of pneumococcal conjugate vaccination with SARS-CoV-2 infection among older adult recipients of COVID-19 vaccines: a longitudinal cohort study.

BACKGROUND: Pneumococcal carriage is associated with increased acquisition and duration of SARS-CoV-2 infection among adults. While pneumococcal conjugate vaccines (PCVs) prevent carriage of vaccine-serotype pneumococci, their potential impact on COVID-19 related outcomes remains poorly understood in populations with prevalent immunity against SARS-CoV-2. METHODS: We undertook a retrospective cohort study of adults aged ≥65 years in the Kaiser Permanente Southern California (KPSC) healthcare system who had received ≥2 COVID-19 vaccine doses, comparing risk of SARS-CoV-2 infection between 1 January, 2021 and 31 December, 2022 among recipients and non-recipients of PCV13. We estimated adjusted hazard ratios via Cox proportional hazards models, employing multiple strategies to mitigate bias from differential test-seeking behavior. RESULTS: The adjusted hazard ratio (aHR) of confirmed SARS-CoV-2 infection comparing PCV13 recipients to non-recipients was 0.92 (95% confidence interval: 0.90-0.95), corresponding to prevention of 3.9 (2.6-5.3) infections per 100 person-years. Following receipt of 2, 3, and ≥4 COVID-19 vaccine doses, aHRs were 0.85 (0.81-0.89), 0.94 (0.90-0.97), and 0.99 (0.93-1.04), respectively. The aHR for persons who had not received COVID-19 vaccination in the preceding 6 months was 0.90 (0.86-0.93), versus 0.94 (0.91-0.98) within 6 months after receipt of any dose. Similarly, the aHR was 0.92 (0.89-0.94) for persons without history of documented SARS-CoV-2 infection, versus 1.00 (0.90-1.12) for persons with documented prior infection. CONCLUSIONS: Among older adults who had received ≥2 COVID-19 vaccine doses, PCV13 was associated with modest protection against SARS-CoV-2 infection. Protective effects of PCV13 were greater among individuals expected to have weaker immune protection against SARS-CoV-2 infection.

Effectiveness of Pneumococcal Conjugate Vaccination Against Virus-Associated Lower Respiratory Tract Infection Among Adults: A Case-Control Study.

BACKGROUND: Interactions of Streptococcus pneumoniae with viruses feature in the pathogenesis of numerous respiratory illnesses. METHODS: We undertook a case-control study among adults at Kaiser Permanente Southern California between 2015 and 2019. Case patients had diagnoses of lower respiratory tract infection (LRTI; including pneumonia or nonpneumonia LRTI diagnoses), with viral infections detected by multiplex polymerase chain reaction testing. Controls without LRTI diagnoses were matched to case patients by demographic and clinical attributes. We measured vaccine effectiveness (VE) for 13-valent (PCV13) against virus-associated LRTI by determining the adjusted odds ratio for PCV13 receipt, comparing case patients and controls. RESULTS: Primary analyses included 13 856 case patients with virus-associated LRTI and 227 887 matched controls. Receipt of PCV13 was associated with a VE of 24.9% (95% confidence interval, 18.4%-30.9%) against virus-associated pneumonia and 21.5% (10.9%-30.9%) against other (nonpneumonia) virus-associated LRTIs. We estimated VEs of 26.8% (95% confidence interval, 19.9%-33.1%) and 18.6% (9.3%-27.0%) against all virus-associated LRTI episodes diagnosed in inpatient and outpatient settings, respectively. We identified statistically significant protection against LRTI episodes associated with influenza A and B viruses, endemic human coronaviruses, parainfluenza viruses, human metapneumovirus, and enteroviruses but not respiratory syncytial virus or adenoviruses. CONCLUSIONS: Among adults, PCV13 conferred moderate protection against virus-associated LRTI. The impacts of pneumococcal conjugate vaccines may be mediated, in part, by effects on polymicrobial interactions between pneumococci and respiratory viruses.

Burden of Lower Respiratory Tract Infections Preventable by Adult Immunization With 15- and 20-Valent Pneumococcal Conjugate Vaccines in the United States.

BACKGROUND: Updated recommendations of the US Advisory Committee on Immunization Practices indicate that all adults aged ≥65 years and adults aged <65 years with comorbid conditions should receive 15- and 20-valent pneumococcal conjugate vaccines (PCV15/20). We aimed to assess the potential impact of these recommendations on the burden of lower respiratory tract infections (LRTIs) among adults. METHODS: We estimated the incidence of LRTI cases and associated hospital admissions among enrollees of Kaiser Permanente Southern California from 2016 through 2019. We used a counterfactual inference framework to estimate excess LRTI-associated risk of death up to 180 days after diagnosis. We used prior estimates of PCV13 effectiveness against LRTI to model potential direct effects of PCV15/20 by age group and risk status. RESULTS: Use of PCV15 and PCV20, respectively, could prevent 89.3 (95% confidence interval, 41.3-131.8) and 108.6 (50.4-159.1) medically attended LRTI cases; 21.9 (10.1-32.0) and 26.6 (12.4-38.7) hospitalized LRTI cases; and 7.1 (3.3-10.5) and 8.7 (4.0-12.7) excess LRTI-associated deaths, each per 10 000 person-years. Among at-risk adults aged <65 years, use of PCV15 and PCV20 could prevent 85.7 (39.6-131.5) and 102.7 (47.8-156.7) medically attended LRTI cases per 10 000 person-years; 5.1 (2.4-8.6) and 6.2 (2.8-10.2) LRTI hospitalizations per 10 000 person-years, and 0.9 (0.4-1.4) and 1.1 (0.5-1.7) excess LRTI-associated deaths per 10 000 person-years. CONCLUSIONS: Our findings suggest recent recommendations, including PCV15/20 within adult pneumococcal vaccine series, may substantially reduce LRTI burden.

Validation of Claims-Based Algorithm for Lyme Disease, Massachusetts, USA.

Compared with notifiable disease surveillance, claims-based algorithms estimate higher Lyme disease incidence, but their accuracy is unknown. We applied a previously developed Lyme disease algorithm (diagnosis code plus antimicrobial drug prescription dispensing within 30 days) to an administrative claims database in Massachusetts, USA, to identify a Lyme disease cohort during July 2000-June 2019. Clinicians reviewed and adjudicated medical charts from a cohort subset by using national surveillance case definitions. We calculated positive predictive values (PPVs). We identified 12,229 Lyme disease episodes in the claims database and reviewed and adjudicated 128 medical charts. The algorithm's PPV for confirmed, probable, or suspected cases was 93.8% (95% CI 88.1%-97.3%); the PPV was 66.4% (95% CI 57.5%-74.5%) for confirmed and probable cases only. In a high incidence setting, a claims-based algorithm identified cases with a high PPV, suggesting it can be used to assess Lyme disease burden and supplement traditional surveillance data.

Effectiveness of 13-Valent Pneumococcal Conjugate Vaccine Against Medically Attended Lower Respiratory Tract Infection and Pneumonia Among Older Adults.

BACKGROUND: Among older adults, 13-valent pneumococcal conjugate vaccine (PCV13) has been found efficacious against nonbacteremic pneumonia associated with vaccine-serotype pneumococci. However, the burden of lower respiratory tract infection (LRTI) and pneumonia preventable by direct immunization of older adults continues to be debated. METHODS: We analyzed data from an open cohort of adults aged ≥65 years enrolled in Kaiser Permanente Southern California health plans from 2016 to 2019 who received PCV13 concordant with US Advisory Committee on Immunization Practices guidelines. We estimated PCV13 vaccine effectiveness (VE) via the adjusted hazard ratio for first LRTI and pneumonia episodes during each respiratory season, comparing PCV13-exposed and PCV13-unexposed time at risk for each participant using a self-matched inference framework. Analyses used Cox proportional hazards models, stratified by individual. RESULTS: Among 42 700 adults who met inclusion criteria, VE was 9.5% (95% confidence interval [CI], 2.2% to 16.3%) against all-cause medically attended LRTI and 8.8% (95% CI, -.2% to 17.0%) against all-cause medically attended pneumonia. In contrast, we did not identify evidence of protection against LRTI and pneumonia following receipt of the 23-valent pneumococcal polysaccharide vaccine. PCV13 prevented 0.7 (95% CI, .2 to 1.4) and 0.5 (95% CI, .0 to 1.0) cases of LRTI and pneumonia, respectively, per 100 vaccinated persons annually; over 5 years, 1 case of LRTI and 1 case of pneumonia were prevented for every 27 and 42 individuals vaccinated, respectively. CONCLUSIONS: PCV13 vaccination among older adults substantially reduced incidence of medically attended respiratory illness. Direct immunization of older adults is an effective strategy to combat residual disease burden associated with PCV13-type pneumococci.

Characterization of Streptococcus pneumoniae isolates obtained from the middle ear fluid of US children, 2011-2021.

Introduction: Pneumococcal conjugate vaccines (PCVs), including higher valency vaccines such as PCV20, have the potential to reduce pediatric otitis media. We assessed serotype distribution, potential PCV coverage, and antimicrobial susceptibility of Streptococcus pneumoniae isolates cultured from middle ear fluid (MEF) of US children age ≤5 years. Methods: S. pneumoniae isolates identified from US hospitals participating in the SENTRY Antimicrobial Surveillance program from 2011 to 2021 were included. Serotypes were determined by in silico analysis based on Pneumococcal Capsular Typing methodology. The percentage of isolates belonging to serotypes included in PCV13 (serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F), PCV15 (PCV13 plus 22F, 33F), and PCV20 (PCV13 plus, 8, 10A, 11A, 12F, 15B, 22F and 33F) was calculated. Antimicrobial susceptibility testing was performed by broth microdilution and interpreted using CLSI criteria. Nonsusceptibility was defined as isolates that were intermediate or resistant to a selected antimicrobial. Results: Among the 199 S. pneumoniae isolates that were identified, 56.8% were from children age <2 years. Six serotypes accounted for around 60% of isolates: 35B (16.6%), 15B (14.6%), 15A (7.5%), 19A (7.5%), 19F (7.5%), and 3 (7.0%). Serotypes included in PCV13, PCV15, and PCV20 accounted for 23.1%, 30.2%, and 54.8% of isolates, respectively. Overall, 45.2% of isolates were penicillin non-susceptible, and 13.6% were MDR, of which 48% were serotype 19A. Seven serotypes (19A, 15A, 15B, 15C, 23A, 33F, and 35B) accounted for the majority of non-susceptible isolates. Discussion: PCVs, particularly PCV20, may prevent a substantial fraction of S. pneumoniae otitis media (OM), including OM due to non-susceptible serotypes. The addition of serotypes 15A, 23A, and 35B would improve coverage against susceptible and non-susceptible pneumococcal OM.

Cost-effectiveness and impact on infections and associated antimicrobial resistance of 20-valent pneumococcal conjugate vaccine in US children previously immunized with PCV13.

AIM: The US Food and Drug Administration approved the 20-valent pneumococcal conjugate vaccine (PCV20) to prevent pneumococcal disease. In the context of routine PCV20 vaccination, we evaluated the cost-effectiveness and public health and economic impact of a PCV20 catch-up program and estimated the number of antibiotic prescriptions and antibiotic-resistant infections averted. MATERIALS AND METHODS: A population-based, multi-cohort, decision-analytic Markov model was developed using parameters consistent with previous PCV20 cost-effectiveness analyses. In the intervention arm, children aged 14-59 months who previously completed PCV13 vaccination received a supplemental dose of PCV20. In the comparator arm, no catch-up PCV20 dose was given. The direct and indirect benefits of vaccination were captured over a 10-year time horizon. RESULTS: A PCV20 catch-up program would prevent 5,469 invasive pneumococcal disease cases, 50,286 hospitalized pneumonia cases, 218,240 outpatient pneumonia cases, 582,302 otitis media cases, and 1,800 deaths, representing a net gain of 30,014 life years and 55,583 quality-adjusted life years. Furthermore, 720,938 antibiotic prescriptions and 256,889 antibiotic-resistant infections would be averted. A catch-up program would result in cost savings of $800 million. These results were robust to sensitivity and scenario analyses. CONCLUSIONS: A PCV20 catch-up program could prevent pneumococcal infections, antibiotic prescriptions, and antimicrobial-resistant infections and would be cost-saving in the US.

Annual public health and economic burden of medically attended respiratory syncytial virus illnesses among US adults.

BACKGROUND: Respiratory syncytial virus (RSV) is a common cause of lower respiratory tract disease (LRTD) among adults and can lead to serious morbidity and mortality; however, evidence on the magnitude of the public health and economic burden of adult RSV-LRTD is limited. This study was undertaken to project annual clinical outcomes and economic costs of medically attended RSV-LRTD among US adults, and to identify subgroups responsible for a disproportionate share of disease burden. METHODS: Clinical outcomes of RSV-LRTD were projected for subgroups of US adults defined by age and comorbidity profile (with vs. without chronic/immunocompromising medical conditions) based on corresponding population sizes, episode (disease) rates, and case-fatality rates. Economic costs comprised medical (i.e., direct) costs and non-medical (i.e., indirect) costs of RSV-LRTD, and were generated based on numbers of episodes and unit costs in relation to setting of care, age, and comorbidity profile. RESULTS: Among 265 million US adults aged ≥18 years in 2023, 6.5 million medically attended episodes of RSV-LRTD were projected to occur including 349,260 requiring hospitalization, 357,892 requiring an emergency department visit (not leading to hospitalization), and 5.8 million requiring other ambulatory care. Direct costs ($15.2 billion) and indirect costs ($9.7 billion) were projected to total $25.0 billion. Persons aged 60-99 years accounted for 31 % of the adult population and over 50 % of the economic burden of RSV-LRTD, while adults aged <60 years with chronic/immunocompromising medical conditions accounted for 10 % of the population and 27 % of the economic burden. CONCLUSIONS: Annual burden of RSV-LRTD among US adults-especially older adults and those of all ages with underlying medical conditions-is substantial. Preventive measures, such as recently approved RSV vaccines, have the potential to yield important improvements in public and patient health, and to reduce the economic burden of RSV-LRTD from the US healthcare system and societal perspectives.

Invasive Pneumococcal Disease After 2 Decades of Pneumococcal Conjugate Vaccine Use.

OBJECTIVES: We sought to describe the evolving epidemiology of invasive pneumococcal disease (IPD) among children in Massachusetts, United States, over the last 2 decades during which sequential 7-valent pneumococcal conjugate vaccines (PCV7) and 13-valent PCVs (PCV13) were implemented. METHODS: Cases of IPD in children aged <18 years were detected between 2002 and 2021 through an enhanced population-based, statewide surveillance system. Streptococcus pneumoniae isolates from normally sterile sites were serotyped and evaluated for antimicrobial susceptibility. IPD incidence rates and rate ratios with 95% confidence intervals (CIs) were calculated. RESULTS: We identified 1347 IPD cases. Incidence of IPD in children aged <18 years declined 72% over 2 decades between 2002 and 2021 (incidence rate ratios 0.28, 95% CI 0.18-0.45). IPD rates continued to decline after replacement of PCV7 with PCV13 (incidence rate ratios 0.25, 95% CI 0.16-0.39, late PCV7 era [2010] versus late PCV13 era [2021]). During the coronavirus disease 2019 pandemic years, 2020 to 2021, the rate of IPD among children aged <18 years reached 1.6 per 100 000, the lowest incidence observed over the 20 years. In PCV13 era, approximately one-third of the IPD cases in children aged >5 years had at least 1 underlying condition (98, 30.3%). Serotypes 19A and 7F contributed 342 (48.9%) of all cases before implementation of PCV13 (2002-2010). Serotype 3 (31, 8.6%), and non-PCV13 serotypes 15B/C (39, 10.8%), 33F (29, 8.0%), 23B (21, 0.8%), and 35B (17, 4.7%) were responsible for 37.8% of cases in PCV13 era (2011-2021). Penicillin nonsusceptibility continued to decline (9.8% vs 5.3% in pre-/late PCV13 era, P = .003), however has become more common among non-PCV13 serotypes compared with vaccine serotypes (14.8% vs 1.4%, P < .001). CONCLUSIONS: Robust ongoing surveillance networks are critical for identifying emerging serotypes and development of next-generation vaccine formulations.

The Cost of Seasonal Influenza: A Systematic Literature Review on the Humanistic and Economic Burden of Influenza in Older (≥ 65 Years Old) Adults.

INTRODUCTION: Adults aged ≥ 65 years contribute a large proportion of influenza-related hospitalizations and deaths due to increased risk of complications, which result in high medical costs and reduced health-related quality of life (HRQoL). Although seasonal influenza vaccines are recommended for older adults, the effectiveness of current vaccines is dependent on several factors including strain matching and recipient demographic factors. This systemic literature review aimed to explore the economic and humanistic burden of influenza in adults aged ≥ 65 years. METHODS: An electronic database search was conducted to identify studies assessing the economic and humanistic burden of influenza, including influenza symptoms that impact the HRQoL and patient-related outcomes in adults aged ≥ 65 years. Studies were to be published in English and conducted in Germany, France, Spain, and Italy, the UK, USA, Canada, China, Japan, Brazil, Saudi Arabia, and South Africa. RESULTS: Thirty-eight studies reported on the economic and humanistic burden of influenza in adults aged ≥ 65 years. Higher direct costs were reported for people at increased risk of influenza-related complications compared to those at low risk. Lower influenza-related total costs were found in those vaccinated with adjuvanted inactivated trivalent influenza vaccine (aTIV) compared to high-dose trivalent influenza vaccine (TIV-HD). Older age was associated with an increased occurrence and longer duration of certain influenza symptoms. CONCLUSION: Despite the limited data identified, results show that influenza exerts a high humanistic and economic burden in older adults. Further research is required to confirm findings and to identify the unmet needs of current vaccines.

Cost-effectiveness of 20-valent pneumococcal conjugate vaccine in US infants.

BACKGROUND: As of June 2023, two pneumococcal conjugate vaccines, 20- (PCV20) and 15- (PCV15) valent formulations, are recommended for US infants under a 3 + 1 schedule. This study evaluated the health and economic impact of vaccinating US infants with a new expanded valency PCV20 formulation. METHODS: A population-based, multi cohort, decision-analytic Markov model was developed to estimate the public health impact and cost-effectiveness of PCV20 from both societal and healthcare system perspectives over 10 years. Epidemiological data were based on published studies and unpublished Active Bacterial Core Surveillance System (ABCs) data. Vaccine effectiveness was based on PCV13 effectiveness and PCV7 efficacy studies. Indirect impact was based on observational studies. Costs and disutilities were based on published data. PCV20 was compared to both PCV13 and PCV15 in separate scenarios. RESULTS: Replacing PCV13 with PCV20 in infants has the potential to avert over 55,000 invasive pneumococcal disease (IPD) cases, 2.5 million pneumonia cases, 5.4 million otitis media (OM) cases, and 19,000 deaths across all ages over a 10-year time horizon, corresponding to net gains of 515,000 life years and 271,000 QALYs. Acquisition costs of PCV20 were offset by monetary savings from averted cases resulting in net savings of $20.6 billion. The same trend was observed when comparing PCV20 versus PCV15, with a net gain of 146,000 QALYs and $9.9 billion in net savings. A large proportion of the avoided costs and cases were attributable to indirect effects in unvaccinated adults and elderly. From a health-care perspective, PCV20 was also the dominant strategy compared to both PCV13 and PCV15. CONCLUSIONS: Infant vaccination with PCV20 is estimated to further reduce pneumococcal disease and associated healthcare system and societal costs compared to both PCV13 and PCV15.

Cost-Effectiveness of 20-Valent Pneumococcal Conjugate Vaccine Among US Children with Underlying Medical Conditions.

INTRODUCTION: A 20-valent pneumococcal conjugate vaccine (PCV20) was recently recommended for use among US children. We evaluated the cost-effectiveness of PCV20 among children aged 6 years with chronic medical conditions (CMC+) and children aged 6 years with immunocompromising conditions (IC) versus one and two doses of 23-valent pneumococcal polysaccharide vaccine (PPSV23), respectively. METHODS: A probabilistic model was employed to depict 10-year risk of clinical outcomes and economic costs of pneumococcal disease, reduction in life years from premature death, and expected impact of vaccination among one cohort of children with CMC+ and IC aged 6 years. Vaccine uptake was assumed to be 20% for both PCV20 and PPSV23. Cost per quality-adjusted life year (QALY) gained was evaluated from the US societal and healthcare system perspectives; deterministic and probabilistic sensitivity analyses (DSA/PSA) were also conducted. RESULTS: Among the 226,817 children with CMC+ aged 6 years in the US, use of PCV20 (in lieu of PPSV23) was projected to reduce the number cases of pneumococcal disease by 5203 cases, medical costs by US$8.7 million, and nonmedical costs by US$6.2 million. PCV20 was the dominant strategy versus PPSV23 from both the healthcare and societal perspectives. In the PSA, 99.9% of the 1000 simulations yielded a finding of dominance for PCV20. Findings in analyses of children with IC aged 6 years in the USA were comparable (i.e., PCV20 was the dominant vaccination strategy). Scenario analyses showed that increasing PCV20 uptake to 100% could potentially prevent > 22,000 additional cases of pneumococcal disease and further reduce medical and nonmedical costs by US$70.0 million among children with CMC+ and IC. CONCLUSIONS: Use of PCV20 among young children with CMC+ and IC in the USA would reduce the clinical burden of pneumococcal disease and yield overall cost savings from both the US healthcare system and societal perspectives. Higher PCV20 uptake could further reduce the number of pneumococcal disease cases in this population.

First clinical isolates of Cronobacter spp. (Enterobacter sakazakii) in Argentina: characterization and subtyping by pulsed-field gel electrophoresis.

Cronobacter species are opportunistic pathogens associated with severe infections in neonates and immunocompromised infants. From January 2009 through September 2010, two cases of neonatal infections associated with Cronobacter malonaticus and one case associated with Cronobacter sakazakii, two of them fatal, were reported in the same hospital. These are the first clinical isolates of Cronobacter spp. in Argentina. The objective of this work was to characterize and subtype clinical isolates of Cronobacter spp. in neonate patients, as well as to establish the genetic relationship between these isolates and the foodborne isolates previously identified in the country. Pulsed-field gel electrophoresis analysis showed a genetic relationship between the C. malonaticus isolates from two patients. Different results were found when the pulsed-field gel electrophoresis patterns of clinical isolates were compared with those deposited in the National Database of Cronobacter spp.

Serum bactericidal activity against circulating and reference strains of meningococcal serogroup B in the United States: A review of the strain coverage of meningococcal serogroup B (MenB) vaccines in adolescents and young adults.

Invasive meningococcal disease (IMD) is rare but associated with high morbidity and mortality. In the United States, the most vulnerable age groups are infants and adolescents/young adults, and the most common type of IMD is caused by serogroup B (MenB). MenB is preventable among adolescents and young adults with the use of two licensed vaccines, MenB-FHbp (Trumenba®, bivalent rLP2086; Pfizer Inc, Collegeville, PA) and MenB-4C (Bexsero®; GSK Vaccines, Srl, Italy). Because the effectiveness of MenB vaccination is dependent on broad vaccine coverage across circulating disease-causing strains, we reviewed the available clinical and real-world evidence regarding breadth of coverage of the two licensed vaccines in adolescents and young adults in the United States. Both vaccines protect against various MenB strains. More controlled data regarding breadth of coverage across MenB strains are available for MenB-FHbp compared with MenB-4C, whereas more observational data regarding US outbreak strain susceptibility are available for MenB-4C.

Cost-effectiveness analysis of PCV20 to prevent pneumococcal disease in the Canadian pediatric population.

This study assessed the cost-effectiveness of the 20-valent pneumococcal conjugate vaccine (PCV20) in Canadian infants aged <2 years versus the standard of care (SoC), a 13-valent pneumococcal conjugate vaccine (PCV13), or a potential 15-valent pneumococcal conjugate vaccine (PCV15). A decision-analytic Markov model was developed to compare PCV20 with PCV13 or PCV15 in a 2 + 1 schedule over 10 years. Vaccine effect estimates (direct and indirect) across all ages were informed by PCV13 clinical effectiveness and impact studies as well as PCV7 efficacy studies. Epidemiologic, clinical, health state utilities, utility decrements, cost per event, and list price data were from Canadian sources where available. Clinical and economic outcomes related to invasive pneumococcal disease (IPD), hospitalized and non-hospitalized pneumonia, and simple and complex otitis media (OM) were calculated for each strategy. Cost-effectiveness was evaluated from the publicly funded healthcare system perspective. Over 10 years, PCV20 versus PCV13 was estimated to avert over 11,000 IPD cases, 316,000 hospitalized and non-hospitalized pneumonia cases, 335,000 simple and complex OM cases, and 15,000 deaths, resulting in cost savings of over 3.2 billion Canadian dollars (CAD) and 47,000 more quality-adjusted life years (i.e. dominant strategy). Compared with PCV15, PCV20 was estimated to result in over 1.4 billion CAD in cost savings and 21,000 more QALYs (i.e. dominant strategy). PCV20 was dominant over both PCV13 and PCV15. Given broader serotype coverage, substantial incremental benefits and cost-savings, PCV20 should be considered as a replacement for the SoC in the publicly funded Canadian infant immunization program.

Understanding the Global Burden of Influenza in Adults Aged 18-64 years: A Systematic Literature Review from 2012 to 2022.

INTRODUCTION: Adults aged 18-64 years comprise most of the working population, meaning that influenza infection can be disruptive, causing prolonged absence from the workplace, and reduced productivity and the ability to care for dependents. Influenza vaccine uptake is relatively low, even among the older adults in this population (i.e., aged 50-64 years), reflecting a lack of perceived need for vaccination. This systematic literature review (SLR) aimed to characterize the global burden of influenza in the 18-64 years population. METHODS: An electronic database search was conducted and supplemented with conference and gray literature searches. Eligible studies described at least one of clinical, humanistic, or economic outcomes in adults aged 18-64 years and conducted across several global regions. Included studies were published in English, between January 1, 2012, and September 20, 2022. RESULTS: A total of 40 publications were included, with clinical, humanistic, and economic outcomes reported in 39, 5, and 15, respectively. Risk of influenza-associated clinical outcomes were reported to increase with age among the 18-64 years population, including hospitalizations (Yamana et al. in Intern Med 60:3401-3408, 2021; Derqui et al. in Influenza Other Respir Viruses 16:862-872, 2022; Fuller et al. in Influenza Other Respir Viruses 16:265-275, 2022; Ortiz et al. in Crit Care Med 42:2325-2332, 2014; Yandrapalli et al. in Ann Transl Med 6:318, 2018; Zimmerman et al. in Influenza Other Respir Viruses 16:1133-1140, 2022). ICU admissions, mortality, ER/outpatient visits, and use of mechanical ventilation were recorded. Adults aged 18-64 years with underlying comorbidities were at higher risk of influenza-related hospitalizations, ICU admission, and mortality than otherwise healthy individuals. Length of hospital stay increased with age, although a lack of stratification across other economic outcomes prevented identification of further trends across age groups. CONCLUSIONS: High levels of hospitalization and outpatient visits demonstrated a clinical influenza-associated burden on patients and healthcare systems, which is exacerbated by comorbidities. Considering the size and breadth of the general population aged 18-64 years, the limited humanistic and economic findings of this SLR likely reflect an underreported burden. Greater investigation into indirect costs and prolonged absenteeism associated with influenza infection is required to fully understand the economic burden in this population.

Burden of Acute-Care Hospitalization for Community-Acquired Pneumonia in Canadian Adults Aged 50 Years or Older: Focusing on Most Responsible Diagnosis Tells Only Part of the Story.

The burden of all-cause community-acquired pneumonia (CAP), including pneumococcal pneumonia, is typically estimated using ICD codes where pneumonia is coded as the most responsible diagnosis (MRDx). Pneumonia may also be coded as other than most responsible diagnosis (ODx) based on administrative and reimbursement criteria. Analyses including pneumonia as MRDx only likely underestimate hospitalized CAP incidence. The aim of this study was to estimate the burden of hospitalized all-cause CAP in Canada and to assess the contribution of ODx-coded cases to the overall disease burden. This longitudinal retrospective study obtained data from the Canadian Institutes of Health Information (CIHI) for adults 50+ years hospitalized for CAP between 1 April 2009 and 31 March 2019. Cases were identified as those where pneumonia was either diagnosis code type M (MRDx) or pre-admit comorbidity type 1 (ODx). Reported outcomes include pneumonia incidence rate, in-hospital mortality, hospital length of stay, and cost. Outcomes were stratified by age group, case coding, and comorbidity. Between 2009-2010 and 2018-2019, CAP incidence increased from 805.66 to 896.94 per 100,000. During this time, 55-58% of cases had pneumonia coded as ODx. Importantly, these cases had longer hospital stays, higher in-hospital mortality, and higher cost of hospitalization. The burden of CAP remains substantial and is significantly greater than that estimated by solely focusing on MRDx-coded cases. Our findings have implications for policy decision making related to current and future immunization programs.

Understanding the Barriers and Attitudes toward Influenza Vaccine Uptake in the Adult General Population: A Rapid Review.

Influenza is a common respiratory infection associated with a substantial clinical, humanistic, and economic burden globally. Vaccines are essential to prevent and control influenza and are recommended by public-health agencies, such as the WHO and US CDC; however, vaccination rates vary considerably across the globe. This review aimed to investigate the perceived barriers and attitudes to influenza vaccination in the global population, in order to identify strategies that may improve influenza vaccination coverage. A structured literature search was undertaken to identify studies that reported on patient-reported attitudes towards influenza vaccination, focused on the adult general population in 16 prespecified countries. Eighty studies were included in this review. Negative attitude towards healthcare were found to be the most agreed upon barrier to vaccine uptake (31.1% agreement). The most agreed promoter of influenza vaccination was trust in healthcare services (62.0% agreement). Approximately 50% of participants intended to receive the influenza vaccine in the following season. To improve influenza vaccination coverage, healthcare workers must strengthen the foundation of substantial trust in healthcare services and provide educational materials that improve influenza vaccination knowledge among the adult general population.

Clinical outcomes of COVID-19 and influenza in hospitalized children <5 years in the US.

Introduction: We compared hospitalization outcomes of young children hospitalized with COVID-19 to those hospitalized with influenza in the United States. Methods: Patients aged 0-<5 years hospitalized with an admission diagnosis of acute COVID-19 (April 2021-March 2022) or influenza (April 2019-March 2020) were selected from the PINC AI Healthcare Database Special Release. Hospitalization outcomes included length of stay (LOS), intensive care unit (ICU) admission, oxygen supplementation, and mechanical ventilation (MV). Inverse probability of treatment weighting was used to adjust for confounders in logistic regression analyses. Results: Among children hospitalized with COVID-19 (n = 4,839; median age: 0 years), 21.3% had an ICU admission, 19.6% received oxygen supplementation, 7.9% received MV support, and 0.5% died. Among children hospitalized with influenza (n = 4,349; median age: 1 year), 17.4% were admitted to the ICU, 26.7% received oxygen supplementation, 7.6% received MV support, and 0.3% died. Compared to children hospitalized with influenza, those with COVID-19 were more likely to have an ICU admission (adjusted odds ratio [aOR]: 1.34; 95% confidence interval [CI]: 1.21-1.48). However, children with COVID-19 were less likely to receive oxygen supplementation (aOR: 0.71; 95% CI: 0.64-0.78), have a prolonged LOS (aOR: 0.81; 95% CI: 0.75-0.88), or a prolonged ICU stay (aOR: 0.56; 95% CI: 0.46-0.68). The likelihood of receiving MV was similar (aOR: 0.94; 95% CI: 0.81, 1.1). Conclusions: Hospitalized children with either SARS-CoV-2 or influenza had severe complications including ICU admission and oxygen supplementation. Nearly 10% received MV support. Both SARS-CoV-2 and influenza have the potential to cause severe illness in young children.

High Clinical Burden of Influenza Disease in Adults Aged ≥ 65 Years: Can We Do Better? A Systematic Literature Review.

INTRODUCTION: Influenza is a respiratory infection associated with a significant clinical burden globally. Adults aged ≥ 65 years are at increased risk of severe influenza-related symptoms and complications due to chronic comorbidity and immunosenescence. Annual influenza vaccination is recommended; however, current influenza vaccines confer suboptimal protection, in part due to antigen mismatch and poor durability. This systematic literature review characterizes the global clinical burden of seasonal influenza among adults aged ≥ 65 years. METHODS: An electronic database search was conducted and supplemented with a conference abstract search. Included studies described clinical outcomes in the ≥ 65 years population across several global regions and were published in English between January 1, 2012 and February 9, 2022. RESULTS: Ninety-nine publications were included (accounting for > 156,198,287 total participants globally). Clinical burden was evident across regions, with most studies conducted in the USA and Europe. Risk of influenza-associated hospitalization increased with age, particularly in those aged ≥ 65 years living in long-term care facilities, with underlying comorbidities, and infected with A(H3N2) strains. Seasons dominated by circulating A(H3N2) strains saw increased risk of influenza-associated hospitalization, intensive care unit admission, and mortality within the ≥ 65 years population. Seasonal differences in clinical burden were linked to differences in circulating strains. CONCLUSIONS: Influenza exerts a considerable burden on adults aged ≥ 65 years and healthcare systems, with high incidence of hospitalization and mortality. Substantial influenza-associated clinical burden persists despite increasing vaccination coverage among adults aged ≥ 65 years across regions included in this review, which suggests limited effectiveness of currently available seasonal influenza vaccines. To reduce influenza-associated clinical burden, influenza vaccine effectiveness must be improved. Next generation vaccine production using mRNA technology has demonstrated high effectiveness against another respiratory virus-SARS-CoV-2-and may overcome the practical limitations associated with traditional influenza vaccine production.