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Background: The Advisory Committee on Immunization Practices (ACIP) uses the Evidence to Recommendations Framework that includes cost-effectiveness analyses (CEA) for determining vaccine recommendations. ACIP's preference for protecting adults ≥ 65 years is enhanced vaccines, including recombinant influenza vaccine (RIV4), adjuvanted or high dose influenza vaccine. Less is known about the CEA of enhanced vaccines for younger adults., Methods: We used decision analysis modeling from a societal perspective to determine the cost-effectiveness, measured in quality adjusted life years (QALYs), of RIV4 compared with standard dose quadrivalent influenza vaccine (SD-IIV4) in adults 18-64 years old. Model inputs included 2018-2020 vaccine effectiveness (VE) estimates based on medical record data from a large local health system, 2019-2020 national vaccination and influenza epidemic parameters, with costs and population distributions fitted to the season., Results: Among adults ages 18-64 years, RIV4 cost $94,186/QALY gained, compared to SD-IIV4. Among those 50-64 years old, RIV4 was relatively more cost-effective ($61,329/QALY gained). Cost-effectiveness estimates for 18-64-year-olds were sensitive to the absolute difference in VE between SD-IIV4 and RIV4, among other parameters. Use of RIV4 in 18-64-year-olds would result in fewer cases (669,984), outpatient visits (261,293), hospitalizations (20,046) and deaths (1,018) annually. The majority (59 %; 597 of 1018) of the decreases in deaths occurred in the 50-64-year-olds., Conclusions: While RIV4 was effective and cost-effective relative to SD-IIV4 for both 50-64-year-old and 18-64-year-old adults, cost-effectiveness was sensitive to small changes in parameters among 18-64-year-olds. Because substantial public health benefits occur with enhanced vaccines, health systems and policy makers may opt for preferential product use in select age/risk groups (e.g., 50-64 year olds) to maximize their cost-benefit ratios., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Jonathan M Raviotta reports financial support was provided by Sanofi Pasteur Inc. Richard K Zimmerman reports a relationship with Sanofi Pasteur Inc that includes: funding grants. Mary Patricia Nowalk reports a relationship with Sanofi Pasteur Inc that includes: funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper]., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Indirect effects of childhood pneumococcal conjugate vaccines (PCV) have diminished the cost-effectiveness of current adult vaccine recommendations. An in-development adult-formulated 21-valent pneumococcal conjugate vaccine (PCV21) may play a critical role in reducing pneumococcal illness by targeting a larger number of serotypes responsible for adult pneumococcal infections. This study assesses the cost-effectiveness of PCV21 in US adults aged 50 years or older compared with currently recommended pneumococcal vaccines, from both the societal and healthcare perspectives. A Markov model evaluated the lifetime cost-effectiveness of PCV21 (given at age 50 years only, at ages 50/65 years, and risk-based at ages < 65 years plus age-based at age 65 years) compared to no vaccination and to currently recommended pneumococcal vaccines given either as currently recommended or routinely at ages 50/65 years. The analysis was conducted in hypothetical Black and non-Black cohorts aged 50 years or older, with and without considering childhood pneumococcal vaccination indirect effects. Model parameters were based on US data. Parameter uncertainty was assessed using 1-way and probabilistic sensitivity analyses. From the societal perspective, PCV21 at ages 50/65 years compared to PCV21 at age 50 years cost $7,410 per quality adjusted life year (QALY) gained in Black cohort analyses and $85,696/QALY gained in the non-Black cohort; PCV21 at ages 50/65 years had the most favorable public health outcomes. From the healthcare perspective, compared to no vaccination, PCV21 at age 50 years cost $46,213/QALY gained in the Black cohort and $86,629/QALY in non-Blacks. All other strategies were dominated in both cohorts and from both perspectives. When considering childhood pneumococcal vaccination indirect effects, costs of PCV21 at ages 50/65 years remained less than $140,000/QALY gained from the societal perspective in both populations. PCV21 is potentially cost-effective compared to currently approved pneumococcal vaccines in adults aged 50 years or older from both the societal and healthcare perspectives., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Wateska has had a research grant from NIAID in the past 3 years. Dr. Nowalk has had research grants from Merck & Co., Inc. and Sanofi Pasteur. in the past 3 years. Dr. Schaffner has had a research grant from CDC in the past 3 years. Dr. Zimmerman has had research grants from NIH and Sanofi Pasteur. in 3 years. Dr. Smith has had research grants from NIAID and Sanofi Pasteur. in the past 3 years. Other authors have no competing interests to disclose., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Relative effectiveness of various vaccine formulations provide important input for vaccine policy decisions and provider purchasing decisions. We used electronic databases to conduct a test-negative case control study to determine relative vaccine effectiveness (rVE) of recombinant influenza vaccine (RIV4) compared with standard dose vaccines (SD-IIV4) against influenza hospitalization., Methods: Adults 18-64 and ≥65 years of age hospitalized in a large U.S. health system (19 hospitals) in 2018-2019 and 2019-2020 who were clinically tested for influenza using reverse transcription polymerase chain reaction (RT-PCR) assays were included. The hospital system electronic medical record (EMR) and the state immunization registry were used to confirm influenza vaccination. Propensity scores with inverse probability weighting were used to adjust for potential confounders and determine rVE., Results: Of the 14,590 individuals included in the primary analysis, 3,338 were vaccinated with RIV4 and 976 were vaccinated with SD-IIV4, with the balance of 10,276 being unvaccinated. Most participants were white (80 %), most (70 %) had a high-risk condition, just over half were female (54 %) and age 65 years or older (53 %). Overall RIV4 rVE was significant when adjusted for propensity scores with inverse probability weights (rVE = 31; 95 % CI = 11 %, 46 %). Among younger adults (18-64 years-old), overall rVE of RIV4 was significant (rVE = 29; 95 % CI = 4 %, 47 %)., Conclusions: Over all adults, both RIV4 and SD-IIV4 were effective against influenza hospitalization, with RIV4 providing better protection compared with SD-IIV4 overall, for females, younger adults, and those with no high-risk conditions., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Drs. Zimmerman, Raviotta, Nowalk, and Balasubramani received investigator-initiated grant funding from Sanofi for this project. Drs. Nowalk and Balasubramani, have grant funding from Merck & Co., Inc. for an unrelated project. Ms. Dauer and Mr. Clarke have no conflicts to report., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: CDC pneumococcal vaccination recommendations for older adults now include either 15- or 20-valent pneumococcal conjugate vaccine (PCV15/PCV20). However, an in-development 21-valent vaccine (PCV21), formulated based on adult pneumococcal disease epidemiology, could substantially increase coverage of disease-causing pneumococcal serotypes, particularly in Black older adults, who are at greater risk. The potential public health impact and cost-effectiveness of PCV21 compared to currently recommended vaccines in older adults is unclear., Methods: A Markov decision model compared current pneumococcal vaccination recommendations to PCV21 use in Black and non-Black 65-year-old cohorts. CDC Active Bacterial Core surveillance data informed population and serotype-specific pneumococcal disease risk. Vaccine effectiveness was estimated using Delphi panel estimates and clinical trial data, with variation in sensitivity analyses. Potential indirect effects on adult disease from PCV15 childhood vaccination were examined. All model parameters were varied individually and collectively in sensitivity analyses. Scenarios with decreased PCV21 effectiveness and potential COVID-19 pandemic effects were also examined., Results: In the Black cohort, the PCV21 strategy cost $88,478 per quality adjusted life-year (QALY) gained without and $97,952/QALY with childhood PCV15 indirect effects. PCV21 in the non-Black cohort cost $127,436/QALY gained without and $141,358/QALY with childhood PCV15 effects. Current recommendation strategies were economically unfavorable, regardless of population or indirect childhood vaccination effects. Results favoring PCV21 use were robust in sensitivity analyses and alternative scenarios., Conclusion: An in-development PCV21 vaccine would likely be economically and clinically favorable compared to currently recommended pneumococcal vaccines in older adults. While PCV21 was more favorable in Black cohort analyses, results for both Black and non-Black populations were economically reasonable, highlighting the potential importance of adult-specific pneumococcal vaccine formulations and, pending further investigation, potentially justifying a future general population recommendation for PCV21 use in older adults., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Drs. Smith and Zimmerman have an active research grant from Sanofi Pasteur on unrelated topics. Dr. Nowalk has grant funding from Merck & Co., Inc. on an unrelated topic and had research grants within 3 years from Pfizer, Inc. and Sanofi Pasteur on unrelated topics that are no longer active. Dr. Schaffner is a member of a data safety monitoring board (DSMB) for Pfizer, former member of a DSMB for Merck, and has served as a consultant to Roche Diagnostics. Dr. Harrison has served as a consultant to GSK, Merck, Pfizer, and Sanofi Pasteur. All other authors have no competing interests to disclose., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Immune responses to influenza vaccination tend to be lower among older, frequently vaccinated adults. Use of egg-free influenza vaccines is increasing, but limited data exist on factors associated with their immunogenicity in older adults., Methods: Community-dwelling older adults ≥ 56 years of age were enrolled in a prospective, observational study of immunogenicity of 2018-2019 influenza vaccine. Hemagglutination inhibition (HAI) antibody titers were measured pre-vaccination (Day 0) and four weeks after vaccination (Day 28) to calculate geometric mean titers, seropositivity (HAI titers ≥ 1:40), seroconversion (fourfold rise in HAI titer with post-vaccination titer ≥ 1:40) and geometric mean fold rise (GMFR). Linear regression models assessed the association of predictors of GMFR for each vaccine antigen., Results: Among 91 participants who received egg-free influenza vaccines, 84 (92.3 %) received quadrivalent recombinant influenza vaccine (RIV4, Flublok, Sanofi Pasteur), and 7 (7.7 %) received quadrivalent cell culture-based influenza vaccine (ccIIV4, Flucelvax, Seqirus). Pre-vaccination seropositivity was 52.8 % for A(H1N1), 94.5 % for A(H3N2), 61.5 % for B/Colorado and 48.4 % for B/Phuket. Seroconversion by antigen ranged from 16.5 % for A(H1N1) and B/Colorado to 37.4 % for A(H3N2); 40 participants failed to seroconvert to any antigen. Factors independently associated with higher GMFR in multivariable models included lower pre-vaccination HAI antibody titer for A(H1N1), B/Colorado and B/Phuket, and younger age for A(H1N1)., Conclusion: Overall pre-vaccination seropositivity was high and just over half of the cohort seroconverted to ≥ 1 vaccine antigen. Antibody responses were highest among participants with lower pre-vaccination titers. Among older adults with high pre-existing antibody titers, approaches to improve immune responses are needed., Competing Interests: Declaration of Competing Interest RKZ has received unrelated funding by Sanofi.  MPN has research funding from Merck & Co., Inc. and Sanofi Pasteur for unrelated studies., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: The 15- and 20-valent pneumococcal conjugate vaccines (PCV15/PCV20) were recently recommended for US adults, giving either PCV20 alone or PCV15 followed by 23-valent pneumococcal polysaccharide vaccine (PPSV23) to all 65 + -year-olds and to high-risk younger adults. However, general population recommendations to vaccinate all 50-year-olds could reduce racial pneumococcal disease disparities given greater risk in underserved minority populations., Methods: A Markov model examining hypothetical 50-year-old Black cohorts (serving as a proxy for underserved minorities) and non-Black cohorts estimated the incremental cost effectiveness of US adult pneumococcal vaccination recommendations compared to PCV20 or PCV15/PPSV23 for all 50-year-olds with no vaccination thereafter, or PCV20 or PCV15/PPSV23 for all at ages 50 and 65 years (50/65). Model parameters came from US databases, clinical trials, and Delphi panels. Cohorts were followed over their lifetimes from a healthcare perspective discounted at 3 %/year., Results: PCV15/PPSV23 given at ages 50/65 had greatest public health impact. In Black cohorts, PCV15/PPSV23 at age 50 cost $104,723/quality adjusted life year (QALY) gained compared to PCV20 at age 50, while PCV15/PPSV23 at 50/65 cost $240,952/QALY gained compared to PCV15/PPSV23 at age 50. Both current recommendation options were more expensive and less effective than other strategies in both cohorts. In sensitivity analyses, age-based PCV20 or PCV15/PPSV23 use at ages 50 or 50/65 could be favorable depending on vaccine effectiveness or differential vaccine uptake, while current recommendations remained unfavorable., Conclusion: Recent risk-based US adult pneumococcal vaccination recommendations for adults < 65-years-old, were economically and clinically unfavorable compared to general population vaccination of all 50-year-olds in Black and non-Black cohorts. An age-based pneumococcal vaccination recommendation at age 50 years may reduce inequities in pneumococcal disease burden., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: We sought to evaluate the trends of HPV vaccination between 03/2019-09/2021 and whether the impact of the COVID pandemic on HPV vaccination varied by race/ethnicity and neighborhood deprivation index (NDI)., Methods: Electronic medical records at Kaiser Permanente Southern California were used to assess monthly volume of HPV vaccine doses administered among children aged 9-12.9yrs, and up-to-date coverage (% vaccinated) by age 13 between 03/2019-09/2021. Modified Poisson models were used to evaluate the interactions between race/ethnicity, NDI and the pandemic periods on HPV vaccine coverage., Results: HPV vaccine doses administered in 2020/2021 have returned to the 2019 level after the initial drop. The average up-to-date coverage in 05/2021-09/2021 (54.8%) remained lower than the pre-pandemic level (58.5%). The associations between race/ethnicity, NDI and HPV vaccine coverage did not vary due to the pandemic., Conclusion: HPV vaccine promotion efforts are needed to address COVID-19 pandemic's lasting impact on HPV vaccination coverage., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Chao CR received research funding from Merck for an unrelated project., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Influenza vaccines can mitigate illness severity, including reduced risk of ICU admission and death, in people with breakthrough infection. Less is known about vaccine attenuation of mild/moderate influenza illness. We compared subjective severity scores in vaccinated and unvaccinated persons with medically attended illness and laboratory-confirmed influenza. Participants were prospectively recruited when presenting for care at five US sites over nine seasons. Participants aged ≥ 16 years completed the EQ-5D-5L visual analog scale (VAS) at enrollment. After controlling for potential confounders in a multivariable model, including age and general health status, VAS scores were significantly higher among 2,830 vaccinated participants compared with 3,459 unvaccinated participants, indicating vaccinated participants felt better at the time of presentation for care. No differences in VAS scores were observed by the type of vaccine received among persons aged ≥ 65 years. Our findings suggest vaccine-associated attenuation of milder influenza illness is possible., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: ‘Dr. Gaglani reports grants from CDC outside the submitted work. Dr. McLean reports grants from Seqirus outside the submitted work. Dr. Nowalk reports grants from Merck & Co outside the submitted work. Dr. Zimmerman reports grants from Sanofi Pasteur outside the submitted work. Dr. L. Jackson reports grants from Novavax outside the submitted work. Dr. Martin reports personal fees from Pfizer outside the submitted work. All other authors have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.’, (Published by Elsevier Ltd.)

Background: Numerous studies in the U.S. have made estimates of the RSV burden among adults that vary widely due to differences in methodology, reliance on influenza surveillance, which does not adequately capture all RSV clinical symptoms, and lack of diagnostic methods to identify RSV when viral loads are low. Nevertheless, accurate burden estimates can inform healthcare planning, resource allocation and potentially, RSV vaccine policy., Methods: A simple method combined with statewide and local hospitalization, medical record and U.S. Census data were used to estimate population-based RSV hospitalization burden among adults ages 18-64 years, ≥65 years, and including immunocompetent, immunocompromised and pregnant individuals during 2015-2018 for Allegheny County, Pennsylvania. Economic burden of hospitalization was estimated using state-provided average hospitalization charges for comparisons across patient groups., Results: The largest burden was borne by adults ≥ 65 years of age whose rates per 100,000 population of that age group (939/100,000) were 7.0-9.0 times those of adults 18-64 years of age (118/100,000). Immunosuppressed patients bore the greatest relative burden of RSV hospitalizations (1,288-1,562/100,000 immunosuppressed individuals). RSV burden ranged from 0 to 808/100,000 pregnant women. Average total charges for RSV hospitalization in Allegheny County across all adults increased from $39 million in 2015-2016 to $57 million in 2016-2017 to $89 million in 2017-2018, due to both increased average charges for an acute respiratory hospitalization and increased numbers of RSV cases., Conclusions: These RSV burden estimates add to the body of knowledge to guide public health policy makers and offer a method for simply and easily producing population-based burden estimates., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: MPN reports an investigator-initiated grant from Merck & Co. outside the submitted work. RKZ and MPN report an investigator-initiated grant from Sanofi Pasteur outside the submitted work., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Introduction: Interventions to curb the spread of COVID-19 during the 2020-2021 influenza season essentially eliminated influenza during that season. Given waning antibody titers over time, future residual population immunity against influenza will be reduced. The implication for the subsequent 2021-2022 influenza season is unknown., Methods: An agent-based model of influenza implemented in the Framework for Reconstructing Epidemiological Dynamics simulation platform was used to estimate cases and hospitalizations over 2 successive influenza seasons. The impact of reduced residual immunity owing to protective measures in the first season was estimated over varying levels of similarity (cross-immunity) between influenza strains over the seasons., Results: When cross-immunity between first- and second-season strains was low, a decreased first season had limited impact on second-season cases. High levels of cross-immunity resulted in a greater impact on the second season. This impact was modified by the transmissibility of strains in the 2 seasons. The model estimated a possible increase of 13.52%-46.95% in cases relative to that in a normal season when strains have the same transmissibility and 40%-50% cross-immunity in a season after a very low one., Conclusions: Given the light 2020-2021 influenza season, cases may increase by as much as 50% in 2021-2022, although the increase could be much less, depending on cross-immunity from past infection and transmissibility of strains. Enhanced vaccine coverage or continued interventions to reduce transmission could reduce this high season. Young children may have a higher risk in 2021-2022 owing to limited exposure to infection in the previous year., (Copyright © 2021 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Hemagglutination inhibition (HAI) titers to the live-attenuated influenza vaccine (LAIV4) are typically lower than its counterpart egg-based inactivated influenza vaccines (IIV). Similar comparisons have not been made between LAIV4 and the 4-strain, cell-culture inactivated influenza vaccine (ccIIV4). We compared healthy children's and young adults' HAI titers against the 2019-2020 LAIV4 and ccIIV4., Methods: Participants aged 4-21 years were randomized 1:1 to receive ccIIV4 (n = 100) or LAIV4 (n = 98). Blood was drawn prevaccination and on day 28 (21-35) post vaccination. HAI assays against egg-grown A/H1N1, A/H3N2, both vaccine B strains and cell-grown A/H3N2 antigens were conducted. Primary outcomes were geometric mean titers (GMT) and geometric mean fold rise (GMFR) in titers., Results: GMTs to A/H1N1, A/H3N2 and B/Victoria increased following both ccIIV and LAIV and to B/Yamagata following ccIIV (p < 0.05). The GMFR range was 2.4-3.0 times higher for ccIIV4 than for LAIV4 (p < 0.001). Within vaccine types, egg-grown A/H3N2 GMTs were higher (p < 0.05) than cell-grown GMTs [ccIIV4 day 28: egg = 205 (95% CI: 178-237); cell = 136 (95% CI:113-165); LAIV4 day 28: egg = 96 (95% CI: 83-112); cell = 63 (95% CI: 58-74)]. The GMFR to A/H3N2 cell-grown and egg-grown antigens were similar. Pre-vaccination titers inversely predicted GMFR., Conclusion: The HAI response to ccIIV4 was greater than LAIV4 in this study of mostly older children, and day 0 HAI titers inversely predicted GMFR for both vaccines. Lower prevaccination titers were associated with greater GMFR in both vaccine groups., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [RKZ has received unrelated funding by Sanofi. MPN has research funding from Merck & Co., Inc. for an unrelated study. JMM has received unrelated funding from Merck, Sharp and Dohme.]., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Introduction: Many vaccination studies rely on self-reported vaccination status, with its inherent biases. Accuracy of influenza vaccination self-report has been evaluated periodically, typically using the medical record as the gold standard. The burgeoning of electronic medical records (EMRs) and immunization information systems (IISs) and the rise of adult vaccine administration in community pharmacies suggest the need for a reevaluation of self-reported vaccination status., Methods: Vaccination data from self-report, the state IIS, the health system EMR and other sources were compared for participants in outpatient and inpatient influenza vaccine effectiveness studies for four seasons (2016-2017 to 2019-2020). Agreement among the sources was calculated along with sensitivity and specificity. Tests for trend assessed changes in completeness of the Pennsylvania - Statewide IIS (PA-SIIS) data over time., Results: With self-report as the gold standard, agreement with the local EMR, PA-SIIS, and all sources was 62%, 77% and 85%, respectively. Sensitivity of the EMR was 42% (95% CI = 41, 43) and specificity was 91% (90, 92). With PA-SIIS-as the gold standard, agreement with the local EMR and all sources was 77% and 78%, respectively. Sensitivity of all sources combined was 96% (95, 97) and specificity was (63% (62, 64). Capture of influenza vaccinations in the IIS has not consistently improved over time, with a significant increase among children (P = 0.001), no change among working-age adults and a decrease among older adults (P = 0.004). However, PA-SIIS provided the largest percentage of verified vaccines (69.3%) compared with EMR (43.3%) and other sources (12.4%)., Conclusion: Both self-report and PA-SIIS are good estimates of actual vaccine uptake. When high accuracy data are required, such as for vaccine effectiveness studies, triangulation using multiple sources should be conducted., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: The COVID-19 pandemic is causing declines in childhood immunization rates. We examined potential COVID-19-related changes in pediatric 13-valent pneumococcal conjugate vaccine (PCV13) use, subsequent impact on childhood and adult pneumococcal disease rates, and how those changes might affect the favorability of PCV13 use in non-immunocompromised adults aged ≥65 years., Methods: A Markov model estimated pediatric disease resulting from decreased PCV13 use in children aged <5 years; absolute decreases from 10 to 50% for 1-2 years duration were examined, assuming no catch-up vaccination and that decreased vaccination led to proportionate increases in PCV13 serotype pneumococcal disease in children and seniors. Integrating pediatric model output into a second Markov model examining 65-year-olds, we estimated the cost effectiveness of older adult pneumococcal vaccination strategies while accounting for potential epidemiologic changes from decreased pediatric vaccination., Results: One year of 10-50% absolute decreases in PCV13 use in <5-year-olds increased pneumococcal disease by an estimated 4-19% in seniors; 2 years of decreased use increased senior rates by 8-38%. In seniors, a >53% increase in pneumococcal disease was required to favor PCV13 use in non-immunocompromised seniors at a $200,000 per quality-adjusted life-year gained threshold, which corresponded to absolute decreases in pediatric PCV13 vaccination of >50% over a 2-year period. In sensitivity analyses, senior PCV13 vaccination was unfavorable if absolute decreases in pediatric PCV13 receipt were within plausible ranges, despite model assumptions favoring PCV13 use in seniors., Conclusion: COVID-19-related decreases in pediatric PCV13 use would need to be both substantial and prolonged to make heightened PCV13 use in non-immunocompromised seniors economically favorable., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Zimmerman has no current conflicts of interest but within 3 years had research grants from Sanofi Pasteur on unrelated topics. Dr. Nowalk has an active research grant from Merck & Co. on an unrelated topic, and had research grants within 3 years from Pfizer and Sanofi Pasteur on unrelated topics that are no longer active. Dr. Schaffner is a member of a data safety monitoring board (DSMB) for Pfizer, former member of a DSMB for Merck, and has served as a consultant to Roche Diagnostics. Dr. Harrison has served as a consultant to GSK, Merck, Pfizer, and Sanofi Pasteur. Other authors have no competing interests to disclose., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Many persons with religious convictions report hesitancy about COVID-19 vaccines, in part due to ethical concerns that fetal cell lines are used in the development of certain vaccines. The issue of abortion is contentious and, given the potential impact on COVID-19 vaccination, it is important for clinicians to be aware of this issue, whatever their personal beliefs. I provide four responses that clinicians may offer their patients: 1) Ethical analyses of moral complicity and COVID vaccines. 2) Altruism and protecting others from a virus that is often transmitted while asymptomatic or pre-symptomatic. 3) Religious texts and many religious leaders support prevention and, therefore, vaccination. 4) Administration of vaccines not developed in fetal cell lines. Although I wish for all my patients to be vaccinated, I respect their autonomy to make the choice to be or not to be vaccinated and understand that many have a deep regard for fetal life., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Zimmerman has a pending grant with Sanofi Pasteur on an unrelated topic., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Introduction: Use of the 13-valent pneumococcal conjugate vaccine in nonimmunocompromised adults aged ≥65 years is controversial. Higher-valency conjugate vaccines (15-valent and 20-valent ) are under development; their potential cost effectiveness in older adults is unknown, particularly when potential indirect (herd immunity) effects from childhood vaccination are considered., Methods: A Markov model estimated the cost effectiveness of current U.S. recommendations and alternative strategies using currently available and in-development pneumococcal conjugate vaccines in seniors. Separately, strategies using a hypothetical 20-valent vaccine adding the 7 most common disease-causing non-13-valent vaccine serotypes were considered. Sensitivity analyses were performed and alternative scenarios were examined. Data were gathered and the analyses were performed in 2020., Results: In analyses considering only existing and in-development vaccines, sole 20-valent vaccine use cost $172,491/quality-adjusted life year gained compared with current U.S. recommendations under baseline assumptions (equal serotype effectiveness and no childhood vaccination indirect effects). Strategies using 15-valent vaccine were more costly and less effective. When 13-valent/20-valent vaccines were assumed ineffective against pneumococcal serotype 3 and 15-valent vaccine was fully effective, 15-valent vaccine cost $237,431/quality-adjusted life year gained. With indirect effects considered, 15-valent or 20-valent vaccine cost >$449,000/quality-adjusted life year gained. When adding hypothetical 20-valent vaccine under baseline assumptions, hypothetical 20-valent vaccine cost $139,348/quality-adjusted life year gained., Conclusions: In-development pneumococcal conjugate vaccines may be economically unreasonable in older adults, regardless of serotype effectiveness assumptions, particularly when considering potential indirect effects from use of those vaccines in children. Adult vaccines containing high-risk serotypes not contained in childhood vaccines may be more promising., (Copyright © 2021 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Pneumococcal vaccination policy for US adults is evolving, but previous research has shown that programs to increase vaccine uptake are economically favorable, despite parameter uncertainty. Using value of information (VOI) analysis and prior analyses, we examine the value of further research on vaccine uptake program parameters., Methods: In US 50-64-year-olds, current vaccine recommendations with and without an uptake program were analyzed. In older adults, current recommendations and an alternative strategy (polysaccharide vaccine for all, adding conjugate vaccine only for the immunocompromised) with and without uptake programs were examined. Uptake program parameters were derived from a clinical trial (absolute uptake increase 12.3% [range 0-25%], per-person cost $1.78 [range $0.70-$2.26]), with other parameters obtained from US databases. VOI analyses incorporated probabilistic sensitivity analysis outputs into R-based regression techniques., Results: In 50-64-year-olds, an uptake program cost $54,900/QALY gained compared to no uptake program. For ages ≥65, the program cost $287,000/QALY gained with the alternative strategy and $765,000/QALY with current recommendations. In younger adults, population-level expected value of perfect information (EVPI) was $59.7 million at $50,000/QALY gained and $2.8 million at $100,000/QALY gained. In older adults, EVPI values ranged from ~$1 million to $34.5 million at $100,000 and $200,000/QALY thresholds. The population expected value of partial perfect information (EVPPI) for combined uptake program cost and uptake improvement parameters in the younger population was $368,700 at $50,000/QALY and $43,900 at $100,000/QALY gained thresholds. In older adults, population EVPPI for vaccine uptake program parameters was $0 at both thresholds, reaching a maximum value of $445,000 at a $225,000/QALY threshold. Other model parameters comprised larger components of the global EVPI., Conclusion: VOI results do not support further research on pneumococcal vaccine uptake programs in adults at commonly cited US cost-effectiveness benchmarks. Further research to reduce uncertainty in other aspects of adult pneumococcal vaccination is justifiable., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Zimmerman has no current conflicts of interest but within 3 years had research grants from Sanofi Pasteur on unrelated topics. Dr. Nowalk has an active research grant from Merck & Co. on an unrelated topic, and had research grants within 3 years from Pfizer and Sanofi Pasteur on unrelated topics that are no longer active. Dr. Schaffner is a member of a data safety monitoring board (DSMB) for Pfizer, former member of a DSMB for Merck, and has served as a consultant to Roche Diagnostics. Dr. Harrison has served as a consultant to GSK, Merck, Pfizer, and Sanofi Pasteur. Other authors have no competing interests to disclose., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Introduction: Mid-season influenza vaccine effectiveness (VE) estimates are a useful tool to help guide annual influenza vaccine strain selection, vaccine policy, and public health messaging. We propose using a sample size-driven approach with data-driven inputs for publication of mid-season influenza VE., Methods: We used pooled inputs for VE by (sub)type and average vaccine coverage by age groups using data from eight seasons of the US Influenza VE Network to calculate sample sizes needed to estimate mid-season VE., Results: We estimate that 135 influenza-positive cases would be needed to detect an overall VE of 40% with 55% vaccine coverage among test-negative controls. Larger sample sizes would be required to produce reliable estimates specifically against influenza A/H3N2 and for older age groups., Conclusion: Using an existing network, most of the recent influenza seasons in the US would facilitate valid mid-season VE estimates using the proposed sample sizes for broad age groupings., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Ltd.)

Background: In some settings, research methods to determine influenza vaccine effectiveness (VE) may not be appropriate because of cost, time constraints, or other factors. Administrative database analysis of viral testing results and vaccination history may be a viable alternative. This study compared VE estimates from outpatient research and administrative databases., Methods: Using the test-negative, case-control design, data for 2017-2018 and 2018-2019 influenza seasons were collected using: 1) consent, specimen collection, RT-PCR testing and vaccine verification using multiple methods; and 2) an administrative database of outpatients with a clinical respiratory viral panel combined with electronic immunization records. Odds ratios for likelihood of influenza infection by vaccination status were calculated using multivariable logistic regression. VE = (1 - aOR) × 100., Results: Research participants were significantly younger (P < 0.001), more often white (69% vs. 59%; P < 0.001) than non-white and less frequently enrolled through the emergency department (35% vs. 72%; P < 0.001) than administrative database participants. VE was significant against all influenza and influenza A in each season and both seasons combined (37-49%). Point estimate differences between methods were evident, with higher VE in the research database, but insignificant due to low sample sizes. When enrollment sites were separately analyzed, there were significant differences in VE estimates for all influenza (66% research vs. 46% administrative P < 0.001) and influenza A (67% research vs. 49% administrative; P < 0.001) in the emergency department., Conclusions: The selection of the appropriate method for determining influenza vaccine effectiveness depends on many factors, including sample size, subgroups of interest, etc., suggesting that research estimates may be more generalizable. Other advantages of research databases for VE estimates include lack of clinician-related selection bias for testing and less misclassification of vaccination status. The advantages of the administrative databases are potentially shorter time to VE results and lower cost., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Drs. Nowalk and Balasubramani, Ms. Eng and Mr. Lyons have grant funding from Merck & Co., Inc. for an unrelated project. Dr. Zimmerman has grant funding from Sanofi Pasteur and Merck & Co., Inc. Mr. Clarke has no conflicts to report]., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: New influenza vaccine formulations are designed to improve vaccine effectiveness and protect those most vulnerable to infection. High dose trivalent inactivated influenza vaccine (HD-IIV3), licensed for ages ≥65 years, produces greater antibody responses and efficacy in clinical trials, but post-licensure vaccine effectiveness (VE) compared to standard dose (SD-IIV3/4) vaccine remains an open question., Methods: Using a test-negative, case control design and propensity analyses to adjust for confounding, US Influenza VE Network data from the 2015-2016 through 2018-2019 seasons were analyzed to determine relative VE (rVE) between HD-IIV3 and SD-IIV3/4 among outpatients ≥65 years old presenting with acute respiratory illness. Influenza vaccination status was derived from electronic medical records and immunization registries., Results: Among 3861 enrollees, 2993 (78%) were vaccinated; 1573 (53%) received HD-IIV3 and 1420 (47%) received SD-IIV3/4. HD-IIV3 recipients differed from SD-IIV3/4 recipients by race, previous vaccination, number of outpatient visits in the previous year and timing of vaccination, and were balanced in the propensity model except the timing of vaccination. Compared with no vaccination, significant protection against any influenza A was observed from both HD-IIV3 (VE = 29%; 95%CI = 10%, 44%) and SD-IIV3/4 (VE = 24%; 95%CI = 5%, 39%); rVE = 18% (95%CI = 0%, 33%, SD as referent). When stratified by virus type, against A/H1N1, HD-IIV3 VE was 30% (95%CI = -7%, 54%), SD-IIV3/4 VE was 40% (95%CI = 10%, 61%), and rVE = -32%; (95%CI = -94%, 11%); Against A/H3N2, HD-IIV3 VE was 31% (95%CI = 9%, 47%), SD-IIV3/4 VE was 19% (95%CI = -5%, 37%), and rVE = 27%; (95% CI = 9%, 42%)., Conclusions: Among adults ≥65 years of age, recipients of standard and high dose influenza vaccines differed significantly in their characteristics. After adjusting for these differences, high dose vaccine offered more protection against A/H3N2 and borderline significant protection against all influenza A requiring outpatient care during the 2015-2018 influenza seasons., Competing Interests: Declaration of Competing Interest RKZ has/had a research grant from Sanofi Pasteur, Inc. RKZ and MPN have/had research grant funding from Merck & Co, Inc. MLG has received institutional research grant from AstraZeneca-MedImmune. MLJ reports research funding from Sanofi Pasteur, unrelated to the present work. ASM reports consulting fees from Sanofi, Seqirus and Roche. ETM reports consulting fees from Pfizer. HQM reports research funding from Seqirus unrelated to the present work. The other authors have no conflicts to report., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Current influenza vaccine effectiveness (VE) improvement efforts focus on minimizing egg adaptation mutations during manufacture. This study compared immune response of two FDA-approved quadrivalent inactivated influenza vaccines in an unblinded randomized controlled trial., Methods: Participants were 144 community dwelling, healthy children/adolescents aged 4-20 years, randomized 1:1 in blocks of 4 to a vaccine grown in cell culture (ccIIV4 [Flucelvax®]; n = 85); or in egg medium (IIV4 [Fluzone ®]; n = 83). Blood was drawn at day 0 prevaccination and at day 28 (19-35 days) post vaccination. Hemagglutination inhibition (HI) assays against A/H1N1 and both B strains and microneutralization (MN) assays against egg-based and cell-based A/H3N2 strains were conducted. The primary outcome measure was seroconversion (day 28/day 0 titer ratio ≥ 4 with day 28 titer ≥ 40). Secondary outcomes were elevated titers (day 28 HI titer ≥ 1:110), geometric mean titers (GMTs) and mean fold rise (MFR) in titers. Outcomes were compared for 74 ccIIV4 recipients and 70 IIV4 recipients, and for those vaccinated and unvaccinated the previous year. Only the HI and MN laboratory analysis team was blinded to group assignment., Results: In this racially diverse (81% non-white) group of children with a median age of 14 years, baseline demographics did not differ between vaccine groups. At day 0, half or more in each vaccine group had elevated HI or MN titers. Low seroconversion rates (14%-35%) were found; they did not differ between groups. Among 2018-19 ccIIV4 recipients, those unvaccinated in the previous season showed significantly higher MFR against A/H1N1 and A/H3N2 cell-grown virus than the previously vaccinated. Similar results were found for MFR against B/Victoria among 2018-2019 IIV4 recipients., Conclusion: In mostly older children with high baseline titers, no differences in seroconversion or other measures of antibody titers were found between ccIIV4 and IIV4 recipients against egg- and cell-grown influenza vaccine viruses., Clinical Trials No: NCT03614975., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Drs. Zimmerman, Nowalk and Lin report grant funding from Sanofi Pasteur and Merck & Co., Inc. Dr. Zimmerman reports grant funding from Pfizer. Dr. Alcorn has grant funding from MedImmune, LLC for unrelated research. Dr. Moehling and Mr. Susick have had research funding from Sanofi Pasteur. Dr. Martin has research funding from Novus Therapeutics, MedImmune, GSK and Merck & CO, Inc. The other authors have no conflicts to report.]., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Introduction: Recommending both the conjugate and polysaccharide pneumococcal vaccines to all U.S. seniors may have little public health impact and be economically unreasonable. Public health impact and cost-effectiveness of using both vaccines in all adults aged ≥65 years were estimated compared with an alternative strategy (omitting pneumococcal conjugate vaccine in the nonimmunocompromised) and with the newly revised recommendation (giving or omitting conjugate vaccine based on patient-physician shared decision making)., Methods: Strategies were examined in hypothetical U.S. 65-year-old population cohorts and segmented into health states based on age- and population-specific data in a Markov state-transition model with a lifetime time horizon from a healthcare perspective. Black population cohorts were examined separately given greater illness risk and lower vaccine uptake. Model parameters came from the Centers for Disease Control Active Core Bacterial Surveillance network, National Health Interview Survey, and Nationwide Inpatient Sample data. Outcomes included incremental costs per quality-adjusted life year gained and pneumococcal disease outcomes for each strategy. Data were gathered and analysis performed in 2018., Results: Giving both vaccines, either routinely or with shared decision making, was most effective, reducing pneumococcal disease incidence compared with no vaccination, but costing $765,000-$2.18 million/quality-adjusted life year gained. Depending on examined population and scenario, the alternative strategy cost $65,700-$226,700/quality-adjusted life year gained (less in black populations) and reduced cases and deaths by 0.3%-0.9%., Conclusions: A vaccination strategy that omits pneumococcal conjugate vaccine in immunocompetent U.S. seniors may be economically reasonable, particularly for black seniors. Use of both pneumococcal vaccines was more effective but substantially more expensive., (Copyright © 2019 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

Introduction: Tradeoffs exist between efforts to increase influenza vaccine uptake, including early season vaccination, and potential decreased vaccine effectiveness if protection wanes during influenza season. U.S. older adults increasingly receive vaccination before October. Influenza illness peaks vary from December to April., Methods: A Markov model compared influenza likelihood in older adults with (1) status quo vaccination (August-May) to maximize vaccine uptake or (2) vaccination compressed to October-May (to decrease waning vaccine effectiveness impact). The Centers for Disease Control and Prevention data were used for influenza incidence and vaccination parameters. Prior analyses showed that absolute vaccine effectiveness decreased by 6%-11% per month, favoring later season vaccination. However, compressed vaccination could decrease overall vaccine uptake. Influenza incidence was based on average monthly incidence with earlier and later peaks also examined. Influenza strain distributions from two seasons were modeled in separate scenarios. Sensitivity analyses were performed to test result robustness. Data were collected and analyzed in 2018., Results: Compressed vaccination would avert ≥11,400 influenza cases in older adults during a typical season if it does not decrease vaccine uptake. However, if compressed vaccination decreases vaccine uptake or there is an early season influenza peak, more influenza can result. In probabilistic sensitivity analyses, compressed vaccination was never favored if it decreased absolute vaccine uptake by >5.5% in any scenario; when influenza peaked early, status quo vaccination was favored., Conclusions: Compressed vaccination could decrease waning vaccine effectiveness and decrease influenza cases in older adults. However, this positive effect is negated when early season influenza peaks occur and diminished by decreased vaccine uptake that could occur with shortening the vaccination season., (Copyright © 2018 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Changing pneumococcal disease epidemiology due to childhood vaccination has prompted re-examination of US adult pneumococcal vaccination policies, as have considerations of greater pneumococcal disease incidence and higher prevalence of conditions that increase risk in underserved minority populations. Prior analyses suggest routine pneumococcal vaccination at age 50 could be considered, which could disproportionately benefit underserved populations., Methods: A Markov cohort model estimated the cost-effectiveness of US pneumococcal vaccination policies in hypothetical 50-year-old underserved minority and general population cohorts. Strategies included receiving one or both available pneumococcal vaccines based on age- or chronic condition-specific criteria. US databases and medical literature data calibrated pneumococcal illness incidence, vaccine serotype distributions, age- and race-specific chronic condition distributions, and costs. Black population data were used as a proxy for underserved minorities. We took a US healthcare perspective, discounting at 3%/year. One-way and probabilistic sensitivity analyses were performed and scenarios modeling differing vaccine assumptions were examined., Results: In both black and general population 50-year-olds, giving both pneumococcal vaccines to all 50-year-olds prevented the most disease, but cost >$250,000 per quality adjusted life year (QALY) gained. Current CDC recommendations (both vaccines for the immunocompromised, polysaccharide vaccine for other high-risk conditions) were economically favorable in either population when analyses assumed polysaccharide vaccine was ineffective against nonbacteremic pneumococcal pneumonia (NBP). If polysaccharide vaccine is effective against NBP or if less complex age-based vaccination recommendations result in increased vaccine uptake, giving polysaccharide vaccine to all 50-year-olds cost <$100,000/QALY; this effect was more pronounced in black cohorts. Results were robust in 1-way and probabilistic sensitivity analyses., Conclusions: Despite changes in pneumococcal epidemiology, current CDC recommendations were favored in underserved minority and general population cohorts. Polysaccharide vaccine for all 50-year-olds could be considered under some vaccine uptake and effectiveness assumptions, particularly if mitigating racial health disparities in pneumococcal disease is a priority., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Annual influenza vaccination has been recommended for persons with high-risk conditions since the 1960s. However, few estimates of influenza vaccine effectiveness (VE) for persons with high-risk conditions are available., Methods: Data from the U.S. Influenza Vaccine Effectiveness Network from 2012 to 2016 were analyzed to compare VE of standard-dose inactivated vaccines against medically-attended influenza among patients aged ≥6 months with and without high-risk medical conditions. Patients with acute respiratory illness were tested for influenza by RT-PCR. Presence of high-risk conditions and vaccination status were obtained from medical records. VE by influenza virus type/subtype and age group was calculated for patients with and without high-risk conditions using the test-negative design. Interaction terms were used to test for differences in VE by high-risk conditions., Results: Overall, 9643 (38%) of 25,369 patients enrolled during four influenza seasons had high-risk conditions; 2213 (23%) tested positive for influenza infection. For all ages, VE against any influenza was lower among patients with high-risk conditions (41%, 95% CI: 35-47%) than those without (48%, 95% CI: 43-52%; P-for-interaction = 0.02). For children aged <18 years, VE against any influenza was 51% (95% CI: 39-61%) and 52% (95% CI: 39-61%) among those with and without high-risk conditions, respectively (P-for-interaction = 0.54). For adults aged ≥18 years, VE against any influenza was 38% (95% CI: 30-45%) and 44% (95% CI: 38-50%) among those with and without high-risk conditions, respectively (P-for-interaction = 0.21). For both children aged <18 and adults aged ≥18 years, VEs against illness related to influenza A(H3N2), A(H1N1)pdm09, and influenza B virus infection were similar among those with and without high-risk conditions., Conclusions: Influenza vaccination provided protection against medically-attended influenza among patients with high-risk conditions, at levels approaching those observed among patients without high-risk conditions. Results from our analysis support recommendations of annual vaccination for patients with high-risk conditions., (Published by Elsevier Ltd.)

Background: There have been inconsistent reports of decreased vaccine effectiveness (VE) against influenza viruses among older adults (aged ≥ 65 years) compared with younger adults in the United States. A direct comparison of VE over multiple seasons is needed to assess the consistency of these observations., Methods: We performed a pooled analysis of VE over 5 seasons among adults aged ≥ 18 years who were systematically enrolled in the U.S. Flu VE Network. Outpatients with medically-attended acute respiratory illness (cough with illness onset ≤ 7 days prior to enrollment) were tested for influenza by reverse transcription polymerase chain reaction. We compared differences in VE and vaccine failures among older adult age group (65-74, ≥75, and ≥ 65 years) to adults aged 18-49 years by influenza type and subtype using interaction terms to test for statistical significance and stratified by prior season vaccination status., Results: Analysis included 20,022 adults aged ≥ 18 years enrolled during the 2011-12 through 2015-16 influenza seasons; 4,785 (24%) tested positive for influenza. VE among patients aged ≥ 65 years was not significantly lower than VE among patients aged 18-49 years against any subtype with no significant interaction of age and vaccination. VE against A(H3N2) viruses was 14% (95% confidence interval [CI] -14% to 36%) for adults ≥ 65 years and 21% (CI 9-32%) for adults 18-49 years. VE against A(H1N1)pdm09 was 49% (95% CI 22-66%) for adults ≥ 65 years and 48% (95% CI 41-54%) for adults 18-49 years and against B viruses was 62% (95% CI 44-74%) for adults ≥ 65 years and 55% (95% CI 45-63%) for adults 18-49 years. There was no significant interaction of age and vaccination for separate strata of prior vaccination status., Conclusions: Over 5 seasons, influenza vaccination provided similar levels of protection among older and younger adults, with lower levels of protection against influenza A(H3N2) in all ages., (Published by Elsevier Ltd.)

Background: Annual influenza vaccination is a key to preventing widespread influenza infections. Recent reports of influenza vaccine effectiveness (VE) indicate that vaccination in prior years may reduce VE in the current season, suggesting vaccine interference. The purpose of this study is to evaluate the potential effect of repeat influenza vaccinations in the presence of vaccine interference., Methods: Using literature-based parameters, an age-structured influenza equation-based transmission model was used to determine the optimal vaccination strategy, while considering the effect of varying levels of interference., Results: The model shows that, even in the presence of vaccine interference, revaccination reduces the influenza attack rate and provides individual benefits. Specifically, annual vaccination is a favored strategy over vaccination in alternate years, as long as the level of residual protection is less than 58% or vaccine interference effect is minimal. Furthermore, the negative impact of vaccine interference may be offset by increased vaccine coverage levels., Conclusions: Even in the presence of potential vaccine interference, our work provides a population-level perspective on the potential merits of repeated influenza vaccination. This is because repeat vaccination groups had lower attack rates than groups that omitted the second vaccination unless vaccine interference was at very high, perhaps implausible, levels., (Copyright © 2017. Published by Elsevier Ltd.)

Background: In recent influenza seasons, the live attenuated influenza vaccine (LAIV) has not demonstrated the same level of vaccine effectiveness as that observed among children who received the inactivated influenza vaccine (IIV). To better understand this difference, this study compared the mRNA sequencing transcription profile (RNA seq) in children who received either IIV or LAIV., Methods: Children 3-17years of age receiving quadrivalent influenza vaccine were enrolled. Blood samples were collected on Day 0 prior to vaccination and again on Day 7 (range 6-10days) following vaccination. Total RNA was isolated from PAXgene tubes and sequenced for a custom panel of 89 transcripts using the TruSeq Targeted RNA Expression method. Fold differences in normalized RNA seq counts from Day 0 to Day 7 were calculated, log 2 transformed and compared between the two vaccine groups., Results: Of 72 children, 46 received IIV and 26 received LAIV. Following IIV vaccination, 7 genes demonstrated significant differential expression at Day 7 (down-regulated). In contrast, following LAIV vaccination, 8 genes demonstrated significant differential expression at Day 7 (5 up-regulated and 3 down-regulated). Only two genes demonstrated similar patterns of regulation in both groups., Conclusions: Differential regulation of genes was observed between 2015-16 LAIV and IIV recipients. These results help to elucidate the immune response to influenza vaccines and may be related to the difference in vaccine effectiveness observed in recent years between LAIV and IIV., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objectives: To report the results of an intervention using the 4 Pillars™ Practice Transformation Program (4 Pillars™ Program) to increase adolescent vaccinations including human papillomavirus vaccine (HPV) and influenza vaccines, which remain underutilized in this population., Study Design: Eleven pediatric and family medicine practices, previously control sites from a randomized controlled cluster trial, with ≥50 adolescent patients participated. The 4 Pillars™ Program was the foundation of the intervention. De-identified demographic, office visit and vaccination data were derived from electronic medical record extractions for patients whose date of birth was 4/1/1997 to 4/1/2004 (ages 11-17years at baseline). Vaccination rates for HPV, influenza, tetanus-pertussis-diphtheria (Tdap) and meningococcal (MenACWY) vaccines were determined for all eligible patients pre- and post intervention (i.e., vaccination rates on 4/1/2015 and 4/30/2016)., Results: Among 9473 patients ages 11-17years at baseline (4/1/2015), mean pre-intervention vaccination rates for HPV initiation and completion, meningococcal, Tdap and influenza vaccines were below national levels. Rates increased significantly post intervention (P<0.001) for HPV initiation which increased 17.1 percentage points (PP) from 51.4%; HPV completion increased 14.8PP from 30.7%, meningococcal vaccine uptake increased 16.6PP from 79.1%, Tdap vaccine uptake increased 14.6PP from 76.9%. Influenza vaccine uptake did not increase significantly (2.3PP from 40.1%). In the regression using generalized estimating equations, odds of vaccination were higher for younger, non-white adolescents for all vaccines; being in a smaller practice decreased the odds of Tdap vaccination but increased the odds of influenza vaccination., Conclusion: Clinically and statistically significant improvements in HPV series initiation and completion, and meningococcal and Tdap vaccinations were observed in primary care practices implementing the 4 Pillars™ Practice Transformation Program. Clinical Trial Registry Number: NCT02165722., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Purpose: High-dose trivalent inactivated influenza vaccine (HD-IIV3) or recombinant trivalent influenza vaccine (RIV) may increase influenza vaccine effectiveness (VE) in adults with conditions that place them at high risk for influenza complications. This analysis models the public health impact and cost-effectiveness (CE) of these vaccines for 50-64year-olds., Methods: Markov model CE analysis compared 5 strategies in 50-64year-olds: no vaccination; only standard-dose IIV3 offered (SD-IIV3 only), only quadrivalent influenza vaccine offered (SD-IIV4 only); high-risk patients receiving HD-IIV3, others receiving SD-IIV3 (HD-IIV3 & SD-IIV3); and high-risk patients receiving HD-IIV3, others receiving SD-IIV4 (HD-IIV3 & SD-IIV4). In a secondary analysis, RIV replaced HD-IIV3. Parameters were obtained from U.S. databases, the medical literature and extrapolations from VE estimates. Effectiveness was measured as 3%/year discounted quality adjusted life year (QALY) losses avoided., Results: The least expensive strategy was SD-IIV3 only, with total costs of $99.84/person. The SD-IIV4 only strategy cost an additional $0.91/person, or $37,700/QALY gained. The HD-IIV3 & SD-IIV4 strategy cost $1.06 more than SD-IIV4 only, or $71,500/QALY gained. No vaccination and HD-IIV3 & SD-IIV3 strategies were dominated. Results were sensitive to influenza incidence, vaccine cost, standard-dose VE in the entire population and high-dose VE in high-risk patients. The CE of RIV for high-risk patients was dependent on as yet unknown parameter values., Conclusions: Based on available data, using high-dose influenza vaccine or RIV in middle-aged, high-risk patients may be an economically favorable vaccination strategy with public health benefits. Clinical trials of these vaccines in this population may be warranted., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Introduction: Decreased live attenuated influenza vaccine (LAIV) effectiveness in the U.S. prompted the Advisory Committee on Immunization Practices in August 2016 to recommend against this vaccine's use. However, overall influenza uptake increases when LAIV is available and, unlike the U.S., LAIV has retained its effectiveness in other countries. These opposing countercurrents create a dilemma., Methods: To examine the potential consequences of the decision to not recommend LAIV, which may result in decreased influenza vaccination coverage in the U.S. population, a Markov decision analysis model was used to examine influenza vaccination options in U.S. children aged 2-8 years. Data were compiled and analyzed in 2016., Results: Using recently observed low LAIV effectiveness values, fewer influenza cases will occur if LAIV is not used compared with having LAIV as a vaccine option. However, having the option to use LAIV may be favored if LAIV effectiveness returns to prior levels or if the absence of vaccine choice substantially decreases overall vaccine uptake., Conclusions: Continued surveillance of LAIV effectiveness and influenza vaccine uptake is warranted, given their importance in influenza vaccination policy decisions., (Copyright © 2017 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: In a prior agent-based modeling study, offering a choice of influenza vaccine type was shown to be cost-effective when the simulated population represented the large, Washington DC metropolitan area. This study calculated the public health impact and cost-effectiveness of the same four strategies: No Choice, Pediatric Choice, Adult Choice, or Choice for Both Age Groups in five United States (U.S.) counties selected to represent extremes in population age distribution., Methods: The choice offered was either inactivated influenza vaccine delivered intramuscularly with a needle (IIV-IM) or an age-appropriate needle-sparing vaccine, specifically, the nasal spray (LAIV) or intradermal (IIV-ID) delivery system. Using agent-based modeling, individuals were simulated as they interacted with others, and influenza was tracked as it spread through each population. Influenza vaccination coverage derived from Centers for Disease Control and Prevention (CDC) data, was increased by 6.5% (range 3.25%-11.25%) to reflect the effects of vaccine choice., Results: Assuming moderate influenza infectivity, the number of averted cases was highest for the Choice for Both Age Groups in all five counties despite differing demographic profiles. In a cost-effectiveness analysis, Choice for Both Age Groups was the dominant strategy. Sensitivity analyses varying influenza infectivity, costs, and degrees of vaccine coverage increase due to choice, supported the base case findings., Conclusion: Offering a choice to receive a needle-sparing influenza vaccine has the potential to significantly reduce influenza disease burden and to be cost saving. Consistent findings across diverse populations confirmed these findings., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objective: Uptake of meningococcal vaccine (MCV) and tetanus, diphtheria and pertussis (Tdap) vaccine among adolescents has approached Healthy People 2020 goals, but human papillomavirus (HPV) vaccination has not. This study evaluated an intervention using the 4 Pillars™ Practice Transformation Program to increase HPV, MCV and Tdap uptake among adolescents in primary care practices., Methods: Practices with at least 50 patients 11-17years old with estimated vaccination rates less than national goals, were assigned to intervention (n=11) and control (n=11) groups in a randomized controlled cluster trial; 9 intervention and 11 control sites completed the study. The baseline and active study periods were 7/1/2013-6/30/2014 and 7/1/2014-3/31/2015, respectively. Vaccination and demographic data for patients who had a visit in both study periods were derived from de-identified EMR extractions. Primary outcomes were vaccination rates and percentage point (PP) changes. Data were analyzed in 2015-16., Results: Among the cohort of 10,861 adolescent patients, 38% were 11-13years old; 50% were female; 18% were non-white; and 64% were commercially insured. Average baseline HPV initiation rates were 52.5% for intervention and 61.8% for control groups. After 9months, the intervention sites increased HPV initiation 10.2PP compared with 7.3PP in control sites (P<0.001); HPV series completion rates did not differ between groups. Implementation of >10 strategies to improve rates significantly increased the likelihood of HPV series initiation (OR=2.06, 95% CI=1.43, 2.96)., Conclusions: Using >10 strategies from the 4 Pillars™ Practice Transformation Program is effective for increasing HPV series initiation among adolescents. Clinical trial registry number: NCT02165722., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Introduction: National adult Tdap vaccination rates are low, reinforcing the need to increase vaccination efforts in primary care offices. The 4 Pillars™ Practice Transformation Program is an evidence-based, step-by-step guide to improving primary care adult vaccination with an online implementation tracking dashboard. This study tested the effectiveness of an intervention to increase adult Tdap vaccination that included the 4 Pillars™ Program, provider education, and one-on-one coaching of practice-based immunization champions., Methods: 25 primary care practices participated in a randomized controlled cluster trial (RCCT) in Year 1 (6/1/2013-5/31/2014) and a pre-post study in Year 2 (6/1/2014-1/31/2015). Baseline year was 6/1/2012-5/31/2013, with data analyzed in 2016. Demographic and vaccination data were derived from de-identified electronic medical record (EMR) extractions. The primary outcomes were vaccination rates and percentage point (PP) changes/year., Results: The cohort consisted of 70,549 patients ⩾18years who were seen in the practices ⩾1 time each year, with a baseline mean age=55years; 35% were men; 56% were non-white; 35% were Hispanic and 20% were on Medicare. Baseline vaccination rate averaged 35%. In the Year 1 RCCT, cumulative Tdap vaccination increased significantly in both intervention and control groups; in both cities, the percentage point increases in the intervention groups (7.7 PP in Pittsburgh and 9.9 PP in Houston) were significantly higher (P<0.001) than in the control groups (6.4 PP in Pittsburgh and 7.6 PP in Houston). In the Year 2 pre-post study, in both cities, active intervention groups increased rates significantly more (6.2 PP for both) than maintenance groups (2.2 PP in Pittsburgh and 4.1 PP in Houston; P<0.001)., Conclusions: An intervention that includes the 4 Pillars™ Practice Transformation Program, staff education and coaching is effective for increasing adult Tdap immunization rates within primary care practices. Clinical Trial Registry Name/Number: NCT01868334., Competing Interests: Drs. Zimmerman and Lin have a research grant from Sanofi Pasteur, Inc. Drs. Zimmerman, Nowalk and Lin have research grants from Merck & Co, Inc., and Pfizer, Inc. Dr. Middleton is a lecturer for Sanofi Pasteur and Merck & Co. and a physician advisor for Sanofi Pasteur, Pfizer, Inc. and Merck & Co. The other authors have no conflicts of interest to disclose., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Introduction: Prior studies showed that live attenuated influenza vaccine (LAIV) is more effective than inactivated influenza vaccine (IIV) in children aged 2-8 years, supporting the Centers for Disease Control and Prevention (CDC) recommendations in 2014 for preferential LAIV use in this age group. However, 2014-2015 U.S. effectiveness data indicated relatively poor effectiveness of both vaccines, leading CDC in 2015 to no longer prefer LAIV., Methods: An age-structured model of influenza transmission and vaccination was developed, which incorporated both direct and indirect protection induced by vaccination. Based on this model, the cost effectiveness of influenza vaccination strategies in children aged 2-8 years in the U.S. was estimated. The base case assumed a mixed vaccination strategy where 33.3% and 66.7% of vaccinated children aged 2-8 years receive LAIV and IIV, respectively. Analyses were performed in 2014-2015., Results: Using published meta-analysis vaccine effectiveness data (83% LAIV and 64% IIV), exclusive LAIV use would be a cost-effective strategy when vaccinating children aged 2-8 years, whereas IIV would not be preferred. However, when 2014-2015 U.S. effectiveness data (0% LAIV and 15% IIV) were used, IIV was likely to be preferred., Conclusions: The cost effectiveness of influenza vaccination in children aged 2-8 years is highly dependent on vaccine effectiveness; the vaccine type with higher effectiveness is preferred. In general, exclusive IIV use is preferred over LAIV use, as long as vaccine effectiveness is higher for IIV than for LAIV., (Copyright © 2016 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

Introduction: Prior evidence found live attenuated influenza vaccine (LAIV) more effective than inactivated influenza vaccine (IIV) in children aged 2-8 years, leading CDC in 2014 to prefer LAIV use in this group. However, since 2013, LAIV has not proven superior, leading CDC in 2015 to rescind their LAIV preference statement. Here, the cost effectiveness of preferred LAIV use compared with IIV in children aged 2-8 years is estimated., Methods: A Markov model estimated vaccination strategy cost effectiveness in terms of cost per quality-adjusted life-year gained. Base case assumptions were equal vaccine uptake; IIV use when LAIV was not indicated (in 11.7% of the cohort); and no indirect vaccination effects. Sensitivity analyses included estimates of indirect effects from both equation- and agent-based models. Analyses were performed in 2014-2015., Results: Using prior effectiveness data in children aged 2-8 years (LAIV=83%, IIV=64%), preferred LAIV use was less costly and more effective than IIV (dominant), with results sensitive only to LAIV and IIV effectiveness variation. Using 2014-2015 U.S. effectiveness data (LAIV=0%, IIV=15%), IIV was dominant. In two-way sensitivity analyses, LAIV use was cost saving over the entire range of IIV effectiveness (0%-81%) when absolute LAIV effectiveness was >7.1% higher than IIV, but never cost saving when absolute LAIV effectiveness was <3.5% higher than IIV., Conclusions: Results support CDC's decision to no longer prefer LAIV use and provide guidance on effectiveness differences between influenza vaccines that might lead to preferential LAIV recommendation for children aged 2-8 years., (Copyright © 2016 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: We estimated the burden of outpatient influenza and cases prevented by vaccination during the 2011/2012 and 2012/2013 influenza seasons using data from the United States Influenza Vaccine Effectiveness (US Flu VE) Network., Methods: We defined source populations of persons who could seek care for acute respiratory illness (ARI) at each of the five US Flu VE Network sites. We identified all members of the source population who were tested for influenza during US Flu VE influenza surveillance. Each influenza-positive subject received a sampling weight based on the proportion of source population members who were tested for influenza, stratified by site, age, and other factors. We used the sampling weights to estimate the cumulative incidence of medically attended influenza in the source populations. We estimated cases averted by vaccination using estimates of cumulative incidence, vaccine coverage, and vaccine effectiveness., Results: Cumulative incidence of medically attended influenza ranged from 0.8% to 2.8% across sites during 2011/2012 and from 2.6% to 6.5% during the 2012/2013 season. Stratified by age, incidence ranged from 1.2% among adults 50 years of age and older in 2011/2012 to 10.9% among children 6 months to 8 years of age in 2012/2013. Cases averted by vaccination ranged from 4 to 41 per 1000 vaccinees, depending on the study site and year., Conclusions: The incidence of medically attended influenza varies greatly by year and even by geographic region within the same year. The number of cases averted by vaccination varies greatly based on overall incidence and on vaccine coverage., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Since the 2008 inception of universal childhood influenza vaccination, national rates have risen more dramatically among younger children than older children and reported rates across racial/ethnic groups are inconsistent. Interventions may be needed to address age and racial disparities to achieve the recommended childhood influenza vaccination target of 70%., Purpose: To evaluate an intervention to increase childhood influenza vaccination across age and racial groups., Methods: In 2011-2012, a total of 20 primary care practices treating children were randomly assigned to the intervention and control arms of a cluster randomized controlled trial to increase childhood influenza vaccination uptake using a toolkit and other strategies including early delivery of donated vaccine, in-service staff meetings, and publicity., Results: The average vaccination differences from pre-intervention to the intervention year were significantly larger in the intervention arm (n=10 practices) than the control arm (n=10 practices); for children aged 9-18 years (11.1 pct pts intervention vs 4.3 pct pts control, p<0.05); for non-white children (16.7 pct pts intervention vs 4.6 pct pts control, p<0.001); and overall (9.9 pct pts intervention vs 4.2 pct pts control, p<0.01). In multi-level modeling that accounted for person- and practice-level variables and the interactions among age, race, and intervention, the likelihood of vaccination increased with younger age group (6-23 months); white race; commercial insurance; the practice's pre-intervention vaccination rate; and being in the intervention arm. Estimates of the interaction terms indicated that the intervention increased the likelihood of vaccination for non-white children in all age groups and white children aged 9-18 years., Conclusions: A multi-strategy intervention that includes a practice improvement toolkit can significantly improve influenza vaccination uptake across age and racial groups without targeting specific groups, especially in practices with large percentages of minority children., (Copyright © 2014 American Journal of Preventive Medicine. All rights reserved.)

Purpose: To increase childhood influenza vaccination rates using a toolkit and early vaccine delivery in a randomized cluster trial., Methods: Twenty primary care practices treating children (range for n=536-8183) were randomly assigned to Intervention and Control arms to test the effectiveness of an evidence-based practice improvement toolkit (4 Pillars Toolkit) and early vaccine supplies for use among disadvantaged children on influenza vaccination rates among children 6 months-18 years. Follow-up staff meetings and surveys were used to assess use and acceptability of the intervention strategies in the Intervention arm. Rates for the 2010-2011 and 2011-2012 influenza seasons were compared. Two-level generalized linear mixed modeling was used to evaluate outcomes., Results: Overall increases in influenza vaccination rates were significantly greater in the Intervention arm (7.9 percentage points) compared with the Control arm (4.4 percentage points; P<0.034). These rate changes represent 4522 additional doses in the Intervention arm vs. 1390 additional doses in the Control arm. This effect of the intervention was observed despite the fact that rates increased significantly in both arms - 8/10 Intervention (all P<0.001) and 7/10 Control sites (P-values=0.04 to <0.001). Rates in two Intervention sites with pre-intervention vaccination rates >58% did not significantly increase. In regression analyses, a child's likelihood of being vaccinated was significantly higher with: younger age, white race (Odds ratio [OR]=1.29; 95% confidence interval [CI]=1.23-1.34), having commercial insurance (OR=1.30; 95%CI=1.25-1.35), higher pre-intervention practice vaccination rate (OR=1.25; 95%CI=1.16-1.34), and being in the Intervention arm (OR=1.23; 95%CI=1.01-1.50). Early delivery of influenza vaccine was rated by Intervention practices as an effective strategy for raising rates., Conclusions: Implementation of a multi-strategy toolkit and early vaccine supplies can significantly improve influenza vaccination rates among children in primary care practices but the effect may be less pronounced in practices with moderate to high existing vaccination rates. Clinical trial registry name/number: From Innovation to Solutions: Childhood Influenza/NCT01664793., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: Quadrivalent human papillomavirus (HPV) vaccine, for protection against sexually transmitted HPV infection, is licensed for females and males 9-26 years on a 3-dose schedule (0, 2, and 6 months; Standard schedule). Vaccine uptake has been low and catch-up vaccination of older adolescents using an alternate dosing schedule may increase coverage. This study tested the non-inferiority of the immunogenicity of an alternate dosing schedule (0, 2, 12 months) among college age males., Methods: 220 18-25 year old males were randomly assigned to Standard or Alternate schedules. Blood samples were drawn immediately before Dose 1 and 2-6 weeks after Dose 3 and analyzed for antibody titers using a Luminex immunoassay. A value <1.5 for the upper 95% confidence interval (CI) bound of the Standard to Alternate schedule geometric mean titer (GMT) ratio was deemed non-inferior., Results: Participants averaged 21.3 years old; 19.1% were non-white; completion rate was 93%. The anti-HPV titers for the Alternate schedule group were non-inferior to those of Standard schedule group for all four HPV vaccine virus types. Our results also demonstrated superiority of the Alternate schedule group for all four HPV vaccine virus types., Conclusion: A delayed third dose at 12 months is immunologically non-inferior and superior for four HPV virus types. Using an alternate dosing schedule offers more flexibility to receive the 3-dose HPV vaccine and may result in higher vaccination rates among college-age males., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Health care worker (HCW) influenza vaccination rates are modest. This paper provides a detailed ethical analysis of the major options to increase HCW vaccination rates, comparing how major ethical theories would address the options. The main categories of interventions to raise rates include education, incentives, easy access, competition with rewards, assessment and feedback, declination, mandates with alternative infection control measures, and mandates with administrative action as consequences. The aforementioned interventions, except mandates, arouse little ethical controversy. However, these efforts are time and work intensive and rarely achieve vaccination rates higher than about 70%. The primary concerns voiced about mandates are loss of autonomy, injustice, lack of due process, and subsuming the individual for institutional ends. Proponents of mandates argue that they are ethical based on beneficence, non-maleficence, and duty. A number of professional associations support mandates. Arguments by analogy can be made by mandates for HCW vaccination against other diseases. The ethical systems used in the analyses include evolutionary ethics, utilitarianism, principalism (autonomy, beneficence, non-maleficence, and justice), Kantism, and altruism. Across these systems, the most commonly preferred options are easy access, assessment and feedback, declinations, and mandates with infection control measures as consequences for non-compliance. Given the ethical imperatives of non-maleficence and beneficence, the limited success of lower intensive interventions, and the need for putting patient safety ahead of HCW convenience, mandates with additional infection control measures as consequences for non-compliance are preferred. For those who opt out of vaccination due to conscience concerns, such mandates provide a means to remain employed but not put patient safety at risk., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Objective: Pneumococcal disease is a significant problem in immunocompromised persons, particularly in HIV-infected individuals. The CDC recently updated pneumococcal vaccination recommendations for immunocompromised adults, adding the 13-valent pneumococcal conjugate vaccine (PCV13) to the previously recommended 23-valent pneumococcal polysaccharide vaccine (PPSV23). This analysis estimates the cost-effectiveness of pneumococcal vaccination strategies in HIV-infected individuals and in the broader immunocompromised adult group., Design: Markov model-based cost-effectiveness analysis., Methods: The model considered immunocompromised persons aged 19-64 years and accounted for childhood PCV13 herd immunity; in a separate analysis, an HIV-infected subgroup was considered. PCV13 effectiveness was estimated by an expert panel; PPSV23 protection was modeled relative to PCV13 effectiveness. We assumed that both vaccines prevented invasive pneumococcal disease, but only PCV13 prevented nonbacteremic pneumonia., Results: In all immunocompromised individuals, a single PCV13 cost $70,937 per quality adjusted life year (QALY) gained compared to no vaccination; current recommendations cost $136,724/QALY. In HIV patients, with a longer life expectancy (22.5 years), current recommendations cost $89,391/QALY compared to a single PCV13. Results were sensitive to variation of life expectancy and vaccine effectiveness. The prior recommendation was not favored in any scenario., Conclusions: One dose of PCV13 is more cost-effective for immunocompromised individuals than previous vaccination recommendations and may be more economically reasonable than current recommendations, depending on life expectancy and vaccine effectiveness in the immunocompromised., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: The 13-valent pneumococcal conjugate vaccine (PCV13) is approved by the U.S. Food and Drug Administration for adults, but its role in older adults is unclear., Purpose: To compare PCV13 strategies to currently recommended vaccination strategies in adults aged ≥65 years., Methods: Using a Markov model, the cost effectiveness of PCV13 and the 23-valent pneumococcal polysaccharide vaccine (PPSV23), alone or in combination, was estimated, in adults aged either 65 years or 75 years. No prior vaccination, prior vaccination, and vaccine hyporesponsiveness scenarios were examined. Pneumococcal disease rates, indirect childhood PCV13 effects, and costs were estimated using CDC Active Bacterial Core surveillance data and U.S. national databases. An expert panel estimated vaccine-related protection. A societal perspective was taken and outcomes were discounted 3% per year., Results: In those aged 65 years, single-dose PCV13 cost $11,300 per quality-adjusted life-year (QALY) gained compared to no vaccination; at ages 65 and 80 years, PCV13 cost $83,000/QALY. In those aged 75 years, single-dose PCV13 cost $62,800/QALY gained. PPSV23 cost more and was less effective than PCV13. Results were sensitive to varying vaccine effectiveness and indirect effect estimates. In hyporesponsiveness scenarios, cost-effectiveness ratios increased by 37%-78% for single-dose strategies and 29%-35% for multiple-dose strategies., Conclusions: Single-dose PCV13 strategies are likely to be economically reasonable in older adults., (Copyright © 2013 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Immunization of adults with influenza vaccine and pneumococcal polysaccharide vaccine remains lower than recommended levels. Standing order programs (SOPs) in which non-physician medical personnel are permitted to assess an adult patient's immunization status and administer vaccines without an individual physician order are a proven method of increasing adult vaccinations, yet they are used by less than one half of primary care physicians caring for adults., Methods: Following a national survey of primary care physicians about barriers to SOPs for adult immunizations, a SOP toolkit was developed. After review by a panel of experts, the toolkit was pilot tested in three primary care practices in a health care network with the same electronic medical record (EMR) system and low adult vaccination rates. Practice staffs were trained in the use of SOPs and the toolkit at a group meeting. This study was designed to pilot-test and evaluate the toolkit with the express intention of improving it. Three methods were used to evaluate the toolkit: (1) direct observation and interviews of each practice's staff; (2) surveys of each practice's staff; and (3) influenza and pneumococcal polysaccharide vaccine (PPV) vaccination rates., Results: The staffs at all sites were equally likely to find the presentations and toolkit useful and did not differ in their knowledge of using SOPs for vaccination. They expressed a common set of barriers to implementing SOPs despite using the toolkit, and provided ideas for improving implementation. One site viewed SOPs in general in a more negative light and expressed that SOPs unfairly increased their workload. Vaccination rates in this site did not differ from those of the control site., Conclusion: The evaluation suggested that the SOP toolkit should be expanded to include additional strategies to improve its applicability and effectiveness., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Staphylococcus aureus infections are a substantial problem for hemodialysis patients. Several vaccine candidates are currently under development, with hemodialysis patients being one possible target population. To determine the potential economic value of an S. aureus vaccine among hemodialysis patients, we developed a Markov decision analytic computer simulation model. When S. aureus colonization prevalence was 1%, the incremental cost-effectiveness ratio (ICER) of vaccination was ≤$25,217/quality-adjusted life year (QALY). Vaccination became more cost-effective as colonization prevalence, vaccine efficacy, or vaccine protection duration increased or vaccine cost decreased. Even at 10% colonization prevalence, a 25% efficacious vaccine costing $100 prevented 29 infections, 21 infection-related hospitalizations, and 9 inpatient deaths per 1000 vaccinated HD patients. Our results suggest that an S. aureus vaccine would be cost-effective (i.e., ICERs ≤ $50,000/QALY) among hemodialysis patients over a wide range of S. aureus prevalence, vaccine costs and efficacies, and vaccine protection durations and delineate potential target parameters for such a vaccine., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: The CDC recommends annual influenza vaccination for all children age 6 months and older, yet vaccination rates remain modest. Effective strategies to improve influenza vaccination for children are needed., Methods: Eight focus groups with 91 parents, teens, pediatric healthcare staff and providers, and immunization and marketing experts were conducted, audiotaped, transcribed verbatim, and coded based on grounded theory., Results: Three themes emerged: barriers, facilitators, and strategies. Barriers included fear, misinformation, and mistrust, with exacerbation of these barriers attributed to media messages. Many considered influenza vaccination unnecessary and inconvenient, but would accept vaccination if recipients or other family members were considered high risk, if recommended by their doctor or another trusted person, or if offered or mandated by the school. Access to better information regarding influenza disease burden and vaccine safety and efficacy were notable facilitators, as were prevention of the inconvenience of missing work or important events, and if the child requests to receive the vaccine. Marketing strategies included incentives, jingles, videos, wearable items, strategically-located information sheets or posters, and promotion by informed counselors. Practice-based strategies included staff buy-in, standing orders protocols, vaccination clinics, and educational videos. Teen-specific strategies included message delivery through schools, texting, internet, and social networking sites., Conclusion: To improve influenza vaccination rates for children using practice-based interventions, participants suggested campaigns that provide better information regarding the vaccine, the disease and its implications, and convenient access to vaccination. Strategies targeting adolescents should use web-based social marketing technologies and campaigns based in schools., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Objective: Concern over the rise of vaccine preventable diseases (VPD) coupled with the increasing popularity of homeschooling makes understanding the attitudes and behaviors of homeschoolers regarding immunizations a critical area of investigation. This study was a pilot to investigate the immunization attitudes of homeschooling parents and the vaccination status of their children., Methods: In the spring of 2010, online surveys were sent to a convenience sample of 707 homeschooling parents in Western Pennsylvania with children ages 0-18 years of age. Information was collected on demographic characteristics, vaccination status of children, and attitudes toward vaccination., Results: Surveys were returned by 18 percent of respondents, representing 396 homeschooled children. Demographic characteristics mirrored national homeschooling trends. The majority (95%) surveyed felt that education about vaccines was important. Thirty-eight percent of families had fully vaccinated children while 56% reported partial vaccination and 6% said children had received no vaccines. Respondents who fully vaccinated their children were more likely to agree that vaccinating according to the American Academy of Pediatrics was a good idea (OR: 4.8 [95% CI: 2.0-11.7]) and were more likely to comply with the recommendations of their health care provider (OR: 8.3 [95% CI: 3.6-19.1]). Respondents who vaccinated their children were more likely to believe that vaccines are safe (OR: 7.6 [95% CI: 1.0-56.2]). Beliefs about autism, thimerosal and learning disabilities did not vary significantly with vaccination status in regression analysis., Conclusions: While specific factors influencing vaccination practices were not identified, this study demonstrated that recommendations of physicians and the AAP do not significantly influence homeschooling vaccination practices in the pilot population. Given the results of this pilot study, more research is called for, particularly a larger study with public school controls., (Copyright © 2011 Elsevier Ltd. All rights reserved.)