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.
Abstract
Background
Multivalent influenza vaccine products provide protection against influenza A(H1N1)pdm09, A(H3N2), and B lineage viruses. The 2018–2019 influenza season in the United States ...included prolonged circulation of A(H1N1)pdm09 viruses well-matched to the vaccine strain and A(H3N2) viruses, the majority of which were mismatched to the vaccine. We estimated the number of vaccine-prevented influenza-associated illnesses, medical visits, hospitalizations, and deaths for the season.
Methods
We used a mathematical model and Monte Carlo algorithm to estimate numbers and 95% uncertainty intervals (UIs) of influenza-associated outcomes prevented by vaccination in the United States. The model incorporated age-specific estimates of national 2018–2019 influenza vaccine coverage, influenza virus–specific vaccine effectiveness from the US Influenza Vaccine Effectiveness Network, and disease burden estimated from population-based rates of influenza-associated hospitalizations through the Influenza Hospitalization Surveillance Network.
Results
Influenza vaccination prevented an estimated 4.4 million (95%UI, 3.4 million–7.1 million) illnesses, 2.3 million (95%UI, 1.8 million–3.8 million) medical visits, 58 000 (95%UI, 30 000–156 000) hospitalizations, and 3500 (95%UI, 1000–13 000) deaths due to influenza viruses during the US 2018–2019 influenza season. Vaccination prevented 14% of projected hospitalizations associated with A(H1N1)pdm09 overall and 43% among children aged 6 months–4 years.
Conclusions
Influenza vaccination averted substantial influenza-associated disease including hospitalizations and deaths in the United States, primarily due to effectiveness against A(H1N1)pdm09. Our findings underscore the value of influenza vaccination, highlighting that vaccines measurably decrease illness and associated healthcare utilization even in a season in which a vaccine component does not match to a circulating virus.
We estimated that influenza vaccination prevented an estimated 4.4 million illnesses, 2.3 million medical visits, 58 000 hospitalizations, and 3500 deaths in the 2018–2019 influenza season.
At the start of the 2019-2020 influenza season, concern arose that circulating B/Victoria viruses of the globally emerging clade V1A.3 were antigenically drifted from the strain included in the ...vaccine. Intense B/Victoria activity was followed by circulation of genetically diverse A(H1N1)pdm09 viruses that were also antigenically drifted. We measured vaccine effectiveness (VE) in the United States against illness from these emerging viruses.
We enrolled outpatients aged ≥6 months with acute respiratory illness at 5 sites. Respiratory specimens were tested for influenza by reverse-transcriptase polymerase chain reaction (RT-PCR). Using the test-negative design, we determined influenza VE by virus subtype/lineage and genetic subclades by comparing odds of vaccination in influenza cases versus test-negative controls.
Among 8845 enrollees, 2722 (31%) tested positive for influenza, including 1209 (44%) for B/Victoria and 1405 (51%) for A(H1N1)pdm09. Effectiveness against any influenza illness was 39% (95% confidence interval CI: 32-44), 45% (95% CI: 37-52) against B/Victoria and 30% (95% CI: 21-39) against A(H1N1)pdm09-associated illness. Vaccination offered no protection against A(H1N1)pdm09 viruses with antigenically drifted clade 6B.1A 183P-5A+156K HA genes (VE 7%; 95% CI: -14 to 23%) which predominated after January.
Vaccination provided protection against influenza illness, mainly due to infections from B/Victoria viruses. Vaccine protection against illness from A(H1N1)pdm09 was lower than historically observed effectiveness of 40%-60%, due to late-season vaccine mismatch following emergence of antigenically drifted viruses. The effect of drift on vaccine protection is not easy to predict and, even in drifted years, significant protection can be observed.
Newer influenza vaccine formulations have entered the market, but real-world effectiveness studies are not widely conducted until there is sufficient uptake. We conducted a retrospective ...test-negative case-control study to determine relative vaccine effectiveness (rVE) of recombinant influenza vaccine or RIV4, compared with standard dose vaccines (SD) in a health system with significant RIV4 uptake. Using the electronic medical record (EMR) and the Pennsylvania state immunization registry to confirm influenza vaccination, VE against outpatient medically attended visits was calculated. Immunocompetent outpatients ages 18-64 years seen in hospital-based clinics or emergency departments who were tested for influenza using reverse transcription polymerase chain reaction (RT-PCR) assays during the 2018-2019 and 2019-2020 influenza seasons were included. Propensity scores with inverse probability weighting were used to adjust for potential confounders and determine rVE. Among this mostly white and female cohort of 5,515 individuals, 510 were vaccinated with RIV4 and 557 were vaccinated with SD, with the balance of 4,448 (81%) being unvaccinated. Adjusted influenza VE estimates were 37% overall (95% CI = 27, 46), 40% (95% CI = 25, 51) for RIV4 and 35% (95% CI = 20, 47) for standard dose vaccines. Overall, rVE of RIV4 compared to SD was not significantly higher (11%; 95% CI = −20, 33). Influenza vaccines were moderately protective against medically attended outpatient influenza during the 2018-2019 and 2019-2020 seasons. Although the point estimates are higher for RIV4, the large confidence intervals around VE estimates suggest this study was underpowered to detect significant rVE of individual vaccine formulations.
Most humans have pre-existing immunity to influenza viruses. In this study, volunteers (ages of 18-85 years) were vaccinated with split, inactivated Fluzone™ influenza vaccine in four consecutive ...influenza seasons from 2013 to 2016 seasons. The impact of repeated vaccination on breadth and durability of antibodies was assessed as a result of vaccine strain changes. Total IgG anti-hemagglutinin (HA) binding antibodies and hemagglutination-inhibition (HAI) activity increased in all age groups against both influenza A HA components in the vaccine post-vaccination (day 21). However, younger subjects maintained seroprotective titers to the vaccine strains, which resulted in higher seroconversion rates in the elderly, since the HAI titers in elderly subjects were more likely to decline prior to the next season. Young subjects had significant HAI activity against historical, as well as contemporary H1 and H3 vaccine strains from the mid-1980s to present. In contrast, elderly subjects had HAI activity to H1 strains from all years, but were more likely to have HAI activity to older strains from 1918-1950s. They also had a more restricted HAI profile against H3 viruses compared to young subjects recognizing H3N2 influenza viruses from the mid-2000s to present. Vaccine recipients were then categorized by whether subjects seroconverted from a seronegative or seropositive pre-vaccination state. Regardless of age, immunological recall or 'back-boosting' to antigenically related strains were associated with seroconversion to the vaccine strain. Overall, both younger and older people have the ability to mount a breadth of immune responses following influenza vaccination. This report describes how imprinting exposure differs across age groups, influences antibody cross-reactivity to past hemagglutinin antigenic variants, and shapes immune responses elicited by current split inactivated influenza vaccines. Understanding how current influenza vaccines are influenced by pre-existing immunity in people of different ages is critical for designing the next-generation of 'universal' or broadly-protective influenza vaccines.
Background. Circulating A/H3N2 influenza viruses drifted significantly after strain selection for the 2014-2015 vaccines. Also in 2014-2015, the Advisory committee on Immunization Practices ...recommended preferential use of live attenuated influenza vaccine (LAIV) over inactivated influenza vaccine (IIV) among children aged 2-8 years. Methods. Vaccine effectiveness (VE) across age groups and vaccine types was examined among outpatients with acute respiratory illness at 5 US sites using a test-negative design, that compared the odds of vaccination among reverse transcription polymerase chain reaction-confirmed influenza positives and negatives. Results. Of 9311 enrollees with complete data, 7078 (76%) were influenza negative, 1840 (19.8%) were positive for influenza A (A/H3N2, n=1817), and 395 (4.2%) were positive for influenza B (B/Yamagata, n=340). The overall adjusted VE was 19% (95% confidence interval CI, 10% to 27%) and was statistically significant in all age strata except those aged 18-64 years. The adjusted VE of 6% (95%CI, -5% to 17%) against A/H3N2-associated illness was not statistically significant, unlike VE for influenza B/Yamagata, which was 55% (95%CI, 43% to 65%). Among those aged 2-8 years, VE against A/H3N2 was 15% (95%CI, −16% to 38%) for IIV and -3% (CI, -50% to 29%) for LAIV; VE against B/Yamagata was 40% (95%CI, -20% to 70%) for IIV and 74% (95%CI, 25% to 91%) for LAIV. Conclusions. The 2014-2015 influenza vaccines offered little protection against the predominant influenza A/H3N2 virus but were effective against influenza B. Preferential use of LAIV among young children was not supported.
Guidelines for the treatment of persons with influenza virus infection were prepared by an Expert Panel of the Infectious Diseases Society of America. The evidence-based guidelines encompass ...diagnostic issues, treatment and chemoprophylaxis with antiviral medications, and issues related to institutional outbreak management for seasonal (interpandemic) influenza. They are intended for use by physicians in all medical specialties with direct patient care, because influenza virus infection is common in communities during influenza season and may be encountered by practitioners caring for a wide variety of patients.
•RSV burden among adults vary widely due to differences in methodology, reliance on influenza surveillance, and lack of diagnostic methods to identify RSV when viral loads are low.•Using a simple ...method, statewide and local hospitalization, medical record and U.S. Census data, population-based RSV hospitalization burden among adults was estimated.•The largest burden was borne by adults ≥ 65 years of age; immunosuppressed patients bore the greatest relative burden of RSV hospitalizations.•Hospitalization due to RSV among pregnant women was low.
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.
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.
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.
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.
Background. During the 2012-2013 influenza season, there was cocirculation of influenza A(H3N2) and 2 influenza lineage viruses in the United States. Methods. Patients with acute cough illness for ≤7 ...days were prospectively enrolled and had swab samples obtained at outpatient clinics in 5 states. Influenza vaccination dates were confirmed by medical records. The vaccine effectiveness (VE) was estimated as 100% × (1 - adjusted odds ratio) for vaccination in cases versus test-negative controls. Results. Influenza was detected in 2307 of 6452 patients (36%); 1292 (56%) had influenza A(H3N2), 582 (25%) had influenza B/Yamagata, and 303 (13%) had influenza B/Victoria. VE was 49% (95% confidence interval CI, 43%-55%) overall, 39% (95% CI, 29%-47%) against influenza A(H3N2), 66% (95% CI, 58%-73%) against influenza B/Yamagata (vaccine lineage), and 51% (95% CI, 36%-63%) against influenza B/Victoria. VE against influenza A(H3N2) was highest among persons aged 50-64 years (52%; 95% CI, 33%-65%) and persons aged 6 months-8 years (51%; 95% CI, 32%-64%) and lowest among persons aged ≥65 years (11%; 95% CI, -41% to 43%). In younger age groups, there was evidence of residual protection from receipt of the 2011-2012 vaccine 1 year earlier. Conclusions. The 2012-2013 vaccines were moderately effective in most age groups. Cross-lineage protection and residual effects from prior vaccination were observed and warrant further investigation.
Respiratory syncytial virus (RSV) is becoming increasingly recognized as a serious threat to vulnerable population subgroups. This study describes the statistical analysis plan for a retrospective ...cohort study of adults hospitalized for acute respiratory infection (ARI) to estimate the population burden of RSV especially for groups such as the elderly, pregnant women and solid organ transplant patients. Disease burden estimates are essential for setting vaccine policy, e.g., should RSV vaccine become available, burden estimates may inform recommendations to prioritize certain high-risk groups. The study population is residents of Allegheny County, Pennsylvania ≥18 years of age who were hospitalized in Pennsylvania during the period September 1, 2015-August 31, 2018. Data sources will include U.S. Census, Pennsylvania Health Care Cost Containment Council (PHC4) and the electronic medical record for the health system to which the hospitals belong. The algorithm involves: 1) ARI-associated hospitalizations in PHC4 data; 2) adjustment for ARI hospitalizations among county residents but admitted to hospitals outside the county; and 3) RSV detections from respiratory viral panels. Key sensitivity analyses will adjust for undertesting for viruses in the fall and spring quarters. The results will be population-based estimates, stratified by age and risk groups. Adjusting hospitalization data using a multiplier method is a simple means to estimate the impact of RSV in a given area. This algorithm can be applied to other health systems and localities to estimate RSV and other respiratory pathogen burden in adults, to estimate burden following introduction of RSV vaccine and to make cost-effectiveness estimates.
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