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Abstract

Background: Different types of influenza vaccines are currently produced worldwide. Vaccination of pregnant women is recommended internationally, while healthy adults are targeted in North America. Objectives: To identify, retrieve and assess all studies evaluating the effects (efficacy, effectiveness and harm) of vaccines against influenza in healthy adults, including pregnant women. Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 2), MEDLINE (January 1966 to May 2013) and EMBASE (1990 to May 2013). Selection criteria: Randomised controlled trials (RCTs) or quasi-RCTs comparing influenza vaccines with placebo or no intervention in naturally occurring influenza in healthy individuals aged 16 to 65 years. We also included comparative studies assessing serious and rare harms. Data collection and analysis: Two review authors independently assessed trial quality and extracted data. Main results: We included 90 reports containing 116 data sets; among these 69 were clinical trials of over 70,000 people, 27 were comparative cohort studies (about eight million people) and 20 were case-control studies (nearly 25,000 people). We retrieved 23 reports of the effectiveness and safety of vaccine administration in pregnant women (about 1.6 million mother-child couples). The overall effectiveness of parenteral inactivated vaccine against influenza-like illness (ILI) is limited, corresponding to a number needed to vaccinate (NNV) of 40 (95% confidence interval (CI) 26 to 128). The overall efficacy of inactivated vaccines in preventing confirmed influenza has a NNV of 71 (95% CI 64 to 80). The difference between these two values depends on the different incidence of ILI and confirmed influenza among the study populations: 15.6% of unvaccinated participants versus 9.9% of vaccinated participants developed ILI symptoms, whilst only 2.4% and 1.1%, respectively, developed laboratory-confirmed influenza. No RCTs assessing vaccination in pregnant women were found. The only evidence available comes from observational studies with modest methodological quality. On this basis, vaccination shows very limited effects: NNV 92 (95% CI 63 to 201) against ILI in pregnant women and NNV 27 (95% CI 18 to 185) against laboratory-confirmed influenza in newborns from vaccinated women. Live aerosol vaccines have an overall effectiveness corresponding to a NNV 46 (95% CI 29 to 115). The performance of one-dose or two-dose whole virion pandemic vaccines was higher, showing a NNV of 16 (95% CI 14 to 20) against ILI and a NNV of 35 (95% CI 33 to 47) against influenza, while a limited impact on hospitalisation was found (NNV 94, 95% CI 70 to 1022). Vaccination had a modest effect on time offwork and had no effect on hospital admissions or complication rates. Inactivated vaccines caused local harms. No evidence of association with serious adverse events was found, but the harms evidence base was limited. The overall risk of bias in the included trials is unclear because it was not possible to assess the real impact of bias. Authors' conclusions: Influenza vaccines have a very modest effect in reducing influenza symptoms and working days lost in the general population, including pregnant women. No evidence of association between influenza vaccination and serious adverse events was found in the comparative studies considered in the review. This review includes 90 studies, 24 of which (26.7%) were funded totally or partially by industry. Out of the 48 RCTs, 17 were industry-funded (35.4%).

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... In sum, we simulated a typical search scenario for vaccination information and evaluated how typical-albeit potentially not fully representative-messages are perceived and proliferate in an online setting. While the scientifically-based CDC information was rather successful, our results demonstrate that the impact and transfer of any scientific evidence that would enable fully informed medical decision making (as found in [21,22]) is compar- atively low. Furthermore, the pattern of the ratings for scientific messages suggests that low adoption and transfer rates may be due to a lack of comprehensibility. ...
... In contrast to Study 1, all participants received the same 9 messages (selected from Study 1, and characterized by a balanced stance towards vaccination and high willingness to share; see also [6]) plus the same attention check item, the open text field for transmitting a message (directly after the messages), and related prepost perception measures (intentions to vaccinate, vaccination recommendation, norms, perceived behavioral control, attitudes, flu risk perception, risk perception side effects, knowledge, perceived vaccine effectiveness, as in [6]). For two messages, the visual display was experimentally manipulated between participants: One message providing scientific effectiveness information of the flu vaccine derived from a Cochrane meta-analysis [22] was either displayed as text only (''A meta-analysis summarizing scientific evidence from various studies published by the Cochrane Library in 2014 found that 1 of 100 vaccinated vs. 2 of 100 unvaccinated adults contracted a laboratory-confirmed flu in randomized controlled trials.''), or supplemented with the logo of the Cochrane society, or with an icon array displaying the same statistical information as the text (created by the R package riskyr [25], see Fig. 2). ...
... .]." (CDC website, 2018) are easier to grasp and to communicate than meta-analytic clinical trial information, such as ''15.6% of unvaccinated participants versus 9.9% of vaccinated participants developed [influenza like illness (ILI)] symptoms, whilst only 2.4% and 1.1%, respectively, developed laboratory-confirmed influenza." [22]. ...
Article
Objective: Social media are an increasingly important source of information on the benefits and risks of vaccinations, but the high prevalence of misinformation provides challenges for informed vaccination decisions. It is therefore important to understand which messages are likely to diffuse online and why, and how relevant aspects-such as scientific facts on vaccination effectiveness-can be made more comprehensible and more likely to be shared. In two studies, we (i) explore which characteristics of messages on flu vaccination facilitate their diffusion in online communication, and (ii) whether visual displays (i.e., icon arrays) facilitate the comprehension and diffusion of scientific effectiveness information. Methods: In Study 1, 208 participants each rated a random sample of 15 out of 63 messages on comprehensibility, trustworthiness, persuasiveness, familiarity, informativeness, valence, and arousal, and then reported which information they would share with subsequent study participants. In Study 2 (N = 758), we employed the same rating procedure for a selected set of 9 messages and experimentally manipulated how scientific effectiveness information was displayed. Results: Study 1 illustrated that scientific effectiveness information was difficult to understand and thus did not diffuse well. Study 2 demonstrated that visual displays improved the understanding of this information, which could, in turn, increase its social impact. Conclusions: The comprehensibility of scientific information is an important prerequisite for its diffusion. Visual displays can facilitate informed vaccination decisions by rendering important information on vaccination effectiveness more transparent and increasing the willingness to share this information.
... Many pro-mandatory vaccine physicians and legislators advocate for the benefit of vaccines to eliminate vaccinated diseases but seem unaware of the relevant science that makes total protection and elimination unlikely and that there are no documented long-term safety of vaccines by proper scientific standards. 220,257,259,265,[279][280][281][282][283][284][285] Currently there is an unjustified fear in the general public, public health officials, medical authorities and the media about measles and chicken pox that doesn't correspond to the forgotten facts of these largely benign illnesses in childhood. 238,247,[271][272][273][274][275][276] The low risk of deaths from measles and chicken pox in developed countries can probably further be reduced with proper treatment, although this is as yet unproven. ...
... The CDC statistics on death attributed to influenza are biased and exaggerated. [279][280][281][282] The yearly effectiveness of the inactivated influenza vaccine also appears to be overstated by the CDC and certainly varies depending on the age group and risk factors. [279][280][281][282] The CDC's tracking system and attribution of influenza, as well as their exaggerated claims, are not supported by unbiased, independent, non-industry-funded and rigorous assessments. ...
... [279][280][281][282] The yearly effectiveness of the inactivated influenza vaccine also appears to be overstated by the CDC and certainly varies depending on the age group and risk factors. [279][280][281][282] The CDC's tracking system and attribution of influenza, as well as their exaggerated claims, are not supported by unbiased, independent, non-industry-funded and rigorous assessments. ...
Article
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Introduction: Anthroposophic medicine is a form of integrative medicine that originated in Europe but is not well known in the US. It is comprehensive and heterogenous in scope and remains provocative and controversial in many academic circles. Assessment of the nature and potential contribution of anthroposophic medicine to whole person care and global health seems appropriate. Methods: Because of the heterogenous and multifaceted character of anthroposophic medicine, a narrative review format was chosen. A Health Technology Assessment of anthroposophic medicine in 2006 was reviewed and used as a starting point. A Medline search from 2006 to July 2020 was performed using various search terms and restricted to English. Books, articles, reviews and websites were assessed for clinical relevance and interest to the general reader. Abstracts of German language articles were reviewed when available. Reference lists of articles and the author's personal references were also consulted. Results: The literature on anthroposophic medicine is vast, providing new ways of thinking, a holistic view of the world, and many integrating concepts useful in medicine. In the last 20 years there has been a growing research base and implementation of many anthroposophical concepts in the integrated care of patients. Books and articles relevant to describing the foundations, scientific status, safety, effectiveness and criticisms of anthroposophic medicine are discussed. Discussion: An objective and comprehensive analysis of anthroposophic medicine finds it provocative, stimulating and potentially fruitful as an integrative system for whole person care, including under-recognized life processes and psycho-spiritual aspects of human beings. It has a legitimate, new type of scientific status as well as documented safety and effectiveness in some areas of its multimodal approach. Criticisms and controversies of anthroposophic medicine are often a result of lack of familiarity with its methods and approach and/or come from historically fixed ideas of what constitutes legitimate science.
... Efficacy of TIV in high-risk groups were obtained from published studies (Table 1). Due to annual variations of circulating influenza, vaccine efficacy is likely to vary annually depending on the extent of mismatch between the vaccine and circulating influenza strains [54][55][56]. Therefore, we extracted vaccine efficacy inputs from meta-analyses that included several studies from multiple years [10,12,14,54,57]. ...
... Due to annual variations of circulating influenza, vaccine efficacy is likely to vary annually depending on the extent of mismatch between the vaccine and circulating influenza strains [54][55][56]. Therefore, we extracted vaccine efficacy inputs from meta-analyses that included several studies from multiple years [10,12,14,54,57]. This includes vaccine efficacy against laboratory-confirmed, symptomatic influenza-like-illness, hospitalisation and death, inputted into CETSIV as the relative risk reduction of influenza-associated illnesses and deaths. ...
... Estimates of vaccine efficacy were available for children aged 6-59 months [14,58,59], persons aged ! 65 years [12], pregnant women [54], and healthy adults [54]. However, due to paucity of metaanalyses on PLWHA and persons with other UMCs, vaccine efficacy in these risk groups were inferred using previously published data. ...
Article
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Background Seasonal influenza imposes a significant health and economic burden in South Africa, particularly in populations vulnerable to severe consequences of influenza. This study assesses the cost-effectiveness of South Africa’s seasonal influenza vaccination strategy, which involves vaccinating vulnerable populations with trivalent inactivated influenza vaccine (TIV) during routine facility visits. Vulnerable populations included in our analysis are persons aged ≥ 65 years; pregnant women; persons living with HIV/AIDS (PLWHA), persons of any age with underlying medical conditions (UMC) and children aged 6–59 months. Method We employed the World Health Organisation’s (WHO) Cost Effectiveness Tool for Seasonal Influenza Vaccination (CETSIV), a decision tree model, to evaluate the 2018 seasonal influenza vaccination campaign from a public healthcare provider and societal perspective. CETSIV was populated with existing country-specific demographic, epidemiologic and coverage data to estimate incremental cost-effectiveness ratios (ICERs) by comparing costs and benefits of the influenza vaccination programme to no vaccination. Results The highest number of clinical events (influenza cases, outpatient visits, hospitalisation and deaths) were averted in PLWHA and persons with other UMCs. Using a cost-effectiveness threshold of US$ 3 400 per quality-adjusted life year (QALY), our findings suggest that the vaccination programme is cost-effective for all vulnerable populations except for children aged 6–59 months. ICERs ranged from ~US$ 1 750 /QALY in PLWHA to ~US$ 7 500/QALY in children. In probabilistic sensitivity analyses, the vaccination programme was cost-effective in pregnant women, PLWHA, persons with UMCs and persons aged ≥65 years in >80% of simulations. These findings were robust to changes in many model inputs but were most sensitive to uncertainty in estimates of influenza-associated illness burden. Conclusion South Africa's seasonal influenza vaccination strategy of opportunistically targeting vulnerable populations during routine visits is cost-effective. A budget impact analysis will be useful for supporting future expansions of the programme.
... 87 The consensus group concluded that there was good evidence to recommend giving influenza vaccine to pediatric patients with IBD. Key evidence: In 2 systematic reviews, inactivated influenza vaccines reduced the risk of influenza and influenza-like illness in healthy adults, 65 years and younger, 88 and those older than 65 years. 89 These systematic reviews concluded that CoE in the younger group was moderate for both outcomes but in the elderly was moderate for the outcome of influenza-like illness and low for the outcome of influenza, because of uncertainty over how influenza was diagnosed in the older trials. ...
... The 2 systematic reviews in healthy adults, and the 10 other studies in adults with IBD showed no serious adverse events associated with the use of inactivated influenza vaccine. 88,89,[91][92][93][94][95][96][97][98][99][100] The evidence for efficacy and safety were anchored to the general population. The CoE for efficacy remained moderate because studies suggesting reduced immunogenicity in patients with IBD showed that the European Union Committee for Medicinal Products for Human Use criteria for effective immunogenicity were met in the majority of patients. ...
Article
Background and Aims The effectiveness and safety of vaccinations can be altered by immunosuppressive therapies, and perhaps by inflammatory bowel disease (IBD) itself. These recommendations developed by the Canadian Association of Gastroenterology and endorsed by the American Gastroenterological Association, aim to provide guidance on immunizations in adult and pediatric patients with IBD. This publication focused on inactivated vaccines. Methods Systematic reviews evaluating the efficacy, effectiveness, and safety of vaccines in patients with IBD, other immune-mediated inflammatory diseases, and the general population were performed. Critical outcomes included mortality, vaccine-preventable diseases, and serious adverse events. Immunogenicity was considered a surrogate outcome for vaccine efficacy. Certainty of evidence and strength of recommendations were rated according to the GRADE (Grading of Recommendation Assessment, Development, and Evaluation) approach. Key questions were developed through an iterative online platform, and voted on by a multidisciplinary group. Recommendations were formulated using the Evidence-to-Decision framework. Strong recommendation means that most patients should receive the recommended course of action, whereas a conditional recommendation means that different choices will be appropriate for different patients. Results Consensus was reached on 15 of 20 questions. Recommendations address the following vaccines: Haemophilus influenzae type b, recombinant zoster, hepatitis B, influenza, pneumococcus, meningococcus, tetanus-diphtheria-pertussis, and human papillomavirus. Most of the recommendations for patients with IBD are congruent with the current Centers for Disease Control and Prevention and Canada’s National Advisory Committee on Immunization recommendations for the general population, with the following exceptions. In patients with IBD, the panel suggested Haemophilus influenzae type b vaccine for patients older than 5 years of age, recombinant zoster vaccine for adults younger than 50 year of age, and hepatitis B vaccine for adults without a risk factor. Consensus was not reached, and recommendations were not made for 5 statements, due largely to lack of evidence, including double-dose hepatitis B vaccine, timing of influenza immunization in patients on biologics, pneumococcal and meningococcal vaccines in adult patients without risk factors, and human papillomavirus vaccine in patients aged 27–45 years. Conclusions Patients with IBD may be at increased risk of some vaccine-preventable diseases. Therefore, maintaining appropriate vaccination status in these patients is critical to optimize patient outcomes. In general, IBD is not a contraindication to the use of inactivated vaccines, but immunosuppressive therapy may reduce vaccine responses.
... No Brasil, a estratégia da vacinação contra a influenza foi incorporada no Programa Nacional de Imunizações em 1999, com o propósito de reduzir internações, complicações e mortes na população alvo para a vacinação no Brasil (12) . A vacina monovalente cepa H1N1 pandêmica 2009 é de vírus inativado e registra uma efetividade média maior que 95% (13) , conferindo segurança, enquanto as contraindicações à sua administração são bastante restritas (antecedentes de reação anafilática severa aos componentes da vacina e alergia a ovo de galinha e seus derivados) (14) . A administração da vacina influenza inativada sazonal não é associada com o desencadeamento de esclerose múltipla, neurite óptica ou púrpura trombocitopênica autoimune, assim como não é associada com a síndrome de Guillain-Barré (13) . ...
... A vacina monovalente cepa H1N1 pandêmica 2009 é de vírus inativado e registra uma efetividade média maior que 95% (13) , conferindo segurança, enquanto as contraindicações à sua administração são bastante restritas (antecedentes de reação anafilática severa aos componentes da vacina e alergia a ovo de galinha e seus derivados) (14) . A administração da vacina influenza inativada sazonal não é associada com o desencadeamento de esclerose múltipla, neurite óptica ou púrpura trombocitopênica autoimune, assim como não é associada com a síndrome de Guillain-Barré (13) . As vacinas contra os vírus influenza sazonais são modificadas anualmente segundo as recomendações Organização Mundial da Saúde (OMS) para conferir proteção contra as cepas virais de gripe em circulação (14) . ...
Article
Full-text available
A influenza é uma infecção viral aguda que afeta o sistema respiratório, com alta tendência a se disseminar, devido à sua facilidade de transmissão via secreções respiratórias. A pneumonia adquirida na comunidade (PAC) é uma infecção do trato respiratório inferior, constituindo a principal causa de mortalidade do mundo, e com o advento dos testes moleculares na prática clínica, os vírus vêm ganhando destaque como agentes etiológicos, o que tradicionalmente era entendido como uma PAC de menor gravidade, após a epidemia de influenza A H1N1 em 2009, essa assertiva sofreu uma mudança significante. Este estudo é do tipo observacional transversal e retrospectivo, com análises bibliográficas e levantamento de dados com base no Sistema de Informações Hospitalares do SUS, objetivando comparar a taxa de internação hospitalar por pneumonia em idosos, e a cobertura vacinal contra a gripe H1N1 no município de Vassouras - RJ, de forma a analisar se a vacina está causando impacto na saúde. Os resultados fortalecem a hipótese de que a cobertura vacinal contra a gripe H1N1 tem relação direta na internação hospitalar de idosos por pneumonia no município de Vassouras – RJ, e consequentemente, maiores gastos com a saúde pública.
... Vaccination also lowered the prevalence of ILI from 21.5% to 18.1%. However, due to the low overall population risk of influenza, the number of healthy adults needed to treat to prevent one case (NNT) of influenza and ILI were 71 and 29, respectively [33] (table 1). ...
... Summary of the number needed to treat (NNT) with the influenza vaccine in different age groups to protect against influenza Data compiled from Cochrane reviews on influenza vaccination preventing influenza in healthy adults, children and >65-year-olds[33][34][35]. LAIV: live attenuated influenza vaccine; IIV: inactivated influenza vaccine. ...
Article
Full-text available
p>Influenza virus infection causes seasonal epidemics and occasional pandemics, leading to huge morbidity and mortality worldwide. Vaccination against influenza is needed annually as protection from constantly mutating strains is required. Groups at high risk of poor outcomes include the elderly, the very young, pregnant women and those with chronic health conditions. However, vaccine effectiveness in the elderly is generally poor due to immunosenescence and may be altered due to “original antigenic sin”. Strategies to overcome these challenges in the elderly include high-dose or adjuvant vaccines. Other options include vaccinating healthcare workers and children as this reduces community-level influenza transmission. Current guidelines in the UK are that young children receive a live attenuated nasal spray vaccine, adults aged >65 years receive an adjuvanted trivalent inactivated vaccine and adults aged <65 years with comorbidities receive a quadrivalent inactivated vaccine. The goal of a universal influenza vaccine targeting conserved regions of the virus and avoiding the need for annual vaccination is edging closer with early-phase trials under way.</p
... In 2 systematic reviews, inactivated influenza vaccines reduced the risk of influenza and influenza-like illness in healthy adults, 65 years and younger (88), and those older than 65 years (89). ...
... The 2 systematic reviews in healthy adults, and the 10 other studies in adults with IBD showed no serious adverse events associated with the use of inactivated influenza vaccine (88,89,(91)(92)(93)(94)(95)(96)(97)(98)(99)(100). ...
Article
Full-text available
Background and aims: The effectiveness and safety of vaccinations can be altered by immunosuppressive therapies, and perhaps by inflammatory bowel disease (IBD) itself. These recommendations developed by the Canadian Association of Gastroenterology and endorsed by the American Gastroenterological Association, aim to provide guidance on immunizations in adult and pediatric patients with IBD. This publication focused on inactivated vaccines. Methods: Systematic reviews evaluating the efficacy, effectiveness, and safety of vaccines in patients with IBD, other immune-mediated inflammatory diseases, and the general population were performed. Critical outcomes included mortality, vaccine-preventable diseases, and serious adverse events. Immunogenicity was considered a surrogate outcome for vaccine efficacy. Certainty of evidence and strength of recommendations were rated according to the GRADE (Grading of Recommendation Assessment, Development, and Evaluation) approach. Key questions were developed through an iterative online platform, and voted on by a multidisciplinary group. Recommendations were formulated using the Evidence-to-Decision framework. Strong recommendation means that most patients should receive the recommended course of action, whereas a conditional recommendation means that different choices will be appropriate for different patients. Results: Consensus was reached on 15 of 20 questions. Recommendations address the following vaccines: Haemophilus influenzae type b, recombinant zoster, hepatitis B, influenza, pneumococcus, meningococcus, tetanus-diphtheria-pertussis, and human papillomavirus. Most of the recommendations for patients with IBD are congruent with the current Centers for Disease Control and Prevention and Canada's National Advisory Committee on Immunization recommendations for the general population, with the following exceptions. In patients with IBD, the panel suggested Haemophilus influenzae type b vaccine for patients older than 5 years of age, recombinant zoster vaccine for adults younger than 50 year of age, and hepatitis B vaccine for adults without a risk factor. Consensus was not reached, and recommendations were not made for 5 statements, due largely to lack of evidence, including double-dose hepatitis B vaccine, timing of influenza immunization in patients on biologics, pneumococcal and meningococcal vaccines in adult patients without risk factors, and human papillomavirus vaccine in patients aged 27-45 years. Conclusions: Patients with IBD may be at increased risk of some vaccine-preventable diseases. Therefore, maintaining appropriate vaccination status in these patients is critical to optimize patient outcomes. In general, IBD is not a contraindication to the use of inactivated vaccines, but immunosuppressive therapy may reduce vaccine responses.
... 67 As older adults are at higher risk of complications due to impaired immune function and comorbidities, it is essential to develop messaging and strategies to improve vaccine uptake in this population. 68 The misconception of natural immunity to the vaccine-preventable disease due to age can be addressed by health care professionals providing education on nonvaccination risks, as recommended by the Canadian Public Health Agency. 66 ...
Article
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Background In recent years, Canadian health care professionals have observed an increase in vaccine refusal. The objective of this study is to review published literature and identify the main themes related to vaccine hesitancy and barriers to vaccination in Canadian adults and recent immigrants. Methods A qualitative systematic review was performed. A comprehensive search of MEDLINE (1946 to January 2021) and EMBASE (1974 to January 2021) was conducted to identify existing literature that addressed the primary research question. Studies were eligible for inclusion if the study population involved 1) the general population, 2) Indigenous populations, 3) recent immigrants to Canada or 4) Canadian health care professionals. Results Thirty-four studies were included with a focus on the general population ( n = 22), health care professionals ( n = 10) and recent immigrant populations ( n = 2). The most frequently reported barriers were lack of vaccine information (41%), lack of access to vaccination (38%), fear of adverse reactions (38%), financial reasons (29%), lack of awareness of vaccine existence (29%), antivaccine sentiments (24%), notion that older adults do not need vaccination (18%), misconceptions on vaccine effectiveness (12%), potential sexual health promotion stigma (6%) and fear of needles (3%). Interpretation Barriers to vaccination among Canadians and recent immigrants continue to be a challenge in the health care system. Conclusions The greatest yield in improving vaccination rates is likely to come from supporting vaccine-hesitant individuals in shifting their thinking to greater vaccine acceptance. Pharmacists are well positioned to address vaccine hesitancy and involvement through education, facilitation and administration of vaccines. Can Pharm J (Ott) 2022;155:xx-xx.
... This systematic review concluded that there were some adverse events associated with the vaccination that include an increase in fever, nausea, and vomiting. Also, the benefit of vaccination among the susceptible population like pregnant women and children was found to be modest [49]. ...
Article
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Human health is plagued by several challenges throughout life. Different endogenous and exogenous factors influence the well-being of humans. The endogenous factors may be the enzymes and hormonal functions that alter the normal human physiological status and cause diseases like metabolic disorders, organ dysfunctions (liver diseases, heart diseases), and several others. Also, the human immune system and the cells involved in the immune responses may be disturbed causing autoimmune disorders, and tumors/cancers/malignancies. The exogenous reasons for human illnesses may be infectious diseases caused by microbes, chemicals, toxins, and others to those humans get exposed during their lifetime. The management of such illnesses and diseases is generally carried out by qualified physicians, and surgeons, and respective clinical experts in healthcare institutions that include hospitals. The drugs, devices, and other agents used to manage human diseases are synthesized and tested exhaustively before being approved and marketed for human use for their safety and efficacy by performing clinical research. In this review, we attempt to delineate the different types of clinical research and their implications.
... Different advanced vaccine technologies have already demonstrated their potential in preventing COVID-19, and several such vaccines, including mRNA and adenoviral vector vaccines, are being authorized for use around the globe after successfully completing clinical trials [13,14]. Nevertheless, a more traditional approach, the development of inactivated vaccines, is robust, cost-efficient, and reliable due to its long and successful history of use [15,16]. Several inactivated vaccines against SARS-CoV-2 infection are being developed around the world, and at least five have shown success in preclinical and clinical trials, which led to their authorization for use [17][18][19][20]. ...
Article
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The unprecedented in recent history global COVID-19 pandemic urged the implementation of all existing vaccine platforms to ensure the availability of the vaccines against COVID-19 to every country in the world. Despite the multitude of high-quality papers describing clinical trials of different vaccine products, basic detailed data on general toxicity, reproductive toxicity, immunogenicity, protective efficacy and durability of immune response in animal models are scarce. Here, we developed a β-propiolactone-inactivated whole virion vaccine CoviVac and assessed its safety, protective efficacy, immunogenicity and stability of the immune response in rodents and non-human primates. The vaccine showed no signs of acute/chronic, reproductive, embryo-, and fetotoxicity, or teratogenic effects, as well as no allergenic properties in studied animal species. The vaccine induced stable and robust humoral immune response both in form of specific anti-SARS-CoV-2 IgG and NAbs in mice, Syrian hamsters, and common marmosets. The NAb levels did not decrease significantly over the course of one year. The course of two immunizations protected Syrian hamsters from severe pneumonia upon intranasal challenge with the live virus. Robustness of the manufacturing process was demonstrated as well. These data encouraged further evaluation of CoviVac in clinical trials.
... The authors published the full-text manuscript [56] one year later, and after a complete analysis, they concluded that there is no evidence of safety concerns. Nine systematic reviews consistently supported the safety of influenza vaccines during pregnancy [64][65][66][67][68][69][70][71][72]. In general, cohort studies showed the benefits of vaccination during pregnancy, such as significantly decreased risks for preterm birth, small for gestational age, and fetal death. ...
Article
Full-text available
Background Rapid assessment of COVID-19 vaccine safety during pregnancy is urgently needed. Methods We conducted a rapid systematic review, to evaluate the safety of COVID-19 vaccines selected by the COVID-19 Vaccines Global Access-Maternal Immunization Working Group in August 2020, including their components and their technological platforms used in other vaccines for pregnant persons. We searched literature databases, COVID-19 vaccine pregnancy registries, and explored reference lists from the inception date to February 2021 without language restriction. Pairs of reviewers independently selected studies through COVIDENCE, and performed the data extraction and the risk of bias assessment. Discrepancies were resolved by consensus. Registered on PROSPERO (CRD42021234185). Results We retrieved 6757 records and 12 COVID-19 pregnancy registries from the search strategy; 38 clinical and non-clinical studies (involving 2,398,855 pregnant persons and 56 pregnant animals) were included. Most studies (89%) were conducted in high-income countries and were cohort studies (57%). Most studies (76%) compared vaccine exposures with no exposure during the three trimesters of pregnancy. The most frequent exposure was to AS03 adjuvant, in the context of A/H1N1 pandemic influenza vaccines, (n=24) and aluminum-based adjuvants (n=11). Only one study reported exposure to messenger RNA in lipid nanoparticles COVID-19 vaccines. Except for one preliminary report about A/H1N1 influenza vaccination (adjuvant AS03), corrected by the authors in a more thorough analysis, all studies concluded that there were no safety concerns. Conclusion This rapid review found no evidence of pregnancy-associated safety concerns of COVID-19 vaccines or of their components or platforms when used in other vaccines. However, the need for further data on several vaccine platforms and components is warranted, given their novelty. Our findings support current WHO guidelines recommending that pregnant persons may consider receiving COVID-19 vaccines, particularly if they are at high risk of exposure or have comorbidities that enhance the risk of severe disease.
... Despite the recommendations on vaccinating cancer patients, there are conflicting data on the effectiveness of the vaccine at mounting an immune response in individuals with cancer, particularly while receiving cancer-directed therapies [23][24][25]. For instance, some studies reported low vaccine responses in lymphoma patients after rituximab therapy [26][27][28] but recent data show that individuals treated with rituximab mount an immune response despite the lack of peripheral CD20+ Bcells [29,30]. ...
Article
Full-text available
Background Annual influenza vaccination is recommended for all patients with cancer but vaccine uptake data by cancer type and time since diagnosis is limited. We sought to estimate the vaccination rates across different cancer types in the United States and determine whether rates vary over time since diagnosis. Methods Vaccination rates in individuals with solid tumor and hematological malignancies were estimated using data from 59,917 individuals obtained by the 2016 and 2017 National Health Interview Survey (NHIS) conducted by the Centers for Disease Control and Prevention. Results An average of 64% of the 5,053 individuals with self-reported cancer received the influenza vaccine. Vaccination rates in men and women with solid tumors (66.6% and 60.3%) and hematological malignancies (58.1% and 59.2%) were significantly higher compared to those without cancer (38.9% and 46.8%). Lower rates were seen in uninsured, those younger than 45 years of age, and in African Americans with hematological malignancies but not with solid tumors. Vaccine uptake was similar regardless of time since cancer diagnosis. Conclusions Influenza vaccination rates are higher in men and women with cancer but remain suboptimal, highlighting the need for additional measures to improve vaccine compliance and prevent complications from influenza across all cancer types.
... To the Editor, Vaccination reduces the influenza rate by approximately 60% among individuals ≥16 years of age. 1 In Japan, however, the influenza vaccination rate is only approximately 40% and has plateaued in recent years. 2 According to the 4C model, barriers to vaccination include complacency, convenience, confidence, and calculation. Lack of confidence influenza vaccines, because of misconceptions and negative attitudes, has been the most frequently reported reason for not being vaccinated. ...
Article
Full-text available
Changes in influenza vaccination coverage during the COVID-19 pandemic in Japan were limited. Not only changes in individual behavior and the threat of disease, but also vaccine dissemination policy based on system-based interventions, including behavioral economic approaches, is desirable.
... In der Schweiz wird die Basisimpfung von Mädchen im Alter von 11-14 Jahren mit zwei Dosen Gardasil 9  im Abstand von 6 Monaten empfohlen. Bei Immunschwäche oder wenn nur eine der beiden Impfungen vor dem15. Geburtstag erfolgt, sollen 3 Dosen verabreicht werden. ...
Article
Impfungen sind auch nach dem Säuglingsalter von grosser Bedeutung und in der Regel auch gut verträglich. Allerdings sind nicht für alle verfügbaren Impfungen gleich gute Nachweise des Nutzens verfügbar. Der vorliegende Text beleuchtet diese wichtigen Interventionen kritisch und unterstreicht das Wichtigste. Bitte beachten Sie die Korrigenda!
... [49][50][51] Furthermore, immunoattenuation could differ between children and adults. No trials have assessed immunoattenuation in adults, 52,53 and findings from observational studies have been inconsistent due to heterogeneity in outcomes, illness severity, sample size, age differences, and vaccine-mismatched circulating viruses. A few studies have found higher point estimates of vaccine effectiveness against critical influenza illness (ie, requiring intensive care unit [ICU] admission) versus non-critical illness. ...
Article
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Sterilising immunity that blocks infection for life, and thus prevents illness after infection, is the ultimate goal for vaccines. Neither influenza infection nor vaccination provide sterilising immunity. Mutations during influenza viral genome replication result in the emergence of viruses that evade immunity and cause reinfections. Waning of immunity also results in reinfections to homologous influenza viruses. However, immunity might limit the severity of disease after infection or vaccination (ie, immunoattenuation). We provide a comprehensive examination of experimental and observational peer reviewed evidence since 1933, when the first influenza virus was isolated, on whether immunity blocks subsequent infection or attenuates illness. Although an abundance of experimental evidence supports immunoattenuation, clinical evidence is rudimentary and conflicting. To the extent that immunoattenuation occurs, understanding the varied pathways to illness, pathogenesis, clinical manifestations, and correlates of attenuation can improve the design and evaluation of influenza vaccines. By elucidating the mechanisms of immunoattenuation and phenotypes of illness, we clarify ambiguities and identify unmet needs that, if addressed with priority, could strategically improve the design of vaccines for the prevention of influenza.
... 111 A quadrivalent flu vaccine has also been licenced in the US since 2013; this encompasses an additional B-like virus strain and has been shown to provide similar immunogenicity induced by the strains in the trivalent vaccine. 112,113 Current influenza vaccines need to be administered annually to cover the circulating strains. Further work for effective vaccines in the elderly is essential in both influenza and other respiratory viruses including RSV and SARS-CoV-2. ...
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With the global over 60-year-old population predicted to more than double over the next 35 years, caring for this aging population has become a major global healthcare challenge. In 2016 there were over 1 million deaths in >70 year olds due to lower respiratory tract infections; 13–31% of these have been reported to be caused by viruses. Since then, there has been a global COVID-19 pandemic, which has caused over 2.3 million deaths so far; increased age has been shown to be the biggest risk factor for morbidity and mortality. Thus, the burden of respiratory viral infections in the elderly is becoming an increasing unmet clinical need. Particular challenges are faced due to the interplay of a variety of factors including complex multimorbidities, decreased physiological reserve and an aging immune system. Moreover, their atypical presentation of symptoms may lead to delayed necessary care, prescription of additional drugs and prolonged hospital stay. This leads to morbidity and mortality and further nosocomial spread. Clinicians currently have limited access to sensitive detection methods. Furthermore, a lack of effective antiviral treatments means there is little incentive to diagnose and record specific non-COVID-19 viral infections. To meet this unmet clinical need, it is first essential to fully understand the burden of respiratory viruses in the elderly. Doing this through prospective screening research studies for all respiratory viruses will help guide preventative policies and clinical trials for emerging therapeutics. The implementation of multiplex point-of-care diagnostics as a mainstay in all healthcare settings will be essential to understand the burden of respiratory viruses, diagnose patients and monitor outbreaks. The further development of novel targeted vaccinations as well as anti-viral therapeutics and new ways to augment the aging immune system is now also essential. The reviews of this paper are available via the supplemental material section.
... Kelly et al. demonstrated that the seasonal vaccine has no protection against a pandemic influenza strain in any age group (Kelly and Grant 2009). Vaccine failure or low efficacy refers to poor matching between vaccine strains and circulating strains (Demicheli et al. 2018;Jefferson et al. 2010). Matching and mismatching, in actuality, is not binary, i.e., vaccination is not a perfect match or a perfect mismatch with the circulating strains. ...
Article
The influenza virus causes severe respiratory illnesses and deaths worldwide every year. It spreads quickly in an overcrowded area like the annual Hajj pilgrimage in Saudi Arabia. Vaccination is the primary strategy for protection against influenza. Due to the occurrence of antigenic shift and drift of the influenza virus, a mismatch between vaccine strains and circulating strains of influenza may occur. The objective of this study is to assess the impact of mismatch between vaccine strains and circulating strains during Hajj, which brings together individuals from all over the globe. To this end, we develop deterministic mathematical models of influenza with different populations and strains from the northern and southern hemispheres. Our results show that the existence and duration of an influenza outbreak during Hajj depend on vaccine efficacy. In this concern, we discuss four scenarios: vaccine strains for both groups match/mismatch circulating strains, and vaccine strains match their target strains and mismatch the other strains. Further, there is a scenario where a novel pandemic strain arises. Our results show that as long as the influenza vaccines match their target strains, there will be no outbreak of strain H1N1 and only a small outbreak of strain H3N2. Mismatching for non-target strains causes about 10,000 new H3N2 cases, and mismatching for both strains causes about 2,000 more new H1N1 cases and 6,000 additional H3N2 cases during Hajj. Complete mismatch in a pandemic scenario may infect over 342,000 additional pilgrims (13.75%) and cause more cases in their home countries.
... Valid results have been presented in literatures on the substantial improvements in the number of vaccinated persons following the empowerment of CPs in community-based immunization programs. Such laudable results have been recorded in the reduction of the incidence of influenza, pneumococcal disease, and herpes zoster infection (8,9). ...
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Background: Community pharmacists(CPs) are key providers of basic healthcare in communities, and barriers that may hinder enormous results in their role during the COVID-19 pandemic should be addressed. We conducted training on the strategies for strengthening the Infection Prevention and Control (IPC)among CPs. Methods: Participants were 31 CPs in Ilorin, Kwara State. A quasi-experimental, before-and-after study was carried out. Data were captured using a self-administered questionnaire. The questionnaire had three sections; the frst contained sociodemographic characteristics such as sex, age, and years of practice. The second section contained eight questions used to assess the knowledge of the respondents, each was assigned a score of “1” and the total obtainable score was “8”. The third section identifed the role of CPs in the prevention of COVID-19. Results: The mean age of the 31 CPs who participated in the training was 49.5 ± 13.7 years, and18 (58.1%) were males. The mean pre-test IPC training score was 4.968±1.329, while the meanpost-test IPC training score was 5.323±1.077, (t=-1.611, p=0.118). All respondents identifed that CPs had roles in the prevention of COVID-19. Among them, 27 (87.1%) identifed community health awareness campaigns as their main role in the prevention of COVID-19. Regarding years of practice, 6 (35.3%) respondents with less than 20 years had COVID-19 IPC knowledge gain compared to 10 (71.4%) others with more than 20 and above years of practice (P=0.04). Conclusion: The training achieved its short-term objective. There is a need for supervisory visits on the CPs at their place of practice to ensure knowledge acquired is put to the best use.
... Similar to the critical appraisal in the present article, critical appraisals of reported vaccine efficacy in other studies reveals clinically significant insights. For example, a 2018 review of 52 randomized trials for influenza vaccines that studied over 80,000 healthy adults reported an overall influenza vaccine EER of 0.9% and a 2.3% CER, which calculates to a RRR of 60.8% [32]. This vaccine efficacy is consistent with a 40% to 60% reduction in influenza reported by the Centers for Disease Control and Prevention (CDC) [33]. ...
Article
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Relative risk reduction and absolute risk reduction measures in the evaluation of clinical trial data are poorly understood by health professionals and the public. The absence of reported absolute risk reduction in COVID-19 vaccine clinical trials can lead to outcome reporting bias that affects the interpretation of vaccine efficacy. The present article uses clinical epidemiologic tools to critically appraise reports of efficacy in Pfzier/BioNTech and Moderna COVID-19 mRNA vaccine clinical trials. Based on data reported by the manufacturer for Pfzier/BioNTech vaccine BNT162b2, this critical appraisal shows: relative risk reduction, 95.1%; 95% CI, 90.0% to 97.6%; p = 0.016; absolute risk reduction, 0.7%; 95% CI, 0.59% to 0.83%; p < 0.000. For the Moderna vaccine mRNA-1273, the appraisal shows: relative risk reduction, 94.1%; 95% CI, 89.1% to 96.8%; p = 0.004; absolute risk reduction, 1.1%; 95% CI, 0.97% to 1.32%; p < 0.000. Unreported absolute risk reduction measures of 0.7% and 1.1% for the Pfzier/BioNTech and Moderna vaccines, respectively, are very much lower than the reported relative risk reduction measures. Reporting absolute risk reduction measures is essential to prevent outcome reporting bias in evaluation of COVID-19 vaccine efficacy.
... A Cochrane review by Demicheli 2014 found that in healthy adults (not specifically school teachers and staff), at least 71 people required vaccination to prevent one laboratory-confirmed case of influenza (CI: 64 to 80) [54]. However, many influenza infections are usually not laboratory-confirmed. ...
Article
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Introduction Influenza vaccination, besides protecting traditional risk groups, can protect employees and reduce illness-related absence, which is especially relevant in sectors with staff shortages. This study describes current knowledge of influenza vaccination in teachers and estimates its potential impact. Methods We conducted a scoping review of the considerations for and impact of influenza vaccination of schoolteachers (grey and scientific literature up to 2020 March, complemented with interviews). We then estimated the potential impact of teacher vaccination in the Netherlands, with different scenarios of vaccine uptake for 3 influenza seasons (2016–2019). Using published data on multiple input parameters, we calculated potentially averted absenteeism notifications, averted absenteeism duration and averted doctor visits for influenza. Results Only one scientific paper reported on impact; it showed lower absenteeism in vaccinated teachers, whereas more knowledge of vaccination impact was deemed crucial by 50% of interviewed experts. The impact for the Netherlands of a hypothetical 50% vaccine uptake was subsequently estimated: 74–293 potentially averted physician visits and 11,178–28,896 potentially averted days of influenza absenteeism (on ≈200,000 total teacher population). An estimated 12–32 vaccinations were required to prevent one teacher sick-leave notification, or 3.5–9.1 vaccinations to prevent one day of teacher absenteeism (2016–2019). Conclusion Scientific publications on influenza vaccination in teachers are few, while public interest has increased to reduce teacher shortages. However, school boards and public health experts indicate requiring knowledge of impact when considering this vaccination. Estimations of 3.5–9.1 vaccinated teachers preventing one day of influenza-related sick leave suggest a possible substantial vaccination impact on absenteeism. Financial incentives, more accessible on-site vaccinations at workplaces, or both, are expected to increase uptake, but more research is needed on teachers’ views and vaccine uptake potential and its cost-effectiveness. Piloting free on-site influenza vaccination in several schools could provide further information on teacher participation.
... 136 Ten systematic reviews supported the safety of influenza vaccines during pregnancy. [137][138][139][140][141][142][143][144][145][146] Other systematic reviews also assessed the safety of different vaccines. One systematic review evaluated the safety of the Hepatitis B vaccine, the pneumococcal polysaccharide vaccine, and the meningococcal polysaccharide vaccine during pregnancy and found no clear association with teratogenic effects, preterm labor, or spontaneous abortion. ...
... The healthcare costs of Influenza disease as well as cost, efficacy, and safety of yearly immunization campaigns are aspects worth considering in the ongoing discussion of broadening the vaccine recommendation to healthy working adults, children and adolescents [7][8][9]. Therefore, country-specific economic burden estimates of Influenza disease are required [10]. The German Influenza surveillance mechanisms include estimates of Influenza-associated excess medical visits, excess hospitalizations, Influenza-associated work days lost, need for care and death, but detailed data on direct medical costs stratified by age groups, underlying conditions and complications are not publicly available [11]. ...
Article
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Introduction Detailed and up-to-date data on the epidemiology and healthcare costs of Influenza are fundamental for public health decision-making. We analyzed inpatient data on Influenza-associated hospitalizations (IAH), selected complications and risk factors, and their related direct costs for Germany during ten consecutive years. Methods We conducted a retrospective cost-of-illness study on patients with laboratory-confirmed IAH (ICD-10-GM code J09/J10 as primary diagnosis) by ICD-10-GM-based remote data query using the Hospital Statistics database of the German Federal Statistical Office. Clinical data and associated direct costs of hospital treatment are presented stratified by demographic and clinical variables. Results Between January 2010 to December 2019, 156,097 persons were hospitalized due to laboratory-confirmed Influenza (J09/J10 primary diagnosis). The annual cumulative incidence was low in 2010, 2012 and 2014 (1.3 to 3.1 hospitalizations per 100,000 persons) and high in 2013 and 2015-2019 (12.6 to 60.3). Overall direct per patient hospitalization costs were mean (SD) 3521 EUR (± 8896) and median (IQR) 1805 EUR (1502; 2694), with the highest mean costs in 2010 (mean 8965 EUR ± 26,538) and the lowest costs in 2012 (mean 2588 EUR ± 6153). Mean costs were highest in 60-69 year olds, and in 50-59, 70-79 and 40-49 year olds; they were lowest in 10-19 year olds. Increased costs were associated with conditions such as diabetes (frequency 15.0%; 3.45-fold increase compared to those without diabetes), adiposity (3.3%; 2.09-fold increase) or immune disorders (5.6%; 1.88-fold increase) and with Influenza-associated complications such as Influenza pneumonia (24.3%; 1.95-fold), bacterial pneumonia (6.3%; 3.86-fold), ARDS (1.2%; 10.90-fold increase) or sepsis (2.3%; 8.30-fold). Estimated overall costs reported for the 10-year period were 549.6 Million euros (95% CI 542.7-556.4 million euros). Conclusion We found that the economic burden of IAH in Germany is substantial, even when considering solely laboratory-confirmed IAH reported as primary diagnosis. The highest costs were found in the elderly, patients with certain underlying risk factors and patients who required advanced life support treatment, and median and mean costs showed considerable variations between single years. Furthermore, there was a relevant burden of disease in middle-aged adults, who are not covered by the current vaccination recommendations in Germany.
... The age-specific attack rates in an unvaccinated population were obtained from pooled data within the control arms of several clinical trials. [27][28][29] As the effectiveness of the vaccines varies depending on the season (because of the strain circulation and especially, for TIV, the degree of match), the severity of each influenza season included was considered. To account for the seasonal heterogeneity in influenza infections circulation, the rates were distributed over the seasons using a severity coefficient. ...
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This study aimed to investigate the public health and economic benefit of using a quadrivalent influenza vaccine (QIV) instead of a trivalent influenza vaccine (TIV) in past seasons in Paraguay. The budget impact of switching from TIV to QIV in the Immunization Program was also evaluated. The adapted model includes two modules. The first compared retrospectively Health and Economic outcomes resulting from the use of QIV instead of TIV. The second forecast the spending and savings that would be associated with the switch from TIV to QIV. Our findings estimate that the switch from TIV to QIV during the seasons 2012 to 2017 could have prevented around 2,600 influenza cases, 67 hospitalizations and 10 deaths. An alternative scenario using standardized estimates of the burden of influenza showed that 234 influenza-related hospitalizations and 29 deaths could have been prevented. The estimated annual budget impact of a full switch from TIV to QIV was around USD1,6 million both from the payer and societal perspectives. Those results are mainly driven by vaccine prices and coverage rate. In sum, this manuscript describes how the use of QIV instead of TIV could have prevented influenza cases and subsequent complications that led to hospitalizations and deaths. This could have generated savings for the health system and society, offsetting part of the additional investment needed to switch from TIV to QIV.
... It should not come as a surprise, then, that the development of effective sterilising vaccines to halt quasispecies epidemics is notoriously difficult, as testified by empirical studies under well-controlled settings for both human popula- tions [13] and their livestock [10]. Even if vaccination reduces the number of influenza infections by a particular strand, meta-analysis cannot detect a systematic reduction of the overall number of influenza-like illness episodes [116,117]. Other pathogens or variants seem to happily fill the gap [118,119]. ...
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Epidemic disease spreading is conventionally often modelled and analyzed by means of rate and diffusion equations, following the paradigms of well-controlled chemical reactions and diffusive dynamics in a test tube. Yet, serious worries that this suggestive and appealing similarity might be a false friend were already voiced by the pioneers of mathematical epidemiology. A century later, we can draw on cross-fertilizations from network and game theory and the emerging field of eco-evolutionary dynamics to substantiate them. Epidemiological spreading is thereby revealed as a fundamentally heterogeneous and erratic process that shares certain properties with more unwieldy phenomena, such as earthquakes, hurricanes, traffic jams, and stock crashes. They are all characterised by high tail risks that materialize very rarely but fatally. That they arise from bursts of unlikely chains of localized random "superspreader" events, by which micro-scale fluctuations and uncertainties may get heftily magnified, makes their accurate prediction and control intrinsically and notoriously hard. That epidemic disease spreading is moreover closely intertwined with equally heterogeneous genetic drift and information feedback adds new challenges -- and chances.
Article
Background Each year, up to 10% of unvaccinated adults contracts seasonal influenza, with half of this proportion developing symptoms. As a result, employers experience significant economic losses in terms of employee absenteeism. Influenza vaccines can be instrumental in reducing this burden. Workplace vaccination is expected to reduce employee absenteeism more than linearly as a result of positive externalities. It remains unclear whether workplace influenza vaccination yields a positive return on investment. Methods We simulated the spread of influenza in the seasons 2011–12 up to 2017–18 in Belgium by means of a compartmental transmission model. We accounted for age-specific social contact patterns and included reduced contact behavior when symptomatically infected. We simulated the impact of employer-funded influenza vaccination at the workplace and performed a cost-benefit analysis to assess the employers’ return on workplace vaccination. Furthermore, we look into the cost-benefit of rewarding vaccinated employees by offering an additional day off. Results Workplace vaccination reduced the burden of influenza both on the workplace and in the population at large. Compared to the current vaccine coverage – 21% in the population at large – an employee vaccine coverage of 90% could avert an additional 355 000 cases, of which about 150 000 in the employed population and 205 000 in the unemployed population. While seasonal influenza vaccination has been cost-saving on average at about €10 per vaccinated employee, the cost-benefit analysis was prone to between-season variability. Conclusions Vaccinated employees can serve as a barrier to limit the spread of influenza in the population, reducing the attack rate by 78% at an employee coverage of 90%. While workplace vaccination is relatively inexpensive (due to economies of scale) and convenient, the return on investment is volatile. Government subsidies can be pivotal to encourage employers to provide vaccination at the workplace with positive externalities to society as a whole.
Article
Pneumococcal disease is a leading cause of mortality in young children. The largest burden of pneumococcal disease is in the first six months of life before protection from a complete schedule of direct immunisation is possible. Maternal pneumococcal vaccination has been proposed as a strategy for protection in this period of early childhood; however, limited clinical trial data exists. In this study, we developed an age-structured compartmental mathematical model to estimate the impact of maternal pneumococcal vaccination. Our model demonstrates how maternal pneumococcal vaccination could prevent 73% (range 49–88%) of cases in those aged <1 month and 55% (range 36–66%) in those 1–2 months old. This translates to an estimated 17% reduction in deaths due to invasive pneumococcal disease in children under five. Overall, this study demonstrates the potential for maternal pneumococcal vaccination to meaningfully reduce the burden of infant pneumococcal disease, supporting the case for appropriate field-based clinical studies.
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This study aimed to clarify the attitude of oncologists toward influenza vaccination and the current situation and issues regarding influenza vaccination for patients on chemotherapy in Japan. A web‐based survey of medical oncologists certified by the Japanese Society of Medical Oncology was conducted between November 1 and December 31, 2019. Of the 1369 medical oncologists who were invited to participate, 415 (30.3%) responded to our survey. The questionnaire comprised 4 sections: “oncologist characteristics,” “oncologist attitude toward influenza vaccines and the current status of influenza vaccination for cancer patients undergoing chemotherapy,” “incidence of influenza infection and associated treatment complications,” and “treatment policy for influenza infection.” In total, 153 (36.9%) physicians replied that they did not actively encourage influenza vaccination for patients undergoing chemotherapy. The primary reasons given were lack of evidence (48/153, 31.4%) and uncertainty of appropriate timing (46/153, 30.1%). There was diverse variation in the timing of vaccination and in the levels of encouragement based on the cancer location and medication type. Two hundred eighty‐three (68.2%) oncologists reported that their cancer patients had experienced influenza infection while undergoing chemotherapy, and 169 (40.7%) responded that their patients had experienced an administration delay or discontinuation of medication because of influenza infection. Our surveillance revealed some oncologists considered evidence regarding the administration of influenza vaccine to cancer patients undergoing chemotherapy (particularly the optimal timing and level of recommendation by cancer location and medication) to be lacking. It also exposed the adverse impact of influenza infection in cancer patients.
Article
We provide ethical criteria to establish when vaccine mandates for healthcare workers are ethically justifiable. The relevant criteria are the utility of the vaccine for healthcare workers, the utility for patients (both in terms of prevention of transmission of infection and reduction in staff shortage), and the existence of less restrictive alternatives that can achieve comparable benefits. Healthcare workers have professional obligations to promote the interests of patients that entail exposure to greater risks or infringement of autonomy than ordinary members of the public. Thus, we argue that when vaccine mandates are justified on the basis of these criteria, they are not unfairly discriminatory and the level of coercion they involve is ethically acceptable—and indeed comparable to that already accepted in healthcare employment contracts. Such mandates might be justified even when general population mandates are not. Our conclusion is that, given current evidence, those ethical criteria justify mandates for influenza vaccination, but not COVID-19 vaccination, for healthcare workers. We extend our arguments to other vaccines.
Chapter
Here we describe the different effect measures that are typically used in meta‐analyses of randomized trials, many of which are also used in observational studies. For dichotomous data (e.g. dead or alive), the three main options are the odds ratio (OR), the risk ratio (RR) and the risk difference (RD). We describe how these are computed from results of individual trials, along with measures of uncertainty. For continuous outcomes (e.g. body mass index), the three main options are the difference in means, a standardized difference in means, and the ratio of means (RoM). Again, we provide computational formulae for these, and we also discuss effect measures suitable for time‐to‐event outcomes, rates, and ordinal outcomes. We then explore how one might decide among different effect measures when several are available. The key considerations are (i) the likelihood that effects will be consistent across studies, (ii) mathematical properties, and (iii) ease of interpretation. We close with two case studies to illustrate some of these ideas.
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Abstract Pregnant women have a high risk of severe influenza, associated with obstetrical complications. The World Health Organization (WHO) has recommended influenza vaccination for all pregnant women since 2012. The vaccination coverage remains low worldwide, and in Europe, due to a lack of proposition from the health care providers, and a high refusal rate from the women. The primary aim of this study was to estimate the influenza vaccination coverage (IVC) in a population of pregnant women in France, and to analyse its evolution from 2009 to 2018. The secondary objective was to describe the vaccinated population and to find determinants associated with the vaccination. This retrospective cohort study is based on the EGB French health care database, a representative sample of the French population containing data from the health insurance system. All pregnant women who delivered medically or spontaneously over the 2009–2018 period were included. In the 2009–2018 period, only 1.2% pregnant women were vaccinated against influenza (n = 875/72,207; 95% CI 1.14–1.30). The IVC slightly increased after the 2012 WHO recommendation, from 0.33 to 1.79% (p
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Seasonal Influenza is an acute respiratory illness caused by Influenza A or B viruses. Its presentation is commonly with signs and symptoms of upper respiratory tract involvement such as cough, sore throat and runny nose, associated with generalized systemic symptoms such as fever, headaches, myalgia, and weakness. The severity of symptoms is very variable, ranging from mild self-limiting infection to severe acute respiratory illness requiring intensive interventions. It usually occurs during the winter season and can lead to outbreaks and epidemics worldwide. Influenza is associated with increased morbidity and mortality in high-risk populations including pregnant women and up to two weeks postpartum. Rapid and accurate diagnosis of Influenza is necessary for prompt treatment to reduce morbidity. General public health measures and vaccination are recommended to reduce morbidity and control the spread of the disease. There are many published articles on the several Influenza epidemics that have occurred in this century. In this article, we aim to review the epidemiology, clinical manifestations, diagnosis, treatment, and prevention of seasonal Influenza during pregnancy. We performed an electronic search on PubMed, Cochrane database, National guidelines clearing house and Google Scholar databases.
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Seasonal influenza causes many cases and related deaths in Europe annually, despite ongoing vaccination programs for older adults and people at high-risk of complications. Children have the highest risk of infection and play a key role in disease transmission. Our cost-utility analysis, based on a dynamic transmission model, estimated the impact of increasing the current vaccination coverage with inactivated quadrivalent influenza vaccine in Germany to all (healthy and high-risk) children under 5 years of age (40% uptake), or under 18 years (40% uptake), or only high-risk children under 18 years (90% uptake). Eight influenza complications were modeled, hospitalization and death rates were based on age and risk status. All three vaccination strategies provided more health benefits than the existing vaccination situation, reducing influenza cases, complications, hospitalizations and deaths across the entire population. The strategy targeting all children under 5 years was highly cost-effective (€6/quality-adjusted life-year gained, payer perspective). The other strategies were cost saving from the payer and societal perspectives. The vaccination strategy targeting all children under 18 years was estimated to provide the most health benefits (preventing on average 1.66 million cases, 179,000 complications, 14,000 hospitalizations and 3,600 deaths due to influenza annually) and the most cost savings (annually €20.5 million and €731.3 million from payer and societal perspectives, respectively). Our analysis provides policy decision-makers with evidence supporting strategies to expand childhood influenza vaccination, to directly protect children, and indirectly all other unvaccinated age groups, in order to reduce the humanistic and economic burden on healthcare systems and society.
Article
Background : Epidemiological characteristics profile of the reinfection of the influenza virus has not been well described. Methods : Included all influenza cases of Guangxi, China from January 2011 to December 2019 recorded in National Notifiable Infectious Disease Reporting Information System (NIDRIS) within 24 hours after diagnosis. Results : A total of 53,605.6 person-months and the median time of 8.7 months were observed for reinfection. The median age at the first influenza virus infection was 4.5 (IQR=2.0-7.5) years. The cumulative reinfection incidence was 2% at 6-month, 4% at 12-month, 5% at 24-month, and 7% after 59-month. Living in the rural area (HR=1.37 [95%CI, 1.29-1.45]), age ≤6 years (HR=11.43 [95%CI, 9.47-13.80]) were independent risk factors associated with influenza reinfection. Among 49 patients experiencing twice laboratory tests, 32 patients (65.3%) were with different virus types. The interval between two consecutive laboratory-confirmed episodes of the four groups differed (p=0.148), as the maximum was 72.9 months, and the minimum was 1.2 months. Conclusions : The reinfection of the influenza virus in Guangxi independently and positively associated with the rural area and younger age. The unusually high frequency of reinfection points to a need for further prospective longitudinal studies to better investigate sufficient impact on different subtypes.
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Aim: To establish trends in Implant Dentistry in Latin America in the Covid-19 pandemic. Material and methods: A steering committee and an advisory group of experts in Implant Dentistry were selected among eighteen countries. An open-ended questionnaire by Delphi methodology was validated including 64 questions, divided in 7 topics concerning the various trends in dental implantology. The survey was conducted in two rounds, which provided the participants in the second round with the results of the first. The questionnaires were completed on August 2020 and the online meeting conference was held on September 2020. The final prediction was developed through consensus by a selected group of experts. Results: A total of 197 experts from Latin America answered the first and second questionnaire. In the first round, the established threshold for consensus (65%) was achieved in 30 questions (46.87%). In the second round, performed on average 45 days later, this level was achieved in 47 questions (73.43%). Consensus was completely reached on the item "Diagnostic" (100%), The field with the lowest consensus was "Demand for treatment with dental implants" (37.5%). Conclusions: The present study in Latin America has provided relevant and useful information on the predictions in the education and practice of Implant Dentistry in the Covid-19 era. The consensus points towards a great confidence of clinicians in the biosecurity protocols used to minimize the risk of SARS COV-2 transmission. It is foreseen an important change in education, with introduction of virtual reality and other simulation technologies in implant training.
Article
Introduction Influenza vaccination is a recommended tool in preventing influenza-related illnesses, medical visits, and hospitalizations. With many patients remaining unvaccinated each year, the Emergency Department (ED) represents a unique opportunity to provide vaccinations to patient not yet vaccinated. However, busy urban safety-net EDs maybe challenged to safely execute such a vaccination program. The aim of this quality improvement project was to assess influenza vaccination feasibility in the ED and improve influenza vaccination rates in our community. Methods The quality improvement work-group, comprised of ED physicians, nurses, and pharmacists, designed and implemented an influenza vaccination protocol that aligned with the ED workflow. The outcome measure was the total number of patients vaccinated per month and per influenza season. Process measures included the type of influenza vaccine administered and type of care area within ED. Balancing measures were also included. Results Following the initiative, a total of 337 patients received influenza vaccinations in the ED between September 1, 2018 and December 31, 2020 compared to none during the previous influenza season. With each influenza season, the number of vaccinated patients increased from 61 to 134 and 142, respectively. The average age of the patients was 48.23 ± 15.29, 52.89 ± 15.91, and 44.92 ± 18.97 years old. Most patients received the vaccination while roomed in the high acuity section of the adult ED. No adverse effects or automated dispensing cabinet stockouts were observed. Conclusion Our structured program indicates that influenza vaccine administration to eligible patients is feasible in a busy urban safety-net ED. Piloting new and further developing existing ED-based influenza vaccination programs have the potential to significantly benefit public health.
Article
Pneumonia is a serious complication associated with inflammation of the lungs due to infection with viral pathogens. Seasonal and pandemic influenza viruses, variola virus (agent of smallpox) and severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2; agent of COVID‐19) are some leading examples. Viral pneumonia is triggered by excessive inflammation associated with dysregulated cytokine production, termed ‘cytokine storm’. Several cytokines have been implicated but tumour necrosis factor (TNF) plays a critical role in driving lung inflammation, severe lung pathology and death. Despite this, the exact role TNF plays in the aetiology and pathogenesis of virus infection‐induced respiratory complications is not well understood. In this review, we discuss the pathological and immunomodulatory roles of TNF in contributing to immunopathology and resolution of lung inflammation, respectively, in mouse models of influenza‐ and smallpox (mousepox)‐induced pneumonia. We review studies that have investigated dampening of inflammation on the outcome of severe influenza and orthopoxvirus infections. Most studies on the influenza model have evaluated the efficacy of treatment with anti‐inflammatory drugs, including anti‐TNF agents, in animal models on the day of viral infection. We question the merits of those studies as they are not transferable to the clinic given that individuals generally present at a hospital only after the onset of disease symptoms and not on the day of infection. We propose that research should be directed at determining whether dampening lung inflammation after the onset of disease symptoms will reduce morbidity and mortality. Such a treatment strategy will be more relevant clinically.
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Older adults (≥65 years of age) bear a significant burden of severe disease and mortality associated with influenza, despite relatively high annual vaccination coverage and substantial pre-existing immunity to influenza. To test the hypothesis that host factors, including age and sex, play a role in determining the effect of repeated vaccination and levels of pre-existing humoral immunity to influenza, we evaluated pre- and post-vaccination strain-specific hemagglutination inhibition (HAI) titers in adults over 75 years of age who received a high-dose influenza vaccine in at least four out of six influenza seasons. Pre-vaccination titers, rather than host factors and repeated vaccination were significantly associated with post-vaccination HAI titer outcomes, and displayed an age-by-sex interaction. Pre-vaccination titers to H1N1 remained constant with age. Titers to H3N2 and influenza B viruses decreased substantially with age in males, whereas titers in females remained constant with age. Our findings highlight the importance of pre-existing immunity in this highly vaccinated older adult population and suggest that older males are particularly vulnerable to reduced pre-existing humoral immunity to influenza.
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Background: Standard influenza vaccines are produced using egg-based manufacturing methods. Through the process, the resulting egg-adapted viral strains may differ from the selected vaccine strain. Cell-derived influenza vaccine manufacturing prevents egg-adaptation of the antigen which can improve vaccine effectiveness. We evaluated the cost-effectiveness of quadrivalent cell-derived influenza vaccine (QIVc) versus an egg-based quadrivalent influenza vaccine (QIVe) in preventing seasonal influenza from German societal and payer perspectives. Methods: Adapted version of the individual-based dynamic 4Flu transmission model was combined with a decision-tree to calculate the impact of QIVc versus QIVe on influenza over 20 seasons in Germany. Egg-adaptation, resulting in lower effectiveness of QIVe versus QIVc towards the H3N2 influenza strain, is sourced from a US retrospective study and assumed in 100% (base case) or 55% (conservative scenario) of years. Influenza-related probabilities of outpatient visits, hospitalizations, productivity loss, and mortality, with associated (dis)utilities/costs, were extracted from literature. Costs and outcomes were discounted 3.0%/year. Results: Replacing QIVe with QIVc in subjects aged ≥9 years can annually prevent 167,265 symptomatic cases, 51,114 outpatient visits, 2,091 hospitalizations, and 103 deaths in Germany. The annual number of quality-adjusted life-years (QALYs) increased by 1,628 and healthcare costs decreased by €178M from societal perspective. From payer perspective, the incremental cost-effectiveness ratio was €2,285 per QALY. Scenario analyses confirmed results robustness. Conclusions: The use of QIVc compared to QIVe, in the German Immunization Program, could significantly prevent outpatient visits and hospitalizations and would enable substantial savings from a societal perspective.
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Influenza is a severe, vaccine-preventable disease. Vaccination programs across Latin American countries show contrasting coverage rates, from 29% in Paraguay to 89% in Brazil. This study explores how national influenza vaccination programs in the chosen South American countries address vaccine confidence and convenience, as well as complacency toward the disease. Barriers and facilitators to influenza vaccination programs in their relation to vaccine hesitancy were observed by documentary analysis and interviews with 38 national immunization program officers in high- (Brazil and Chile) and low-performing (Paraguay, Peru, and Uruguay) countries. Influenza vaccination policies, financing, purchasing, coordination, and accessibility are considered good or acceptable. National communication strategies focus on vaccine availability during campaigns. In Chile, Paraguay, and Uruguay, anti-vaccine propaganda was mentioned as a problem. Programming and implementation face human resource shortages across most countries. Statistical information, health information systems, and nominal risk-group records are available, with limitations in Peru and Paraguay. Health promotion, supervision, monitoring, and evaluation are perceived as opportunities to address confidence and complacency. Influenza vaccination programs identify and act on most barriers and facilitators affecting influenza vaccine hesitancy via supply-side strategies which mostly address vaccine convenience. Confidence and complacency are insufficiently addressed, except for Uruguay. Programs have the opportunity to develop integral supply and demand-side approaches.
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There are a variety of challenges in the conduct of systematic reviews of influenza vaccines. We describe our experience of completing four systematic reviews of newer and enhanced inactivated seasonal influenza vaccines. The reporting of the included studies created significant challenges for study identification, data extraction and analysis. Those challenges have implications for the resources required to conduct reviews and, more significantly, for the accuracy of the estimated treatment effect. There is a substantial burden of morbidity and mortality associated with seasonal influenza, and the evidence used to support vaccination strategies requires regular review. An improved review process will facilitate robust decision‐making both nationally and internationally. We recommend the development of reporting guidelines, increased engagement between researchers and decision makers, a database of identified trials, and research into search optimisation.
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The most effective means of preventing seasonal influenza is through vaccination. In this systematic review, we investigated the efficacy, effectiveness and safety of MF59® adjuvanted trivalent and quadrivalent influenza vaccines to prevent laboratory‐confirmed influenza. A systematic literature search was conducted in electronic databases and grey literature sources up to 7 February 2020. Randomised controlled trials and non‐randomised studies of interventions (NRSIs) were eligible for inclusion. The search returned 28,846 records, of which 48 studies on MF59® adjuvanted vaccines met our inclusion criteria. No efficacy trials were identified. In terms of vaccine effectiveness (VE), MF59® adjuvanted trivalent influenza vaccines were effective in preventing laboratory‐confirmed influenza in older adults (aged ≥65 years) compared with no vaccination (VE = 45%, 95% confidence interval (CI) 23%–61%, 5 NRSIs across 3 influenza seasons). By subtype, significant effect was found for influenza A(H1N1) (VE = 61%, 95% CI 44%–73%) and B (VE = 29%, 95% CI 5%–46%), but not for A(H3N2). In terms of relative VE, there was no significant difference comparing MF59® adjuvanted trivalent vaccines with either non‐adjuvanted trivalent or quadrivalent vaccines. Compared with traditional trivalent influenza vaccines, MF59® adjuvanted trivalent influenza vaccines were associated with a greater number of local adverse events (RR = 1.90, 95% CI 1.50–2.39) and systemic reactions (RR = 1.18, 95% CI 1.02–1.38). In conclusion, MF59® adjuvanted trivalent influenza vaccines were found to be more effective than ‘no vaccination’. Based on limited data, there was no significant difference comparing the effectiveness of MF59® adjuvanted vaccines with their non‐adjuvanted counterparts.
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The most effective means of preventing seasonal influenza is through strain‐specific vaccination. In this study, we investigated the efficacy, effectiveness and safety of cell‐based trivalent and quadrivalent influenza vaccines. A systematic literature search was conducted in electronic databases and grey literature sources up to 7 February 2020. Randomised controlled trials (RCTs) and non‐randomised studies of interventions (NRSIs) were eligible for inclusion. Two reviewers independently screened, extracted data and assessed the risk of bias of included studies. Certainty of evidence for key outcomes was assessed using the GRADE methodology. The search returned 28,846 records, of which 868 full‐text articles were assessed for relevance. Of these, 19 studies met the inclusion criteria. No relative efficacy data were identified for the direct comparison of cell‐based vaccines compared with traditional vaccines (egg‐based). Efficacy data were available comparing cell‐based trivalent influenza vaccines with placebo in adults (aged 18–49 years). Overall vaccine efficacy was 70% against any influenza subtype (95% CI 61%–77%, two RCTS), 82% against influenza A(H1N1) (95% CI 71%–89%, 2 RCTs), 72% against influenza A(H3N2) (95% CI 39%–87%, 2 RCTs) and 52% against influenza B (95% CI 30%–68%, 2 RCTs). Limited and heterogeneous data were presented for effectiveness when compared with no vaccination. One NRSI compared cell‐based trivalent and quadrivalent vaccination with traditional trivalent and quadrivalent vaccination, finding a small but significant difference in favour of cell‐based vaccines for influenza‐related hospitalisation, hospital encounters and physician office visits. The safety profile of cell‐based trivalent vaccines was comparable to traditional trivalent influenza vaccines. Compared with placebo, cell‐based trivalent influenza vaccines have demonstrated greater efficacy in adults aged 18–49 years. Overall cell‐based vaccines are well‐tolerated in adults, however, evidence regarding the effectiveness of these vaccines compared with traditional seasonal influenza vaccines is limited.
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This review sought to assess the efficacy, effectiveness and safety of high‐dose inactivated influenza vaccines (HD‐IIV) for the prevention of laboratory‐confirmed influenza in individuals aged 18 years or older. A systematic literature search was conducted in electronic databases and grey literature sources up to 7 February 2020. Randomised controlled trials (RCTs) and non‐randomised studies of interventions (NRSIs) were included. The search returned 28,846 records, of which 36 studies were included. HD‐IIV was shown to have higher relative vaccine efficacy in preventing influenza compared with standard‐dose influenza vaccines (SD‐IIV3) in older adults (Vaccine effectiveness (VE) = 24%, 95% CI 10–37, one RCT). One NRSI demonstrated significant effect for HD‐IIV3 against influenza B (VE = 89%, 95% CI 47–100), but not for influenza A(H3N2) (VE = 22%, 95% CI −82 to 66) when compared with no vaccination in older adults. HD‐IIV3 showed significant relative effect compared with SD‐IIV3 for influenza‐related hospitalisation (VE = 11.8%, 95% CI 6.4–17.0, two NRSIs), influenza‐ or pneumonia‐related hospitalisation (VE = 13.7%, 95% CI 9.5–17.7, three NRSIs), influenza‐related hospital encounters (VE = 13.1%, 95% CI 8.4–17.7, five NRSIs), and influenza‐related office visits (VE = 3.5%, 95% CI 1.5–5.5, two NRSIs). For safety, HD‐IIV were associated with significantly higher rates of local and systemic adverse events compared with SD‐IIV (combined local reactions, pain at injection site, swelling, induration, headache, chills and malaise). From limited data, compared with SD‐IIV, HD‐IIV were found to be more effective in the prevention of laboratory‐confirmed influenza, for a range of proxy outcome measures, and associated with more adverse events.
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Assessing the seroprevalence of the high-risk individuals against the influenza virus is essential to evaluate the progress of vaccine implementation programs and establish influenza virus interventions. Herein, we identified the pre-existing cross-protection of the circulating seasonal influenza viruses among the older-aged population. A cross-sectional study was performed base on the 176 residual sera samples collected from older adults aged 60 to 95 years without a history of vaccination in rural Thailand in 2015. Sera antibody titers against influenza A and B viruses circulating between 2016 and 2019 were determined by hemagglutination inhibition assay. These findings indicated the low titers of pre-existing antibodies to circulating influenza subtypes and showed age-independent antibody titers among the old adults. Moderate seropositive rates (HAI ≥ 1:40) were observed in influenza A viruses (65.9%A(H3N2), 50.0% for A(H1N1) pdm09), and found comparatively lower rates in influenza B viruses (14% B/Yam2, 21% B/Yam3 and 25% B/Vic). Only 5% of individuals possessed broadly protective antibodies against both seasonal influenza A and B virus in this region. Our findings highlighted the low pre-existing antibodies to circulating influenza strains in the following season observed in older adults. The serological study will help inform policy-makers for health care planning and guide control measures concerning vaccination programs.
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The most effective means of preventing seasonal influenza is through vaccination. In this systematic review, we investigated the efficacy, effectiveness and safety of recombinant haemagglutinin (HA) seasonal influenza vaccines to prevent laboratory-confirmed influenza. A systematic literature search was conducted in electronic databases and grey literature sources up to 7 February 2020. Randomised controlled trials and non-randomised studies of interventions were eligible for inclusion. The search returned 28,846 records, of which 10 studies on recombinant HA influenza vaccine met our inclusion criteria. One study found that the quadrivalent recombinant HA influenza vaccine had higher relative vaccine efficacy (rVE) in preventing laboratory-confirmed influenza during the 2014-15 season compared with traditional quadrivalent vaccination in adults aged ≥50 years (rVE = 30%, 95% CI 10%-47%, moderate-certainty evidence). In a subgroup analysis, higher rVE was reported for influenza A (rVE = 36%, 95% CI 14% to 53%), but not for B (non-significant). Another study reported higher efficacy for the trivalent recombinant HA vaccine compared with placebo (VE = 45%, 95% CI 19-63, 1 RCT, low-certainty evidence) in adults aged 18-55 years. With the exception of a higher rate of chills (RR = 1.33, 95% CI 1.03-1.72), the safety profile of recombinant HA vaccines was comparable to that of traditional influenza vaccines. The evidence base for the efficacy and effectiveness of recombinant HA influenza vaccines is limited at present, although one study found that the quadrivalent recombinant HA influenza vaccine had higher rVE compared with traditional quadrivalent vaccination in adults aged ≥50 years.
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Introduction: Health care professionals cover the front line in the battle against infectious diseases. Vaccination of healthcare workers represents a vital element of the strategy for enhancing epidemic safety and improving the quality of health care, inter alia, by limiting microorganism transmission, and reducing patient morbidity and mortality. Method: The study group consisted of all employees of the long-term health care centre in Lublin, Poland. Participants were requested to complete a questionnaire prepared for the purpose of the study, along with a mandatory COVID-19 vaccination interview questionnaire. Results: The vaccination coverage rate for the group of medical workers was 77.3% and of non-medical 86%. The most frequently indicated sources of information on vaccination were the mass media. Males more often than females used the press as a source of information on vaccination. Scientific articles were the most common source of information for both people with higher education and medical professionals. The most common motive for vaccination for females is concern for the health of one's family, and for HCWs and people with at least secondary education-concern for the health of patients. Conclusion: At least one assessed factor influences the decision to be vaccinated. The mass media are of the greatest importance in obtaining information about vaccination.
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Background: Influenza vaccination has been associated with decreased risk of influenza-related infections. However, associations between influenza vaccination and the severity of influenza cases have not been systematically summarized. We conducted a meta-analysis to evaluate whether influenza vaccination could attenuate symptom severity in vaccinated influenza patients. Methods: A systematic literature search was performed using the PubMed, Web of Science, EMBASE, and Scopus databases. A quantitative synthesis of the data was conducted using a fixed/random effects model in the meta-analysis. Results: A total of seven studies, involving 6342 vaccinated and 7036 non-vaccinated patients were included. Compared with non-vaccinated, vaccinated patients were significantly less likely to develop a fever (OR = 0.66, 95% CI: 0.43-0.89), be admitted to the ICU (OR = 0.79, 95% CI: 0.64-0.97), suffer mortality (OR = 0.55, 95% CI: 0.34-0.89), stay in the ICU (WMD = -1.37, 95% CI: -2.15 to -0.60) or stay in the hospital (WMD = -0.32, 95% CI: -0.61 to -0.04). Conclusion: Those benefits that could be highlighted in the communication material to enhance the uptake of influenza vaccination among both the public health nurses and the community as a whole.
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This authoritative textbook provides a much-needed guide for postgraduate trainees preparing for the European Board and College of Obstetrics and Gynaecology (EBCOG) Fellowship examination. Published in association with EBCOG, it fully addresses the competencies defined by the EBCOG curriculum and builds the clinical practice related to these competencies upon the basic science foundations. Volume 1 covers the depth and breadth of obstetrics, and draws on the specialist knowledge of four highly experienced Editors and over 100 contributors from across Europe, reflecting the high-quality training needed to ensure the safety and quality of healthcare for women and their babies. It incorporates key international guidelines throughout, along with colour diagrams and photographs for easy understanding. This is an invaluable resource, not only for postgraduate trainees planning to sit the EFOG examination, but also for practising specialists looking to update their knowledge and skills to meet the ever-evolving complexity of clinical practice.
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As vaccine formulations have progressed from including live or attenuated strains of pathogenic components for enhanced safety, developing new adjuvants to more effectively generate adaptive immune responses has become necessary. In this context, polymeric nanoparticles have emerged as a promising platform with multiple advantages, including the dual capability of adjuvant and delivery vehicle, administration via multiple routes, induction of rapid and long-lived immunity, greater shelf-life at elevated temperatures, and enhanced patient compliance. This comprehensive review describes advances in nanoparticle-based vaccines (i.e., nanovaccines) with a particular focus on polymeric particles as adjuvants and delivery vehicles. Examples of the nanovaccine approach in respiratory infections, biodefense, and cancer are discussed.
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The aim of this study is to investigate the long-term immunogenicity of inactivated split-virion 2009 pandemic influenza A H1N1 vaccine after a single immunization. We recruited 480 adults, aged 18–60 years, for a placebo-controlled, observer-masked, single-center clinical study. We randomly assigned subjects into four groups: 15 μg, 30 μg and 45 μg of hemagglutinin (HA) dosage groups, and a placebo control group. Finally, 259 subjects completed the entire study. The rates of seroconversion and seroprotection and the geometric mean increase (GMI) fulfilled the criteria of the European Medicines Agency (EMEA) for influenza vaccine for 180 days after vaccination in all three dosage groups. However, the seroprotection rates of all dosage groups were below 70% at day 360 post vaccination, while the seroconversion rates and the GMI continued to meet the licensure criteria at this time point. In conclusion, a single dose of 15 μg HA vaccine could induce a protective immune response persisting for at least six months in adults. This study could be beneficial for the future development of influenza vaccines conferring long-term immunity.
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This report updates the 2009 recommendations by CDC's Advisory Committee on Immunization Practices (ACIP) regarding the use of influenza vaccine for the prevention and control of influenza (CDC. Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices [ACIP]. MMWR 2009;58[No. RR-8] and CDC. Use of influenza A (H1N1) 2009 monovalent vaccine---recommendations of the Advisory Committee on Immunization Practices [ACIP], 2009. MMWR 2009;58:[No. RR-10]). The 2010 influenza recommendations include new and updated information. Highlights of the 2010 recommendations include 1) a recommendation that annual vaccination be administered to all persons aged >or=6 months for the 2010-11 influenza season; 2) a recommendation that children aged 6 months--8 years whose vaccination status is unknown or who have never received seasonal influenza vaccine before (or who received seasonal vaccine for the first time in 2009-10 but received only 1 dose in their first year of vaccination) as well as children who did not receive at least 1 dose of an influenza A (H1N1) 2009 monovalent vaccine regardless of previous influenza vaccine history should receive 2 doses of a 2010-11 seasonal influenza vaccine (minimum interval: 4 weeks) during the 2010--11 season; 3) a recommendation that vaccines containing the 2010-11 trivalent vaccine virus strains A/California/7/2009 (H1N1)-like (the same strain as was used for 2009 H1N1 monovalent vaccines), A/Perth/16/2009 (H3N2)-like, and B/Brisbane/60/2008-like antigens be used; 4) information about Fluzone High-Dose, a newly approved vaccine for persons aged >or=65 years; and 5) information about other standard-dose newly approved influenza vaccines and previously approved vaccines with expanded age indications. Vaccination efforts should begin as soon as the 2010-11 seasonal influenza vaccine is available and continue through the influenza season. These recommendations also include a summary of safety data for U.S.-licensed influenza vaccines. These recommendations and other information are available at CDC's influenza website (http://www.cdc.gov/flu); any updates or supplements that might be required during the 2010-11 influenza season also will be available at this website. Recommendations for influenza diagnosis and antiviral use will be published before the start of the 2010-11 influenza season. Vaccination and health-care providers should be alert to announcements of recommendation updates and should check the CDC influenza website periodically for additional information.
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Introduction: Oculo-respiratory syndrome (ORS) is an infrequent adverse event following influenza vaccination. Clinical presentation suggests ORS is an immune mediated phenomenon but studies of symptomatic individuals are few. This study measured cytokine levels in peripheral blood following influenza vaccination in those with and without current ORS symptoms.Methods: Canadian adults receiving the 2010- 2011 seasonal influenza vaccine were recruited and prompted to rapidly report any adverse effects. ORS symptoms occurring 4-48 hours after vaccination were identified using published criteria. Subjects had two blood samples collected to measure plasma cytokines and hemagglutination inhibition antibody (HAI) titers; Visit one during the acute disease phase or 4-72 hours after vaccination for controls and Visit 2 another 21-days post-immunization.Results: 9 ORS cases and 35 controls were enrolled. ORS cases median age was 49 years, and 89% were females. Most cases had multiple symptoms but none required medical care. HAI titers before and after vaccination were similar for cases and controls. Plasma cytokine concentrations did not differ between ORS cases and controls for most cytokines measured (IL-4, -5, -10, -13, IL-1α, IL-8, TNF-α, IFN-γ, IL-17A). However, ORS cases had higher levels of IL-10, IL-3 when compared to controls at Visit 1 and 2 even when all symptoms had subsided.Conclusion: Persistent higher levels of IL-10 and IL-3 in ORS cases suggest that host factors may have predisposed these individuals to develop ORS following influenza vaccination. Further investigations are warranted, as they could potentially identify subjects at risk prior to vaccination.
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Background: Two phylogenetic lineages of influenza B virus coexist and circulate in the human population (B/Yamagata and B/Victoria) but only one B-strain is included in each seasonal vaccine. Mismatch regularly occurs between the recommended and circulating B-strain. Inclusion of both lineages in vaccines may offer better protection against influenza. Methods: This study (NCT00714285) assessed the immunogenicity and safety of two candidate quadrivalent influenza vaccines (QIV) containing two A- and two B-strains (one from each lineage) in adults (18-60 years). Subjects were randomized and stratified by age to receive either QIV (non-adjuvanted or low-dose adjuvanted [LD QIV-AS]) or trivalent influenza vaccine (TIV, non-adjuvanted or low-dose adjuvanted [LD TIV-AS]), N = 105 in all treatment groups. The study evaluated the statistical non-inferiority of the immunological response elicited by QIV and LD QIV-AS versus TIV and LD TIV-AS and the statistical superiority of the response elicited by the quadrivalent vaccines against the B-strain (B/Jiangsu) not included in the TIV. Results: Pre-defined non-inferiority and superiority criteria were reached for both QIVs compared to the TIVs. On Day 21 in all vaccine groups SCRs were ≥54.8%, SPRs ≥88.5% and SCFs ≥5.4 for the A strains and B strain included in all vaccines (B/Malaysia). This fulfilled the European (CHMP) and the US (CBER) licensing criteria for the assessment of influenza vaccines in adults (CHMP criteria: SCR > 40%, SPR > 70%, SCF > 2; CBER criteria: LL of 95% CI for SPR ≥ 70% or SCR ≥ 40%). Only the QIVs met the CHMP and CBER criteria for the B/Jiangsu strain. In the QIV and LD-QIV-AS groups, the SCFs were 9.1 and 8.1, respectively and the SPRs were 98.1% and 95.2%, whereas for the TIV and LD-TIV-AS groups, the SCFs were 2.3 and 2.5, respectively, and the SPRs were 75.0% and 63.8%, with the LLs of the 95% CI <70% for SPR and <40% for SCR. Conclusions: Addition of a fourth strain did not impact the immune response elicited by the three original strains contained in the TIV. A clear immunological benefit was seen with the QIV formulation for the second B-strain, indicating that quadrivalent vaccines could provide broader protection against influenza. Trial registration: ClinicalTrials.gov: NCT00714285.
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Many Canadians received a novel AS03-adjuvanted vaccine during the 2009 influenza A/H1N1 pandemic. Longer term implications of adjuvant use were unclear: would anti-H1N1 immune responses persist at high levels and, if so, could that result in increased or unusual adverse effects upon re-exposure to H1N1pdm09 antigen in the trivalent influenza vaccine (TIV) for 2010-11? To answer these questions, adults given AS03-adjuvanted H1N1pdm09 vaccine (Arepanrix®, GSK Canada) 9-10 mo earlier were enrolled in an evaluator-blinded, crossover trial to receive 2010-2011 non-adjuvanted TIV (Fluviral®, GSK Canada) and placebo 10 d apart, in random order. Adverse effects were monitored for 7 d after each injection. Vaccine-attributable adverse event (VAAE) rates were calculated by subtracting rates after placebo from those after vaccine. Blood was obtained pre-vaccination and 21-30 d afterward to measure hemagglutination inhibiting antibody titers. In total, 326 participants were enrolled and 321 completed the study. VAAE rates were low except for myalgia (18.6%) and injection site pain (63.2%). At baseline, H1N1pdm09 titers ≥ 40 were present in 176/325 subjects (54.2%, 95% confidence interval 48.6, 59.7), with a geometric mean titer (GMT) of 37.4 (95% CI 32.8, 42.6). Post-immunization, 96.0% (95% CI 92.3, 97.8) had H1N1pdm09 titers ≥ 40, with GMT of 167.4 (95% CI 148.7, 188.5). Responses to both influenza A strains in TIV were similar, implying no lasting effect of adjuvant exposure. In summary, titers ≥ 40 persisted in only half the participants 9-10 mo after adjuvanted pandemic vaccine but were restored in nearly all after TIV vaccination, with minimal increase in adverse effects.
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Influenza vaccination has been implicated in Guillain Barré Syndrome (GBS) although the evidence for this link is controversial. A case-control study was conducted between October 2010 and May 2011 in seven Italian Regions to explore the relation between influenza vaccination and GBS. The study included 176 GBS incident cases aged ≥18 years from 86 neurological centers. Controls were selected among patients admitted for acute conditions to the Emergency Department of the same hospital as cases. Each control was matched to a case by sex, age, Region and admission date. Two different analyses were conducted: a matched case-control analysis and a self-controlled case series analysis (SCCS). Case-control analysis included 140 cases matched to 308 controls. The adjusted matched odds ratio (OR) for GBS occurrence within 6 weeks after influenza vaccination was 3.8 (95 % CI: 1.3, 10.5). A much stronger association with gastrointestinal infections (OR = 23.8; 95 % CI 7.3, 77.6) and influenza-like illness or upper respiratory tract infections (OR = 11.5; 95 % CI 5.6, 23.5) was highlighted. The SCCS analysis included all 176 GBS cases. Influenza vaccination was associated with GBS, with a relative risk of 2.1 (95 % CI 1.1, 3.9). According to these results the attributable risk in adults ranges from two to five GBS cases per 1,000,000 vaccinations.
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To assess the safety of an AS03-adjuvanted split virion H1N1 (2009) vaccine (Pandemrix) in persons vaccinated during the national pandemic influenza vaccination campaign in the UK. Prospective, cohort, observational, postauthorisation safety study. 87 general practices forming part of the Medical Research Council General Practice Research Framework and widely distributed throughout England. A cohort of 9143 individuals aged 7 months to 97 years who received at least one dose of the AS03-adjuvanted H1N1 pandemic vaccine during the national pandemic influenza vaccination campaign in the UK was enrolled. 94% completed the 6-month follow-up. Exclusion criteria were previous vaccination with other H1N1 pandemic vaccine and any child in care. PRIMARY AND SECONDARY OUTCOME MEASURES: Medically attended adverse events (MAEs) occurring within 31 days after any dose, serious adverse events (SAEs) and adverse events of special interest (AESIs) following vaccination were collected for all participants. Solicited adverse events (AEs) were assessed in a subset of participants. MAEs were reported in 1219 participants and SAEs in 113 participants during the 31-day postvaccination period. The most frequently reported MAEs and SAEs were consistent with events expected to be reported during the winter season in this population: lower respiratory tract infections, asthma and pneumonia. The most commonly reported solicited AEs were irritability in young children aged <5 years (61.8%), muscle aches in children aged 5-17 years (61.9%) and adults (46.9%). 18 AESIs, experienced by 14 patients, met the criteria to be considered for the observed-to-expected analyses. AESIs above the expected number were neuritis (1 case within 31 days) and convulsions (8 cases within 181 days). There were 41 deaths during the 181-day period after vaccination, fewer than expected. Results indicate that the AS03-adjuvanted H1N1 pandemic vaccine showed a clinically acceptable reactogenicity and safety profile in all age and risk groups studied. ClinicalTrials.gov, NCT00996853.
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Background: Influenza infection during pregnancy is associated with adverse fetal outcomes such as preterm birth and small for gestational age (SGA). Maternal influenza immunization may prevent these adverse infant outcomes during periods of influenza circulation. Methods: We conducted a retrospective cohort study of live births within Kaiser Permanente (KP) Georgia and Mid-Atlantic States (n = 3327) during the period of 2009 influenza A (H1N1) virus circulation. Primary outcomes were third-trimester preterm birth (27-36 weeks), birth weight, low birth weight (LBW, <2500 g), and SGA. Results: There were 327 (9.8%) preterm, 236 (7.4%) LBW, and 267 (8.4%) SGA births. Among H1N1-vaccinated mothers (n = 1125), there were 86 (7.6%) preterm, 68 (6.4%) LBW, and 99 (9.3%) SGA births, and the mean birth weight was 3308.5 g (95% confidence interval [CI], 3276.6-3340.4). Among unvaccinated mothers (n = 1581), there were 191 (12.1%) preterm, 132 (8.8%) LBW, and 123 (8.2%) SGA births, and the mean birth weight was 3245.3 g (95% CI, 3216.5-3274.2). Infants of H1N1-vaccinated mothers had 37% lower odds of being born preterm than infants of unvaccinated mothers (adjusted odds ratio, 0.63 [95% CI, .47-.84]). The mean birth weight difference between infants of H1N1-vaccinated mothers and infants of unvaccinated mothers was 45.1 g (95% CI, 1.8-88.3). There was no significant association between maternal H1N1 influenza immunization and LBW or SGA. Conclusions: Pregnant women who received H1N1 influenza vaccine were less likely to give birth preterm, and gave birth to heavier infants. The findings support US vaccine policy choices to prioritize pregnant women during the 2009 influenza A (H1N1) pandemic.
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Background: During the 2009 influenza A (H1N1) pandemic, pregnant women were at risk for severe influenza illness. This concern was complicated by questions about vaccine safety in pregnant women that were raised by anecdotal reports of fetal deaths after vaccination. Methods: We explored the safety of influenza vaccination of pregnant women by linking Norwegian national registries and medical consultation data to determine influenza diagnosis, vaccination status, birth outcomes, and background information for pregnant women before, during, and after the pandemic. We used Cox regression models to estimate hazard ratios for fetal death, with the gestational day as the time metric and vaccination and pandemic exposure as time-dependent exposure variables. Results: There were 117,347 eligible pregnancies in Norway from 2009 through 2010. Fetal mortality was 4.9 deaths per 1000 births. During the pandemic, 54% of pregnant women in their second or third trimester were vaccinated. Vaccination during pregnancy substantially reduced the risk of an influenza diagnosis (adjusted hazard ratio, 0.30; 95% confidence interval [CI], 0.25 to 0.34). Among pregnant women with a clinical diagnosis of influenza, the risk of fetal death was increased (adjusted hazard ratio, 1.91; 95% CI, 1.07 to 3.41). The risk of fetal death was reduced with vaccination during pregnancy, although this reduction was not significant (adjusted hazard ratio, 0.88; 95% CI, 0.66 to 1.17). Conclusions: Pandemic influenza virus infection in pregnancy was associated with an increased risk of fetal death. Vaccination during pregnancy reduced the risk of an influenza diagnosis. Vaccination itself was not associated with increased fetal mortality and may have reduced the risk of influenza-related fetal death during the pandemic. (Funded by the Norwegian Institute of Public Health.).
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In 2009, pregnant women were specifically targeted by a national vaccination campaign against pandemic A/H1N1 influenza virus. The objectives of the COFLUPREG study, initially set up to assess the incidence of serious forms of A/H1N1 influenza, were to assess the consequences of maternal vaccination on pregnancy outcomes and maternal seroprotection at delivery. Pregnant women, between 12 and 35 weeks of gestation, non vaccinated against A/H1N1 2009 influenza were randomly selected to be included in a prospective cohort study conducted in three maternity centers in Paris (France) during pandemic period. Blood samples were planned to assess hemagglutination inhibition (HI) antibody against A/H1N1 2009 influenza at inclusion and at delivery. Among the 877 pregnant women included in the study, 678 (77.3%) had serum samples both at inclusion and delivery, and 320 (36.5%) received pandemic A/H1N1 2009 influenza vaccine with a median interval between vaccination and delivery of 92 days (95% CI 48-134). At delivery, the proportion of women with seroprotection (HI antibodies titers against A/H1N1 2009 influenza of 1∶40 or greater) was 69.9% in vaccinated women. Of the 422 non-vaccinated women with serological data, 11 (2.6%; 95%CI: 1.3-4.6) had laboratory documented A/H1N1 2009 influenza (1 with positive PCR and 10 with serological seroconversion). None of the 877 study's women was hospitalized for flu. No difference on pregnancy outcomes was evidenced between vaccinated women, non-vaccinated women without seroconversion and non-vaccinated women with flu. Despite low vaccine coverage, incidence of pandemic flu was low in this cohort of pregnant women.No effect on pregnancy and delivery outcomes was evidenced after vaccination.
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Intranasal live attenuated influenza vaccine (LAIV) has potential for self-administration (SA) by adults and adolescents, which could save time and cost in mass vaccination settings. Participants in a study of LAIV in adults (n=4561) selected either SA or health care provider (HCP) administration and were followed for febrile illness during the influenza season. More LAIV recipients chose SA-LAIV (72%) than HCP-LAIV (28%). Overall, 97% of SA-LAIV and 98% of HCP-LAIV recipients had no problems with vaccine administration. Four of 13 study sites enrolled more than 50 subjects in both cohorts. Overall and for these 4 sites, illness incidence was similar with SA-LAIV and HCP-LAIV. Solicited reactogenicity events and adverse events through 7 days post vaccination were comparable for SA-LAIV and HCP-LAIV recipients; both groups exhibited increased runny nose, sore throat, and cough relative to placebo recipients. SA-LAIV and HCP-LAIV appeared similarly effective against influenza-like illness and had comparable safety profiles.
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Concern for a pandemic caused by a newly emerged avian influenza A virus has led to clinical trials with candidate vaccines as preparation for such an event. Most trials have involved vaccines for influenza A (H5N1), A (H7N7) or A (H9N2). To evaluate dosage-related safety and immunogenicity of an inactivated influenza A (H7N7) vaccine in humans. One hundred twenty-five healthy young adults were randomized to receive two doses intramuscularly of placebo or 7.5, 15, 45 or 90 µg of HA of an inactivated subunit influenza A (H7N7) vaccine (25 per group), four weeks apart. Reactogenicity was evaluated closely for one week and for any adverse effect for six months after each dose. Serum hemagglutination-inhibiting and neutralizing antibody responses were determined four weeks after each dose and at six months. Reactogenicity evaluations indicated the vaccinations were well tolerated. Only one subject developed a ≥4-fold serum hemagglutination-inhibition (HAI) antibody response and a final titer of ≥1∶40 four weeks after dose two and only five subjects developed a neutralizing antibody rise and a final titer of ≥1∶40 in tests performed at a central laboratory. Four of the five were given the 45 or 90 µg HA dosage. A more sensitive HAI assay at the study site revealed a dose-response with increasing HA dosage but only 36% in the 90 µg HA group developed a ≥4-fold rise in antibody in this test and only one of these achieved a titer of ≥1∶32. This inactivated subunit influenza A (H7N7) vaccine was safe but poorly immunogenic in humans. ClinicalTrials.gov NCT00546585.
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Immune thrombocytopenia (ITP) remains of unknown cause. Studies have suggested immunizations as possible triggering factors of ITP through molecular mimicry. This case-control study explored potential associations between adult ITP and different routinely administered vaccines. A network of internal medicine and hematology centers across France recruited 198 incident (i.e. newly-diagnosed) cases of ITP between April 2008 and June 2011. These cases were compared with 878 age and sex-matched controls without ITP recruited in general practice. Information on vaccination was obtained from patients' standardized telephone interviews. Sixty-six of 198 cases (33.3%) and 303 of 878 controls (34.5%) received at least one vaccine within the 12 months before the index date. We found no evidence of an increase in ITP following vaccination in the previous 6 or 12 months (adjusted odds ratio for the previous 12 months 1.0, 95% confidence interval 0.7, 1.4). When the 2- month time window was used, higher ORs were observed for all vaccines (OR= 1.3) mainly attributable to the vaccination against diphtheria-tetanus-pertussis-poliomyelitis (OR= 1.5). However this increase was not statistically significant. Our study reports results showing that in an adult population, the exposure to common vaccines is on average not associated with an observable risk of developing ITP.
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1169 Background and objectives Immune thrombocytopenia (ITP) is thought to result from an autoimmune mechanism, and some case-reports have suggested that immunizations could be involved and trigger the autoimmune process. This prospective multicenter case-control study investigated for the first time associations between ITP and vaccination in adults, particularly between ITP and influenza vaccinations. Methods Over a three year period, a network of 15 physicians from hematology and internal medicine referral centers across France recruited newly diagnosed cases of primary ITP in patients aged over 15 years fulfilling the ITP standardized criteria of the American Society of Hematology. Recruiting physicians completed standardized forms for each patient and every patient underwent a standardized 1 hour-interview focused on previous medications and vaccinations in the last 12 months. Incident ITP cases were compared to sex and age-matched controls selected and recruited from general practice settings, also from the same geographically areas of France. The method of referent recruitment has been described elsewhere (Grimaldi-Bensouda et al. 2010 Pharmacoepidemiol Drug Saf 2010;19(6):591–5). Controls were also interviewed in the same standardized way as cases. Cases and control were compared in respect of various descriptive factors and potential risk factors for ITP. Written or other confirmation of vaccinations was sought from both the patient and his/her physician. The time window defining exposure to vaccines was 12 months before the index date. In secondary analysis, the most prevalent vaccines in adults were analyzed. Results Two hundred and twenty four cases fulfilling the inclusion criteria and 4412 were included in the study. Seventy eight of the 224 cases (34.8%) and 1566 of 4412 controls (35.5%) received a vaccination within this time window [adjusted odds ratio 0.97, 95% confidence interval 0.70–1.33]. Twenty percent of the cases and 26% of controls received an influenza vaccine [adjusted odds ratio 0.66, 95% confidence interval 0.45–0.98]. Other prevalent vaccines in adult are currently under study. Conclusions This systematic case-control design is well-suited to study rare disorders such as ITP and few such studies have been conducted. Another advantage was the minimization of recall bias because questions about vaccinations were included in a standardized interview focusing on exposure to all medications. When all vaccines were considered, we found no association between vaccination and the incidence of ITP in either crude or adjusted analyses. Moreover, cases were less likely than controls to have been vaccinated against influenza in the 12 months before the index date. Disclosures Grimaldi-Bensouda: LA-SER: Employment; INSERM: I was the recipient of a research fellowship from the INSERM (French National Institute for Health and Medical Research) at the time of the study. Leighton:LA-SER Europe Ltd: Employment. Aubrun:LA-SER Europe Ltd: Employment. Abenhaim:LA-SER Europe Ltd: I'm a stock owner and chairman of LA-SER, the company conducting the study.
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Influenza epidemics are associated with an excess of mortality not only from respiratory diseases but also from other causes, and cardiovascular mortality increases abruptly during influenza epidemics, with little evidence of a lag period. In a population-based case-control study, the authors examined whether influenza vaccination was associated with a reduced risk of out-of-hospital primary cardiac arrest (PCA), a major contributor to cardiovascular mortality in the community. Cases of PCA (n = 342) without prior heart disease or life-threatening comorbidity that occurred in King County, Washington, were identified from paramedic incident reports from October 1988 to July 1994. Demographically similar controls (n = 549) were identified from the community by using random digit dialing. Spouses of subjects were interviewed to assess treatment with influenza vaccine during the previous year and other risk factors. After adjustment for demographic, clinical, and behavioral risk factors, influenza vaccination was associated with a reduced risk of PCA (odds ratio = 0.51, 95 percent confidence interval: 0.33, 0.79). The authors suggest that while the association of influenza vaccination with a reduced risk of PCA is consistent with cohort studies of influenza vaccination and total mortality, further studies are needed to determine whether the observed association reflects protection or selection.
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Background: Concern about side effects is a barrier to influenza vaccination. This randomized, double-blind, placebo-controlled trial assessed side effects following vaccination among healthy working adults.Methods: Healthy working adults were recruited during October and November 1994 and were randomized to receive influenza vaccine or placebo injections. Local and systemic symptoms during the week following the injection were evaluated through structured telephone interviews.Results: Of 849 subjects enrolled in the study, 425 received a placebo and 424 received influenza vaccine. Base-line characteristics were similar between the groups, and 99% of subjects completed interviews to assess side effects after the study injection. No differences were seen between the 2 groups for the systemic symptoms of fever, myalgias, fatigue, malaise, or headaches. Overall, 35.2% of placebo and 34.1% of vaccine recipients reported at least 1 of these systemic symptoms (P=.78,χ2). Vaccine recipients reported a higher rate of arm soreness at the injection site than did placebo recipients (63.8% vs 24.1%, P<.001). Local reactions were mild in both groups and infrequently resulted in decreased use of the arm. After logistic regression, female sex (odds ratio [OR], 1.5; 95% confidence interval [CI], 1.1-2.1), age younger than 40 years (OR, 1.6; 95% CI, 1.2-2.2), and coincidental upper respiratory tract illness (OR, 4.6; 95% CI, 3.2-6.6) were independently associated with higher rates of systemic symptoms. In the multivariate model, vaccine again was not associated with systemic symptoms (OR, 0.9; 95% CI, 0.7-1.2).Conclusions: Influenza vaccination of healthy working adults is not associated with higher rates of systemic symptoms when compared with placebo injection. These findings should be useful to physicians and other health care providers as they counsel patients to take advantage of an important opportunity for disease prevention and health protection.Arch Intern Med. 1996;156:1546-1550
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An ongoing surveillance program was intensified during the 1979-1980 and the 1980-1981 influenza seasons to determine whether an increased risk of acquiring Guillain-Barré syndrome (GBS) within eight weeks after influenza vaccination existed for adults in the United States who received influenza vaccine, when compared with adults who had not been vaccinated recently. Five hundred twenty-eight cases of GBS with onset between Sept 1 and March 31, including seven following recent vaccination, were reported by participating neurologists in 1979-1980; 459 cases, including 12 following recent vaccination, were reported in 1980-1981. The relative risk of acquiring GBS following influenza vaccination—0.6 in 1979-1980 and 1.4 in 1980-1981—was not significantly different from 1.0 in either season. These results suggest that there was no increased risk of acquiring GBS associated with the influenza vaccines administered during these seasons and that the causative "trigger agent" in the A/New Jersey (swine) influenza vaccine administered in 1976 has not been present in subsequent influenza vaccine preparations. (JAMA 1982;248:698-700)