Consumption Externality and Yield Uncertainty in the Influenza Vaccine Supply Chain: Interventions in Demand and Supply Sides
In: Management Science, Band 58(6), Heft 1072-1091
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In: Management Science, Band 58(6), Heft 1072-1091
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A government-funded trivalent influenza vaccine (TIV) program to prevent seasonal influenza was implemented in Taiwan since 1998. However, mismatch between the vaccine and circulating strains may occur. Alternatively, a quadrivalent influenza vaccine (QIV) includes all 4 influenza lineages could minimize the risk of mismatches. Therefore, QIV could be considered as an alternative strategy to enhance protection against seasonal influenza. The objective of the study was to analyze, from a governmental perspective, the cost-effectiveness of using QIV vs. TIV as a vaccination strategy in Taiwan.
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In: Herrett , E , Van Staa , T , Free , C & Smeeth , L 2014 , ' Text messaging reminders for influenza vaccine in primary care: Protocol for a cluster randomised controlled trial (TXT4FLUJAB) ' BMJ open , vol 4 , no. 5 , e004633 . DOI:10.1136/bmjopen-2013-004633
Introduction: The UK government recommends that at least 75% of people aged under 64 with certain conditions receive an annual influenza vaccination. Primary care practices often fall short of this target and strategies to increase vaccine uptake are required. Text messaging reminders are already used in 30% of practices to remind patients about vaccination, but there has been no trial addressing their effectiveness in increasing influenza vaccine uptake in the UK. The aims of the study are (1) to develop the methodology for conducting cluster randomised trials of text messaging interventions utilising routine electronic health records and (2) to assess the effectiveness of using a text messaging influenza vaccine reminder in achieving an increase in influenza vaccine uptake in patients aged 18-64 with chronic conditions, compared with standard care. Methods and analysis: This cluster randomised trial will recruit general practices across three settings in English primary care (Clinical Practice Research Datalink, ResearchOne and London iPLATO text messaging software users) and randomise them to either standard care or a text messaging campaign to eligible patients. Flu vaccine uptake will be ascertained using routinely collected, anonymised electronic patient records. This protocol outlines the proposed study design and analysis methods. Ethics and dissemination: This study will determine the effectiveness of text messaging vaccine reminders in primary care in increasing influenza vaccine uptake, and will strengthen the methodology for using electronic health records in cluster randomised trials of text messaging interventions. This trial was approved by the Surrey Borders Ethics Committee (13/LO/0872). The trial results will be disseminated at national conferences and published in a peer-reviewed medical journal. The results will also be distributed to the Primary Care Research Network and to all participating general practices. Trial registration number: This study is registered at controlled-trials.com ISRCTN48840025, July 2013.
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In 2009, a novel A(H1N1) influenza virus emerged with rapid human-to-human spread and caused the first pandemic of the 21st century. Although this pandemic was considered mild compared to the previous pandemics of the 20th century, there was still extensive disease and death. This virus replaced the previous A(H1N1) and continues to circulate today as a seasonal virus. It is well established that vaccines are the most effective method to alleviate the mortality and morbidity associated with influenza virus infections, but the 2009 A(H1N1) influenza pandemic, like all significant infectious disease outbreaks, presented its own unique set of problems with vaccine supply and demand. This manuscript describes the issues that confronted governments, international agencies and industries in developing a well-matched vaccine in 2009, and identifies the key improvements and remaining challenges facing the world as the next influenza pandemic inevitably approaches.
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This report was prepared as part of the Project "Monitoring Influenza vaccine effectiveness during influenza seasons and pandemics in the European Union", financed by the European Centre for Disease Prevention and Control, and describes the results obtained in Portugal under the Protocol Agreement celebrated between EpiConcept SARL, Paris and National Health Institute Doutor Ricardo Jorge, Lisbon, signed on December 2014. ; Relatório elaborado em julho de 2015. ; [eng] Background: The EuroEVA project is the Portuguese component of the multicentre I-MOVE study. The results to be presented are related to the 7th EuroEVA season and aimed the estimation of 2014-15 end of season influenza vaccine effectiveness in i) all age groups; ii) by risk group; iii) by influenza subtype and thus contribute to monitor VE estimates every year. Material and methods: The "Protocol for case-control studies to measure seasonal influenza vaccine effectiveness in the European Union and European Economic Area Member States- Portuguese site study version" was implemented entirely with no changes to be added. VE was estimated as one minus the odds ratio of being vaccinated in cases versus controls adjusted for confounders by logistic regression. Potential confounders were investigated and included if they changed crude OR estimate in at least 10% after adjustment by the Mantel-Haenszel method. Results: In Portugal, influenza epidemic occurred between week 1/2015 and week 8/2015 and had a medium- high intensity. Both B and A(H3) virus were circulating, but with dominance of the first one. A(H1)pdm09 was only detected sporadically. From the 50 GP's that accepted to participate in the study, 31 GP's effectively participated in the study by selecting patients (which corresponds to a 62% participation rate). A total of 268 ILI patients were enrolled, each GP recruited in average 8.6 patients. After excluding 19 ILI patients the final sample for analyses consisted on 249 ILI patients (147 cases and 102 controls). From the cases, 68% were positive for type B virus, Yamagata lineage, 31% were positive for influenza A (H3) and 1% for A(H1)pdm09. Antigenic and genetic analysis indicated that influenza A(H3) viruses were genetically and antigenically different from the 2014/2015 vaccine strain, most of them belonging to the new virus cluster 3C.2a. Detected influenza B viruses belong to the same lineage (Yamagata) of the strain represented in the 2014/2015 influenza vaccine. Comparing cases and controls, we verified that they were statistically different in relation to: - Age: controls were older than cases (median age in controls was 51 yrs vs. 44 yrs in cases); - Any chronic disease: the prevalence of at least one chronic condition relevant for influenza vaccination was higher in controls (44.1% vs 28.1%); - Seasonal vaccine in 2013-14: controls were more often vaccinated against influenza in the last season than cases (28.4% vs. 12.3%); - Help bathing: controls needed more help for bathing than cases (0% in cases vs 4.1% in controls). Overall results indicated that vaccine coverage (VC) in controls was statistically higher (p<0.001) than in cases (VC controls=30.7% and VC cases=11.0%). Similar results were obtained for the target group for vaccination by the National Health Authorities (VC cases=26.8% and VC controls=54.9%, p=0.003). Restricting the analysis to type B virus (Yamagata lineage), VC was statistically (p=0.001) higher in controls than in cases (30.7% vs 8.1% in all ILI cases and 53.9% vs 20.0% in the target group). After adjustment for age, chronic disease and month of illness onset, VE adjusted estimates in all population was 63.4% (95% CI: 16.2%; 84.0%). In the target group for vaccination, after adjustment, VE estimates was 65.0% (95% CI: 8.1%; 86.7%). Restricting to B Yamagata cases, similar VE estimates were obtained for all population and target group: VE all population = 78.5% (95% CI: 39.5; 92.4); VE target group = 79.6% (95CI: 34.7; 93.6). Although all crude and adjusted VE estimates were statistically significant, low precision was observed. Conclusions: The 2014-2015 season adjusted VE estimates against B/Yamagata was approximately 79% (statistically significant but low precision). No VE estimates against A(H3) were obtained due to small sample size. All influenza B belonged to genetic group 3, different from genetic group 2, represented by B/Massachusets/02/2012 vaccine strain but antigenically these strains are related. This fact is in line with a moderate/high VE for influenza B in 2014-15 season. ; [pt] O projeto EuroEVA (Efetividade da vacina antigripal na Europa) é a componente portuguesa do estudo europeu multicêntrico I-MOVE. Os resultados apresentados correspondem à implementação do estudo EuroEVA na época 2014-2015 e pretende obter estimativas da efetividade da vacina (EV) sazonal 2014-2015 i) na população geral; ii) no grupo alvo para o qual a vacina é recomendada; iii) por tipo/sub tipo de vírus e desta forma contribuir para a monitorização da EV antigripal todas as épocas. Material e Métodos: O "Protocol for case-control studies to measure seasonal influenza vaccine effectiveness in the European Union and European Economic Area Member States- Portuguese site study version" foi implemetado na integra sem alterações a reportar. A efetividade da vacina (EV) foi estimada através de EV=1-OR sendo OR o odd ratio de estar vacinado nos casos vs controlos ajustado fatores de confundimento foram analisados e incluídos se alteraram o odds-ratio bruto em pelo menos 10% após ajustamento pelo método de Mantel Haenszel. Resultados: Em Portugal o período epidémico ocorreu entre as semanas 1/2015 e 8/2015 tendo-se verificado uma atividade gripal média-alta. Verificou-se a co circulação de vírus do tipo B e do sub-tipo A(H3), tendo o primeiro dominado durante a época. Verificou- se ainda a circulação esporádica de vírus do tipo A(H1)pdm09. De entre os 50 médicos de família (MF) que aceitaram participar no estudo, 31 reportaram doentes com síndroma gripal (SG), correspondendo a uma taxa de participação de 62%. No total foram selecionados 268 doentes com SG, em média cada médico recrutou 8,6 doentes. Após exclusão de 19, por não respeitarem a definição de caso de SG, a amostra final para análise consistia em 249 doentes com SG (147 casos positivos e 102 controlos negativos). De entre os casos, 68% eram do tipo B vírus, linhagem Yamagata, 31% eram positivos para o vírus do subtipo A (H3) e 1% para o tipo A(H1)pdm09. A análise genética e antigénica dos vírus influenza A(H3) revelou que na sua maioria pertencem ao novo grupo genético 3C.2a, que se distinguem da estirpe A(H3) contemplada na vacina da época 2014/2015. Os vírus influenza B detetados pertencem à linhagem Yamagata, à semelhança do vírus do tipo B contemplado na vacina da época 2014/2015. Comparando casos e controlos verifica-se que os grupos eram estatisticamente diferentes nas seguintes variáveis: - Idade: os controlos eram mais velhos que os casos (idade mediana nos controlos o era 51 anos vs 44 anos nos casos); - Doença crónica: a prevalência de pelo menos 1 doença crónica com relevância para a infeção por gripe era mais elevada do que controlos (44,1% vs 28,1%); - Toma da vacina na época anterior: os controlos tinham uma história passada de toma da vacina (época 2013/14) mais frequente (28,4% vs. 12,3%); - Incapacidade (Ajuda na toma de banho): os controlos manifestaram em maior percentagem necessidade de ajuda para tomar banho (0% nos casos vs 4,1% nos controlos) De uma forma geral, a cobertura da vacina (CV) sazonal antigripal 2014/15 foi mais elevada (e com significado estatístico, p<0.001) nos controlos (30,7%) do que nos casos (CV=11,0%). Restringindo a análise para o grupo alvo para a toma da vacina de acordo com as Autoridades de Saúde Nacionais, verificaram-se resultados semelhantes (CV casos=26,8% and CV controlos=54,9%, p=0,003). Relativamente à análise por tipo de vírus dominante (vírus do tipo B/ Yamagata), a CV era estatisticamente superior (p=0,001) nos controlos do que nos casos (30,7% vs 8,1% na população geral e 53,9% vs 20,0% no grupo alvo da vacina). Após ajustamento para idade, presença de doença crónica e mês de início de sintomas, a EV ajustada para a população em geral foi de 63,4% (IC95%: 16,2%-84,0%). No grupo alvo da vacina a estimativa ajustada situa a EV em 65,0% (IC95%: 8,1%-86,7%). Restringindo a análise aos casos B/ Yamagata, obtiveram-se valores similares na população em geral e no grupo alvo da vacina: EV população geral = 78,5% (IC95%: 39,5%-92,4%); EV grupo alvo = 79.6% (IC95%: 34,7%-93,6%). Embora ambas as estimativas tenham significado estatístico, a precisão é baixa. ; European Center for disease Prevention and Control
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This report was prepared as part of the Project "Monitoring Influenza vaccine effectiveness during influenza seasons and pandemics in the European Union" and describes the results obtained in Portugal under the Protocol Agreement celebrated between EpiConcept SARL, Paris and National Health Institute Dr. Ricardo Jorge, Lisbon. Data and activities related to the individuals 65 years and more were funded by European Union's Horizon 2020 research and innovation programme under grant agreement no 634446. ; The results to be presented are related to the 8th EuroEVA season (the Portuguese component of the multicentre I-MOVE study) and aimed the estimation of 2015/2016 end of season influenza vaccine effectiveness in i) all age groups and in <65 and 65 plus years ; ii) by risk group; iii) by influenza subtype and clade. Material and methods: The "Protocol for case-control studies to measure seasonal influenza vaccine effectiveness in the European Union and European Economic Area Member States- Portuguese site study version" was implemented entirely adding a new variable related to statin uptake. Also, a pilot study to incorporate genetic characterization of influenza virus from patients enrolled in vaccine effectiveness (VE) study was implemented. Within this pilot study, influenza A(H1)pdm09 positive cases were randomly selected to be genetically characterized. Selection was conducted in three phases of the epidemic: early, peak and late season. Results: In Portugal, a low intensity influenza epidemic occurred between week 53/2015 and week 8/2016. Influenza A(H1)pdm09 virus predominated during all season. Influenza B/Victoria lineage was detected in co-circulation in late season. From the 84 GP's that accepted to participate in the study, 51 GP's effectively participated in the study selecting patients (60.7% participation rate). A total of 336 ILI patients were enrolled and after excluding 26 ILI patients the final sample for analyses consisted on 310 ILI patients (147 cases and 102 controls). From the cases, 89.5% were positive for influenza A(H1)pdm09, 8.9% were positive for influenza B/Victoria and the remaining (1.6%) were positive for influenza A(H3). For genetic characterization of influenza virus, A(H1)pdm09 virus subtype was selected. The HA1 subunit of the hemaglutinin gene were successfully sequenced for 93 out of 126 cases with detected viruses. Phylogenetic analysis and clade assignment were performed. The majority of A(H1)pdm09 viruses belonged to the subgroup 6B.1 (87.1%) and the remaining viruses belonged to 6B clade. Comparing cases and controls, was confirmed that they were statistically different in relation to time between onset and swab collection, sex, seasonal vaccine uptake in 2014/2015, presence of at least one chronic disease and number of GP consultations in last 12 months. For 2015/2016 trivalent influenza vaccine, confounder- adjusted VE against A(H1)pdm09 was 54.0% (95% CI: -1.5; 79.2%) in all population and 63.9% (95% CI: (7.7%; 85.9%) in the target group for vaccination. Considering the population with less than 65 years, VE against AH1pdm09 was 56.2% (95% CI: -17.5%; 83.7%) and 74.9% (95% CI: -37.1; 95.4%) in the and more years of age. Conclusions: VE estimates during 2015/2016 season indicated that the seasonal flu vaccine conferred moderate protection against A(H1)pdm09 (varied between 54% to 64% considering all population and the target group for vaccination). The vaccine had a better performance in the elderly, where VE point estimates reached 75% (not significant nevertheless). The implementation of the genetic characterization pilot study was well succeeded, with a success rate of influenza virus characterization of 80.2%. For future seasons, the high sampling fraction in the first phase should continue in order to assist the definition of the virus subtype/clade target during the season. ; Os resultados apresentados correspondem à implementação da 8ª época do EuroEVA (a componente portuguesa do estudo multicêntrico I-MOVE) e pretende obter estimativas da efetividade da vacina (EV) sazonal 2015/2016 i) em todos os grupos etários e no grupo com idade inferior a 65 e com 65 e mais anos; ii) por grupo-alvo da vacinação e iii) por subtipo de vírus da gripe e por clade. Material e métodos: O "Protocol for case-control studies to measure seasonal influenza vaccine effectiveness in the European Union and European Economic Area Member States- Portuguese site study version" foi implementado na íntegra, acrescentando um nova variável relacionada com a toma de estatinas. De igual modo, foi implementando um estudo-piloto relacionado com a incorporação da caracterização genética dos participantes no estudo da efetividade. Dentro deste estudo-piloto, os casos positivos de A(H1)pdm09 foram aleatoriamente selecionados para caracterização genética, seleção esta que foi conduzida nas três fases do período epidémico: início, pico e fim. Resultados: Em Portugal o período epidémico ocorreu entre as semanas 53/2015 e 8/2016 tendo-se verificado uma atividade gripal de intensidade baixa. Predominou a circulação de vírus do subtipo Influenza A(H1)pdm09 e o vírus Influenza da linhagem B/Victoria co-circulou no final da época. De entre os 84 médicos de família (MF) que aceitaram participar no estudo, 51 reportaram doentes com síndroma gripal (SG), correspondendo a uma taxa de participação de 60,7%. No total foram selecionados 336 doentes com SG. Após exclusão de 26 doentes, a amostra final consistiu em 310 doentes com SG (147 casos e 102 controlos). De entre os casos, 89,5% eram do subtipo A(H1)pdm2009, 8,9% eram positivos para o vírus do subtipo B/Victoria e os restantes (1,6%) para o tipo A(H3). Para efeito de caracterização genética, o subptipo A(H1)pdm09 foi selecionado. A subunidade HA1 do gene da hemaglutinina foi sequenciada com sucesso para 93 dos 126 casos. A maioria dos casos de A(H1)pdm09 pertencia ao subgrupo 6B.1 (87,1%) e os restantes ao subgrupo 6B. Comparando casos e controlos verifica-se que os grupos eram estatisticamente diferentes no que diz respeito, ao tempo entre início de sintomas e colheita, ao sexo, a toma da vacina na época anterior, à presença de doença crónica relevante para vacinação da gripe e ao número de consultas com o MF nos últimos 12 meses. Para a vacina trivalente antigripal 2015/2016 a EV ajustada para confundimento contra o subtipo A(H1)pdm09 foi 54,0% (IC95%: -1,5; 79,2%) na população em geral e 63,9% (IC95%: (7,7%; 85,9%) no grupo alvo da vacinação contra a gripe. Considerando a população com menos de 65 anos, a EV contra o subtipo A(H1)pdm09 foi de 56,2 % (IC 95%: -17,5%; 83,7%), sendo que foi de 74,9% (IC 95%: -37,1; 95,4%) no grupo com 65 e mais anos de idade. Conclusões: As estimativas da EV da época 2015/2016 indicam que a vacina conferiu proteção moderada contra o subtipo A(H1)pdm09 (variou entre 54% e 64%, para a população em geral e para o grupo alvo da vacina, respetivamente). A vacina parece demonstrar uma melhor performance na população mais idosa, onde as estimativas da EV alcançam os 75% (apesar de não estatisticamente significativas). A implementação do estudo piloto foi bem conseguida, com uma taxa de sucesso de caracterização genética de 80,2%. Em épocas futuras, a amostragem na primeira fase deve manter elevada, de modo a assistir à definição do subtipo/clade do vírus a ser caracterizado.
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Estimating influenza vaccine effectiveness (IVE) early in the season helps measuring the consequences of a mismatch between the vaccine and the circulating strain and guiding alternative or complementary interventions. The European Centre for Disease Prevention and Control is funding a project to develop pilot studies to monitor IVE in the Member States (MS) of the European Union and European Economic Area (EU/EEA) during seasonal and pandemic influenza. To identify key methodological and practical issues in developing protocols for pilot studies, we conducted a survey among EU/EEA MS, a literature review on IVE methods, and consultations of experts. The survey and literature review highlighted the variety of the data sources used to estimate IVE and the difficulty to interpret data on IVE, which varies with age, risk group, outcome specificity and virus-vaccine mismatch. We also found that negative and positive confounding can bias IVE. The experts consultations lead to the following recommendations: to measure IVE in the same population in various seasons; to control for positive/negative confounding (including pre- and post-influenza season IVE estimates); and to include laboratory confirmation as outcome in various study designs. In the 2008-9 influenza season, two cohort studies using general practitioners' databases and six case control studies will be piloted in EU/EEA MS and will adhere to the above recommendations. The pilot studies will be the basis for the development of robust methods to monitor IVE in EU/EEA MS.
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Letters to editor ; This study aimed to provide early 2017/2018 seasonal IVE using data from the Portuguese influenza surveillance system. This analysis included patients with influenza-like illness (ILI) from primary care and emergency departments swabbed for the detection of influenza using RT-PCR between weeks 38/2017 to 5/2018. We used the test-negative case–control study design, where influenza laboratory confirmed incident ILI patients (Cases) were compared to laboratory influenza negative ILI patients (Controls). IVE analysis was restricted to ILI patients with symptoms compatible with the European Union ILI definition, i.e., with sudden onset of at least one systemic and one respiratory symptom. Chi-square test was used to compare baseline characteristics between Cases and Controls. Crude IVE, design adjusted for calendar time, was estimated using 1-odds ratio (OR) of being vaccinated in Cases vs. Controls and was further adjusted for confounding by age group and presence of chronic condition.A total of 732 ILI patients were reported to the NISS and approximately 74% adhered to the ILI definition. In a season with B/Yamagata dominance and with vaccine lineage mismatch, the 2017/2018 trivalent seasonal influenza vaccine conferred moderate protection against medically attended influenza. The use of surveillance data constituted a useful tool to have early in the season IVE estimates. These results assist modifications to health interventions, such as using antiviral treatment in high-risk patients, reinforcement of social eviction and individual hygiene measures to reduce risk of influenza transmission, regardless of the vaccination status. ; info:eu-repo/semantics/publishedVersion
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INTRODUCTION: The UK government recommends that at least 75% of people aged under 64 with certain conditions receive an annual influenza vaccination. Primary care practices often fall short of this target and strategies to increase vaccine uptake are required. Text messaging reminders are already used in 30% of practices to remind patients about vaccination, but there has been no trial addressing their effectiveness in increasing influenza vaccine uptake in the UK. The aims of the study are (1) to develop the methodology for conducting cluster randomised trials of text messaging interventions utilising routine electronic health records and (2) to assess the effectiveness of using a text messaging influenza vaccine reminder in achieving an increase in influenza vaccine uptake in patients aged 18-64 with chronic conditions, compared with standard care. METHODS AND ANALYSIS: This cluster randomised trial will recruit general practices across three settings in English primary care (Clinical Practice Research Datalink, ResearchOne and London iPLATO text messaging software users) and randomise them to either standard care or a text messaging campaign to eligible patients. Flu vaccine uptake will be ascertained using routinely collected, anonymised electronic patient records. This protocol outlines the proposed study design and analysis methods. ETHICS AND DISSEMINATION: This study will determine the effectiveness of text messaging vaccine reminders in primary care in increasing influenza vaccine uptake, and will strengthen the methodology for using electronic health records in cluster randomised trials of text messaging interventions. This trial was approved by the Surrey Borders Ethics Committee (13/LO/0872). The trial results will be disseminated at national conferences and published in a peer-reviewed medical journal. The results will also be distributed to the Primary Care Research Network and to all participating general practices. TRIAL REGISTRATION NUMBER: This study is registered at controlled-trials.com ISRCTN48840025, July 2013.
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In: Journal of racial and ethnic health disparities: an official journal of the Cobb-NMA Health Institute, Band 11, Heft 3, S. 1520-1529
ISSN: 2196-8837
Financial support. The work was funded by the Chief Scientist Office of the Scottish Government under the grant (AUKCAR/14/03) and the NIHR–Health Technology Assessment (HTA) Programme (13/34/14) for the Seasonal Influenza Vaccination Effectiveness II (SIVE II) study. As principal investigator, C. R. S. received a grant for the SIVE-II project from the NIHR HTA. This work was carried out with the support of the Asthma UK Centre for Applied Research (AUK-AC-2012-01), the Farr Institute (MR/M501633/2), Health Data Research UK (an initiative funded by UK Research and Innovation, Department of Health and Social Care England and the devolved administrations and leading medical research charities), the European Union's Horizon 2020 research and innovation programme (under grant agreement No 634446) and European Centre for Disease Prevention and Control (Influenza-Monitoring Vaccine Effectiveness). Acknowledgments. The authors thank and acknowledge all colleagues at the Asthma UK Centre for Applied Research for their support in this study. Disclaimer. The funding bodies had no role in the design of the study, review process, analysis, interpretation, or reporting of data. The views and opinions expressed herein are those of the authors and do not necessarily reflect those of the Health Technology Assessment Programme, National Institute for Health Research (NIHR), National Health Service, or the Department of Health. Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. ; Peer reviewed ; Publisher PDF ; Publisher PDF
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Seasonal influenza places a major burden on public health. Consequently, the World Health Organization (WHO) and over 40% of national governments recommend vaccination of at-risk groups. However, no systematic global data are available to assess vaccine provision nor the effect of immunization policies. To address this situation, IFPMA IVS surveyed global vaccine supply, covering 157 countries from 2004 to 2009. The study also used UN data and a novel vaccine provision "hurdle" rate (set at 15.9% of the population, based on WHO immunization recommendations for the elderly) to compare vaccine supply with development status. In a sub-group of 26 countries, the level of vaccine provision was also correlated to the presence/absence of specific vaccination policies. Between 2004 and 2009, global annual vaccine provision increased 72% to 449 million doses. Europe and the Americas accounted for 75% to 80% of the total each year, with several countries in these regions, as well as China, Japan and Thailand, achieving notable increases during the study period. However, despite the global growth, only 20% of countries reached the study's modest "hurdle" rate. On a per capita basis, dose distribution did not correlate directly with income, and several less developed countries, particularly in Latin America, outperformed more developed nations (notably in Eastern and Southern Europe). In the sub-group analysis, the presence of official public health authority vaccination recommendations did not correlate well with higher vaccine supply (positive:negative correlation = 1.3:1), while reimbursement (4.5:1) and the use of wide-scale communication activities (5.3:1) correlated more strongly than development status (2.7:1). This study shows that globally vaccination levels remain low, and official vaccination recommendations alone are insufficient to drive higher coverage. Rather, policy measures that directly impact patients (i.e. reimbursement and communication) appear more effective, irrespective of countries' development status, and therefore may do more to help protect local populations against influenza. HIGHLIGHT: ► Examined global influenza vaccine provision and the influence of health policies. ► Provision increased 72% to 449 million doses in the 6 years to 2009. ► However, only 20% of countries met the study's modest provision "hurdle" rate. ► Vaccine provision did not correlate directly with national income. ► Official recommendations were insufficient to drive higher uptake. ► Reimbursement and broad communications correlated most strongly with coverage.
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In the fifth season of Influenza Monitoring Vaccine Effectiveness in Europe (I-MOVE), we undertook a multicentre case–control study (MCCS) in seven European Union (EU) Member States to measure 2012/13 influenza vaccine effectiveness against medically attended influenza-like illness (ILI) laboratory confirmed as influenza. The season was characterised by substantial co-circulation of influenza B, A(H1N1)pdm09 and A(H3N2) viruses. Practitioners systematically selected ILI patients to swab ≤7 days of symptom onset. We compared influenza-positive by type/subtype to influenza-negative patients among those who met the EU ILI case definition. We conducted a complete case analysis using logistic regression with study as fixed effect and calculated adjusted vaccine effectiveness (AVE), controlling for potential confounders (age, sex, symptom onset week and presence of chronic conditions). We calculated AVE by type/subtype. Study sites sent 7,954 ILI/acute respiratory infection records for analysis. After applying exclusion criteria, we included 4,627 ILI patients in the analysis of VE against influenza B (1,937 cases), 3,516 for A(H1N1)pdm09 (1,068 cases) and 3,340 for influenza A(H3N2) (730 cases). AVE was 49.3% (95% confidence interval (CI): 32.4 to 62.0) against influenza B, 50.4% (95% CI: 28.4 to 65.6) against A(H1N1)pdm09 and 42.2% (95% CI: 14.9 to 60.7) against A(H3N2). Our results suggest an overall low to moderate AVE against influenza B, A(H1N1)pdm09 and A(H3N2), between 42 and 50%. In this season with many co-circulating viruses, the high sample size enabled stratified AVE by type/subtype. The low estimates indicate seasonal influenza vaccines should be improved to achieve acceptable protection levels.
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Influenza A(H3N2) viruses predominated in Europe in 2016-17. In 2017-18 A(H3N2) and A(H1N1)pdm09 viruses co-circulated. The A(H3N2) vaccine component was the same in both seasons; while the A(H1N1)pdm09 component changed in 2017-18. In both seasons, vaccine seed A(H3N2) viruses developed adaptations/alterations during propagation in eggs, impacting antigenicity. We used the test-negative design in a multicentre primary care case-control study in 12 European countries to measure 2016-17 and 2017-18 influenza vaccine effectiveness (VE) against laboratory-confirmed influenza A(H1N1)pdm09 and A(H3N2) overall and by age group. During the 2017-18 season, the overall VE against influenza A(H1N1)pdm09 was 59% (95% CI: 47-69). Among those aged 0-14, 15-64 and ≥65 years, VE against A(H1N1)pdm09 was 64% (95% CI: 37-79), 50% (95% CI: 28-66) and 66% (95% CI: 42-80), respectively. Overall VE against influenza A(H3N2) was 28% (95% CI: 17-38) in 2016-17 and 13% (95% CI: -15 to 34) in 2017-18. Among 0-14-year-olds VE against A(H3N2) was 28% (95%CI: -10 to 53) and 29% (95% CI: -87 to 73), among 15-64-year-olds 34% (95% CI: 18-46) and 33% (95% CI: -3 to 56) and among those aged ≥65 years 15% (95% CI: -10 to 34) and -9% (95% CI: -74 to 32) in 2016-17 and 2017-18, respectively. Our study suggests the new A(H1N1)pdm09 vaccine component conferred good protection against circulating strains, while VE against A(H3N2) was <35% in 2016-17 and 2017-18. The egg propagation derived antigenic mismatch of the vaccine seed virus with circulating strains may have contributed to this low effectiveness. A(H3N2) seed viruses for vaccines in subsequent seasons may be subject to the same adaptations; in years with lower than expected VE, recommendations of preventive measures other than vaccination should be given in a timely manner. ; This project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement no. 634446 to conduct the study in individuals aged 65 years or more. ECDC has contributed funds for the coordination and some study sites under the Framework contract no. ECDC/2014/026 for the individuals aged less than 65 years. The WHO Regional office for Europe has contributed funds for the Romanian study site. ; Sí
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In the European Union and Canada, an Ann Arbor strain live attenuated influenza vaccine (LAIV) is approved for use in children aged 2–17 years, including those with mild to moderate asthma or prior wheezing. The safety and efficacy of LAIV versus trivalent inactivated influenza vaccine (TIV) in children with asthma aged 6–17 years have been demonstrated. However, few data are available for children younger than 6 years of age with asthma or prior wheezing. Safety and efficacy data were collected for children aged 2–5 years with asthma or prior wheezing from two randomized, multinational trials of LAIV and TIV (N = 1,940). Wheezing, lower respiratory illness, and hospitalization were not significantly increased among children receiving LAIV compared with TIV. Increased upper respiratory symptoms and irritability were observed among LAIV recipients (p < 0.05). Relative efficacies were consistent with the results observed in the overall study populations, which demonstrated fewer cases of culture-confirmed influenza illness in LAIV compared with TIV recipients. Study results support the safety and efficacy of LAIV among children aged 2–17 years with mild to moderate asthma or a history of wheezing. Data regarding LAIV use are limited among individuals with severe asthma or active wheezing within the 7 days before vaccination.
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