The efficacy of influenza vaccination in elderly individuals. A randomized double-blind placebo-controlled trial. Frequency of adverse reactions to influenza vaccine in the elderly. A randomized, placebo-controlled trial. Is influenza vaccination cost effective for healthy people between ages 65 and 74 years? A randomised controlled trial. Adverse reactions to influenza vaccine in elderly people: randomised double blind placebo controlled trial. Effectiveness of the MF59-adjuvanted influenza vaccine in preventing emergency admissions for pneumonia in the elderly over 64 years of age. Efficacy and safety of 1 and 2 doses of live attenuated influenza vaccine in vaccine-naive children. A randomised intervention study to examine the effect on immunisation coverage of making influenza vaccine available at no cost. Efficacy and safety of a live attenuated, cold-adapted influenza vaccine, trivalent against culture-confirmed influenza in young children in Asia. Protective efficacy of combined live intranasal and inactivated influenza A virus vaccines in the elderly. Challenge of conducting a placebo-controlled randomized efficacy study for influenza vaccine in a season with low attack rate and a mismatched vaccine B strain: a concrete example. A cohort study of the effectiveness of influenza vaccine in older people, performed using the United Kingdom general practice research database. Influenza vaccination in children with asthma: randomized double-blind placebo-controlled trial. The influence of health professionals on the uptake of the influenza immunization. Randomised placebo-controlled crossover trial on effect of inactivated influenza vaccine on pulmonary function in asthma. Evaluation of live attenuated influenza vaccines in children 6-18 months of age: safety, immunogenicity, and efficacy. National Institute of Allergy and Infectious Diseases, Vaccine and Treatment Evaluation Program and the Wyeth-Ayerst ca Influenza Vaccine Investigators Group. [The results of state trials of inactivated influenza vaccines for children]. Evaluation of bivalent live attenuated influenza A vaccines in children 2 months to 3 years of age: safety, immunogenicity and dose-response. Influenza vaccination in adults with asthma: safety of an inactivated trivalent influenza vaccine. Age-related responses to influenza vaccination in the Newcastle region during 1983 and 1984. Safety, efficacy, and effectiveness of cold-adapted influenza vaccine-trivalent against community-acquired, culture-confirmed influenza in young children attending day care. Influenza vaccine effectiveness in preventing hospitalizations and deaths in persons 65 years or older in Minnesota, New York, and Oregon: data from 3 health plans. Effectiveness of inactivated influenza vaccine in preventing acute otitis media in young children: a randomized controlled trial. Inactivated influenza vaccine effectiveness in children under 6 years of age during the 2002-2003 season. Improving uptake of influenza vaccination among older people: a randomised controlled trial. Effectiveness of pneumococcal polysaccharide vaccine against pneumonia and cost analysis for the elderly who receive seasonal influenza vaccine in Japan. Efficacy of Influenza Vaccine in Elderly Persons in Welfare Nursing Homes: Reduction in Risks of Mortality and Morbidity During an Influenza A (H3N2) Epidemic. Clinical and epidemiological evaluation of a live, cold-adapted influenza vaccine for 3-14-year-olds. A prospective, Internet-based study of the effectiveness and safety of influenza vaccination in the 2001-2002 influenza season. Effectiveness of influenza vaccination in the elderly in a community in Italy. Acute respiratory illness in patients with COPD and the effectiveness of influenza vaccination: a randomized controlled study. Implementation of universal influenza immunization recommendations for healthy young children: results of a randomized, controlled trial with registry-based recall. Randomized, placebo-controlled double blind study on the efficacy of influenza immunization on absenteeism of health care workers. Can a short period of micronutrient supplementation in older institutionalized people improve response to influenza vaccine? A randomized, controlled trial. Influenza A (H1N1) 2009 two-dose immunization of US children: an observer-blinded, randomized, placebo-controlled trial. Influenza vaccination, hospitalizations, and costs among members of a Medicare managed care plan. Influenza vaccine effectiveness in preventing hospitalization for pneumonia in the elderly. Clinical efficacy of pneumococcal vaccine in the elderly: a randomized, single-blind population-based trial. [Characteristics of the clinical and immunologic safety of inactivated influenza vaccines in children undergoing multiple immunizations]. The efficacy of live attenuated, cold-adapted, trivalent, intranasal influenzavirus vaccine in children. The effectiveness of vaccination against influenza in healthy, working adults. Effectiveness of live, attenuated intranasal influenza virus vaccine in healthy, working adults: a randomized controlled trial. The safety of trivalent influenza vaccine among healthy children 6 to 24 months of age. [The immunogenic properties and prophylactic efficacy of a live polyvalent influenza vaccine in children 5 to 14 years old]. Failure of inactivated influenza A vaccine to protect healthy children aged 6-24 months. Effectiveness and cost-benefit of influenza vaccination of healthy working adults: A randomized controlled trial. Improving compliance with immunization in the older adult: results of a randomized cohort study. [The investigation of the safety, genetic stability and immunogenicity of live influenza vaccine for adults in vaccination of 3-6 years old children]. [Prophylactic effectiveness of a live recombinant influenza type A vaccine in immunizing children aged 3-14 years]. [Immunization program against influenza for adults 65 years or older at a community pharmacy in Puerto Rico]. Clinical reactions and serologic response following inactivated monovalent influenza type B vaccine in young children and infants. Influence of high-risk medical conditions on the effectiveness of influenza vaccination among elderly members of 3 large managed-care organizations. Effectiveness of influenza vaccine in reducing hospital admissions during the 1989-90 epidemic. Postcard reminders from GPs for influenza vaccine: are they more effective than an ad hoc approach? Study of the effectiveness of influenza vaccination in the elderly in the epidemic of 1989-90 using a general practice database. Protective effect of single-dose adjuvanted pandemic influenza vaccine in children. Comparison of three methods of recalling patients for influenza vaccination. Association of influenza immunization with reduction in mortality in an elderly population. A prospective study. [Evaluation of the safety, reactogenicity and antigenic activity of inactivated chromatographic influenza vaccine in school children]. Effectiveness of influenza vaccination in preventing influenza-like illness among community-dwelling elderly: population-based cohort study in Japan. The impact of a public health nurse intervention on influenza vaccine acceptance. The telephone: an overlooked technology for prevention in family medicine. Increasing influenza vaccination among high-risk elderly: a randomized controlled trial of a mail cue in an HMO setting. Influenza vaccination in secondary prevention from coronary ischaemic events in coronary artery disease: FLUCAD study. Efficacy of repeated annual immunization with inactivated influenza virus vaccines over a five year period. A randomised, clinical trial comparing the effectiveness of hospital and community-based reminder systems for increasing uptake of influenza and pneumococcal vaccine in hospitalised patients aged 65 years and over. Vaccine effectiveness against laboratory-confirmed influenza in infants: A matched case control study. Immunogenicity and efficacy of Russian live attenuated and US inactivated influenza vaccines used alone and in combination in nursing home residents. Influenza vaccine effectiveness among elderly nursing home residents: a cohort study. The efficacy and cost effectiveness of vaccination against influenza among elderly persons living in the community.
To determine the efficacy of influenza vaccination in elderly people.
                Randomized double-blind placebo-controlled trial.
                Fifteen family practices in the Netherlands during influenza season 1991-1992.
                A total of 1838 subjects aged 60 years or older, not known as belonging to those high-risk groups in which vaccination was previously given.
                Purified split-virion vaccine containing A/Singapore/6/86(H1N1), A/Beijing/353/89(H3N2), B/Beijing/1/87, and B/Panama/45/90 (n = 927) or intramuscular placebo containing physiological saline solution (n = 911).
                Patients presenting with influenzalike illness up to 5 months after vaccination; self-reported influenza in postal questionnaires 10 weeks and 5 months after vaccination; serological influenza (fourfold increase of antibody titer between 3 weeks and 5 months after vaccination).
                The incidence of serological influenza was 4% in the vaccine group and 9% in the placebo group (relative risk [RR], 0.50; 95% confidence interval [CI], 0.35 to 0.61). The incidences of clinical influenza were 2% and 3%, respectively (RR, 0.53; 95% CI, 0.39 to 0.73). The effect was strongest for the combination of serological and clinical influenza (RR, 0.42; 95% CI, 0.23 to 0.74). The effect was less pronounced for self-reported influenza.
                In the elderly, influenza vaccination may halve the incidence of serological and clinical influenza (in periods of antigenic drift). Concern about side effects constitutes a major deterrent to patient compliance with influenza vaccination, yet there is a paucity of data about the occurrence of adverse reactions in the population targeted for immunization. We conducted a randomized, double-blind, crossover trial to compare the frequency of adverse reactions following administration of 1988-1989 trivalent split-antigen influenza vaccine and saline placebo. Outpatient veterans 65 years of age or over (n = 336) were recruited by mail and were randomly assigned to receive vaccine followed 2 weeks later by placebo injection or placebo followed 2 weeks later by vaccine. There was no significant difference between influenza vaccine and placebo with respect ot the proportion of subjects reporting disability or systemic symptoms. The aim of this study was to determine the cost effectiveness of influenza vaccination for healthy people aged 65-74 years living in the UK. People without risk factors for influenza (chronic heart, lung or renal disease, diabetic, immunosuppressed or those living in an institution) were identified from 20 general practitioner (GP) practices in Liverpool in September 1999. 729/5875 (12.4%) eligible individuals were recruited and randomised to receive either influenza vaccine or placebo (ratio 3:1), with all participants receiving 23-valent-pneumococcal polysaccharide vaccine unless already administered. The primary analysis was the frequency of influenza as recorded by a GP diagnosis of pneumonia or influenza like illness. In 2000, the UK vaccination policy was changed with influenza vaccine becoming available for all people aged 65 years and over irrespective of risk. As a consequence of this policy change, the study had to be fundamentally restructured and only results obtained over a one rather than the originally planned two-year randomised controlled trial framework were used. Results from 1999/2000 demonstrated no significant difference between groups for the primary outcome (relative risk 0.8, 95% CI 0.16-4.1). In addition, there were no deaths or hospitalisations for influenza associated respiratory illness in either group. The subsequent analysis, using both national and local sources of evidence, estimated the following cost effectiveness indicators: (1) incremental NHS cost per GP consultation avoided = 2000 pound sterling; (2) incremental NHS cost per hospital admission avoided = 61,000 pound sterling; (3) incremental NHS cost per death avoided = 1,900,000 pound sterling and (4) incremental NHS cost per QALY gained = 304,000 pound sterling. The analysis suggested that influenza vaccination in this population would not be cost effective. To assess the frequency and type of side effects after influenza vaccination in elderly people.
                Randomised double blind placebo controlled study.
                15 general practices in the southern Netherlands.
                1806 patients aged 60 or older, of whom 904 received influenza vaccine and 902 placebo.
                Adverse reactions reported on postal questionnaire completed four weeks after vaccination.
                210 (23%) patients given vaccine reported one or more adverse reactions compared with 127 (14%) given placebo. The frequency of local adverse reactions were 17.5% in the vaccine group and 7.3% in the placebo group (p < 0.001). There was no difference in systemic adverse reactions (11% v 9.4%; p = 0.34). In general, men reported fewer side effects than women.
                Only local side effects were more common in vaccinated patients and all side effects were mild. Case-control study designed to determine the effectiveness of an MF59-adjuvanted influenza vaccine in the population aged 65 years and older living in the community. Detailed health histories were obtained on both cases and controls that included a functional measure of co-morbidity (Barthel Index). Subjects were all eligible persons admitted to various hospitals with a diagnosis of pneumonia during the winter months and were matched by sex, hospital and admission week to controls admitted for non-medical reasons. The influenza vaccination programme using the MF59-adjuvanted influenza vaccine significantly reduced the probability of being hospitalised for pneumonia in the elderly over 64 years of age, even in a season with a low influenza activity, during which the predominant circulating strains were types B and A (H1N1). We investigated the efficacy and safety of 1 versus 2 doses of live attenuated influenza vaccine (LAIV) in influenza vaccine-naive children aged 6 to <36 months.
                Subjects were randomized to 1 of 4 regimens in year 1: 2 doses LAIV, 1 dose LAIV, excipient placebo, or saline placebo. In year 2, LAIV recipients were to receive 1 dose of LAIV and placebo recipients were to receive saline placebo. Because of an unintended treatment allocation error in year 2, 1 block of subjects who were randomized to LAIV received saline placebo and 1 block who were randomized to placebo received LAIV.
                In year 1, vaccine efficacy versus placebo among recipients of 2 and 1 doses of LAIV was 73.5% and 57.7%, respectively, against antigenically similar strains. In year 2, absolute efficacy of a single dose of LAIV was 73.6% and 65.2%, respectively, in recipients of 2 and 1 doses of LAIV in year 1. Year 2 efficacy was 57.0% in subjects who received 2 doses of LAIV in year 1 and placebo in year 2. Safety and tolerability of LAIV were consistent with previous studies. Reactogenicity was similar between placebo groups. Seroconversion rates were significantly higher in the 2-dose versus the 1-dose LAIV group in year 1 and in both LAIV groups versus placebo in years 1 and 2.
                One dose of LAIV provided clinically significant protection against influenza in young children previously unvaccinated against influenza; 2 doses provided additional protection. Protection after 2 doses in year 1 persisted through a second season without revaccination. LAIV excipients were not a major contributor to reactogenicity. These benefits provide support for increased use of LAIV in children > or =2 years of age. This study aims to assess the effects of two interventions on influenza vaccination coverage: a simple organisational strategy, and making the vaccine available free.
                Sixteen general practitioners in the Auckland region were randomly selected to participate. Patients over 65 years of these general practitioners were randomly allocated to control, letter of invitation for a flu vaccine, or offer of a free flu vaccine. Administration of a flu vaccine for each person in the study was documented in each general practitioner surgery. Vaccine coverage for each of the three groups was measured.
                Results were available for 15 of the 16 participating general practitioners, a total of 2791 subjects. Immunisation coverage rates for control, letter of invitation and vaccine at no cost, were 17%, 27% and 45% respectively. Statistical analysis, allowing for the cluster method used to obtain subjects, showed risk ratios of 1.55 and 2.65 for the two interventions, with p values of < 0.00001.
                A potential source of bias in this study is underreporting of administration of vaccine to people in group 1. Notwithstanding this potential bias, both interventions were highly effective at increasing the uptake of influenza vaccine in the elderly population. General practitioners should be recommended to routinely invite patients over 65 years to have a flu vaccine. Given the commitment of the Ministry of Health to the vaccination against influenza of people over 65, this study would suggest that serious consideration should be given to making the vaccine available at no cost to this age group. This study was designed to evaluate the efficacy and safety of cold-adapted influenza vaccine, trivalent (CAIV-T) against culture-confirmed influenza in children 12 to <36 months of age during 2 consecutive influenza seasons at multiple sites in Asia.
                In year 1, 3174 children 12 to <36 months of age were randomized to receive 2 doses of CAIV-T (n = 1900) or placebo (n = 1274) intranasally > or =28 days apart. In year 2, 2947 subjects were rerandomized to receive 1 dose of CAIV-T or placebo.
                Mean age at enrollment was 23.5 +/- 7.4 months. In year 1, efficacy of CAIV-T compared with placebo was 72.9% [95% confidence interval (CI): 62.8-80.5%] against antigenically similar influenza subtypes, and 70.1% (95% CI: 60.9-77.3%) against any strain. In year 2, revaccination with CAIV-T demonstrated significant efficacy against antigenically similar (84.3%; 95% CI: 70.1-92.4%) and any (64.2%; 95% CI: 44.2-77.3%) influenza strains. In year 1, fever, runny nose/nasal congestion, decreased activity and appetite, and use of fever medication were more frequent with CAIV-T after dose 1. Runny nose/nasal congestion after dose 2 (year 1) and dose 3 (year 2) and use of fever medication after dose 3 (year 2) were the only other events reported significantly more frequently in CAIV-T recipients.
                CAIV-T was well tolerated and effective in preventing culture-confirmed influenza illness over multiple and complex influenza seasons in young children in Asia. To evaluate the efficacy of adding intranasal live attenuated cold-adapted influenza A vaccine to inactivated influenza vaccine to prevent influenza A in elderly residents of long-term-care institutions.
                Randomized, double-blind, placebo-controlled study conducted over 3 years.
                Three large nursing homes.
                A total of 523 residents of nursing homes (mean age, 84.2 years).
                All participants received trivalent inactivated influenza vaccine parenterally and were randomly assigned to receive either live attenuated influenza A (H3N2) virus vaccine or placebo intranasally.
                Laboratory-documented influenza A was defined as a respiratory illness plus isolation of influenza A virus from nasal secretions, significant serologic response, or both. Participants were considered to have been exposed to influenza A if they resided in an institution in which cases of influenza A were documented. Outbreak-associated illnesses were defined as those occurring between the first and last isolation of influenza virus from within the institution, +/- 3 days.
                Participants who received intranasal vaccine and were subsequently exposed to influenza A had significantly lower rates of laboratory-documented influenza A (9 of 162 vaccine recipients compared with 24 of 169 placebo recipients; vaccine protective efficacy, 60.6%; 95% CI, 18% to 82%), outbreak-associated respiratory illnesses (13 of 162 vaccine recipients compared with 34 of 169 placebo recipients; vaccine protective efficacy, 56.8%; CI 23% to 76%), and outbreak-associated influenza-like illnesses (6 of 162 vaccine recipients compared with 18 of 169 placebo recipients; vaccine protective efficacy, 65.0%; CI 17% to 86%).
                Intranasal immunization with live attenuated influenza A virus vaccine provided additional protection against influenza A when added to parenteral trivalent inactivated influenza vaccine among elderly nursing home residents. Our aim was to determine the efficacy of a trivalent inactivated split virus influenza vaccine (TIV) against culture-confirmed influenza A and/or B in adults 18 to 64 years of age during the 2005/2006 season in the Czech Republic.
                6203 subjects were randomized to receive TIV (N = 4137) or placebo (N = 2066). The sample size was based on an assumed attack rate of 4% which provided 90% power to reject the hypothesis that vaccine efficacy (VE) was > or = 45%. Cases of influenza like illness (defined as fever (oral temperature > or =37.8 degrees C) plus cough and/or sore throat) were identified both by active (biweekly phone contact) and passive (self reporting) surveillance and nasal and throat swabs were collected from subjects for viral culture.
                TIV was well tolerated and induced a good immune response. The 2005/2006 influenza season was exceptionally mild in the study area, as it was throughout Europe, and only 46 culture-confirmed cases were found in the study cohort (10 influenza A and 36 influenza B). Furthermore among the B isolates, 35 were identified as B/Hong Kong 330/2001-like (B/Victoria/2/87 lineage) which is antigenically unrelated to the vaccine B strain (B/Yamagata/16/88 lineage). The attack rate in the vaccine group (0.7%) was not statistically significantly different from the attack rate in the placebo group (0.9%).
                Due to the atypical nature of the influenza season during this study we were unable to assess TIV efficacy. This experience illustrates the challenge of conducting a prospective influenza vaccine efficacy trial during a single season when influenza attack rates and drift in circulating strains or B virus lineage match can be difficult to estimate in advance.
                Clinical trial registery: NCT00197223. The effectiveness of influenza vaccination against hospitalization and death can only ethically be assessed in observational studies. A concern is that individuals who are vaccinated are healthier than individuals who are not vaccinated, potentially biasing estimates of effectiveness upward.
                We conducted a historical cohort study of individuals >64 years of age, for whom there were data available in the General Practice Research Database for 1989 to 1999 in England and Wales. Rates of admissions for acute respiratory diseases and rates of death due to respiratory disease were compared over 692,819 person-years in vaccine recipients and 1,534,280 person-years in vaccine nonrecipients.
                The pooled effectiveness of vaccine against hospitalizations for acute respiratory disease was 21% (95% confidence interval [CI], 17%-26%). The rate reduction attributable to vaccination was 4.15 hospitalizations/100,000 person-weeks in the influenza season. Among vaccine recipients, no important reduction in the number of admissions to the hospital was seen outside influenza seasons. The pooled effectiveness of vaccine against deaths due to respiratory disease was 12% (95% CI, 8%-16%). A greater proportionate reduction was seen among people without medical disorders, but absolute rate reduction was higher in individuals with medical disorders, compared with individuals without such disorders (6.14 deaths due to respiratory disease/100,000 person-weeks vs. 3.12 deaths due to respiratory disease/100,000 person-weeks). Clear protection against death due to all causes was not seen.
                Influenza vaccination reduces the number of hospitalizations and deaths due to respiratory disease, after correction for confounding in individuals >64 years of age who had a high risk or a low risk for influenza. For elderly people, untargeted influenza vaccination is of confirmed benefit against serious outcomes. There is little evidence that influenza vaccination reduces asthma exacerbations. We determined whether influenza vaccination is more effective than placebo in 6-18-year-old children with asthma. We performed a randomized, double-blind, placebo-controlled trial. Parenteral vaccination with inactivated influenza vaccine or placebo took place approximately November 1, and children were followed until April 1 of the next year. Airway symptoms were reported in a diary. When symptom scores reached a predefined level, a pharyngeal swab was taken. Primary outcome was the number of asthma exacerbations associated with virologically proven influenza infection. Three hundred forty-nine children were assigned placebo, and 347 were assigned vaccine. Pharyngeal swabs positive for influenza were related to 42 asthma exacerbations, 24 in the vaccine group and 18 in the placebo group, a difference of 33% favoring placebo (31% after adjustment for confounders; 95% confidence interval, -34% to 161%). Influenza-related asthma exacerbations were of similar severity in both groups; they lasted 3.1 days shorter in the vaccine group (95% confidence interval, -6.2 to 0.002 days, p = 0.06). We conclude that influenza vaccination did not result in a significant reduction of the number, severity, or duration of asthma exacerbations caused by influenza. Additional studies are warranted to justify routine influenza vaccination of children with asthma. Influenced by the Department of Health's aim to increase the uptake of the influenza immunization to 70% among those eligible, this study aimed to compare three methods of promoting influenza immunization among over 65 year old patients in a GP practice, and to identify if a particular promotion method was more effective among either of two defined age groups. The sample (n = 90) was randomly allocated into three intervention groups, and then subdivided into two age groups. A different subject experimental design was used to compare the groups. Statistical analysis of the data showed no significant difference in influenza immunization uptake between the three intervention groups, or the age-defined sub-groups. However, although not significant at 5% significance level, participants aged 72 years and over showed a greater uptake among those visited by a health professional. The findings suggest that a larger study using the same interventions would produce significant results. Despite current recommendations, many people with asthma do not receive annual vaccination against influenza, partly because of concern that vaccine may trigger exacerbations. Colds can trigger exacerbations, which may be mistaken for vaccine-related adverse events. We undertook a double-blind placebo-controlled multicentre crossover study to assess the safety of influenza vaccine in patients with asthma, with allowance for the occurrence of colds.
                We studied 262 patients, aged 18-75 years, who recorded daily peak expiratory flow (PEF), respiratory symptoms, medication, medical consultations, and hospital admissions for 2 weeks before the first injection and until 2 weeks after the second injection. Order of injection (vaccine and placebo) was assigned randomly. There was an interval of 2 weeks between injections. The main outcome measure was an exacerbation of asthma within 72 h of injection (defined as a fall in PEF of >20%).
                Among 255 participants with paired data, 11 recorded a fall in PEF of more than 20% after vaccine compared with three after placebo (McNemar's test p=0.06); a fall of more than 30% was recorded by eight after vaccine compared with none after placebo (binomial test p=0.008). However, when participants with colds were excluded, there was no significant difference in the numbers with falls of more than 20% between vaccine and placebo (six vs three; binomial test p=0.51), although the difference for PEF decreases of more than 30% approached significance (five vs none; binomial test, p=0.06). This association was confined to first-time vaccinees.
                Our findings indicate that pulmonary-function abnormalities may occur as a complication of influenza vaccination. However, the risk of pulmonary complications is very small and outweighed by the benefits of vaccination. Live attenuated, cold-adapted (ca) monovalent and bivalent influenza A vaccines were evaluated in seronegative infants (ages 6-18 months) in a double-blind placebo-controlled trial to assess safety and immunogenicity. A total of 182 seronegative subjects received a single intranasal dose (10(6.2) TCID50) of ca A/Kawasaki/9/86 (H1N1) or ca A/Los Angeles/2/87 (H3N2), both as a bivalent vaccine, or placebo. Respiratory and systemic symptoms did not differ between groups after vaccination. Hemagglutination antibody seroconversions (> or = 1:8) to H3N2 exceeded 90%. In contrast, seroconversions to A/Kawasaki/9/86 (H1N1) were significantly less frequent in bivalent ca vaccine recipients (31%) than in monovalent ca H1N1 recipients (83%) (P < .002). During a subsequent H3N2 epidemic, nasal washes were cultured for viruses from any subject with respiratory illness. H3N2 infections documented by virus isolation were reduced by 65% in ca H3N2 recipients compared with placebo or ca HIM recipients (P = .01). Controlled epidemiological surveillance covering the total number of 13,355 schoolchildren aged 11-14 years and adolescents was carried out with a view to compare the efficacies of inactivated influenza vaccines. The children were immunized intradermally in a single injection with inactivated influenza vaccines containing A (H3N2) and A (H1N1) hemagglutinins, 3.5 micrograms per 0.2 ml of the preparation each. The studies demonstrated the safety and low reactogenicity of these vaccines, as well as their high antigenic potency. In 1984 during mixed influenza B + A (H1N1) epidemic the preparations produced a pronounced prophylactic effect: the efficacy indices were 1.6-1.9 (p less than 0.001). The results obtained in these studies made it possible to recommend two inactivated influenza vaccines (chromatographic and centrifugal) for practical medicine with the aim of protecting children aged 11 years and over from influenza. 1126 children, 2 months to 3 years old, received a single intranasal dose of 10(4), 10(6), or 10(7) TCID50 of cold adapted (ca) A/Kawasaki/9/86 (H1N1) and A/Beijing/352/89 (H3N2) or placebo, in a double blind, placebo-controlled, safety and immunogenicity trial. No reactogenicity attributable to vaccine was demonstrated. A single bivalent 10(6) or 10(7) dose produced high rates of seroconversion to H1N1 (77%) and H3N2 (92%) in seronegative children > 6 months old; serologic responses were lower to H1N1 (P < 0.001) and H3N2 (P = 0.01) in younger infants. A single 10(6) dose of bivalent ca influenza A vaccine can be immunogenic in children, but response is age dependent. Despite recommendations in most countries for giving inactivated influenza vaccine to people with asthma, only a minority currently receive it. One reason for low vaccine coverage has been concern that vaccination may induce exacerbations of asthma. In this randomized trial, 291 patients between 18 and 65 years of age received either an inactivated influenza vaccine followed 14 days later by a saline placebo or placebo followed by the vaccine. Each patient received 1 dose of vaccine and 1 dose of placebo. The percentage of patients reporting at least one asthma exacerbation within 14 days after injection was similar following vaccine or placebo (28.3% and 25.5%, respectively). The combined exacerbation rate during the first 14-day interval was higher (31.5%) than that during the second 14-day interval (22.4%, P = 0.0135), indicating that the occurrence of exacerbations was not likely to be related to the sequence of injections. The percentages of individuals with solicited systemic symptoms were 56.6% and 44.8% after vaccine or placebo injection, respectively. We conclude that influenza vaccination did not increase the incidence of asthma exacerbations compared to placebo in this study and the vaccine was well tolerated. The results thus support annual influenza vaccination in patients with asthma. A study was carried out in Newcastle to assess responses to influenza vaccines in elderly nursing home patients and in younger adults during 1983 and 1984. The decision to vaccinate the elderly subjects was made by their general practitioners. A concurrent randomized placebo-controlled trial of the same vaccine was performed in young adult volunteers. Elderly subjects generally possessed higher levels of pre-existing antibody to the influenzal haemagglutinins that were present in the vaccines than did younger subjects. The highest levels were observed in the 52-63 years' age group. Younger subjects showed significantly greater responses to vaccines compared with elderly subjects (P less than 0.05). Peak responses were noted in the 16-24 years' age group. Of a total of 326 elderly subjects (70% of whom had been vaccinated), six participants, two of whom had been vaccinated, contracted laboratory-proven influenza during 1983. Only one unvaccinated subject of a total of 365 subjects (50% of whom had been vaccinated) contracted influenza during 1984. In both years illness was produced by strain A/Philippines/2/82. The goal was to evaluate the safety, tolerability, and efficacy of an investigational, refrigerator-stable formulation of live attenuated influenza vaccine (cold-adapted influenza vaccine-trivalent) against culture-confirmed influenza, acute otitis media, and effectiveness outcomes in young children in day care over 2 consecutive influenza seasons.
                Children 6 to <36 months of age who were attending day care were assigned randomly in year 1 to receive 2 doses of vaccine or placebo intranasally, 35 +/- 7 days apart. In year 2, subjects received 1 dose of the same treatment as in year 1.
                A total of 1616 subjects (vaccine: 951 subjects; placebo: 665 subjects) in year 1 and 1090 subjects (vaccine: 640 subjects; placebo: 450 subjects) in year 2 were able to be evaluated for efficacy. The mean age at first vaccination was 23.4 +/- 7.9 months. In year 1, the overall efficacy of the vaccine against influenza subtypes similar to the vaccine was 85.4%; efficacy was 91.8% against A/H1N1 and 72.6% against B. In year 2, the overall efficacy was 88.7%; efficacy was 90.0% against H1N1, 90.3% against A/H3N2, and 81.7% against B. Efficacy against all episodes of acute otitis media associated with culture-confirmed influenza was 90.6% in year 1 and 97.0% in year 2. Runny nose or nasal discharge after dose 1 in year 1 was the only reactogenicity event that was significantly more frequent with cold-adapted influenza vaccine-trivalent (82.3%) than placebo (75.4%).
                Cold-adapted influenza vaccine-trivalent was well tolerated and effective in preventing culture-confirmed influenza illness in children as young as 6 months of age who attended day care. This study developed methods and determined the impact of influenza vaccination on elderly persons in 3 large health plans: Kaiser Permanente Northwest, HealthPartners, and Oxford Health Plans. Data for the 1996-1997 and 1997-1998 seasons were extracted from administrative databases. Subjects were health plan members > or = 65 years old. Comorbid conditions collected from the preceding year were used for risk adjustment with logistic regression. The virus-vaccine match was excellent for year 1 and fair for year 2. Both years, during peak and total periods, vaccination reduced all causes of death and hospitalization for pneumonia and influenza: hospitalizations were reduced by 19%-20% and 18%-24% for years 1 and 2, respectively, and deaths were reduced by 60%-61% and 35%-39% for the same periods. These results show that all elderly persons should be immunized annually for influenza. The methods used in this study are an efficient cost-effective way to study vaccine impact and similar questions. Acute otitis media (AOM) frequently complicates influenza infection. Previous studies have found influenza vaccine effective in reducing the occurrence of AOM in children mainly older than 2 years.
                To evaluate the effectiveness of inactivated influenza vaccine in preventing AOM in children aged 6 to 24 months.
                Randomized, double-blind, placebo-controlled trial of 786 children aged 6 to 24 months enrolled at Children's Hospital of Pittsburgh before the 1999-2000 (411 children) and 2000-2001 (375 children) respiratory seasons (defined as December 1 through March 31 of the respective following year). Children received influenza vaccine or placebo in a 2:1 ratio. The first cohort was observed for 1 year and the second cohort until the end of the ensuing respiratory season.
                Two doses (0.25 mL each) of inactivated trivalent subvirion influenza vaccine or placebo were administered intramuscularly approximately 4 weeks apart.
                Proportion of children who developed AOM, monthly occurrence rate of AOM, estimated proportion of time with middle ear effusion, and utilization of selected health care and related resources.
                Of the 66 children in the vaccine group from whom serum samples were collected, seroconversion against strains in the vaccine formulations developed in 88.6% to 96.8%, depending on the specific strain. The efficacy of the vaccine against culture-confirmed influenza was 66% (95% confidence interval [CI], 34%-82%) in 1999-2000 and -7% (95% CI, -247% to 67%) in 2000-2001; however, influenza attack rates differed between these 2 periods (in the placebo group, 15.9% and 3.3%, respectively). Compared with placebo, influenza vaccine did not reduce the proportion of children who had at least 1 episode of AOM during the respiratory season (in the first cohort: vaccine, 49.2% vs placebo, 52.2%; P =.56 ]; in the second cohort: vaccine, 55.8% vs placebo, 48.3%; P =.17). The vaccine also did not reduce the monthly rate of AOM; the estimated proportion of time with middle ear effusion; or the utilization of selected health care and related resources. There were also no differences between the vaccine and placebo groups regarding any of these outcomes during peak influenza periods. The vaccines administered to both cohorts of children were well tolerated.
                Administration of inactivated trivalent influenza vaccine to children aged 6 to 24 months did not reduce their burden of AOM or their utilization of selected health care and related resources. This study was carried out to investigate the effectiveness of influenza vaccine among 2913 children (1512 vaccinees and 1401 nonvaccinees) under 6 years of age during the 2002-2003 season. Study subjects were recruited from 54 paediatric clinics, located in eight areas in Japan. Maximum body temperatures were obtained weekly from parents between 2002 December 16 and 2003 April 13. Influenza-like illness (ILI) was defined as an acute febrile illness (> or =38.0 degrees C) during the peak epidemic period in each study area. The vaccine antigens included were A/New Caledonia/20/99(H1N1), A/Panama/2007/99(H3N2) and B/Shandong/7/97. Vaccine effectiveness was analyzed by comparing the frequencies of ILI between vaccinees and nonvaccinees. The adjusted odds ratio (OR) and its 95% confidence interval (95% CI) were calculated by the proportional odds model using logistic regression with three-level outcome variables (<38.0/38.0-38.9/> or =39.0 degrees C). A significantly decreased OR of vaccination was observed (OR: 0.76; 95% CI: 0.66-0.88), corresponding to a vaccine effectiveness (1-OR) of 24% (95% CI: 12%-34%). When the analysis was confined to those aged > or =2 years, a more pronounced OR (0.67, 0.56-0.79) was obtained with a vaccine effectiveness of 33% (21%-44%). On the other hand, no significant vaccine effectiveness was detected among very young children; the ORs were 1.84 (0.81-4.19) for those <1 year of age and 0.99 (0.72-1.36) for those 1.0-1.9 years of age and 1.07 (0.80-1.44) when these two age groups were combined. Thus, among very young children vaccine effectiveness could not be demonstrated. The uptake of influenza vaccination among older people is suboptimal. Contact with a doctor or nurse is associated with older people deciding to accept influenza vaccination.
                To compare different forms of approach in improving uptake of influenza vaccination among patients aged 75 years and over in primary care.
                Randomised controlled trial.
                One large rural general practice serving the town and surrounding area of Melton Mowbray, Leicestershire.
                All 2,052 patients aged 75 years and over, registered with the practice and not living in nursing/residential homes or sheltered accommodation, were included in the study. One-third of patients were randomised to receive an offer of influenza vaccination as part of an over-75 health check administered by a practice nurse in the patient's home, and two-thirds of patients were randomised to receive a personal letter of invitation to attend an influenza vaccination clinic held at the surgery. The main outcome measure was uptake of influenza vaccination.
                Six hundred and eighty patients were randomised to the health check arm of the trial and 1,372 were randomised to receive a personal letter. Of those randomised to the health check arm, 468 received the health check from the nurse. Overall, the difference in influenza vaccination uptake was 6.4% (95% confidence interval [CI] = 2.2% to 10.4%) with 67.9% (n = 932) of those who were sent a personal letter actually receiving the vaccine, compared with 74.3% (n = 505) of those offered a combined health check and influenza vaccination (P = 0.003).
                Combining home-based over- 75 health checks with influenza vaccination can improve uptake among older patients. However this intervention is likely to be costly and its effect on influenza vaccination rates is modest. The difference in uptake is greater among those who do not routinely comeforwardfor vaccination and a more viable option may be to target these patients. To determine the clinical efficacy and cost-saving effect of pneumococcal polysaccharide vaccine (PPV) against community-acquired pneumonia (CAP), an open-label, randomized clinical trial was conducted involving 786 Japanese subjects older than 65 years of age receiving a routine influenza vaccine during the 2-year period. Study subjects were randomly assigned to either a PPV group (n=394) or to a non-PPV group (n=392). The incidence, admission and the medical cost for all-cause pneumonia were compared between these two groups. PPV vaccination significantly reduced the incidence of admission for all-cause pneumonia for subjects older than 75 years of age (41.5%, P=0.039) and for those who had difficulty walking (62.7%, P=0.005), but not for all study subjects older than 65 years of age (P=0.183), for the 2-year period. The Kaplan-Meier survival curves for subjects who had difficulty walking free from all-cause pneumonia demonstrated a significant difference (P=0.0146) between the two groups. PPV vaccination significantly reduced medical costs for all study subjects during the first year period (P=0.027). Our present data demonstrated that PPV was effective for all-cause pneumonia for study subjects older than 75 years of age, although the effect was not significant for all study subjects older than 65 years of age.
                Copyright © 2010 Elsevier Ltd. All rights reserved. The effect of influenza vaccination on the occurrence and severity of influenza virus infection in a population residing in nursing homes was studied through a program by the Osaka Prefectural Government, which is the first and official support for influenza vaccination of the elderly population during an influenza A (H3N2) epidemic in JAPAN:
                A cohort study located in the Osaka Prefecture, Japan, followed the outcomes of elderly nursing home residents who received influenza vaccinations (n = 10,739) in comparison with control subjects who did not receive influenza vaccinations (n = 11,723) and monitored clinically the onset of serious morbidity and mortality of influenza illness. Subjects were 22,462 persons older than 65 years who resided in 301 welfare nursing homes in the Osaka Prefecture, Japan during an influenza A (H3N2) epidemic in 1998 to 1999.
                Of 22,462 individuals living in 301 nursing homes, 10,739 received either one dose (2027 subjects) or two doses (8712 subjects) of inactivated, subunit trivalent influenza vaccine. Through the period from November 1998 to March 1999, there were 950 cases of influenza infection diagnosed clinically with cases by virus isolation and/or serology. There were statistically significantly fewer clinical cases of influenza, hospital admissions due to severe infection, and deaths due to influenza in the vaccinated cohort (256 cases, 32 hospital admissions, and one death) compared with the unvaccinated controls (694 cases, 150 hospital admissions, and five deaths). Vaccination was equally effective in those who received one dose of vaccine as in those who received two doses. No serious adverse reactions to vaccination were recorded. Thus, influenza vaccination is safe and effective in this population and should be an integral part of the routine care of persons aged 65 years and older residing in nursing homes.
                This study provides an analysis of the clinical efficacy of influenza vaccination in a large cohort of nursing home residents in JAPAN: Annual influenza vaccine administration requires the attention of all nursing home attendants, physicians, and public health organizations. Reported is a study of live, cold-adapted (CA) reassortant mono-, di-, and trivalent influenza type A and B vaccines in a series of controlled clinical and epidemiological investigations involving nearly 130 000 children aged 3-15 years. The results of clinical, immunological, and morbidity investigations of the vaccinees and a control group over 6-months' follow-up indicated that the vaccines were completely attenuated by the children. Transient febrile reactions occurred in < 1% of the children after vaccination, including double seronegative individuals with low antibody titres. The type A reisolates examined were genetically stable. The reassortants did not suppress each other after simultaneous inoculation of children and stimulated antibody response to influenza virus strains A1, A3, and B. The incidence of influenza-like diseases was approximately 30-40% lower among the vaccinated group than among the control group. The study demonstrates, for the first time, the efficacy of CA vaccine against infections caused by influenza B virus. The effectiveness of the influenza vaccine used in the 2001-2002 influenza season in Japan was investigated in a large-scale, geographically widely distributed, Internet-based study. Data were collected from 8841 of 9902 subjects registered by 38 clinics prior to the start of influenza season. Subjects were categorized into three groups by vaccination regimen: unvaccinated, vaccinated once, and vaccinated twice. Efficacy was also analyzed for three age groups: 0-15, 16-64, and 65-104 years. Influenza-like illness (ILI) was diagnosed according to Ministry of Health (MWH, Labor and Welfare in Japan) criteria. Laboratory-confirmed influenza cases were analyzed separately. The respective vaccine efficacy in the 0-15 years group for the one- and two-dose regimens was 67.6 and 84.5% for ILI and 54.0 and 79.8% for laboratory-confirmed influenza. Influenza vaccination was also shown to be effective in subjects 16-64 years. Vaccine effectiveness was not able to be determined for the over 65 years group, probably due to an insufficient number of infected patients. These results suggest that influenza vaccination is effective for children and adults and that a two-dose regimen is superior to a single dose in children 0-15 years. Assess the effectiveness of influenza vaccination in reducing hospitalization due to pneumonia and influenza among elderly subjects in a community in central Italy. Estimate the hospitalization fraction preventable by extending the vaccination program.
                Case-control study. Cases were subjects aged 65+ at hospital admission (1 December 1994-31 March 1995). For each case two population controls were randomly chosen, matched by sex, age and residence. Variables of interest were recorded through a postal questionnaire and telephone interview. A matched-set analysis was carried out adjusting for concomitant chronic diseases, education, type of home heating, and smoking habits. The preventable fraction of hospitalization was computed through the application of the attributable risk estimate. The setting was 33 municipalities in central Italy including 169,370 residents aged 65 years or more.
                Two hundred and seventy-five cases 550 controls were analyzed. Influenza vaccination was effective in preventing 33% of hospitalization due to pneumonia/influenza. The fraction of hospital admissions preventable by extending the vaccination was 17%. When the analysis was limited to self-respondents to the questionnaire (excluding next-of-kin) and to pneumonia/influenza as primary discharge diagnosis, protection from hospitalization by vaccination almost reached 50%, a better result in comparison with most case-control studies.
                Influenza vaccination was shown to be successful in reducing hospital admissions due to pneumonia and influenza. A large number of hospitalizations could be reduced extending the vaccination campaign. To determine the effectiveness of influenza vaccination on influenza-related acute respiratory illness (ARI) and overall ARI in patients with COPD, and its relationship to the degree of airflow obstruction.
                Stratified, randomized, double-blind, placebo-controlled trial.
                From June 1997 to November 1998 at a single university hospital. Patients and interventions: One hundred twenty-five patients with COPD were stratified based on their FEV(1) as having mild, moderate, and severe COPD. Within each group, they were randomized to the vaccine group (62 patients who received purified, trivalent, split-virus vaccine) or the placebo group (63 patients).
                The number of episodes and severity of total ARI, classified as outpatient treatment, hospitalization, and requirement of mechanical ventilation; and the number of episodes and severity of influenza-related ARI.
                The incidence of influenza-related ARI was 28.1 per 100 person-years and 6.8 per 100 person-years in the placebo group and vaccine group, respectively (relative risk [RR], 0.24 [p = 0.005]; vaccine effectiveness, 76%). The incidences were 28.2, 23.8, and 31.2 per 100 person-years in the patients with mild, moderate, and severe COPD, respectively, in the placebo group, and 4.5, 13.2, and 4.6 per 100 person-years in the patients with mild, moderate, and severe COPD, respectively, in the vaccine group (RR, 0.16 [p = 0.06]; vaccine effectiveness, 84%; RR, 0.55 [p = 0.5]; vaccine effectiveness, 45%; and RR, 0.15 [p = 0.04]; vaccine effectiveness, 85%, in the patients with mild, moderate, and severe COPD, respectively). Bivariate analysis revealed that the effectiveness of influenza vaccination was not modified by the severity of COPD, comorbid diseases, age, gender, or current smoking status. There was no difference in the incidence or severity of total ARI between the placebo group and the vaccine group.
                Influenza vaccination is highly effective in the prevention of influenza-related ARI regardless of the severity of COPD. Influenza vaccination does not prevent other ARIs unrelated to influenza. The effectiveness of influenza vaccination in the prevention of overall ARI in patients with COPD will depend on how much the proportion of influenza-related ARI contributes to the incidence of total ARI. Influenza vaccination should be recommended to all patients with COPD. An Advisory Committee on Immunization Practices policy of encouraging influenza vaccination for healthy 6- to 23-month-old children was in effect during the 2003-2004 influenza season, which was unusually severe in Colorado. We collaborated with 5 pediatric practices to attempt universal influenza immunization in this age group.
                The objectives were (1) to assess the maximal influenza immunization rates that could be achieved for healthy young children in private practice settings, (2) to evaluate the efficacy of registry-based reminder/recall for influenza vaccination, and (3) to describe methods used by private practices to implement the recommendations.
                The study was conducted in 5 private pediatric practices in Denver, Colorado, with a common billing system and immunization registry. Although recommendations by the Advisory Committee on Immunization Practices included children who were 6 to 23 months of age at any point during the influenza season, our practices chose not to recall children 22 to 23 months of age, because they would have become >24 months of age during the study period. Therefore, our study population consisted of all healthy children 6 to 21 months of age from the 5 practices (N = 5193), who were randomized to intervention groups (n = 2595) that received up to 3 reminder/recall letters or to control groups (n = 2598) that received usual care. The primary outcome was receipt of >or=1 influenza immunization, as noted either in the immunization registry or in billing data.
                Immunization rates for >or=1 dose of influenza vaccine for the intervention groups in the 5 practices were 75.9%, 75.4%, 68.1%, 55.6%, and 44.3% at the end of the season. Overall, 62.4% of children in the intervention groups and 58.0% of children in the control groups were immunized (4.4% absolute difference), with absolute differences, compared with control values, ranging from 1.0% to 9.1% according to practice. However, before intensive media coverage of the influenza outbreak began (November 15, 2003), absolute differences, compared with control values, ranged from 5.1% to 15.3% and were 9.6% overall. Before November 15, significant effects of recall were seen for children in the intervention groups, in both the 12- to 21-month age category (10.4% increase over control) and the 6- to 11-month category (8.1% increase over control); at the end of the season, however, significant effects of recall were seen only for the older age group (6.2% increase over control). The rates of receipt of 2 vaccine doses >or=1 month apart for eligible children ranged from 21% to 48% among the practices. Four of the 5 practices held influenza immunization clinics during office hours, evenings, or weekends, and these clinics achieved higher coverage rates.
                These results demonstrated that, in an epidemic influenza year, private practices were able to immunize the majority of 6- to 21-month-old children in a timely manner. Although media coverage regarding the epidemic blunted the effect of registry-based recall, recall was effective in increasing rates early in the epidemic, especially for children between 1 and 2 years of age. The practices that achieved the highest immunization rates were proactive in planning influenza clinics to handle the extra volume of immunizations required. In healthy adults influenza immunization reduces absenteeism caused by respiratory infections, but data on its efficacy among health care workers are scarce.
                To determine the effect of the conventional inactivated influenza A vaccine on reducing absenteeism related to respiratory infections among pediatric health care providers.
                A randomized, placebo-controlled, double blind study on vaccine efficacy was conducted in two pediatric hospitals during the winter season 1996 to 1997. The primary endpoint was days of work lost from the hospital because of respiratory infections. The documentation of absenteeism was based on personal sickness logs.
                Of the 547 randomized vaccinees 427 (78%) persons completed the 4-month follow-up and returned the sickness logs. Immunization failed to reduce episodes of respiratory infections (1.8 episodes/study period among vaccinees vs. 2.0 among controls). Similarly the vaccine failed to affect the total number of days the vaccinees suffered from respiratory infections (13.5 days vs. 14.6 days, respectively). However, days of work lost because of respiratory infections (1.0 days vs. 1.4 days, respectively, P = 0.02) and especially total numbers of days the study persons felt themselves unable to work when either on or off duty (2.5 days vs. 3.5 days, P 0.02) were significantly decreased.
                Influenza vaccination reduced absenteeism related to respiratory infections by 28%. We therefore believe that routine annual influenza immunizations should be recommended to health care providers working in pediatric settings. To test the hypothesis that a micronutrient supplement can improve seroconversion after influenza immunization in older institutionalized people.
                : Randomized, double-blind, placebo-controlled study.
                Nursing and residential homes in Liverpool, United Kingdom.
                One hundred sixty-four residents aged 60 and older from 31 homes were initially randomized; of these, 119 (72.6%) completed the study.
                Participants were randomized to receive a micronutrient supplement providing the reference nutrient intake for all vitamins and trace elements or identical placebo. Tablets were taken over an 8-week period during September and October 2000; influenza vaccine was administered 4 weeks after their commencement.
                The hemagglutination-inhibiting antibody response as defined by a fourfold or greater titer rise over 4 weeks and assessed separately for each of the three antigens contained in the 2000/2001 influenza vaccine (A/New Caledonia/20/99 (H1N1), A/Moscow/10/99 (H3N2), B/Beijing/184/93 (B)).
                Despite a significant increase in serum concentrations of vitamins A, C, D3, E, folate, and selenium in the supplemented group, there was no significant difference between groups (supplemented vs placebo, respectively) in the proportion of participants seroconverting to H1N1 (41% vs 49%, P=.374), H3N2 (49% vs 58%, P=.343), or B (41% vs 40%, P=.944).
                A micronutrient supplement providing the reference nutrient intake administered over 8 weeks had no beneficial effect on antibody response to influenza vaccine in older people living in long-term care. The goal of this pediatric clinical trial was to assess the safety and immunogenicity of two different doses of a monovalent inactivated pandemic (H1N1) 2009 vaccine in US children aged 6 months to 9 years of age. Randomized, observer-blinded, US multicenter phase 2 study assessing 2 doses of vaccine given 21 days apart in 474 children aged 6-35 months or 3-9 years. Children in each age group were randomly assigned to receive either a pandemic (H1N1) 2009 vaccine containing 7.5 or 15 μg of hemagglutinin (HA) or placebo in a 4:4:1 ratio. Primary outcome was hemagglutination inhibition (HI) antibody responses 21 days following each vaccination. Safety was monitored throughout the study. The first dose of either A H1N1 vaccine formulation was more immunogenic in children older than 3 years than in younger children. 45-50% of children aged 6-35 months and 69-75% of children aged 3-9 year-old attained HI titers of ≥ 1:40. A second dose of A H1N1 vaccine further increased HI antibody responses with seroprotection and seroconversion rates reaching 90-99% in both age groups. Interestingly, the pandemic (H1N1) 2009 vaccine formulations elicited similar rates of solicited and unsolicited injection site and systemic reactions as the placebo. The data therefore demonstrate the high level immunogenicity in infants and children of an (H1N1) 2009 influenza vaccine displaying a safety and reactogenicity profile similar to placebo.
                Copyright © 2011 Elsevier Ltd. All rights reserved. To evaluate the effectiveness and possible cost savings of influenza vaccination.
                Members age 65 and older in a Medicare managed care plan during the 1994-1995, 1995-1996, and 1996-1997 influenza seasons.
                The study examined administrative data on influenza vaccination and subsequent hospitalizations. Outcomes included hospitalization with pneumonia or influenza, with any respiratory condition, and with congestive heart failure (CHF).
                Vaccinated subjects experienced fewer hospitalizations with respiratory conditions or CHF than had unvaccinated subjects (OR=0.8 (95% CI, 0.7, 0.9) in analyses adjusted for age, sex, pneumococcal vaccination, health utilization, and morbidity). Analyses adjusted in addition for ethnicity obtained similar results among the subgroup of members whose ethnicity was known. Subjects without major disease in the previous 12 months had lower odds ratios for vaccination than subjects with major disease (OR values of 0.5 [95% CI, 0.4, 0.7] and 0.9 [95% CI, 0.8, 1.1], respectively). Subjects ages 65 to 79 had lower odds ratios for vaccination than subjects ages 80 and older (OR values of 0.7 [95% CI, 0.6, 0.9] and 0.9 [95% CI, 0.8, 1.1], respectively). Estimated cost savings averaged about $80 per vaccinated subject.
                Subjects ages 65 to 79 who had received influenza vaccination experienced fewer hospitalizations and had lower costs than had unvaccinated subjects. Associations were weaker for subjects age 80 and older. The results, consistent with recommendations for the use of influenza vaccine, suggest that people ages 65 to 79 should be heavily targeted for vaccination. During the winter of 1989-1990, influenza type A(H3N2) circulated widely, causing excess morbidity and mortality nationwide. From November through April, 1989-1990, hospitalized cases of pneumonia and influenza occurring among noninstitutionalized individuals 65 or more years of age were identified by 20 acute care hospitals in southern lower Michigan. These cases were group matched on age, sex, race, and zip code to randomly sampled, community-based controls from a comprehensive listing of Medicare beneficiaries residing in the study area. Self-reported data were collected from cases and controls on influenza vaccine status for the 1989-1990 season and on a number of other factors which could have influenced vaccination status or outcome. Questionnaires were completed by 1,907 individuals, 449 of whom were cases, resulting in an overall response rate of 76%. A community-based influenza surveillance system was implemented to determine the timing and intensity of viral activity and influenza-like illness. Vaccine effectiveness in preventing overall pneumonia and influenza hospitalizations was estimated by logistic regression. During the 3-month period of surveillance-confirmed peak influenza type A(H3N2) circulation, vaccine effectiveness was 45% (95% confidence interval 14-64, p = 0.009). However, during the 3-month period of low or absent virus activity, identical methodology and model specification resulted in an effectiveness estimate of 21% that was not statistically different from zero (p = 0.36). The effectiveness determined during the peak period of virus circulation is felt to be a conservative estimate, since agents other than influenza are responsible for pneumonia and influenza hospitalizations, even during times of peak influenza activity. To study the efficacy of pneumococcal capsular polysaccharide vaccine among the elderly by use of a population-based intervention in one township, Varkaus, Eastern Finland.
                A randomized, controlled trial in which elderly inhabitants (aged 60 years or older) of the catchment area were randomized to receive either pneumococcal and influenza vaccines (PI group = vaccinated) or influenza vaccine alone (I group = controls) and offered participation. The response rate was 67.4%. The PI group consisted of 1,364 persons and the I group of 1,473 persons. The vaccinations were performed in the municipal health center in the fall of 1982, and all elderly inhabitants were followed for 3 years for the development of radiologically confirmed pneumonia. Pneumococcal etiology was identified by serological methods.
                The incidence of pneumonia was 18.8 per 1,000 person-years in the PI group (73 pneumonia episodes) and 16.6 per 1,000 person-years in the I group (69 episodes). Pneumococcal etiology was found in 27 episodes in the PI group (incidence 7.0 per 1,000 person-years) and in 36 episodes in the I group (incidence 8.6 per 1,000 person-years). In controls (I group) the incidence of pneumococcal pneumonia was significantly higher among persons with increased risk for contracting pneumonia (19 per 1,000 person-years) than among controls with low risk status (4 per 1,000 person-years). No significant protection from pneumococcal pneumonia was found in the study group as a whole (vaccine efficacy 15%, 95% CI -43% to 50%). However, in persons with medical risk factors for contracting pneumonia, there was a statistically significant protective efficacy of 59% (95% CI, 6% to 82%).
                Pneumococcal vaccination significantly reduced the incidence of pneumococcal pneumonia in elderly persons at increased risk for contracting pneumonia. This increased/high-risk category comprised 34% of the population aged 60 years or older. Because targeted vaccination of this large group may be difficult to organize in an efficient manner, vaccinating all elderly persons may be the best strategy to prevent this rather common and often fatal disease. In a strictly controlled epidemiological trial on 12,643 school children aged 11-14 years the reactogenic properties and safety of killed influenza chromatographic vaccine under the conditions of multiple immunization were studied. A single immunization dose of the vaccine (0.2 ml) contained the hemagglutinins of influenza viruses A/Philippines/82 (H3N3) and A/Kiev/59/79 (H1N1), 3.5 micrograms each. The preparation was introduced by means of a jet injector. The vaccine was shown to be clinically and immunologically safe under the conditions of the regular multiple immunization of children over the period of 4 years. Influenzavirus vaccine is used infrequently in healthy children, even though the rates of influenza in this group are high. We conducted a multicenter, double-blind, placebo-controlled trial of a live attenuated, cold-adapted, trivalent influenzavirus vaccine in children 15 to 71 months old.
                Two hundred eighty-eight children were assigned to receive one dose of vaccine or placebo given by intranasal spray, and 1314 were assigned to receive two doses approximately 60 days apart. The strains included in the vaccine were antigenically equivalent to those in the inactivated influenzavirus vaccine in use at the time. The subjects were monitored with viral cultures for influenza during the subsequent influenza season. A case of influenza was defined as an illness associated with the isolation of wild-type influenzavirus from respiratory secretions.
                The intranasal vaccine was accepted and well tolerated. Among children who were initially seronegative, antibody titers increased by a factor of four in 61 to 96 percent, depending on the influenza strain. Culture-positive influenza was significantly less common in the vaccine group (14 cases among 1070 subjects) than the placebo group (95 cases among 532 subjects). The vaccine efficacy was 93 percent (95 percent confidence interval, 88 to 96 percent) against culture-confirmed influenza. Both the one-dose regimen (89 percent efficacy) and the two-dose regimen (94 percent efficacy) were efficacious, and the vaccine was efficacious against both strains of influenza circulating in 1996-1997, A(H3N2) and B. The vaccinated children had significantly fewer febrile illnesses, including 30 percent fewer episodes of febrile otitis media (95 percent confidence interval, 18 to 45 percent; P<0.001).
                A live attenuated, cold-adapted influenzavirus vaccine was safe, immunogenic, and effective against influenza A(H3N2) and B in healthy children. Although influenza causes substantial morbidity and mortality in all age groups, current recommendations emphasize annual immunization for people at high risk for complications of influenza. We conducted a double-blind, placebo-controlled trial of vaccination against influenza in healthy, working adults.
                In the fall of 1994, we recruited working adults from 18 to 64 years of age from in and around the Minneapolis-St. Paul area and randomly assigned them to receive either influenza vaccine or placebo injections. The primary study outcomes included upper respiratory illnesses, absenteeism from work because of upper respiratory illnesses, and visits to physicians' offices for upper respiratory illnesses. The economic benefits of vaccination were analyzed by estimating the direct and indirect costs associated with immunization and with upper respiratory illnesses.
                We enrolled a total of 849 subjects. Baseline characteristics were similar in the two groups. During the follow-up period, consisting of the 1994-1995 influenza season (December 1, 1994, through March 31, 1995), those who received the vaccine reported 25 percent fewer episodes of upper respiratory illness than those who received the placebo (105 vs. 140 episodes per 100 subjects, P < 0.001), 43 percent fewer days of sick leave from work due to upper respiratory illness (70 vs. 122 days per 100 subjects, P = 0.001), and 44 percent fewer visits to physicians' offices for upper respiratory illnesses (31 vs. 55 visits per 100 subjects, P = 0.004). The cost savings were estimated to be $46.85 per person vaccinated.
                Vaccination against influenza has substantial health-related and economic benefits for healthy, working adults. Influenza virus is a major cause of illness, disruption to daily life, and increased use of health care in all age groups.
                To assess the safety and effectiveness of intranasally administered trivalent, live, attenuated influenza virus (LAIV) vaccine for reducing illness, absenteeism, and health care use among healthy, working adults.
                Randomized, double-blind, placebo-controlled trial conducted from September 1997 through March 1998.
                Thirteen centers across the United States.
                A total of 4561 healthy, working adults aged 18 to 64 years recruited through health insurance plans, at work sites, and from the general population.
                Participants were randomized 2:1 to receive intranasally administered trivalent LAIV vaccine (n = 3041) or placebo (n = 1520) in the fall of 1997.
                Episodes of febrile illness, severe febrile illness, febrile upper respiratory tract illness, work loss, and health care use during the peak and total influenza outbreak periods, and adverse events.
                Recipients of LAIV vaccine were as likely to experience 1 or more febrile illnesses as placebo recipients during peak outbreak periods (13.2% for vaccine vs 14.6% for placebo; P=.19). However, vaccination significantly reduced the numbers of severe febrile illnesses (18.8% reduction; 95% confidence interval [CI], 7.4%-28.8%) and febrile upper respiratory tract illnesses (23.6% reduction; 95% CI, 12.7%-33.2%). Vaccination also led to fewer days of illness across all illness syndromes (22.9% reduction for febrile illnesses; 27.3% reduction for severe febrile illnesses), fewer days of work lost (17.9% reduction for severe febrile illnesses; 28.4% reduction for febrile upper respiratory tract illnesses), and fewer days with health care provider visits (24.8% reduction for severe febrile illnesses; 40.9% reduction for febrile upper respiratory tract illnesses). Use of prescription antibiotics and over-the-counter medications was also reduced across all illness syndromes. Vaccine recipients were more likely to experience runny nose or sore throat during the first 7 days after vaccination, but serious adverse events between the groups were not significantly different. The match between the type A(H3N2) vaccine strain and the predominant circulating virus strain (A/Sydney/05/97[H3N2]) for the 1997-1998 season was poor, suggesting that LAIV provided substantial cross-protection against this variant influenza A virus strain.
                Intranasal trivalent LAIV vaccine was safe and effective in healthy, working adults in a year in which a drifted influenza A virus predominated. The objective of this study was to assess the safety of routine trivalent influenza vaccine (TIV) administration among healthy children 6 through 23 months of age, after the Advisory Committee on Immunization Practices recommendation.
                The study was a retrospective case-control study of children receiving TIV in the first 2 seasons after the Advisory Committee on Immunization Practices recommendation. We assessed outcomes in the 42 days after vaccination in a population of 13,383 children. Each case subject was matched, according to age and gender, with 3 control subjects. Hazard ratios were calculated with conditional logistic regression analysis.
                We found no statistically significantly elevated hazard ratios for the first TIV dose. An elevated risk of pharyngitis was found for children receiving a second TIV dose. No elevated risk of seizure was found.
                These results, for a population of healthy children, showed no medically significant adverse events related to TIV among children 6 to 23 months of age. Production lots of a live influenza vaccine made of strains A/47/T (N1H1), A/47/6/2 (H3N2), and B/60/32 were used for vaccination of 3663 children aged from 5 to 14 years inoculated twice with monovaccines, a trivaccine made of the above strains, or placebo. Both mono- and polyvaccine were practically areactogenic. An average per cent of subjects with a significant rise in antibody titres to the respective three antigens was 60%. The efficacy of the vaccination was 31.0-42.8% for monopreparations and 36.3% for the trivaccine. The studies showed the possibility and expedience of using for children the live influenza vaccine in the form of a polyvalent preparation including current influenza type A and B viruses. The efficacy of inactivated influenza vaccine in healthy infants and children younger than 24 months has not been confirmed. The aim of the present study was to determine the prophylactic effect of inactivated influenza vaccine against influenza A in healthy children aged 6-24 months.
                Healthy infants and young children (6-24 months old) were immunized by subcutaneous injection of inactivated influenza vaccine before influenza seasons. Age matched children were randomly assigned as the control. These children were followed up from January to April in each year (2000, 2001 and 2002). The attack rates of influenza A infection was compared and statistically assessed.
                The attack rate of influenza A virus infection in the vaccine group and the control group were 14.8% (n = 27) vs 12.5% (n = 32) in 2000 (P = 0.526); 2.8% (n = 72) vs 7.2% (n = 69) in 2001 (P = 0.203); and 3.4% (n = 52) vs 8.9% (n = 56) in 2002 (P = 0.205). The attack rates of influenza A between the two groups were not significantly different.
                Inactivated influenza vaccine did not reduce the attack rate of influenza A infection in 6-24 month old children. Although the cost-effectiveness and cost-benefit of influenza vaccination are well established for persons aged 65 years or older, the benefits for healthy adults younger than 65 years are less clear.
                To evaluate the effectiveness and cost-benefit of influenza vaccine in preventing influenza-like illness (ILI) and reducing societal costs of ILI among healthy working adults.
                Double-blind, randomized, placebo-controlled trial conducted during 2 influenza seasons.
                Healthy adults aged 18 to 64 years and employed full-time by a US manufacturing company (for 1997-1998 season, n = 1184; for 1998-1999 season, n = 1191).
                For each season, participants were randomly assigned to receive either trivalent inactivated influenza vaccine (n = 595 in 1997-1998 and n = 587 in 1998-1999) or sterile saline injection (placebo; n = 589 in 1997-1998 and n = 604 in 1998-1999). Participants in 1997-1998 were rerandomized if they participated in 1998-1999.
                Influenza-like illnesses and associated physician visits and work absenteeism reported in biweekly questionnaires by all participants, and serologically confirmed influenza illness among 23% of participants in each year (n = 275 in 1997-1998; n = 278 in 1998-1999); societal cost of ILI per vaccinated vs unvaccinated person.
                For 1997-1998 and 1998-1999, respectively, 95% (1130/1184) and 99% (1178/1191) of participants had complete follow-up, and 23% in each year had serologic testing. In 1997-1998, when the vaccine virus differed from the predominant circulating viruses, vaccine efficacy against serologically confirmed influenza illness was 50% (P =.33). In this season, vaccination did not reduce ILI, physician visits, or lost workdays; the net societal cost was $65.59 per person compared with no vaccination. In 1998-1999, the vaccine and predominant circulating viruses were well matched. Vaccine efficacy was 86% (P =.001), and vaccination reduced ILI, physician visits, and lost workdays by 34%, 42%, and 32%, respectively. However, vaccination resulted in a net societal cost of $11.17 per person compared with no vaccination.
                Influenza vaccination of healthy working adults younger than 65 years can reduce the rates of ILI, lost workdays, and physician visits during years when the vaccine and circulating viruses are similar, but vaccination may not provide overall economic benefits in most years. JAMA. 2000;284:1655-1663. To compare three approaches for improving compliance with influenza and pneumococcal vaccination of elderly patients.
                Randomized controlled trial using three parallel group practices at a public urban teaching hospital.
                Public teaching hospital.
                All patients 65 years of age and older (n = 1202) seen by resident physicians (n = 66) attending three ambulatory medical practices from October 1, 1989 to March 31, 1990.
                All three provider groups received intensive education in immunization standards. The control group received no further intervention. Staff in the second group offered education to patients at their visits. In the third group, the prevention team, a flowsheet was used, patient education offered, and staff had their tasks redefined to facilitate compliance; for vaccinations, eg, nurses could vaccinate independent of MD initiative.
                Medical records were reviewed for the 1202 patients seen, including 756 patients seen during both the 1988-89 and 1989-90 influenza seasons, to determine documented offering and receipt of vaccinations. During the intervention period (1989-90), influenza vaccinations were offered significantly more frequently to prevention team patients (68.3%) than to patients in either the patient education (50.4%) or control (47.6%) groups (P = 0.006), even after adjusting for the patients' prior vaccination status, age, gender, race, and high-risk co-morbidity and for physicians' level of training. Likewise, pneumococcal vaccinations were offered more frequently to previously unvaccinated prevention team patients (28.3%) than to patient education (6.5%) or control (5.4%) group patients (P = 0.001), even after adjusting for the factors using multivariate analysis. Compliance rates did not differ between patient education and control subjects for either vaccine. Pre-intervention physician surveys documented higher perceived than actual compliance for both vaccines, with 89.0% and 52.8% of physicians believing that they complied with influenza and pneumococcal vaccination guidelines, respectively.
                The results of this trial provide strong support for organizational changes that involve non-physician personnel to enhance vaccination rates among older adults. The study of the based on the A/Leningrad/134/17/57/(H2N2) attenuated adult live influenza vaccine (LIV) investigated features for immunization of the children, aged 3-6 years. During autumn, 1999, out of 256 children, aged 3-6 years, residents of the Leningrad region, who attended the kindergarten, 184 children were immunized with 1 or 2 doses of the live influenza vaccine, and 72 ones were given placebo. There were no any moderate or strong temperature reactions revealed after the inoculation. The LIV was shown to be genetically stable. After a single dose of the vaccine seroconversion to influenza type A virus and to influenza type B virus was observed respectively in 58% and in 39% of seronegative 3-6 year old vaccinees. The twofold LIV administration failed to give any advantages in stimulation of the immune response. During 6 months after immunization the morbidity rate in vaccinees did not exceed the morbidity rate in unvaccinated children. Thus LIV for adults proved safe and immunogenic and can be recommended for single dose immunization both of adults and children. Children aged 3 to 14 were immunized with live recombinant influenza A vaccine; about 120,000 children were followed up for 6 months. Analysis of the morbidity (excepting ARVI and influenza) of the immunized and control groups permitted a conclusion about the safety of the preparation. The protective index of vaccine efficacy during influenza epidemic caused by A/Taiwan/1/86(H1N1) virus was 1.3 to 1.42. Live recombinant influenza vaccine is recommended for public health to be used for protection of children aged 3 to 14 from influenza. Evaluate the educational needs of adults over 65 years or more with regards to the vaccine, vaccination and immunization against the influenza, design strategies to assist the educational needs and implant and evaluate an immunization program at an independent community pharmacy. A study divided into three phases: Phase I--evaluation of the educational needs related to the vaccine, vaccination and immunization. Phase II--designing of strategies to assist the needs. Phase III--a random longitudinal controlled study to evaluate an immunization program against the influenza implanted at an independent community pharmacy. One hundred (100) patients participated, randomly assigned to a controlled and experimental group. Three months into the study's Phase III, a 68% of the experimental group had been vaccinated and showed a tendency to improvement in knowledge; in the controlled group, a 32% had been vaccinated and did not show a tendency in improvement of knowledge. A year into the study's Phase III, a 76% of the experimental group had been vaccinated and 24% of the controlled group was vaccinated. The satisfaction average of the experimental group towards the pharmacist was 3.94 +/- 0.18 and, in the controlled group was 3.98 +/- 0.20, whiting a scale of 0-04. People who participated in an educational activity offered by a pharmacist showed: more knowledge, remembered what they learned and an increase in influenza vaccination. A monovalent, zonally purified, inactivated influenza B vaccine was administered to 29 children, 3 to 6 years of age, and 16 infants, 12 to 28 months of age, as a single dose of 0.25 ml containing 250 chick cell agglutinating units. The vaccine was both antigenic and well tolerated in the older group of preschool children. In the infants the vaccine was also antigenic but poorly tolerated clinically. Febrile reactions to 102 or greater were seen in 9 of the 16 infants, and two of these infants experienced a seizure following vaccination. The clinical reactions observed with the administration of influenza B vaccine in the dose used in this study would suggest significant limitations on its use in children under 3 years of age. This serial cohort study assessed the risk of hospitalization or death associated with influenza and the effectiveness of influenza vaccination among subgroups of elderly members of 3 managed-care organizations in the United States. Data on baseline characteristics and outcomes were obtained from computerized databases. A total of 122,974 (1996-1997 season) and 158,454 (1997-1998 season) persons were included in the cohorts. Among unvaccinated persons, hospitalizations for pneumonia/influenza or death occurred in 8.2 of 1000 healthy and 38.4 of 1000 high-risk persons in year 1, and in 8.2 of 1000 healthy and 29.3 of 1000 high-risk persons in year 2. After adjustments, vaccination was associated with a 48% reduction in the incidence of hospitalization or death (95% confidence interval [CI], 42-52) in year 1 and 31% (95% CI, 26-37) in year 2. Effectiveness estimates were statistically significant and generally consistent across the healthy and high-risk subgroups. The absolute risk reduction, however, was 2.4- to 4.7-fold higher among high-risk than among healthy elderly persons. All elderly individuals may substantially benefit from vaccination. However, the impact of influenza is greater in persons with high-risk medical conditions. The effectiveness of influenza vaccine in reducing hospital admissions for pneumonia, influenza, bronchitis, or emphysema was assessed by a case-control study of people aged 16 years and older who were admitted to 10 Leicestershire hospitals between 1 December 1989 and 31 January 1990. Hospital and general practitioners' records for 156 admissions (the cases) and 289 controls matched for age and sex were reviewed. Information was collected on demography, the usual place of residence (institutional or non-institutional), the existence of chronic illness, and vaccination during the 5 years before admission. The odds ratio for hospital admission among vaccinees was 0.67 (95% CI 0.39-1.12) giving an estimate of vaccine effectiveness in this setting of 33% (95% CI 0-61). However, multivariate logistic regression, adjusting for the effects of institutional care and chronic illness, revealed that influenza vaccination reduced hospital admissions by 63% (95% CI 17-84%). There was a strong trend towards improved vaccine effectiveness when used in institutional settings. Influenza vaccine is effective in reducing hospital admissions for influenza, pneumonia, bronchitis and emphysema, and effectiveness is comparable to that observed for influenza and pneumonia admissions in North America. All persons 65 years and older are recommended to be immunised against influenza each autumn. As immunisation rates remain low, we conducted a randomised control trial in a three-partner urban general practice to evaluate the differential effectiveness of a single postcard reminder in a general practice setting compared to usual care. All non-residential patients aged 65 years and over were identified from the age/sex/disease register. After exclusions, 325 patients were stratified by sex (125 men and 200 women) and randomised to receive either a postcard reminder in large print mailed in April or usual care. General practitioners (GPs) were blind to the randomisation. A blinded record audit performed in July demonstrated that the postcard was effective in increasing immunisation for men (chi(2)1df = 3.85; p = 0.05) but not for women (chi(2)1df = 0.45; p = 0.50). After adjusting for 1995 immunisation status, the effect of the postcard on immunisation rates was even stronger in men (Wald chi(2)1df = 6.20; p = 0.01) but remained non-significant in women (Wald chi(2)1df = 1.38; p = 0.24). With this adjustment, the odds of having the 1996 flu vaccine for men sent the postcard reminder were three times that of men in the control group (OR = 3.0; 95% CI 1.3-6.9). In a general practice setting, a single postcard reminder appears to be a promising way to boost influenza immunisation rates among ageing men. Replication of the study is recommended. The effectiveness of influenza vaccination in preventing serious illness and death was determined in an elderly population during the influenza epidemic of was determined in an elderly population during the influenza epidemic of was determined in an elderly population during the influenza epidemic of 1989-90. A retrospective cohort study was carried out using computerized general practitioner records on nearly 10,000 patients aged 55 years and over. After adjustment for potential confounding factors, recent immunization was found to have a protective effect of 75% (95% confidence intervals: 21-92%) against death. Protection did not appear to vary with either age or the presence of underlying chronic disease. As the complications of influenza are most common in those with underlying chronic disease, the study findings are consistent with the recommended policy for the use of influenza vaccine in the UK. Further work is necessary to determine the cost-effectiveness of extending immunization to other groups. During the first wave of A/California/7/2009(H1N1) influenza, high rates of hospitalization in children under 5 years were seen in many countries. Subsequent policies for vaccinating children varied in both type of vaccine and number of doses. In Canada, children 36 months to <10 years received a single dose of 0.25 ml of the GSK adjuvanted vaccine (Arepanrix) equivalent to 1.9 microg HA. Children 6 months to 35 months received two doses as did those 36-119 months with chronic medical conditions.
                We conducted a community-based case-control vaccine effectiveness (VE) review of children under 10 years with influenza like illness who were tested for H1N1 infection at the central provincial laboratory. Laboratory-confirmed influenza was the primary outcome, and vaccination status the primary exposure to assess VE after a single 0.25-ml dose.
                If vaccination was designated to be effective after 14 days, no vaccinated child had laboratory-confirmed influenza compared to 38% of controls. The VE of 100% was statistically significant for children <10 years of age and <5 years considered separately. If vaccination was considered effective after 10 days, VE dropped to 96% overall but was statistically significant and over 90% in all age subgroups, including those under 36 months.
                A single 0.25-ml dose of the GSK adjuvanted vaccine (Arepanrix) protects children against laboratory-confirmed pandemic influenza potentially avoiding any increased reactogenicity associated with second doses. Adjuvanted vaccines offer hope for improved seasonal vaccines in the future. Despite recommendations supporting annual influenza vaccination for people aged 65 years or older, vaccination rates remain low. Several studies have evaluated the effect of sending mailed reminders, but few have compared alternative ways of reminding patients to receive the vaccine. In a randomized trial of 939 patients aged 65 years or older in four family practices carried out between Oct. 23 and Dec. 31, 1984, we compared three ways of reminding elderly patients to receive the vaccine: personal reminder by the physician, telephone reminder by the nurse and reminder by letter. The vaccination rates for the three groups were 22.9%, 37% and 35.1% respectively. No reminder was issued to a control group, and the rate was 9.8%. Some patients could not be reached by telephone, and some did not see the physician during the specified time. Among the patients whom the nurse actually contacted, the vaccination rate was 43.5%; the rate for patients whom the doctor actually saw was 45.1%. Overall, a telephone reminder by the nurse was the most effective method, and at an hourly salary of $16 or less this method would also be the most cost-effective. The reminders used in this study were automatically generated from a computerized medical record system. The study shows how a computerized system can be used to identify patients for whom preventive procedures are due. We prospectively studied the efficacy of influenza vaccine during an influenza A/Arizona/80 (H3N2) outbreak at the Jewish Home and Hospital for the Aged in New York in the winter season of 1982 to 1983. All patients had been offered influenza vaccine before the outbreak; 181 chose to be vaccinated and 124 refused vaccination but agreed to participate in the study. Among those with serologic evidence of influenza infection, respiratory illness was significantly more common in the unvaccinated group (six of 14 vs one of 22). The overall mortality was 13 (7.2%) of 181 in the vaccinated group and 22 (17.7%) of 124 in the control group. The vaccinated and the control groups were examined for comparability. A logistic regression analysis, which controlled for differences in sex and level of nursing care, indicated that the difference in mortality was still significant, with a summary odds ratio of 2.7. The relative risk of death in the unvaccinated group was comparable at 2.18. Influenza vaccine reduced the mortality by 59% in the vaccinated group compared with the control group. To evaluate the safety, reactogenicity and immunogenicity of inactivated chromatographic influenza vaccine A(H3N2) produced by the Pasteur Research Institute of Epidemiology and Microbiology in Leningrad, children aged 7-15 years received the vaccine intradermally in doses of 114-228 IU, and 152 children received placebo. In this study inactivated influenza vaccine introduced parenterally to children aged 11-15 years in a dose of 228 IU proved to be nonreactogenic. The reactogenicity index of the preparation injected in a dose of 114 IU to children aged 7-10 years was 0.6%. Immunization in a single injection was accompanied by significant seroconversions in 87.5%-96.0% of children with the highly pronounced growth of antibody titers (21.1-34.6 times). The complex of clinico-laboratory tests showed the safety of this preparation for both age groups. A population-based cohort study was conducted during the 2003-2004 season to examine the effectiveness of influenza vaccine among community-dwelling elderly. The subjects consisted of 4787 elderly, ranging from 65 to 79 years. We either interviewed the elderly directly or their families regarding acute febrile illness, hospital visits, hospitalization and death by telephone every month. The vaccination status and physician-diagnosed clinical influenza (hereinafter referred as clinical influenza) were determined based on data obtained from the city office and hospitals, respectively. Influenza-like illness (ILI) was defined as an acute febrile illness (> or = 38.5 degrees C) during the epidemic period. After adjusting for confounders, vaccination decreased ILI significantly (odds ratio [OR], 0.38; 95% confidence interval [CI], 0.17-0.85), but not clinical influenza (OR, 0.76; 95% CI, 0.28-2.06). The results were inconclusive for preventing hospitalization for influenza or pneumonia (OR, 0.37; 95% CI, 0.09-1.47) and death (OR, 3.68; 95% CI, 0.75-18.12), due to the inadequate sample size. In conclusion, the influenza vaccination was thus found to be associated with a decreased ILI during the epidemic period in community-dwelling elderly. Public health clients in an Ontario community 65 years of age or older were randomly allocated to receive an intervention by a public health nurse during a home visit promoting either influenza immunization or safety measures. There was no statistically significant differences in influenza immunization rates between these two groups (56.1% vs 56.6%). Men were significantly more likely to receive immunization. Annual influenza vaccination has long been recommended for the elderly population. Despite this recommendation, immunization rates have remained very low. This study measured the effects of two approaches to the provision of influenza immunization to the 65-years-and-over age group in a single family practice. The "drop-in" group (N=123) was informed of the availability of the vaccine at visits made during the vaccination period. The "phone" group (N=120) was notified of the availability of the vaccine by telephone and was invited to come in for the shot. An immunization rate of 50.8% for the "phone" group and 26.8% for the "drop-in" group was obtained (P=.0002). These results contrast strongly with the overall immunization rates of 5.9% and 9.5% obtained during the previous two years, when no active immunization policy was in place. The telephone approach was found to benefit the type of patient at greatest risk from influenza: the chronically ill and the aged. It is clear that having a defined immunization policy substantially improves the provision of influenza vaccination. The authors discuss the effectiveness and practicality of these approaches to the delivery of influenza vaccine and their applicability to other forms of prevention in family medicine. A randomized controlled trial demonstrated that a single mailed influenza vaccination cue increased the vaccination rate among elderly HMO members with high-risk chronic conditions (n = 2217) from 30 per cent to 39 per cent during the fall and winter of 1984/85. To evaluate the effect of influenza vaccination on the coronary events in patients with confirmed coronary artery disease (CAD).
                Randomized, double-blind, placebo controlled study. We included 658 optimally treated CAD patients; 477 men, mean age 59.9+/-10.3 years. Three hundred and twenty-five patients received the influenza vaccine, and 333 patients placebo. Median follow-up was 298 (interquartile range 263-317) days. Primary endpoint was the cardiovascular death. Its estimated 12-month cumulative event rate was 0.63% in the vaccine vs. 0.76% in controls (HR 1.06 95% CI: 0.15-7.56, P = 0.95). There were two secondary composite endpoints: (i) the MACE (cardiovascular death, myocardial infarction, coronary revascularization) tended to occur less frequently in the vaccine group vs. placebo with the event rate 3.00 and 5.87%, respectively (HR 0.54;95% CI: 0.24-1.21, P = 0.13). (ii) Coronary ischaemic event (MACE or hospitalization for myocardial ischaemia) estimated 12-month event rate was significantly lower in the vaccine group 6.02 vs. 9.97% in controls (HR 0.54; 95% CI: 0.29-0.99, P = 0.047).
                In optimally treated CAD patients influenza vaccination improves the clinical course of CAD and reduces the frequency of coronary ischaemic events. Large-scale studies are warranted to evaluate the effect of influenza vaccination on cardiovascular mortality. (ClinicalTrials.gov: NCT 00371098). Some reports have suggested that influenza virus vaccine is less effective in persons that have received prior annual vaccination(s) than in those receiving it for the first time. This issue was addressed by evaluating the efficacy of annual influenza vaccinations over a 5 year period in healthy adults employing commercially-available, inactivated whole-virus vaccine. Influenza vaccination had minimal effects on overall respiratory illnesses during epidemic periods. However, it reduced influenza virus shedding by an average of 38.8% and conferred protection against influenza virus infection during each epidemic. Some variation in infection rates were noted between vaccine groups given one or more than one annual immunization, and between years, but no consistent pattern of differences was noted in relation to number of successive years of vaccination. These results suggest that the current recommendation for annual influenza vaccination of persons at special risk of serious disease and complications is appropriate, but that continued efforts to improve the effectiveness of our prophylactic measures against influenza are needed. Hospitalisation represents an opportunity to identify unimmunised people at risk for the complications of influenza and pneumococcal disease. We conducted a randomised controlled trial of two strategies to increase uptake of influenza and pneumococcal vaccines in eligible, hospitalised subjects aged 65 years or more, admitted between May and September 1998 to a Melbourne hospital. Unvaccinated participants were allocated randomly to alert systems for hospital staff or community general practitioners (GPs). Follow-up occurred at 1 and 3 months. The baseline vaccination rates were 70% for influenza (426/606) and 41% (248/606) for pneumococcal disease. For unvaccinated subjects, the hospital alert resulted in 67% uptake compared to 55% following a GP alert for pneumococcal vaccine; and 63% in hospital compared to 53% following a GP alert for influenza vaccine. Although there was a trend toward a higher uptake in hospital, neither of these differences was statistically significant. The majority (75%) of vaccinations following a GP alert occurred within 1 month of discharge. Despite hospital and community-based reminder systems, there are still significant missed opportunities for vaccination. We did not demonstrate significant differences between hospital and GP reminder systems, but there was a trend towards higher uptake with opportunistic vaccination in hospital.
                Copyright 2003 S. Karger AG, Basel Influenza is a common and potentially serious infection in infants. Previous studies of influenza vaccine in this age group have reported widely varying estimates of vaccine effectiveness, and few have used laboratory confirmation of influenza diagnoses. We evaluated the effectiveness of 1 and 2 doses of the trivalent inactivated vaccine against laboratory-confirmed influenza in children aged 6 to 23 months within the Kaiser Permanente Northern California Medical Care Program for the 2003-2004, 2004-2005 and 2005-2006 influenza seasons. 1,648 children were included in the analyses, with an average of 4.5 controls matched to each of the 300 cases (213, 29 and 58 cases identified for each of the influenza seasons, respectively) based on birth month/year and zip code. Vaccination status was determined as of 14 days prior to the case patient's positive test result. Conditional logistic regression was used to calculate vaccine effectiveness for each season, adjusting for chronic medical conditions and other possible confounders. During the 2005-2006 influenza season, when predominant circulating virus strains and vaccine strains were well matched, vaccination was 76% [95% CI: 37-91%] effective against laboratory-confirmed infection. There was no statistically significant effect of vaccination, however, for the 2003-2004 or 2004-2005 seasons. Our results highlight the need for further study of influenza vaccine effectiveness in this age group. The immunogenicity and efficacy of Russian live attenuated and US inactivated trivalent influenza vaccines administered alone or in three different combinations were evaluated in a randomized, placebo-controlled, double-blinded study of 614 elderly or chronically ill nursing home residents in St. Petersburg, Russia during the 1996-97 influenza season. Postvaccination serum antibody responses were more frequent among individuals administered the combination vaccines than among those vaccinated with live or inactivated vaccine alone. Only individuals who received live vaccine, alone or in combination with inactivated vaccine, achieved significant postvaccination increases in virus-specific nasal IgA. Efficacy in preventing laboratory-confirmed influenza in vaccinated versus nonvaccinated individuals was 67% (95%CI, 36-81%) for recipients of a combination of the vaccines compared with 51% (95%CI, -17-79%) for recipients of live vaccine alone and 50% (95%CI, -26-80%) for recipients of inactivated vaccine alone. These results suggest that administration of a combination of influenza vaccines may provide a strategy for improved influenza vaccination of elderly people. Outbreaks of influenza in nursing homes still occur, even when a large portion of residents have been inoculated with inactivated vaccine. Data were collected in 1991--1992 from 83 eligible skilled nursing homes located in southern Lower Michigan to determine the effectiveness of inactivated influenza vaccine in preventing influenza-like illness and influenza-associated pneumonia. Surveillance was conducted to identify the occurrence of influenza in the homes and, at the end of the season, specific data were gathered on all residents of homes with influenza activity. Age- and sex-adjusted estimates of vaccine effectiveness were calculated using Cox proportional hazards models for each nursing home. Estimates were pooled using precision-based weights calculated from data for each home. Vaccine was found to be 33% effective in preventing total respiratory illness (influenza-like illness and clinically diagnosed pneumonia). In prevention of pneumonia alone, vaccine was 43% effective. The estimate for prevention of pneumonia rose to 55% if the period under consideration was limited to the time of peak influenza activity. Given the number of eligible homes and the cohort methodology used, the results support continuation of current policy, encouraging use of vaccine in all nursing home residents. Despite recommendations for annual vaccination against influenza, more than half of elderly Americans do not receive this vaccine. In a serial cohort study, we assessed the efficacy and cost effectiveness of influenza vaccine administered to older persons living in the community.
                Using administrative data bases, we studied men and women over 64 years of age who were enrolled in a large health maintenance organization in the Minneapolis-St. Paul area. We examined the rate of vaccination and the occurrence of influenza and its complications in each of three seasons: 1990-1991, 1991-1992, and 1992-1993. Outcomes were adjusted for age, sex, diagnoses indicating a high risk, use of medications, and previous use of health care services.
                Each cohort included more than 25,000 persons 65 years of age or older. Immunization rates ranged from 45 percent to 58 percent. Although the vaccine recipients had more coexisting illnesses at base line than those who did not receive the vaccine, during each influenza season vaccination was associated with a reduction in the rate of hospitalization for pneumonia and influenza (by 48 to 57 percent, P < or = 0.002) and for all acute and chronic respiratory conditions (by 27 to 39 percent, P < or = 0.01). Vaccination was also associated with a 37 percent reduction (P = 0.04) in the rate of hospitalization for congestive heart failure during the 1991-1992 season, when influenza A was epidemic. The costs of hospitalization for all types of illness studied were lower in the vaccinated group during 1991-1992 (range of reduction, 47 to 66 percent; P < 0.005) and for acute and chronic respiratory conditions and congestive heart failure in 1990-1991 (reductions of 37 percent and 43 percent, respectively; P < or = 0.05). Direct savings per year averaged $117 per person vaccinated (range, $21 to $235), with cumulative savings of nearly $5 million. Vaccination was also associated with reductions of 39 to 54 percent in mortality from all causes during the three influenza seasons (P < 0.001).
                For elderly citizens living in the community, vaccination against influenza is associated with reductions in the rate of hospitalization and in deaths from influenza and its complications, as compared with the rates in unvaccinated elderly persons, and vaccination produces direct dollar savings.
The available evidence is of poor quality and provides no guidance regarding the safety, efficacy or effectiveness of influenza vaccines for people aged 65 years or older. To resolve the uncertainty, an adequately powered publicly-funded randomised, placebo-controlled trial run over several seasons should be undertaken.