[The results of state trials of inactivated influenza vaccines for children]. Clinical and epidemiological evaluation of a live, cold-adapted influenza vaccine for 3-14-year-olds. Pilot study of influenza vaccine effectiveness in urban Australian children attending childcare. [Characteristics of the clinical and immunologic safety of inactivated influenza vaccines in children undergoing multiple immunizations]. The safety of trivalent influenza vaccine among healthy children 6 to 24 months of age. Protective effect of single-dose adjuvanted pandemic influenza vaccine in children. Influenza vaccine in healthy preschool children. 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 efficacy of live attenuated, cold-adapted, trivalent, intranasal influenzavirus vaccine in children. [A comparative study of live and inactivated influenza vaccines: the organization of the observation and the results of a study of their reactogenicity and immunogenicity]. Study of live recombinant cold-adapted influenza bivalent vaccine of type A for use in children: an epidemiological control trial. Failure of inactivated influenza A vaccine to protect healthy children aged 6-24 months. Implementation of universal influenza immunization recommendations for healthy young children: results of a randomized, controlled trial with registry-based recall. Prophylactic effect of inactivated influenza vaccine on young children. Efficacy and safety of a live attenuated, cold-adapted influenza vaccine, trivalent against culture-confirmed influenza in young children in Asia. [A comparative study of the protective properties of live recombinant and inactivated influenza vaccines made from strain A/Philippines/2/82 (H3N2) in 8- to 15-year-old children]. [The comparative characteristics of the safety, immunogenic activity and prophylactic potency of the adult and children types of live influenza vaccine in schoolchildren aged 7-14 years]. Evaluation of bivalent live attenuated influenza A vaccines in children 2 months to 3 years of age: safety, immunogenicity and dose-response. Safety, efficacy, and effectiveness of cold-adapted influenza vaccine-trivalent against community-acquired, culture-confirmed influenza in young children attending day care. Effectiveness of virosomal subunit influenza vaccine in preventing influenza-related illnesses and its social and economic consequences in children aged 3-14 years: a prospective cohort study. Comparison of immunogenicity and safety of a virosome influenza vaccine with those of a subunit influenza vaccine in pediatric patients with cystic fibrosis. Vaccine Effectiveness Against Laboratory-confirmed Influenza in Healthy Young Children: A Case-Control Study. Effectiveness of inactivated influenza vaccine in preventing acute otitis media in young children: a randomized controlled trial. Influenza vaccination in children with asthma: randomized double-blind placebo-controlled trial. [Influence of multiplicity of immunizations of children with inactivated influenza vaccine on immune response and the effectiveness of protection]. [Results of coded trials of the activity of the trivalent subunit influenza vaccine Grippovak in Moscow kindergartens in December 1983 through the 1st quarter of 1984]. Influenza A (H1N1) 2009 two-dose immunization of US children: an observer-blinded, randomized, placebo-controlled trial. Clinical reactions and serologic response following inactivated monovalent influenza type B vaccine in young children and infants. [A comparative study of the inoculation properties of live recombinant and inactivated influenza vaccines made from strain A/Philippines/2/82 (H3N2) in 8- to 15-year-old children]. Inactivated influenza vaccine effectiveness in children under 6 years of age during the 2002-2003 season. Prospective, randomized, placebo-controlled evaluation of the safety and immunogenicity of three lots of intranasal trivalent influenza vaccine among young children. Evaluation in children of cold-adapted influenza B live attenuated intranasal vaccine prepared by reassortment between wild-type B/Ann Arbor/1/86 and cold-adapted B/Leningrad/14/55 viruses. [The investigation of the safety, genetic stability and immunogenicity of live influenza vaccine for adults in vaccination of 3-6 years old children]. [Evaluation of the safety, reactogenicity and antigenic activity of inactivated chromatographic influenza vaccine in school children]. Effectiveness of pandemic H1N1 vaccine against influenza-related hospitalization in children. Vaccine effectiveness against laboratory-confirmed influenza in infants: A matched case control study. Efficacy of Influenza Vaccine in Elderly Persons in Welfare Nursing Homes: Reduction in Risks of Mortality and Morbidity During an Influenza A (H3N2) Epidemic. [The immunogenic properties and prophylactic efficacy of a live polyvalent influenza vaccine in children 5 to 14 years old]. Effectiveness of the 2003-2004 influenza vaccine among children 6 months to 8 years of age, with 1 vs 2 doses. Protective efficacy of combined live intranasal and inactivated influenza A virus vaccines in the elderly. Efficacy of sequential annual vaccination with inactivated influenza virus vaccine. Comparison of the efficacy and safety of live attenuated cold-adapted influenza vaccine, trivalent, with trivalent inactivated influenza virus vaccine in children and adolescents with asthma. A cohort study of the effectiveness of influenza vaccine in older people, performed using the United Kingdom general practice research database. Influenza immunisation in children with solid tumours. Live attenuated and inactivated influenza vaccine in school-age children. Comparison of heterotypic protection against influenza A/Taiwan/86 (H1N1) by attenuated and inactivated vaccines to A/Chile/83-like viruses. Is influenza vaccination cost effective for healthy people between ages 65 and 74 years? A randomised controlled trial. Response to influenza immunisation during treatment for cancer. 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. Vaccine effectiveness against laboratory-confirmed influenza in children 6 to 59 months of age during the 2003-2004 and 2004-2005 influenza seasons. Efficacy and safety of 1 and 2 doses of live attenuated influenza vaccine in vaccine-naive children. Safety and tolerability of cold-adapted influenza virus vaccine in children and adolescents with asthma. [Prophylactic effectiveness of a live recombinant influenza type A vaccine in immunizing children aged 3-14 years]. The safety of inactivated influenza vaccine in adults and children with asthma. Identification and recall of children with chronic medical conditions for influenza vaccination. Effectiveness of maternal influenza immunization in mothers and infants. Efficacy of live attenuated and inactivated influenza vaccines in schoolchildren and their unvaccinated contacts in Novgorod, Russia. Safety and immunogenicity of low and high doses of trivalent live cold-adapted influenza vaccine administered intranasally as drops or spray to healthy children. Effectiveness of inactivated influenza vaccine for prevention of otitis media in children. Influenza vaccine effectiveness in preventing hospitalization for pneumonia in the elderly. Comparison of live attenuated cold-adapted and avian-human influenza A/Bethesda/85 (H3N2) reassortant virus vaccines in infants and children. Randomized, placebo-controlled double blind study on the efficacy of influenza immunization on absenteeism of health care workers. A prospective, Internet-based study of the effectiveness and safety of influenza vaccination in the 2001-2002 influenza season. Immunization of infants and young children with live attenuated trivalent cold-recombinant influenza A H1N1, H3N2, and B vaccine. Influenza vaccination in adults with asthma: safety of an inactivated trivalent influenza vaccine. Immune response after influenza vaccination in children with cancer. Randomised placebo-controlled crossover trial on effect of inactivated influenza vaccine on pulmonary function in asthma. A randomised intervention study to examine the effect on immunisation coverage of making influenza vaccine available at no cost. Effectiveness of an adjuvanted monovalent vaccine against the 2009 pandemic strain of influenza A(H1N1)v, in Stockholm County, Sweden. Effectiveness of influenza vaccination in the elderly in a community in Italy.
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. 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. Influenza outbreaks in the childcare setting are a significant cause of excess winter morbidity. This study explored methods of follow up and sample collection for a proposed randomised controlled trial of influenza vaccination in children attending childcare.
                The study was conducted in four Sydney childcare centres during 2007. Healthy children aged 6-59 months eligible for vaccination were recruited in two centres, with another two acting as controls. Data on influenza-like illness (ILI: ≥37.8°C plus at least one respiratory symptom) occurrence were collected weekly. In those children with an ILI, parents were asked to collect nasal swabs and send via surface mail for viral polymerase chain reaction. Vaccine efficacy (VE) for ILI was estimated overall and for subgroups aged 6-23 and 24-59 months using the formula VE = 1 - relative risk (RR).
                Sixty-three per cent (151/238) of eligible children had parents give consent. Sixty-three children received influenza vaccine and 88 participated as controls. Of 26 specimens returned, a virus was detected in 18 (69%); none with influenza. Two symptomatic children had positive near-patient influenza tests in general practice (one a vaccine failure). The RR with 95% confidence interval in all children and those aged 6-23 months were less than one, 0.56 (0.32-1.02) and 0.46 (0.15-1.45), respectively.
                This study demonstrated the feasibility and utility of parent-collected and mailed respiratory specimens for VE research in the childcare setting. Two-thirds of parent-collected swabs proved positive for at least one virus. Finding ways to reduce reluctance of parents to submit samples could improve the representativeness of samples collected and the power of the study. No evidence was found for influenza VE, but point estimates were in the direction of protection.
                © 2011 The Authors. Journal of Paediatrics and Child Health © 2011 Paediatrics and Child Health Division (Royal Australasian College of Physicians). 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. 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. 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. Studies of influenza vaccination in healthy children have not definitely answered the question of their efficacy.
                We have carried out a randomized trial in a well selected population of healthy preschool children in Sardinia, Italy. During October 1995, 344 children aged 1 to 6 years, were randomly assigned to receive influenza vaccine (n=177) or no treatment (n=167). Two doses of a trivalent subvirion vaccine, containing 15mg of highly purified surface antigens from the component strains A/Johannesburg/33/94-like, A/Singapore/6/86-like and B/ Beijing/184/ 93-like were administered. Follow-up data were collected from December 1, 1995 through April 30, 1996.
                Seroconversion was documented in 17 out of 17 children. No specific systemic symptoms or severe local reactions were observed after vaccination. Influenza-like episodes, defined by the presence of fever and cough or sore throat that lasted at least 72 hours, occurred in 63 (37.7%) of unvaccinated children and in 22 (12.4%) of vaccinated ones. The corresponding reduction in disease incidence was 67% (95% CI: 0.59-0.74). Three episodes of otitis were observed among children in the control group versus zero among vaccinated children (p=0.07). Mean duration of day care center absenteism was significantly reduced by vaccination (2.3 days in unvaccinated and 0.5 day in vaccinated children, p<0.001)
                Influenza vaccine is safe and effective in healthy preschool children. However the favourable implications of vaccination on disease rate in subsequent years have to be evaluated. 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). 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. Schoolchildren of 30 to 34 schools of Novgorod were vaccinated over a three-year period with Russian live cold-adapted attenuated vaccine for children and whole-virus inactivated vaccines and placebo for comparative field study of the vaccines properties and efficacy. In control trials both bi- and trivalent live attenuated vaccines were well tolerated and areactogenic. A whole-virus inactivated trivalent vaccine induced mild and moderate fever and local reactions in 2-4% of the vaccinees. Special observations are necessary to establish the possibility of use and to determine a dose of this inactivated vaccine for immunization of children, especially those of 7-10 years of age. All the vaccines induced HI antibody production in 50-80% and antineuraminidase in 50-70% of seronegative children. The pattern of the results was similar to that in revaccinated children with preexisting antibody at a level of 1:20, but much lower in children with the initial titre above 1:20. After the 3rd year of vaccination the immune response of the vaccinees was similar, most of the results depending on the initial antibody titre and also on the change of vaccine strains. This raises a question of the expediency of annual influenza revaccination of the same person after 2 years of successful immunization and of the necessity of vaccine strains replacement after 2-3 years of use. Live cold-adapted recombinant bivalent vaccine of influenza type A was studied in a controlled field trial in 1982-1983 among nearly 30,000 children 3-15 years old. The bivalent vaccine consisted of recombinants 47/25/1 (H1N1) and 47/7/2 (H3N2) of wild-type viruses A/Brazil/11/78 (H1N1) and A/Bangkok/1/79 (H3N2) with cold-adapted donor A/Leningrad/134/47/57 (H2N2). The recombinants which received mutant nonglycoprotein genes from cold-adapted donor did not suppress each other after simultaneous inoculation of children and stimulated antibody response to both strains. The bivalent vaccine was completely attenuated for children. It caused less than 1% transient febrile reactions during five days after the first vaccination, including double seronegative individuals with low antibody titres to both vaccinal strains. The cold-adapted bivalent vaccine tested proved to be safe for children according to the analysis of morbidity studies among vaccines and a control group performed during the five days and the following six months after the first immunization. There is a similar distribution of non-influenza illnesses and a statistically significant decrease in influenza-like diseases among vaccines compared to the control group. In the four months after the immunization programme was completed, epidemics of influenza A H1N1 and H3N2 occurred. The incidence of influenza-like diseases was approximately 50% less in the vaccinated than in the control groups. This is the first evidence of safety and protective efficacy of recombinant live influenza vaccine for children 3-15 years of age. 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. 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. The effectiveness of inactivated influenza vaccine in healthy infants and young children has been controversial. The aim of this study was to determine the prophylactic effect of inactivated influenza vaccine in young children.
                Eighty-six healthy infants and children younger than 7-years-old were immunized by a subcutaneous injection of inactivated influenza vaccine before the 1999/2000 influenza season. Ninety-four age-matched children were randomly assigned as the control. These children were followed-up from January to April, 2000. A diagnosis of influenza A virus infection was made rapidly by a positive result of the the enzyme immunoassay membrane test using enzyme-conjugated monoclonal antibodies specific for a conserved epitope of influenza A nucleoprotein. The incidence of influenza A infection was compared and statistically assessed.
                The prevalence of influenza A virus infection, diagnosed by the influenza A rapid detection test, was 5.8% in the vaccine group and 17.0% in the control group, that is significantly lower in the vaccine receiving group than the non-receiving group (P = 0.016). However, four out of five infected children in the vaccine group were younger than 2-years-old.
                We conclude that inactivated influenza vaccine reduces the incidence of influenza A virus infection in 2-6-year-old children. 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. A limited controlled comparative study for the evaluation of the epidemiological efficacy of live recombinant and inactivated virion vaccines from A/Philippines/2/82-like strains of influenza A (H3N2) virus was carried out in schoolchildren of 8 to 15 years of age. During the influenza epidemic of 1987-1988 caused by influenza A/Sichuan/2/87 (H3N2)-like strains and by influenza B virus in 8.2-17% of cases, a statistically significant efficacy index for live influenza vaccine was 1.8 for the laboratory confirmed A (H3N2) cases. In the group vaccinated with the inactivated vaccine the number of serologically diagnosed A (H3N2) cases was 1.6 times lower than in the group receiving placebo, this difference being statistically significant. Thus, under the conditions of significant difference in the antigenic structure of the vaccine and epidemic A (H3N2) strains, both vaccines produced some diminished but statistically significant preventive effect in vaccinated children although its level was below the optimal. Revaccination of some children with a live influenza vaccine from a new A/Sichuan/2/87-like variant of A (H3N2) virus in the autumn of 1988 with reisolation of the vaccine strain also revealed the presence of some, though weak, resistance to this strain in the children vaccinated with both vaccines. In Russia for prevention of influenza in children, aged from 3 to 14 years, the children's live influenza vaccine (LIV), based upon A/Leningrad/134/47/57(H2N2) master strain (LIVI) is used. The need for double immunization appears to be one out of the faulties of this preparation. The study was aimed to comparing the safety, immunogenic activity and prevention of influenza by LIV for adults (LIVII) (A/Leningrad/134/17/57(H2N2 master strain) and LIVI in children aged from 7 to 17 years under similar administration schedule. The safety, the preventive efficacy, humoral and secretory immunity were studied. In total 2486 persons, including 539 children, twice inoculated with LIVI, 971 persons once inoculated with LIVII, and 840 treated by placebo were obserbed. From the data of the clinical observations during 7 days after immunization both vaccines appeared to be low reactogenic. The LIVII advantages in induction of the humoral and secretory antibodies in comparison with children's vaccine had been revealed. Both vaccines were highly efficacious, the efficiency of both preparations was more pronounced after serologic correction of the diagnosis. The results obtained permit to recommend the single immunization by the variant of LIV at the base on A/Leningrad/134/17/57/(H2N2) master strain for prevention of influenza in school children. 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. 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. To evaluate the effectiveness of a virosomal subunit influenza vaccine in preventing influenza-related illnesses and its social and economic consequences in children aged 3-14 years, a prospective cohort study was carried out during the 2004-2005 influenza season in 11 private pediatric clinics in the Barcelona metropolitan area. One dose of a virosomal subunit inactivated influenza vaccine (Inflexal V Berna) was given during September and October 2004 to healthy children aged 3-14 years attended in 5 of the 11 clinics. Who comprised the vaccinated cohort (n=966). The non-vaccinated cohort (n=985) was comprised of children attended in the other six clinics. Informed consent was obtained from all parents. The follow up was performed between 1 November 2004 and 31 March 2005. Using a self-administered questionnaire, information was collected from parents or guardians on any type of acute, febrile respiratory illness suffered by their children during the study period, including antibiotic use, and absence from school or work-loss of parents as a result of the illness. RT-PCR (influenza A+B+C) was carried out on pharyngeal and nasal samples obtained from children attended by pediatricians during this period in these clinics with the following symptoms: fever> or =38.5 degrees lasting at least 72h, cough or sore throat (influenza-like illness). Adjusted vaccination effectiveness was 58.6% (95% CI 49.2-66.3) in preventing acute febrile respiratory illnesses, 75.1% (95% CI 61.0-84.1) in preventing cases of influenza-like illnesses and 88.4% (95% CI 49.2-97.3) in preventing laboratory-confirmed cases of influenza A. The adjusted vaccination effectiveness in reducing antibiotic use (18.6%, 95% CI -4.2 to 3.64), absence from school (57.8%, 95% CI 47.9-65.9) and work-loss of parents (33.3%, 95% CI 8.9-51.2) in children affected by an acute febrile respiratory illness was somewhat lower. Vaccination of children aged 3-14 years in pediatric practices with one dose of virosomal subunit inactivated influenza vaccine has the potential to considerably reduce the health and social burdens caused by influenza-related illnesses. The objective of this study was to compare the immunogenicity and safety of a single-dose regimen and a two-dose regimen of a trivalent virosome influenza vaccine (Inflexal Berna V) with those of a trivalent subunit influenza vaccine (Influvac) in children and adolescents with cystic fibrosis (CF). In an open, randomized, multicenter study with parallel groups, 11 young children with CF (1 to 6 years old) and 53 older children and adolescents with CF (>6 years old) were randomly assigned to one of the following immunization regimens: virosome vaccine at 0.5 ml on study day 0 or 0.25 ml on days 0 and 28 or a standard regimen of subunit vaccine, i. e., 0.5 ml on day 0 for older children and 0.25 ml on days 0 and 28 for younger children. Safety assessments, i.e., recording of systemic and local adverse events (AEs) and vital signs, were made for a 5-day observation period after each immunization. Hemagglutination inhibition (HI) titers were determined at baseline and 4 weeks after the single-dose and the two-dose immunizations, respectively. Immunogenicity was assessed according to the criteria of the European Agency for the Evaluation of Medicinal Products (EMEA). Both vaccines induced comparable HI antibody titers. Seroconversion (> or =4-fold rise in HI antibody titers, reaching a titer of > or =1:40) was achieved in 41 to 100% of the participants. Seroprotection (HI titer, > or =1:40) and a >2.5-fold increase in geometric mean titers were achieved in 100% of the participants. Thus, all three EMEA requirements for influenza vaccine efficacy were met by all treatment groups and for both vaccines. The virosome vaccine, when administered as a single dose, seemed to induce superior immunogenicity compared with the standard pediatric two-dose regimen. Totals of 42 and 57% of vaccinees receiving virosome and subunit vaccines, respectively, reported at least one local AE (predominantly pain). Totals of 84 and 71% of subjects receiving virosome and subunit vaccines, respectively, complained in response to questions of at least one systemic AE (mainly cough, fatigue, coryza, or headache). The majority of events were mild or moderate and lasted 1 or 2 days only. No obvious relationship was found between AE reporting rate and vaccine formulation, age group, or dose regimen. The relatively high AE reporting rate seemed to be partly related to the symptomatology of the underlying CF disease. In summary, the virosome and subunit vaccines induced in both age groups and against all three influenza strains an efficient immune response and were well tolerated by the children and adolescents with CF. the Western Australian Influenza Vaccine Effectiveness study commenced in 2008 to evaluate a new program to provide free influenza vaccine to all children aged 6 to 59 months. We aimed to assess the protective effect of inactivated influenza vaccination in these children.
                We conducted a prospective case-control study in general practices and a hospital emergency department, testing all eligible patients for influenza and a range of other common respiratory viruses. Influenza vaccine effectiveness (VE) against laboratory-confirmed influenza was estimated with cases defined as children with an influenza-like illness who tested positive and controls as those with an influenza-like illness who tested negative for influenza virus. We calculated VE using the adjusted odds ratio from multivariate logistic regression. As a surrogate marker for adequate specimen collection, we explored the difference in VE point estimates defining controls as children in whom another respiratory virus was detected.
                a total of 75 children were enrolled from general practices and 214 through the emergency department, with 12 (27%) and 36 (17%), respectively, having laboratory-confirmed influenza. Using all the influenza-negative controls, the adjusted VE was 58% (95% confidence interval, 9-81). When controls were limited to those with another virus present, the adjusted VE was 68% (95% confidence interval, 26-86).
                VE estimates were higher when controls included only those children with another respiratory virus detected. Testing for other common respiratory viruses enables the control group to be restricted to those for whom an adequate sample is likely. 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. 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. The formation of immunity and epidemiological effectiveness of inactivated influenza vaccines in children, regularly immunized against influenza for three years, were evaluated. The study revealed that a year after each immunization the number of children having antibodies in liters regarded as protective decreased 2-2.5 times. At the periods of epidemics morbidity rate among the vaccines dynamically decreased in these years 1.3, 2.0 and 2.8 times. Considering that a year after the second immunization a high immune stratum (60-78%) was retained in the group under study, we propose that annual immunization of the same children be limited by a period of three years, followed by an interval of one year. During the autumn-winter epidemic of influenza-like diseases in December, 1983--first quarter, 1984, in Moscow commissioned coded observations on the effectiveness of prophylactic vaccination against influenza of 3-7-year-old children with a preparation "Grippovak SE-AZh" were carried out in day-care centers. In the previous large-scale trials, 1981-1984, the "Grippovak" had been evaluated positively as a completely harmless, serologically and immunologically active preparation reducing 3-3.5-fold the number of laboratory-verified cases of viral type A and B influenza in the vaccinees. In 1986, however, the "Journal of Microbiology, Epidemiology, Immunology" (JMEI, 2: 49-54) published a paper whose authors, on behalf of the Commission which had checked the preparation in the day-care centers (Z.A. Bashliaeva, A.A. Sumarokov, et al.), came to a conclusion that "Grippovak" was ineffective in children. Other members of the above Commission disagreeing with this conclusion made a repeat analysis of the decoded materials of the observations in the day-care centers using computer methods and demonstrated that because of significant prevalence of non-influenza ARD cases and recurrent (up to 44%) ARD cases in children in the 4 months of observation, it was impossible to judge the effectiveness of the vaccine by comparison of the total incidence of influenza and ARD from the clinical data alone in the vaccinees and controls.(ABSTRACT TRUNCATED AT 250 WORDS) 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. 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 study was carried out to compare reactogenicity, immunogenicity, and efficacy of live attenuated and inactivated influenza vaccines prepared from influenza A/Philippines/2/82-like virus strains. Schoolchildren of a boarding school of Moscow were randomly divided into three groups: (1) vaccinated with a live attenuated vaccine, (2) vaccinated with inactivated influenza vaccine, and (3) given placebo. Both vaccines were well tolerated by the children, with practically no severe general or local reactions. The inactivated vaccine was found to be superior to the live one in its capacity to stimulate humoral immunity studied by HI, EIA, and microneutralization tests. In 69.7% of the children given the inactivated vaccine, seroconversion to the vaccine strain was detected by two or three methods of antibody titration used. Only 35.4% seroconversions were demonstrated in children immunized with the live influenza vaccine. Enzyme immunoassay was found to be a more sensitive but less specific method for antibody titration as compared with HI test whereas microneutralization proved to be more specific but less sensitive for titration of antibodies to influenza A (H3N2) viruses. 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. Trivalent formulations of an experimental, cold-adapted, intranasal influenza (CAIV) vaccine have been shown to be safe, immunogenic and efficacious in young children.
                We evaluated the safety and immunogenicity of three consistency lots of CAIV in children 12 to 36 months of age randomized to one of five groups: Groups 1, 2 and 3 received separate lots containing A/Shenzhen/227/95 (H1N1), A/Wuhan/359/95(H3N2) and B/Harbin/7/94-like viral strains. Group 4 received an earlier efficacy trial lot which included a different H1N1 strain (A/Texas/36/91-like); and Group 5 received placebo. We performed strain-specific serum hemagglutination inhibition antibody levels against type A (H3N2 or H1N1) or type B as appropriate.
                Overall 474 children received 2 doses, 2 months apart. Each lot was well-tolerated, and there were no significant group differences between consistency lots in the proportion of children with fever and local or systemic reactions after vaccination. The 3 consistency lots were not statistically different with regard to immunogenicity as measured by seroconversion or absolute geometric mean titer. Immune responses were more robust among initially seronegative children and for H3N2 and B strains than for H1N1 strains. After 2 doses of vaccine 97, 84 and 62% had hemagglutination inhibition titers > or = 1/32 against A/H3N2, B and H1N1 strains, respectively. For A/H3N2 only, immune responses after 1 dose of vaccine are similar to those seen after 2 doses.
                Each consistency lot of CAIV is as or more immunogenic than a lot used in a large efficacy trial. A reassortant cold-adapted (ca) influenza B experimental live attenuated intranasal vaccine was evaluated for safety and immunogenicity in children by means of a blind, placebo controlled study. The vaccine contained the haemagglutinin and neuraminidase genes, and the gene for its non-structural proteins from wild-type (wt) B/Ann Arbor/1/86 virus, the contemporary strain at the time of the study. Other genes were derived from ca B/Leningrad/14/55 virus. No increase in illness rates was seen in the children from ages 3-15 years given vaccine at maximum potency (a one in two dilution of infectious allantoic fluid, having a titre of 10(7.0) EID50) compared to children given placebo. About 60% of seronegative children, ages 3-7 years, exhibited a detectible antibody response following one dose of intranasal vaccine, with the seroresponse rate rising to greater than 70% after two doses of vaccine. Immunogenicity was lowest in seropositive children age 8-15 years, reaching a maximum of 36% after two doses. Results indicated that the vaccine was highly attenuated, and probably of adequate immunogenicity for kindergarten age children. The lower immunogenicity in older children suggests the vaccine might be overly attenuated for use in school-age children who are more likely to have a history of prior natural infection with influenza B virus. Further clinical and epidemiological studies of protection are needed to fully assess this. 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. 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. Young children are generally considered immunologically naive with respect to influenza exposure opportunities; thus, a 2-dose schedule is recommended when a child is first immunized with conventional influenza vaccine lacking adjuvant. We estimated the effectiveness of a single pediatric dose of AS03-adjuvanted vaccine against hospitalization for confirmed pandemic influenza A/H1N1 (pH1N1) infection in children aged 6 months to 9 years during the fall 2009 vaccination campaign.
                In a matched case-control design, case subjects were children hospitalized for pH1N1 infection in the Fall of 2009, in Quebec, Canada. Controls were nonhospitalized children, matched by age and region of residence. Vaccination status in case subjects and controls was ascertained in relation to the case subject's date of illness onset. Vaccine effectiveness was estimated through conditional logistic regression.
                The overall effectiveness of a single pediatric dose of vaccine administered ≥14 days before illness onset was 85% (95% confidence interval [CI]: 61% to 94%), varying according to age category but with wide and overlapping CIs: 92% (95% CI: 51% to 99%) in 6-23 month-old children, 89% (95% CI: 34% to 98%) in 2-4 year-olds, and 79% (95% CI: -31% to 96%) in 5-9 year-olds. Overall vaccine effectiveness for immunization ≥10 days before illness onset was slightly lower at 80% (95% CI: 60% to 90%), with similar variation according to age.
                In children aged 6 months to 9 years, a single pediatric dose of the AS03-adjuvanted pH1N1 vaccine was highly protective against hospitalization beginning at 10 and 14 days after vaccination. 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 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. 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. To evaluate the effectiveness of 1 and 2 doses of the 2003-2004 influenza vaccine in preventing medically attended influenza-like illness (ILI) among children 6 to 23 months and 6 months to 8 years of age. Design and
                Outpatient and emergency department visits and immunization records were used to conduct a retrospective cohort study among children 6 months to 8 years of age. ILI and pneumonia and influenza (P&I) outcomes were defined on the basis of International Classification of Diseases, Ninth Revision, codes. Influenza vaccine effectiveness (VE) was calculated as (1 - hazard rate ratio) x 100.
                A total of 29726 children were included in the analyses; 17.3% were 6 to 23 months of age. By November 19, 2003, the start of peak influenza activity, 7.5% and 9.9% of children 6 months to 8 years were fully or partially vaccinated against influenza, respectively. For fully vaccinated children 6 to 23 months of age, VE against ILI and P&I was 25% and 49%, respectively. No statistically significant reduction in ILI or P&I rates was observed for partially vaccinated children 6 to 23 months of age (-3% and 22%, respectively). For fully vaccinated children 6 months to 8 years of age, VE against ILI and P&I was 23% and 51%, respectively. For partial vaccination, VE was significant only for P&I (23%).
                Despite a suboptimal match between the influenza vaccine and predominant circulating strains, influenza vaccination provided substantial protection for fully vaccinated children and possibly some protection for partially vaccinated children <9 years of age. These findings support vaccinating targeted children even when the vaccine match is suboptimal, and they highlight the need to vaccinate previously unvaccinated children with 2 doses for optimal protection. 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. Inactivated influenza virus vaccine efficacy after annual revaccination has been reported to be less than that after first vaccination in boarding school children. We prospectively examined the immunogenicity and efficacy of this vaccine in healthy 30- to 60-year-old volunteers in Houston, Texas, over two epidemic seasons (1983-1985) encompassing outbreaks due to influenza A (H3N2 and H1N1) and influenza B viruses. A placebo group that had never (or not in recent years) received inactivated influenza virus vaccine, a group that received the vaccine for the first time (first vac), and a group given two or more recent vaccinations (multivac) were evaluated in a double-blind fashion each year. Vaccination induced higher frequencies of rise in serum antibody titer to vaccine components in first vac than in multivac volunteers, but mean postvaccination titers were similar. Clinical and virologic evaluations of illnesses during both epidemics and of influenza infections diagnosed serologically over the epidemic seasons revealed no overall reduction in illness from that in the placebo group for either vaccine group; modest reductions in influenza infection-related illness that were significant only for the multivac group against A/H3N2-related illness (55%; p less than 0.04); reduction in moderate-to-severe lower respiratory and/or systemic illness due to influenza for multivac (73%, p less than 0.025) but not first vac (15%, p greater than 0.10) volunteers during the A/H3N2 epidemic; reduction in influenza virus shedding in the multivac (54%, p less than 0.05) but not the first vac (16%, p greater than 0.10) group when compared with the placebo group for both years; and overall 63-81% reductions in documented infections with each influenza virus for both vaccine groups with the exception of A/H1N1 for the first vac group (24%, p greater than 0.10) and type B for the multivac group (58%, p = 0.067). Vaccine efficacy was only modest in these studies, but in contrast to the earlier report in boarding school children, efficacy appeared to be somewhat greater after repeated annual vaccination than after first administration. Despite their potential for increased morbidity, 75% to 90% of asthmatic children do not receive influenza vaccination. Live attenuated influenza vaccine (LAIV), a cold-adapted, temperature-sensitive, trivalent influenza vaccine, is approved for prevention of influenza in healthy children 5 to 19 years of age. LAIV has been studied in only a small number of children with asthma.
                Children 6 to 17 years of age, with a clinical diagnosis of asthma, received a single dose of either intranasal CAIV-T (an investigational refrigerator-stable formulation of LAIV; n = 1114) or injectable trivalent inactivated influenza vaccine (TIV; n = 1115) in this randomized, open-label study during the 2002-2003 influenza season. Participants were followed up for culture-confirmed influenza illness, respiratory outcome, and safety.
                The incidence of community-acquired culture-confirmed influenza illness was 4.1% (CAIV-T) versus 6.2% (TIV), demonstrating a significantly greater relative efficacy of CAIV-T versus TIV of 34.7% (90% confidence interval [CI] 9.4%-53.2%; 95% CI = 3.9%-56.0%). There were no significant differences between treatment groups in the incidence of asthma exacerbations, mean peak expiratory flow rate findings, asthma symptom scores, or nighttime awakening scores. The incidence of runny nose/nasal congestion was higher for CAIV-T (66.2%) than TIV (52.5%) recipients. Approximately 70% of TIV recipients reported injection site reactions.
                CAIV-T was well tolerated in children and adolescents with asthma. There was no evidence of a significant increase in adverse pulmonary outcomes for CAIV-T compared with TIV. CAIV-T had a significantly greater relative efficacy of 35% compared with TIV in this high-risk population. 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. We assessed response to immunisation with trivalent split virus influenza vaccine in children with non-leukaemic malignant disease. Children with solid tumours and lymphoma received one or two doses of influenza vaccine, according to current UK guidelines, in autumn 2001 and/or 2002. Children were currently receiving chemotherapy or were within 6 months of completing chemotherapy. Pre and post vaccination sera were assessed for antibodies to the prevalent influenza strains by haemagglutination inhibition (HI). Sixty six children were assessed prior to 69 episodes of vaccination. In 30% episodes, children were susceptible to all three circulating influenza viruses (65% to H1N1, 42% to H3N2 and 90% to B) and only one patient showed protective titres (HI32) against all three strains. Seroresponse rates (4-fold rise in HI) for H1N1, H3N2 and B were 52%, 33% and 51% in 65 episodes. Following immunisation protective titres to all three viruses were seen in 25 episodes (38%) and protective responses to one or two viruses were seen in a further 12 (19%) episodes. There was no significant difference in response rates among children on treatment and off treatment and by intensity of chemotherapy. Children with solid tumours and lymphoma are highly susceptible to influenza infection. Influenza vaccine was well tolerated in this patient group and children showed a significant response to immunisation. These findings support the recommendation for annual influenza vaccination in these children. In 1985, we enrolled 189 school-age children by family in a double-blind study to determine protection against influenza by a single dose of cold-recombinant bivalent A vaccine or commercial trivalent inactivated vaccine compared with placebo. All children in school or day care, 3 to 18 years of age, in an enrolled family received the same preparation. Following vaccination, 60% and 21% of cold-recombinant bivalent A vaccine recipients and 73% and 83% of trivalent inactivated vaccine recipients demonstrated fourfold or greater response in hemagglutination-inhibition antibody titer to A/H1N1 and A/H3N2, respectively. Sixty-seven percent of all trivalent inactivated vaccine recipients demonstrated a fourfold or greater serologic response to H1N1, H3N2, and influenza B following a single dose of vaccine. During the 1985-1986 influenza B/Ann Arbor epidemic, heterotypic protection afforded by the influenza B/USSR component of trivalent inactivated vaccine was 62% compared with placebo. A single dose of trivalent inactivated vaccine protected school-age children, 6 to 19 years of age, from influenza B infection; the rate of protection was 64% against infection and 73% against febrile illness. Children (n = 192) aged 3-19 years from 98 families completed this double-blind, placebo-controlled study comparing the efficacy of a bivalent attenuated (CR) vaccine with trivalent inactivated (TI) vaccine. Both vaccines contained A/Chile/83 (H1N1)-like antigens. After vaccination the geometric mean titer to A/Taiwan/86 (H1N1) was 1:36 in the CR group, 1:92 in the TI group, and 1:5 in the placebo group. During the influenza A/Taiwan/86 (H1N1) epidemic, 21.4% of CR recipients, 16.7% of TI recipients, and 43.9% of placebo recipients were infected with influenza A/Taiwan. TI vaccine provided better heterotypic protection than did CR vaccine for children aged 10-18 years (infection rate, 0 vs. 24%, respectively; P less than .025); in contrast, in the younger children (3-9 years), CR vaccine tended to be more protective (19% vs. 26% for TI). 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 annual risk of influenza infection in children with cancer and the immunogenicity of a trivalent split virus influenza vaccine in these children.
                Eighty four children with cancer were tested for susceptibility to the circulating strains of influenza virus in autumn 1995 and 1996. Non-immunised children were reassessed the following spring for serological evidence of natural infection. Forty two patients received two doses of influenza vaccine. These children were receiving continuing chemotherapy for acute lymphoblastic leukaemia or were within six months of completing chemotherapy.
                Among the 84 children tested for influenza virus susceptibility only 8% of patients were fully protected (antibody titres >/= 40) against all three of the prevalent influenza virus strains; 33% were susceptible to all three viruses. Evidence of acquired natural infection was seen in 30% of unimmunised patients. Among immunised susceptible patients, 66% made some protective response to the vaccine and 55% showed protective antibody titres to all three viral strains following vaccination. Older age was associated with increased response to the H1N1 and H3N2 vaccine components, but total white cell count or neutrophil count at immunisation, type of cancer, or length of time on treatment for acute lymphoblastic leukaemia did not affect response.
                Most children with cancer studied were at risk of influenza infection. A significant response to immunisation was seen, supporting annual influenza vaccination for children being treated for cancer. 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 goal was to estimate the effectiveness of influenza vaccination against laboratory-confirmed influenza during the 2003-2004 and 2004-2005 influenza seasons in children 6 to 59 months of age.
                We conducted a case-control study with children with medically attended, acute respiratory infections who received care in an inpatient, emergency department, or outpatient clinic setting during 2 consecutive influenza seasons. All children residing in Monroe County, New York, Davidson County, Tennessee, or Hamilton County, Ohio, were enrolled prospectively at the time of acute illness and had nasal/throat swabs tested for influenza with cultures and/or polymerase chain reaction assays. Children with laboratory-confirmed influenza were case subjects and children who tested negative for influenza were control subjects. Child vaccination records from the parent and the child's physician were used to determine and to validate influenza vaccination status. Influenza vaccine effectiveness was calculated as (1 - adjusted odds ratio) x 100.
                We enrolled 288 case subjects and 744 control subjects during the 2003-2004 season and 197 case subjects and 1305 control subjects during the 2004-2005 season. Six percent and 19% of all study children were fully vaccinated according to immunization guidelines in the respective seasons. Full vaccination was associated with significantly fewer influenza-related inpatient, emergency department, or outpatient clinic visits in 2004-2005 (vaccine effectiveness: 57%) but not in 2003-2004 (vaccine effectiveness: 44%). Partial vaccination was not effective in either season.
                Receipt of all recommended doses of influenza vaccine was associated with halving of laboratory-confirmed influenza-related medical visits among children 6 to 59 months of age in 1 of 2 study years, despite suboptimal matches between the vaccine and circulating influenza strains in both years. 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. Influenza infections can cause severe respiratory disease in high risk persons such as those with asthma, but immunization rates for high risk groups remain suboptimal. An investigational influenza virus vaccine, trivalent, types A and B, live, cold-adapted (CAIV-T) administered by intranasal spray was shown previously to be effective in healthy adults and healthy children.
                To assess the safety and tolerability of CAIV-T in subjects 9 years of age and older with moderate to severe asthma.
                In this randomized, double blind, placebo-controlled study, spirometry was performed twice before vaccination to establish a baseline forced expiratory volume at 1 s (FEV1) and once 2 to 5 days thereafter. The primary outcome index was the percent change in percent predicted FEV1 before and after vaccination. Peak flows, clinical asthma symptom scores and nighttime awakening scores were measured daily from 7 days pre- to 28 days postvaccination.
                The primary outcome index (percentage change in percent predicted FEV1) was not different between the two groups (0.2% vs. 0.4% for the treatment and placebo groups, respectively; P = 0.78). Secondary outcomes did not differ between the two groups; these included the number of subjects with a decrease in FEV1 > or =15% from baseline, reductions in peak flows > or =15%, > or =30% or > or =2 sd below baseline, use of beta-adrenergic rescue medications, asthma exacerbations and clinical asthma symptom scores before and after vaccination. The same proportion of subjects in each group experienced postvaccination symptoms within 10 days (92% and 91%, respectively; P = 1.0). No serious adverse event occurred.
                CAIV-T was generally safe and well-tolerated in children and adolescents with moderate to severe asthma. 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. Influenza causes substantial morbidity in adults and children with asthma, and vaccination can prevent influenza and its complications. However, there is concern that vaccination may cause exacerbations of asthma.
                To investigate the safety of the inactivated trivalent split-virus influenza vaccine in adults and children with asthma, we conducted a multicenter, randomized, double-blind, placebo-controlled, cross-over trial in 2032 patients with asthma (age range, 3 to 64 years). The order of injection of vaccine and placebo was assigned randomly, with a mean of 22 days between the injections. Each day during the two weeks after each injection, the patients recorded peak expiratory flow rates, symptoms thought to be related to the injection, use of asthma medications, unscheduled health care visits for asthma, and asthma-related absences from school or work. The primary outcome measure was an exacerbation of asthma in the two weeks after the injections.
                The frequency of exacerbations of asthma was similar in the two weeks after the influenza vaccination and after placebo injection (28.8 percent and 27.7 percent, respectively; absolute difference, 1.1 percent; 95 percent confidence interval, -1.4 percent to 3.6 percent). The exacerbation rates were similar in subgroups defined according to age, severity of asthma, and other factors. Among symptoms thought to be associated with the injection, only body aches were more frequent after the vaccine injection than after placebo injection (25.1 percent vs. 20.8 percent, P<0.001).
                The inactivated influenza vaccine is safe to administer to adults and children with asthma, including those with severe asthma. Given the morbidity of influenza, all those with asthma should receive the vaccine annually. Despite long-standing recommendations to provide annual influenza vaccination to children with chronic medical conditions, immunization rates are <10% in most primary care settings. Many obstacles impede implementation of these recommendations, including the challenge of identifying targeted children and the need to immunize yearly in a short time interval. The objective of this study was to assess the accuracy of billing data for identifying children who have high-risk conditions (HRCs) and need influenza vaccination and 2) to evaluate the efficacy of reminder/recall for children with HRCs.
                The study was conducted in 4 private pediatric practices in metropolitan Denver, Colorado, that share a computerized billing system and also participate in an immunization registry. For all children aged 6 to 72 months, registry records were linked with the billing database. Patients with >or=1 encounters for an HRC in the previous 24 months were selected, with HRCs identified from International Classification of Diseases, Ninth Revision, Clinical Modification diagnostic codes. Using medical records as the "gold standard," we reviewed 327 randomly selected records to determine the sensitivity, specificity, and accuracy of billing data for identifying HRCs. For children with an HRC, we then conducted a randomized, controlled trial of reminder/recall for influenza vaccination. The primary outcome of the recall trial was receipt of influenza vaccine.
                Billing data had a sensitivity of 72% (95% confidence interval [CI]: 48%-95%), specificity of 95% (95% CI: 90%-100%), and overall accuracy of 90% (95% CI: 84%-96%) in determining which children had an HRC. Of the 17,273 patients aged 6 to 72 months, 2007 had >or=1 HRCs (12% overall; range: 9%-14% per practice). Asthma/reactive airways disease accounted for 87% of all HRCs. Reminder/recall significantly increased influenza immunization in children with HRCs, with a vaccination rate of 42% in those recalled, compared with 25% in control subjects. Recalled subjects were more likely to have an office visit (68% vs 60%) and less likely to have a missed opportunity to immunize (28% vs 37%) compared with control subjects.
                Diagnosis-based billing data accurately identified children who had HRCs and needed annual influenza vaccination, and registry-driven reminder/recall significantly increased influenza immunization in targeted children. Young infants and pregnant women are at increased risk for serious consequences of influenza infection. Inactivated influenza vaccine is recommended for pregnant women but is not licensed for infants younger than 6 months of age. We assessed the clinical effectiveness of inactivated influenza vaccine administered during pregnancy in Bangladesh.
                In this randomized study, we assigned 340 mothers to receive either inactivated influenza vaccine (influenza-vaccine group) or the 23-valent pneumococcal polysaccharide vaccine (control group). Mothers were interviewed weekly to assess illnesses until 24 weeks after birth. Subjects with febrile respiratory illness were assessed clinically, and ill infants were tested for influenza antigens. We estimated the incidence of illness, incidence rate ratios, and vaccine effectiveness.
                Mothers and infants were observed from August 2004 through December 2005. Among infants of mothers who received influenza vaccine, there were fewer cases of laboratory-confirmed influenza than among infants in the control group (6 cases and 16 cases, respectively), with a vaccine effectiveness of 63% (95% confidence interval [CI], 5 to 85). Respiratory illness with fever occurred in 110 infants in the influenza-vaccine group and 153 infants in the control group, with a vaccine effectiveness of 29% (95% CI, 7 to 46). Among the mothers, there was a reduction in the rate of respiratory illness with fever of 36% (95% CI, 4 to 57).
                Inactivated influenza vaccine reduced proven influenza illness by 63% in infants up to 6 months of age and averted approximately a third of all febrile respiratory illnesses in mothers and young infants. Maternal influenza immunization is a strategy with substantial benefits for both mothers and infants. (ClinicalTrials.gov number, NCT00142389.)
                Massachusetts Medical Society Children aged 7-14 years in Novgorod, Russia, were given Russian live cold-adapted or inactivated influenza vaccines or placebo over a 2-year period. Schools were randomly assigned as a whole to one of the preparations. In the first year, the vaccines were bivalent, containing types A (H3N2) and A (H1N1) components. In the second year, the vaccines also contained a type B component. In the first year, all viruses isolated were type A (H3N2); in the second, about three-quarters of the isolates were type B and the rest type A (H1N1). During both years, the vaccines protected the vaccinated children. Where significant differences existed, the live attenuated vaccine was more protective than the inactivated. Vaccination rates in schools in which live attenuated vaccines had been used were inversely related to illness rates of staff and unvaccinated children, suggesting that viral transmission had been reduced by the vaccine. The safety and immunogenicity of various doses of trivalent cold-adapted influenza vaccine (CAIV-T) administered intranasally by drops or spray to children aged 18-71 months was examined. CAIV-T containing A/Johannesburg/33/94 (H3N2), B/Panama/45/90, and A/Texas/36/91 (H1N1) was safe and well-tolerated. At the highest CAIV-T dose, 90%, 50%, and 16% of initially seronegative subjects seroconverted to the H3N2, B, and H1N1 antigens, respectively. The lower immunologic response to the H1N1 vaccine strain compared with the other strains was associated with a low frequency of H1N1 shedding. No statistically significant differences in reactogenicity or immunogenicity were detected between subjects who received CAIV-T by drops or spray. In conclusion, this CAIV-T was safe and induced acceptable immunologic responses to 2 of the 3 vaccine strains. Studies are needed to confirm previous observations that receipt of two doses of this vaccine results in immunologic responses that confer protection to all 3 circulating influenza virus strains. The objective of this study was to evaluate the effectiveness of inactivated influenza vaccine in preventing acute otitis media (AOM) and otitis media with effusion (OME) in children aged 6 to 60 months who attend day care.
                This prospective, single-blind study was conducted in 8 day care centers in Ankara, Turkey. One hundred nineteen (61 vaccinated and 58 unvaccinated against influenza) healthy children were examined at study entry and at 6-week intervals for 6 months by the same 2 otorhinolaryngologists who were blinded about the vaccination status of the children. The frequency of AOM and OME is compared between the 2 groups and the effect of influenza season on frequency of episodes was evaluated. Based on national influenza laboratory data, the influenza season was determined to be the period between December 15, 2003, and January 31, 2004.
                The frequencies of AOM, OME and total otitis media episodes in vaccinated children were 2.3%, 22.8% and 25.2%, respectively, and these frequencies were 5.2%, 31.1% and 36.3% in the unvaccinated group. The difference was statistically significant (P < 0.01). This difference was especially prominent in the influenza season (P < 0.05).
                Influenza vaccine is effective in reducing AOM and OME episodes in 6- to 60-month-old day care children, especially during influenza season. 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. Randomized, placebo-controlled studies with 10(3)-10(7) 50% tissue-culture infectious dose (TCID50) of avian-human (ah) and cold-adapted (ca) influenza A/Bethesda/85 (H3N2) reassortant viruses were completed in 106 seronegative young children 6-48 months of age. Although the reassortants differed in six of eight RNA segments, they exhibited similar properties in level of attenuation, infectivity, immunogenicity, and efficacy. The 50% human infectious dose was 10(4.6) TCID50 for ah and 10(4.4) for ca vaccines. Both reassortants were satisfactorily attenuated with restricted replication and were no more reactogenic than placebo. The mean peak titer of virus shed was 10(1.5) (ah) to 10(2.0) (ca) TCID50/ml, and each of 37 isolates tested retained their characteristic vaccine phenotypes. Infection with ah or ca virus conferred immunity to experimental challenge with homologous virus. These findings indicate that both ah and ca influenza A/Bethesda/85 (H3N2) reassortants should be suitable vaccine candidates for use in healthy infants and young children. 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. 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. Seventeen triply seronegative infants and young children, and 15 infants and young children seropositive to all three influenza virus strains were vaccinated intranasally with 10(5) TCID50 of each of three (H1N1, H3N2, and B) live attenuated, cold-adapted influenza vaccine strains. Seventeen controls were given placebo. Vaccination with trivalent influenza vaccine was not associated with adverse reactions in triply seronegative or seropositive children. Overall, 12 (71%), 13 (76%), and 13 (76%) of seronegative children were infected by H1N1, H3N2, or B vaccine viruses, respectively, as indicated by viral shedding or by hemagglutination inhibition assay or ELISA antibody response. Of the triply seronegative children, 47% shed all three viruses; 7 children had an antibody rise to all three vaccine viruses and 4 shed all three viruses. A dose of 10(4.4) - 10(5.0) TCID50 of each of three intranasally administered vaccine viruses was safe, immunogenic and antigenic; however, strategies to increase the proportion of children infected by each of the vaccine viruses should be studied, including higher doses and multiple doses of live trivalent vaccine. 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. To assess the immune response to inactivated trivalent split influenza vaccine in children with cancer.
                Forty-four children with various types of malignancies received two doses of influenza vaccine 2-4 weeks apart. Hemagglutinin-inhibition (HI) antibody titers were determined in paired sera obtained just before the first vaccination and 4 weeks after the second vaccination.
                Influenza vaccine was administered to all children without any serious adverse effects. Protective titer rates (proportion of patients achieving antibody titers > or =40 among those with pre-vaccination titers <40) and response rates (proportion of patients with fourfold or more antibody rise) were 72% and 65% for H1N1, 60% and 40% for H3N2, and 38% and 46% for influenza B, respectively. However, patients on chemotherapy showed a significantly lower immune response to influenza A than those having completed chemotherapy; protection titer rates were 42% versus 90% for H1N1 (P = 0.006) and 25% versus 83% for H3N2 (P = 0.019). For influenza B, patients with low IgG showed a lower response rate than those with high IgG (29% vs. 61%, P = 0.040). Multivariate analysis revealed that factors significantly associated with a lower immune response were low IgG (P < 0.001) and administration of chemotherapy (P = 0.003) for H1N1, administration of chemotherapy (P = 0.008) for H3N2, and low white blood cell (WBC) count (P = 0.030) and low IgG (P = 0.030) for influenza B.
                Influenza vaccination given to children with cancer was safe and induced immune reaction comparable to healthy children, although patients on chemotherapy and/or with chemotherapy-related conditions had a limited ability to produce a sufficient immune response.
                (c) 2005 Wiley-Liss, Inc. 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. 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. Vaccination against the pandemic influenza A(H1N1)v was performed in many countries during 2009, but population-based data on vaccine effectiveness are lacking.
                We conducted a prospective cohort study involving all inhabitants in Stockholm County (n = 2,019,183) who were offered a monovalent AS03-adjuvanted influenza A(H1N1)v vaccine (Pandemrix, GSK), between 12 October and 31 December 2009. Overall vaccine coverage was 52%. A Web-based register with data on all vaccinated was linked by unique personal identification number to mandatory reports of influenza A(H1N1)v diagnoses. Vaccine failure was defined as a diagnosis or admission to hospital because of influenza >14 days after vaccination. Risk factors associated with vaccine failure were investigated by conditional stepwise logistic regression in a nested case-control study. The weekly incidence rate ratio for being diagnosed with influenza among vaccinated versus nonvaccinated persons was calculated.
                Vaccine failure was seen in 25 patients, 11 children and 14 adults, of 2594 patients diagnosed with influenza A(H1N1)v. Compared with age-matched controls, patients with vaccine failure were more often immunocompromised (Hazard Ratio, 4.89; 95% confidence interval [CI], 2.19-10.89). During the 4 weeks with maximum influenza activity, the relative risk per week for an influenza A(H1N1)v diagnosis in the vaccinated population was .06 (95% CI .008-.41), .13 (95% CI .06-.27), .05 (95% CI .02-.12), and .07 (95% CI .03-.15), respectively, corresponding to a weekly vaccine effectiveness of 87-95%.
                The monovalent AS03-adjuvanted influenza vaccine was highly effective in prevention of the pandemic influenza in Stockholm County. A single dose seemed to be sufficient in most, both children and adults, except in immunocompromised hosts. 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.
Influenza vaccines are efficacious in preventing cases of influenza in children older than two years of age, but little evidence is available for children younger than two years of age. There was a difference between vaccine efficacy and effectiveness, partly due to differing datasets, settings and viral circulation patterns. No safety comparisons could be carried out, emphasising the need for standardisation of methods and presentation of vaccine safety data in future studies. In specific cases, influenza vaccines were associated with serious harms such as narcolepsy and febrile convulsions. It was surprising to find only one study of inactivated vaccine in children under two years, given current recommendations to vaccinate healthy children from six months of age in the USA, Canada, parts of Europe and Australia. If immunisation in children is to be recommended as a public health policy, large-scale studies assessing important outcomes, and directly comparing vaccine types are urgently required. The degree of scrutiny needed to identify all global cases of potential harms is beyond the resources of this review.
This review includes trials funded by industry. An earlier systematic review of 274 influenza vaccine studies published up to 2007 found industry-funded studies were published in more prestigious journals and cited more than other studies independently from methodological quality and size. Studies funded from public sources were significantly less likely to report conclusions favourable to the vaccines. The review showed that reliable evidence on influenza vaccines is thin but there is evidence of widespread manipulation of conclusions and spurious notoriety of the studies. The content and conclusions of this review should be interpreted in the light of this finding.