Failure of inactivated influenza A vaccine to protect healthy children aged 6-24 months. [The evaluation of the reactogenicity, harmlessness and prophylactic efficacy of Grippol trivalent polymer-subunit influenza vaccine administered to schoolchildren]. [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]. Clinical and epidemiological evaluation of a live, cold-adapted influenza vaccine for 3-14-year-olds. Immunization of infants and young children with live attenuated trivalent cold-recombinant influenza A H1N1, H3N2, and B vaccine. [Prophylactic effectiveness of a live recombinant influenza type A vaccine in immunizing children aged 3-14 years]. Vaccine effectiveness against laboratory-confirmed influenza in infants: A matched case control study. Efficacy and safety of a live attenuated, cold-adapted influenza vaccine, trivalent against culture-confirmed influenza in young children in Asia. Various factors associated with the manifestation of influenza-like illness. I-MOVE multi-centre case control study 2010-11: overall and stratified estimates of influenza vaccine effectiveness in Europe. Effectiveness of the 2003-2004 influenza vaccine among children 6 months to 8 years of age, with 1 vs 2 doses. Effectiveness of pandemic H1N1 vaccine against influenza-related hospitalization in 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]. Clinical reactions and serologic response following inactivated monovalent influenza type B vaccine in young children and infants. Safety and immunogenicity of low and high doses of trivalent live cold-adapted influenza vaccine administered intranasally as drops or spray to healthy children. Comparison of heterotypic protection against influenza A/Taiwan/86 (H1N1) by attenuated and inactivated vaccines to A/Chile/83-like viruses. [Influence of multiplicity of immunizations of children with inactivated influenza vaccine on immune response and the effectiveness of protection]. Efficacy and safety of 1 and 2 doses of live attenuated influenza vaccine in vaccine-naive children. [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]. Effectiveness of an adjuvanted monovalent vaccine against the 2009 pandemic strain of influenza A(H1N1)v, in Stockholm County, Sweden. Efficacy of live attenuated and inactivated influenza vaccines in schoolchildren and their unvaccinated contacts in Novgorod, Russia. [Evaluation of the safety, reactogenicity and antigenic activity of inactivated chromatographic influenza vaccine in school children]. Class-specific antibody responses in school children vaccinated with an A/Brazil/11/78 (H1N1)-like recombinant influenza virus prepared from the A/Leningrad/134/57 paediatric cold-adapted donor strain. Effectiveness of vaccine against medical consultation due to laboratory-confirmed influenza: results from a sentinel physician pilot project in British Columbia, 2004-2005. Pilot study of influenza vaccine effectiveness in urban Australian children attending childcare. [Results of a study of a live intranasal influenza vaccine in the immunization of children 3 to 15 years old]. Comparison of US inactivated split-virus and Russian live attenuated, cold-adapted trivalent influenza vaccines in Russian schoolchildren. Safety, efficacy, and effectiveness of cold-adapted influenza vaccine-trivalent against community-acquired, culture-confirmed influenza in young children attending day care. [The effectiveness of influenza prevention with a special variation of live influenza vaccine for children in the 1969 epidemic]. [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]. Assessment of effectiveness of Vaxigrip. Estimates of pandemic influenza vaccine effectiveness in Europe, 2009-2010: results of Influenza Monitoring Vaccine Effectiveness in Europe (I-MOVE) multicentre case-control study. [Results of studying the effectiveness of a live influenza vaccine for peroral use on preschool and schoolchildren]. The efficacy of live attenuated, cold-adapted, trivalent, intranasal influenzavirus vaccine in children. Single-dose trials of monovalent A/New Jersey/76 (Hsw1N1) influenza virus vaccine in children in Durham, North Carolina. [Characteristics of the clinical and immunologic safety of inactivated influenza vaccines in children undergoing multiple immunizations]. [The results of state trials of inactivated influenza vaccines for children]. Vaccine effectiveness for laboratory-confirmed influenza in children 6-59 months of age, 2005-2007. Effectiveness of school-based influenza vaccination. Study of live recombinant cold-adapted influenza bivalent vaccine of type A for use in children: an epidemiological control trial. Evaluation of a neuraminidase-specific influenza A virus vaccine in children: antibody responses and effects on two successive outbreaks of natural infection. Influenza vaccine in healthy preschool children. Multidose, live attenuated, cold-recombinant, trivalent influenza vaccine in infants and young children. Prophylactic effect of inactivated influenza vaccine on young children. Influenza A (H1N1) 2009 two-dose immunization of US children: an observer-blinded, randomized, placebo-controlled trial. Effectiveness of inactivated influenza vaccine for prevention of otitis media in children. 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. The A/Mallard/6750/78 avian-human, but not the A/Ann Arbor/6/60 cold-adapted, influenza A/Kawasaki/86 (H1N1) reassortant virus vaccine retains partial virulence for infants and children. Outbreak of influenza A (H3N2) in a highly-vaccinated religious community: a retrospective cohort study. Vaccine effectiveness against laboratory-confirmed influenza in children 6 to 59 months of age during the 2003-2004 and 2004-2005 influenza seasons. [The investigation of the safety, genetic stability and immunogenicity of live influenza vaccine for adults in vaccination of 3-6 years old children]. Vaccine Effectiveness Against Laboratory-confirmed Influenza in Healthy Young Children: A Case-Control Study. [The immunogenic properties and prophylactic efficacy of a live polyvalent influenza vaccine in children 5 to 14 years old]. Inactivated influenza vaccine effectiveness in children under 6 years of age during the 2002-2003 season. Safety and immunogenicity following administration of a live, attenuated monovalent 2009 H1N1 influenza vaccine to children and adults in two randomized controlled trials. 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. Live attenuated and inactivated influenza vaccine in school-age children. The impact of mass school immunization on school attendance. Effectiveness of the pandemic H1N1 influenza vaccines against laboratory-confirmed H1N1 infections: population-based case-control study. Evaluation of bivalent live attenuated influenza A vaccines in children 2 months to 3 years of age: safety, immunogenicity and dose-response. 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 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. Prospective, randomized, placebo-controlled evaluation of the safety and immunogenicity of three lots of intranasal trivalent influenza vaccine among young 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]. Influenza vaccine effectiveness in healthy 6- to 21-month-old children during the 2003-2004 season. [The inoculation properties of live recombinant influenza vaccine types A and B used separately and jointly in children 3 to 14]. Effectiveness of inactivated influenza vaccine in preventing acute otitis media in young children: a randomized controlled trial. Comparison of live attenuated cold-adapted and avian-human influenza A/Bethesda/85 (H3N2) reassortant virus vaccines in infants and children. A prospective, Internet-based study of the effectiveness and safety of influenza vaccination in the 2001-2002 influenza season.
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. Vaccine "Grippol"--has been developed at the State Research Center--Institute of Immunology. The preparation belongs to new generation vaccines and is a trivalent polymer-subunit vaccine containing the sterile conjugate of influenza virus surface proteins, types A and B, bound with copolymer polyoxidonium. The administration of "Grippol" to children of school age (6-18 years) demonstrated low reactogenicity of the vaccine, its safety and sufficient prophylactic effectiveness. During observations on total morbidity (with the exception of influenza and acute respiratory diseases) no side effects produced by "Grippol" were registered. At the same time the fact that the morbidity rate of upper respiratory tract disease in the group of children immunized with the vaccine decreased in comparison with the control group (by 2.4 times) cannot be disregarded. 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. 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. 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. 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 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. 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 survey enrolling 814 schoolchildren was conducted immediately after a peak epidemic in the 1988-1989 influenza season and then a case-control study for influenza-like illness (ILI) was carried out using information concerning illness onset and usual lifestyle. Based on the analysis of the correlations among symptoms and actions taken due to symptoms, cases were defined as those with fever greater than or equal to 38 degrees C and subsequent absenteeism and medical consultation during peak epidemic; within this, mild-ILI (MILI) was defined as fever greater than or equal to 38 degrees C and less than 39 degrees C, and severe-ILI (SILI) as fever greater than or equal to 39 degrees C. Controls were defined as those with no symptoms (NS) during that period. Adjusted odds ratios (OR) were obtained through an unconditional logistic regression model between the MILI (80) or SILI (48) and NS (196) groups from among respondents (803). For MILI, increased risks were observed for easily-inflamed tonsils (OR = 3.0, 95% CI: 1.7-5.4); and larger family size (1.9, 1.1-3.4); with decreased risks for higher school grades (0.4, 0.2-0.9); frequent intake of vegetables or fruits other than green/yellow vegetables (0.5, 0.3-1.0); and larger room space per capita (0.4, 0.2-0.9). For SILI, there were increased risks for easily-inflamed tonsils (3.8, 1.8-8.1) and history of doctor-diagnosed asthma (2.9, 1.2-6.7); and decreased risks for higher grades (0.2, 0.1-0.6), frequent intake of milk or dairy products (0.3, 0.1-0.6) and vaccination (0.3, 0.1-0.8). In the third season of I-MOVE (Influenza Monitoring Vaccine Effectiveness in Europe), we undertook a multicentre case-control study based on sentinel practitioner surveillance networks in eight European Union (EU) member states to estimate 2010/11 influenza vaccine effectiveness (VE) against medically-attended influenza-like illness (ILI) laboratory-confirmed as influenza.
                Using systematic sampling, practitioners swabbed ILI/ARI patients within seven days of symptom onset. We compared influenza-positive to influenza laboratory-negative patients among those meeting the EU ILI case definition. A valid vaccination corresponded to > 14 days between receiving a dose of vaccine and symptom onset. We used multiple imputation with chained equations to estimate missing values. Using logistic regression with study as fixed effect we calculated influenza VE adjusting for potential confounders. We estimated influenza VE overall, by influenza type, age group and among the target group for vaccination.
                We included 2019 cases and 2391 controls in the analysis. Adjusted VE was 52% (95% CI 30-67) overall (N = 4410), 55% (95% CI 29-72) against A(H1N1) and 50% (95% CI 14-71) against influenza B. Adjusted VE against all influenza subtypes was 66% (95% CI 15-86), 41% (95% CI -3-66) and 60% (95% CI 17-81) among those aged 0-14, 15-59 and ≥60 respectively. Among target groups for vaccination (N = 1004), VE was 56% (95% CI 34-71) overall, 59% (95% CI 32-75) against A(H1N1) and 63% (95% CI 31-81) against influenza B.
                Results suggest moderate protection from 2010-11 trivalent influenza vaccines against medically-attended ILI laboratory-confirmed as influenza across Europe. Adjusted and stratified influenza VE estimates are possible with the large sample size of this multi-centre case-control. I-MOVE shows how a network can provide precise summary VE measures across Europe. 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. 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. 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. 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. 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. 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 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. 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. 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. 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. 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. 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. Forty-three school children from 8 to 11 years old were vaccinated intranasally with two doses of a paediatric attenuated influenza vaccine developed by reassortment between cold-adapted A/Leningrad/134/57(H2N2) and an A/Brazil/11/78(H1N1)-like strain. Two vaccine doses were administered 1 month apart in a randomized, blind, placebo-controlled study. Although the first vaccine dose had a low infectivity titre, overall 65% of children who received two doses of vaccine showed serological evidence of infection by HI tests. Serum IgA antibody responses against the vaccine strain were detected in nearly 50% of the vaccines and serum IgG antibody responses were detected in approximately equal to 40% by an enzyme immunoassay. nan 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). A total of 10,971 children aged 3-15 years were immunized with live influenza vaccine (the variant intended for children), type A (H1N1). The vaccine proved to be nonreactogenic and produced no harmful effect on the child organism. The genetic stability of the vaccine strain and its high immunogenic activity were shown. In a blinded, placebo-controlled study, the reactogenicity, immunogenicity, and clinical efficacy of single doses of US inactivated split-virus and Russian live attenuated, cold-adapted influenza vaccines were compared in 555 schoolchildren in Vologda, Russia. Serial serum samples were collected and school absenteeism was assessed. Systemic reactions were rare, but local reactions (primarily erythema at the injection site) were observed in 27% of the inactivated vaccine group, and coryza (12%) and sore throat (8%) were observed in the attenuated vaccine group. At 4 weeks after vaccination a > or = 4-fold rise in titer of hemagglutination inhibition antibody to A (H1N1), A (H3N2), and B was noted, respectively, among 78%, 88%, and 53% of children who received inactivated vaccine and among 55%, 79%, and 30% of children who received attenuated vaccine. The vaccine efficacy for preventing school absenteeism due to respiratory illness during the period of peak influenza activity was 56% for inactivated vaccine and 47% for attenuated vaccine. 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. nan 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) In order to assess the effectiveness of Vaxigrip in 1996-1997, we chose 1356 people in the Chinese Army, who had not recently had influenza and who were divided into an injection group and a control group. The injection group consisted of 80 children aged 3-6 years, 363 adults aged 18-59 years and 235 people over 60 years of age. The control group consisted of 88 children aged 3-6, 372 adults aged 18-59 and 218 people over 60. They were observed from the 21st day to the 6th month after Vaxigrip administration. Each person was requested to report having a body temperature over 38.5 degrees C, headache, myalgia or arthalgia, cough, pharyngodynia or nasal obstruction. Fever due to other causes was not included in the influenza symptoms. We counted the symptoms of influenza and common cold only once during the observation period. Our final finding was that the incidence rates of the influenza and common cold symptoms were reduced by 84.8% in children, 74.0% in adults and 68.6% in elderly people. In comparison with the control group, the incidence rate of influenza-like symptoms was reduced by 71.1% in the injection group, and the incidence rate of common cold symptoms in the injection group was lower than that in the control group. There was no large difference by age. The incidence rate of symptoms of upper respiratory tract infection in the injection group was 47.5% lower than that in the control group. Our findings are basically the same as those in other countries. A multicentre case-control study based on sentinel practitioner surveillance networks from seven European countries was undertaken to estimate the effectiveness of 2009-2010 pandemic and seasonal influenza vaccines against medically attended influenza-like illness (ILI) laboratory-confirmed as pandemic influenza A (H1N1) (pH1N1).
                Sentinel practitioners swabbed ILI patients using systematic sampling. We included in the study patients meeting the European ILI case definition with onset of symptoms >14 days after the start of national pandemic vaccination campaigns. We compared pH1N1 cases to influenza laboratory-negative controls. A valid vaccination corresponded to >14 days between receiving a dose of vaccine and symptom onset. We estimated pooled vaccine effectiveness (VE) as 1 minus the odds ratio with the study site as a fixed effect. Using logistic regression, we adjusted VE for potential confounding factors (age group, sex, month of onset, chronic diseases and related hospitalizations, smoking history, seasonal influenza vaccinations, practitioner visits in previous year). We conducted a complete case analysis excluding individuals with missing values and a multiple multivariate imputation to estimate missing values. The multivariate imputation (n = 2902) adjusted pandemic VE (PIVE) estimates were 71.9% (95% confidence interval [CI] 45.6-85.5) overall; 78.4% (95% CI 54.4-89.8) in patients <65 years; and 72.9% (95% CI 39.8-87.8) in individuals without chronic disease. The complete case (n = 1,502) adjusted PIVE were 66.0% (95% CI 23.9-84.8), 71.3% (95% CI 29.1-88.4), and 70.2% (95% CI 19.4-89.0), respectively. The adjusted PIVE was 66.0% (95% CI -69.9 to 93.2) if vaccinated 8-14 days before ILI onset. The adjusted 2009-2010 seasonal influenza VE was 9.9% (95% CI -65.2 to 50.9).
                Our results suggest good protection of the pandemic monovalent vaccine against medically attended pH1N1 and no effect of the 2009-2010 seasonal influenza vaccine. However, the late availability of the pandemic vaccine and subsequent limited coverage with this vaccine hampered our ability to study vaccine benefits during the outbreak period. Future studies should include estimation of the effectiveness of the new trivalent vaccine in the upcoming 2010-2011 season, when vaccination will occur before the influenza season starts. nan 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. Ninety-two children received single doses of one of 13 monovalent vaccines derived from influenza virus strain A/New Jersey/8/76 (A/NJ), and 18 children received placebo. Five influenza virus vaccines were whole-virus vaccines, and eight were split-product vaccines. Samples of sera were taken once three weeks after vaccination. All of the 29 children receiving whole-virus vaccines developed a titer of antibody to A/NJ virus of greater than or equal to 1:20, and the geometric mean titers were 1:14-1:45. One of the 60 children who received split-product vaccines developed a titer of antibody to A/NJ of greater than or equal to 1:20, and geometric mean titers were all less than 1:10. There was a trend toward correlation between titers of hemagglutination-inhibiting (HAI) antibody to A/NJ and titers of HAI antibody to A/Victoria/3/75 viruses, with a correlation coefficient of 0.40 for children who received whole-virus vaccines. Three of 60 recipients of split-product vaccines and two of 20 recipients of whole virus developed a fever of greater than or equal to 38 C. One of the two febrile children who had received whole-virus vaccine had otitis media. Therefore, reactogenicity of whole-virus vaccines and split-product vaccines appeared to be similar in these children. 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. 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. To estimate the effectiveness of influenza vaccine against medical care visits for laboratory-confirmed influenza in young children we conducted a matched case-control study in children with acute respiratory illness or fever from 2005-2007. Influenza vaccine effectiveness (VE) was calculated using cases with laboratory-confirmed influenza and controls who tested negative for influenza. The effectiveness of influenza vaccine in fully vaccinated children 6-59 months of age was 56% (95% CI: 25%-74%); a significant VE was not found for partial vaccination.
                Copyright © 2011 Elsevier Ltd. All rights reserved. Vaccination of children in school is one strategy to reduce the spread of influenza in households and communities.
                We identified 11 demographically similar clusters of elementary schools in four states, consisting of one school we assigned to participate in a vaccination program (intervention school) and one or two schools that did not participate (control schools). During a predicted week of peak influenza activity in each state, all households with children in intervention and control schools were surveyed regarding demographic characteristics, influenza vaccination, and outcomes of influenza-like illness during the previous 7 days.
                In all, 47% of students in intervention schools received live attenuated influenza vaccine. As compared with control-school households, intervention-school households had significantly fewer influenza-like symptoms and outcomes during the recall week. Paradoxically, intervention-school households (both children and adults) had higher rates of hospitalization per 100 persons than did control-school households. However, there was no difference in the overall hospitalization rates for children or adults in households with vaccinated children, as compared with those with unvaccinated children, regardless of study-group assignment. Rates of school absenteeism for any cause (based on school records) were not significantly different between intervention and control schools.
                Most outcomes related to influenza-like illness were significantly lower in intervention-school households than in control-school households. (ClinicalTrials.gov number, NCT00192218.)
                2006 Massachusetts Medical Society 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. Three groups of children were immunized with an inactivated Port Chalmers (H3ChN2Ch) influenza vaccine (group A), a neuraminidase-specific (Heq1N2Ch) influenza vaccine (group B), or a placebo. Immunization induced seroconversion for H3Ch and N2Ch-specific antibody in group A and for N2Ch antibody in group B. The protective efficacies observed against naturally acquired illness with the Port Chalmers strain of influneza A virus were 68.7% and 37.4% in groups A and B, respectively, in comparison to the placebo group, and those against illness produced by the subsequent outbreak of the Victoria strain were 80.0% and 72.7%. These data support the role of neuraminidase-specific immunization in protection against influenza. Although the degree of protection after vaccination with the Heq1N2Ch vaccine was less than that provided by the biphasic H3ChN2Ch vaccine against the Port Chalmers strain, it appeared to be similar in the two vaccine study groups against the Victoria strain. 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. Twenty-two healthy infants and children received either cold-recombinant, trivalent influenza vaccine or placebo in a three-dose vaccine trial. Most (82%) who received vaccine were seronegative to all three vaccine strains (10(6) TCID50/dose each): A/Kawasaki/9/86 (H1N1), A/Los Angeles/2/87 (H3N2), and B/Yamagata/16/88. Vaccine was administered intranasally at time 0 and 2 and 4 months later. The vaccine was well tolerated and immunogenic when administered in a multidose regimen. The first dose stimulated antibody to H1, H3, and B in 59%, 94%, and 35% of vaccinees, respectively, by hemagglutination inhibition (HAI) or ELISA. After two doses of vaccine, 93%, 93%, and 80% had antibody by HAI or ELISA to H1, H3, and B, respectively. Most vaccinees (67%) responded to all three viruses after two doses of vaccine. The third dose contributed little to the vaccine's immunogenicity. Multidose trivalent influenza vaccine is safe and induces an immune response in most vaccinees after two doses. 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. 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. 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. 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. Characteristics of avian-human (ah) and cold-adapted (ca) influenza A/Kawasaki/9/86 (H1N1) reassortant vaccine viruses were compared in 37 seronegative adults and 122 seronegative infants and children. The 50% human infectious dose (HID50) in infants and children was 10(2.9) and 10(2.6) TCID50 for the ah and ca vaccine, respectively. The ah influenza A/Kawasaki/9/86 reassortant was reactogenic: 24% of infants and children infected with greater than or equal to 100 HID50 had fever greater than or equal to 39.4 degrees C. Since H3N2 ah vaccines were previously shown to be adequately attenuated, it is reasonable to suggest that the genes that code for hemagglutinin and neuraminidase of the H1N1 virus apparently influence the reactogenicity of reassortant viruses derived from the avian influenza A/Mallard/New York/6750/78 donor virus. Because this avian virus does not reproducibly confer a satisfactory level of attenuation to each subtype of influenza A virus, it is not a suitable donor virus for attenuation of wild-type influenza viruses. In contrast, the ca A/Ann Arbor/6/60 donor virus reliably confers attenuation characteristics to a variety of H1N1 and H3N2 influenza A viruses. An outbreak of influenza occurred at the end of the 2001-2 winter season in a highly-vaccinated, semi-enclosed, religious community. On the basis of retrospective self reporting, 43% met the case definition (151/350) and 81% (25/31) of throat swabs from cases were polymerase chain reaction (PCR) -positive for influenza A (H3N2). The risk of developing influenza in people aged 65 or more was lower than that of children aged 2 years and under (odds ratio 0.1, 95% confidence interval 0.02 to 0.38). The risk of developing symptoms of influenza was not significantly different between people who had been vaccinated in the United Kingdom and those who had not been vaccinated (OR 1.14, CI 0.41 to 3.14). Chronic disease was an independent risk factor for developing symptoms of influenza (OR 1.9, CI 1 to 3.63). Timing of the outbreak, the age structure and mode of communal living may have influenced the efficacy of the influenza vaccine, which was well matched to circulating strains at the time of the outbreak. It is important to consider the diagnosis of influenza even in a highly-vaccinated community. 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. 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. 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. 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. This study was carried out to investigate the effectiveness of influenza vaccine among 2913 children (1512 vaccinees and 1401 nonvaccinees) under 6 years of age during the 2002-2003 season. Study subjects were recruited from 54 paediatric clinics, located in eight areas in Japan. Maximum body temperatures were obtained weekly from parents between 2002 December 16 and 2003 April 13. Influenza-like illness (ILI) was defined as an acute febrile illness (> or =38.0 degrees C) during the peak epidemic period in each study area. The vaccine antigens included were A/New Caledonia/20/99(H1N1), A/Panama/2007/99(H3N2) and B/Shandong/7/97. Vaccine effectiveness was analyzed by comparing the frequencies of ILI between vaccinees and nonvaccinees. The adjusted odds ratio (OR) and its 95% confidence interval (95% CI) were calculated by the proportional odds model using logistic regression with three-level outcome variables (<38.0/38.0-38.9/> or =39.0 degrees C). A significantly decreased OR of vaccination was observed (OR: 0.76; 95% CI: 0.66-0.88), corresponding to a vaccine effectiveness (1-OR) of 24% (95% CI: 12%-34%). When the analysis was confined to those aged > or =2 years, a more pronounced OR (0.67, 0.56-0.79) was obtained with a vaccine effectiveness of 33% (21%-44%). On the other hand, no significant vaccine effectiveness was detected among very young children; the ORs were 1.84 (0.81-4.19) for those <1 year of age and 0.99 (0.72-1.36) for those 1.0-1.9 years of age and 1.07 (0.80-1.44) when these two age groups were combined. Thus, among very young children vaccine effectiveness could not be demonstrated. The safety, tolerability, and immunogenicity of a monovalent intranasal 2009 A/H1N1 live attenuated influenza vaccine (LAIV) were evaluated in children and adults.
                Two randomized, double-blind, placebo-controlled studies were completed in children (2-17 y) and adults (18-49 y). Subjects were assigned 4:1 to receive 2 doses of H1N1 LAIV or placebo 28 days apart. The primary safety endpoint was fever ≥38.3°C during days 1-8 after the first dose; the primary immunogenicity endpoint was the proportion of subjects experiencing a postdose seroresponse. Solicited symptoms and adverse events were recorded for 14 days after each dose and safety data were collected for 180 days post-final dose. In total, 326 children (H1N1 LAIV, n = 261; placebo, n = 65) and 300 adults (H1N1 LAIV, n = 240; placebo, n = 60) were enrolled. After dose 1, fever ≥38.3°C occurred in 4 (1.5%) pediatric vaccine recipients and 1 (1.5%) placebo recipient (rate difference, 0%; 95% CI: -6.4%, 3.1%). No adults experienced fever following dose 1. Seroresponse rates in children (H1N1 LAIV vs. placebo) were 11.1% vs. 6.3% after dose 1 (rate difference, 4.8%; 95% CI: -9.6%, 13.8%) and 32.0% vs. 14.5% after dose 2 (rate difference, 17.5%; 95% CI: 5.5%, 27.1%). Seroresponse rates in adults were 6.1% vs. 0% (rate difference, 6.1%; 95% CI: -5.6%, 12.6%) and 14.9% vs. 5.6% (rate difference, 9.3%; 95% CI: -0.8%, 16.3%) after dose 1 and dose 2, respectively. Solicited symptoms after dose 1 (H1N1 LAIV vs. placebo) occurred in 37.5% vs. 32.3% of children and 41.7% vs. 31.7% of adults. Solicited symptoms occurred less frequently after dose 2 in adults and children. No vaccine-related serious adverse events occurred.
                In subjects aged 2 to 49 years, two doses of H1N1 LAIV have a safety and immunogenicity profile similar to other previously studied and efficacious formulations of seasonal trivalent LAIV.
                ClinicalTrials.gov NCT00946101, NCT00945893. 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. 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. The purpose of this study was to assess the impact a free, on-site influenza immunization program could have on attendance in Title 1 schools. Four Title 1 elementary schools participated in the study. Students at 2 schools were offered free FluMist immunizations on site, and students at 2 control schools were not. Compliance on receiving FluMist was measured on the percentage of students participating after evaluating for medical exclusions. Documentation on the reason for absences at all 4 schools included self- or parent-reported influenza. Attendance rates for the year also were compared with the previous year for all 4 schools. A comparison was done of total days absent versus total days enrolled between schools receiving FluMist and schools not receiving the vaccine. Despite the fact that FluMist is a new vaccine and is not required for children, 57% of those medically eligible to receive it had parental permission and received the vaccine. The 2 schools receiving FluMist increased their attendance rates from 95.3% and 93.9% to 96.1% and 95.8%. Previously, the comparison schools each had a 94.6% attendance rate; one fell to 94.4% and the other rose very slightly to 94.7%. The differences in self- or parent-reported influenza absences were not significant. However, the difference in days absent between individual vaccinated and nonvaccinated schools was statistically significant. Excellent immune responses following 1 or 2 doses of the monovalent inactivated pandemic H1N1 vaccines have been documented, but the effectiveness of these vaccines against laboratory-confirmed H1N1 infections in the general population is not clear. We evaluated the effectiveness of the pandemic H1N1 and seasonal trivalent influenza vaccines (TIV) used during the 2009 mass vaccination campaign in Manitoba (Canada) in preventing laboratory-confirmed H1N1 infections.
                A population-based case-control study using data from Cadham Provincial Laboratory (CPL) and the Manitoba Immunization Monitoring System (MIMS). All Manitoba residents ≥6 months of age who had a respiratory specimen tested at CPL for H1N1 were included in the study. Cases were individuals who tested positive for pandemic H1N1 influenza A by reverse transcriptase-PCR (N=1435). Controls were individuals who tested negative for both influenza A and B (N=2309). Information on receipt of TIV or H1N1 vaccine was obtained by record linkage with MIMS, the population-based province-wide immunization registry.
                Overall, the adjuvanted H1N1 vaccine was 86% (95%CI 75-93%) effective in preventing laboratory-confirmed H1N1 infections when vaccination occurred ≥14 days before testing. Effectiveness seemed lower among older (≥50 years) individuals [51% (-51 to 84%)] and among those with immunocompromising conditions [67% (-13 to 90%)]. There was also evidence that the H1N1 vaccine might be less effective among those who had received the 2009/10 TIV.
                The adjuvanted H1N1 vaccine used during Manitoba's H1N1 mass vaccination campaign was highly effective against laboratory-confirmed pandemic H1N1 infection, especially among children and younger adults.
                Copyright © 2011 Elsevier Ltd. All rights reserved. 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. 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). 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. 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. 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. To assess the clinical effectiveness of influenza vaccine in preventing influenza-like illness (ILI) office visits.
                We analyzed billing and immunization registry data for healthy 6- to 21-month-olds from 5 Denver, Colorado pediatric practices (n = 5193). ILI and pneumonia/influenza (a subset of ILI) were defined from International Classification of Diseases, Ninth Revision, Clinical Modification codes for office visits occurring during peak influenza season. Partially vaccinated (PV) and fully vaccinated (FV) patients were defined as having 1 shot and 2 shots, respectively, more than 14 days before the first ILI visit. The likelihood of an ILI visit was determined using a Cox proportional hazards model accounting for patient characteristics, practice site, and immunization status.
                A total of 28% of the patients had an ILI office visit, and 5% had a pneumonia/influenza visit. Hazard ratios (HRs) for FV versus UV were 0.31 (95% confidence interval [CI] = 0.3 to 0.4) for ILI and 0.13 (95% CI = 0.1 to 0.2) for pneumonia/influenza, corresponding to a vaccine effectiveness (1 - HR x 100) of 69% for ILI and 87% for pneumonia/influenza. The corresponding HRs for PV versus UV were 1.0 (95% CI = 0.9 to 1.2) and 1.1 (95% CI = 0.8 to 1.5).
                Although 2 doses of vaccine were 69% effective against ILI office visits and 87% effective against pneumonia/influenza office visits, 1 dose did not prevent office visits during the 2003-2004 influenza season. The reactogenicity and immunizing activity of vaccine influenza virus A (H1N1) and B strains used as mono- and bi-preparations in children of 3 to 14 years was studied. No increased reactogenicity after the use of bivaccine was observed in the children. Febrile reactions as well as 9 other clinical symptoms which could indicate the reactogenicity of the vaccines were identical for mono- and bivaccine and corresponded to the requirements of the technical documents for the vaccine. The optimal conditions for the evaluation of the immunogenicity of the B component by HI test were developed, and the necessity of using additionally the enzyme immunoassay for this purpose is substantiated. The above method demonstrated that the immunogenicity of the live influenza type A and B vaccine was high in children. No significant inhibition of immunological parameters was observed when the two viruses were combined in the bivaccine. 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. 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. 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.
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.