[The immunogenic properties and prophylactic efficacy of a live polyvalent influenza vaccine in children 5 to 14 years old]. [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]. Reactions and serologic responses after administration of inactivated monovalent influenza A/swine virus vaccines. I. Immunization of children and adults with influenza A/Shope virus vaccines. Evaluation of a cold-adapted influenza B/Texas/84 reassortant virus (CRB-87) vaccine in young children. A randomized, double blind study in young healthy adults comparing cell mediated and humoral immune responses induced by influenza ISCOM vaccines and conventional vaccines. Effectiveness of influenza vaccination of day care children in reducing influenza-related morbidity among household contacts. Safety of cold-adapted live attenuated influenza vaccine in a large cohort of children and adolescents Compliance with influenza vaccination in Israel in two successive winters, 1998/1999 and 1999/2000. A controlled double-blind comparison of reactogenicity, immunogenicity, and protective efficacy of whole-virus and split-product influenza vaccines in children. From the National Institute of Allergy and Infectious Diseases of the National Institutes of Health, the Center for Disease Control, and the Bureau of Biologics of the Food and Drug Administration. Summary of clinical trials of influenza vaccines--II. Protective efficacy of live influenza vaccines. Its assessment in field and experimental conditions. Influenza B virus vaccines in children and adults: adverse reactions, immune response, and observations in the field. [Vaccination of infants and schoolchildren with an influenza subunit vaccine (author's transl)]. Summary of clinical trials of inactivated influenza vaccine - 1978. Simultaneous administration of live, attenuated influenza A vaccines representing different serotypes. A/New Jersey/76 influenza vaccine trial in seronegative schoolchildren: Comparison of a subunit vaccine with a whole-virus vaccine Efficacy of intranasal virosomal influenza vaccine in the prevention of recurrent acute otitis media in children. Direct and total effectiveness of the intranasal, live-attenuated, trivalent cold-adapted influenza virus vaccine against the 2000-2001 influenza A(H1N1) and B epidemic in healthy children. Cost-effectiveness analysis of an intranasal influenza vaccine for the prevention of influenza in healthy children. Value of cerebrospinal fluid leukocyte aggregation in distinguishing the causes of meningitis in children. A Trial of Oil-Adjuvant Influenza Vaccine in a Non-Epidemic Season Clinical evaluation of neuraminidase monospecific (HEqN2) recombinant influenza vaccine in children. The efficacy of live attenuated, cold-adapted, trivalent, intranasal influenzavirus vaccine in children. Three year follow up study of national influenza vaccination practices in Japan. Cell-mediated immune responses to the hemagglutinin and neuraminidase antigens of influenza A virus after immunization in humans. Evaluation of a live, attenuated recombinant influenza vaccine in high school children. Assessment of effectiveness of Vaxigrip. Clinical and epidemiological evaluation of a live, cold-adapted influenza vaccine for 3-14-year-olds. Single-dose trials of monovalent A/New Jersey/76 (Hsw1N1) influenza virus vaccine in children in Durham, North Carolina. Correlates of immune protection induced by live, attenuated, cold-adapted, trivalent, intranasal influenza virus vaccine. A clinical trial with monovalent influenza A/New Jersey/76 virus vaccine in preschool and school-age children. Socioeconomic impact of influenza on healthy children and their families Efficacy of live attenuated and inactivated influenza vaccines in schoolchildren and their unvaccinated contacts in Novgorod, Russia. Studies on reactogenicity and immunogenicity of attenuated bivalent cold recombinant influenza type A (CRA) and inactivated trivalent influenza virus (TI) vaccines in infants and young children. Comparison of live attenuated cold-adapted and avian-human influenza A/Bethesda/85 (H3N2) reassortant virus vaccines in infants and children. Safety and immunogenicity of a purified F protein respiratory syncytial virus (PFP-2) vaccine in seropositive children with bronchopulmonary dysplasia. [The inoculation properties of live recombinant influenza vaccine types A and B used separately and jointly in children 3 to 14]. 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. Field trial with human and equine influenza vaccines in children: protection and antibody titres. Clinical reactions and serologic response following inactivated monovalent influenza type B vaccine in young children and infants. Incidence of influenza in Finnish children Safety and immunogenicity of a trivalent, inactivated, mammalian cell culture-derived influenza vaccine in healthy adults, seniors, and children. Reactions and serologic responses after administration of inactivated monovalent influenza A/swine virus vaccines. II. Immunization of children with influenza A/New Jersey/X-53 virus vaccines. Prophylactic effect of inactivated influenza vaccine on young children. Prospective, randomized, placebo-controlled evaluation of the safety and immunogenicity of three lots of intranasal trivalent influenza vaccine among young children. Safety of the trivalent, cold-adapted influenza vaccine in preschool-aged children. Potential for single high-dose influenza immunization in unprimed children. Safety and immunogenicity of a purified haemagglutinin antigen in very young high-risk children. Comparison of Immunogenicity and Safety of a Virosome Influenza Vaccine with Those of a Subunit Influenza Vaccine in Pediatric Patients with Cystic Fibrosis Efficacy of inactivated vaccine in preventing antigenically drifted influenza type A and well-matched type B. 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. Failure of inactivated influenza A vaccine to protect healthy children aged 6-24 months. Safety and immunogenicity of a cold‐adapted influenza A (H1N1) reassortant virus vaccine administered to infants less than six months of age ASSESSMENT OF INACTIVATED INFLUENZA-A VACCINE AFTER THREE OUTBREAKS OF INFLUENZA A AT CHRIST'S HOSPITAL Effectiveness of inactivated influenza vaccine in preventing acute otitis media in young children: a randomized controlled trial. Studies of the 1996-1997 inactivated influenza vaccine among children attending day care: immunologic response, protection against infection, and clinical effectiveness. 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. Natural challenge of subjects vaccinated with WRL 105 strain live influenza vaccine in a residential community. [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]. A comparison of live and killed influenza-virus vaccines. Report to the Medical Research Council's Committee on Influenza and other Respiratory Virus Vaccines. Immunization of infants and young children with live attenuated trivalent cold-recombinant influenza A H1N1, H3N2, and B vaccine. Developments in mucosal influenza virus vaccines. Controlled trial of inactivated influenza vaccine containing the a-Hong Kong strain during an outbreak of influenza due to the a-England-42-72 strain. Safety, efficacy and effectiveness of the influenza virus vaccine, trivalent, types A and B, live, cold-adapted (CAIV-T) in healthy children and healthy adults. Safety and immunogenicity of a live-attenuated influenza vaccine blended and filled at two manufacturing facilities. Live attenuated and inactivated influenza vaccine in school-age children. Monovalent inactivated A/New Jersey/8/76 (Hsw1N1) vaccine in healthy children aged three to five years. Use of influenza A virus vaccines in seronegative children: live cold-adapted versus inactivated whole virus. Comparison of live attenuated and inactivated influenza vaccines in schoolchildren in Russia: I. Safety and efficacy in two Moscow schools, 1987/88. [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]. Estimation of the efficacy of live, attenuated influenza vaccine from a two-year, multi-center vaccine trial: implications for influenza epidemic control. A TritonX-100-split virion influenza vaccine is safe and fulfills the committee for proprietary medicinal products (CPMP) recommendations for the European Community for Immunogenicity, in Children, Adults and the Elderly. Efficacy of inactivated and cold-adapted vaccines against influenza A infection, 1985 to 1990: the pediatric experience 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. Study of live recombinant cold-adapted influenza bivalent vaccine of type A for use in children: an epidemiological control trial. Comparison of heterotypic protection against influenza A/Taiwan/86 (H1N1) by attenuated and inactivated vaccines to A/Chile/83-like viruses. Multidose, live attenuated, cold-recombinant, trivalent influenza vaccine in infants and young children. Clinical trials with inactivated monovalent (A/New Jersey/76) and bivalent (A/New Jersey/76-A/Victoria/75) influenza vaccines in Los Angeles children. An attenuated influenza virus vaccine: Reactogenicity, transmissibility, immunogenicity, and protective efficacy. Comparison of monovalent and trivalent live attenuated influenza vaccines in young children. Influenza A vaccine decreases the incidence of otitis media in 6- to 30-month-old children in day care. A randomized controlled trial of cold-adapted and inactivated vaccines for the prevention of influenza A disease. Reactivity and immunogenicity of monovalent A/New Jersey/76 influenza virus vaccines in children. Safety, vaccine virus shedding and immunogenicity of trivalent, cold-adapted, live attenuated influenza vaccine administered to human immunodeficiency virus-infected and noninfected children. [The investigation of the safety, genetic stability and immunogenicity of live influenza vaccine for adults in vaccination of 3-6 years old children]. Efficacy of live attenuated influenza A/Scotland/74 (H3N2) virus vaccine against challenge with influenza A/Victoria/3/75 (H3N2) virus. Protection with split and whole virus vaccines against influenza. Vaccinations may induce diabetes-related autoantibodies in one-year-old children. Efficacy of vaccination with live attenuated, cold-adapted, trivalent, intranasal influenza virus vaccine against a variant (A/Sydney) not contained in the vaccine. Clinical and immunologic evaluation of neuraminidase-specific influenza A virus vaccine in humans. Comparison of US inactivated split-virus and Russian live attenuated, cold-adapted trivalent influenza vaccines in Russian schoolchildren. 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. Safety and immunogenicity of adjuvanted and unadjuvanted subunit influenza vaccines administered intranasally to healthy adults. [Immunisation against influenza with a new subunit vaccine tested on children at risk (author's transl)]. Evaluation of bivalent live attenuated influenza A vaccines in children 2 months to 3 years of age: safety, immunogenicity and dose-response.
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 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 aim ed 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 Reactivity and immunogenicity of three inactivated , zonally purified , monovalent influenza A/swine virus vaccines were studied in children and adults . Each dose of vaccine contained either 400 chick cell-agglutinating ( CCA ) units/0.5 ml or 200 CCA units/0.25 ml . The vaccines contained either whole virus or ether-extracted , subunit virus with or without 1.5 mg of A1PO4/0.5 ml . Children younger than 10 years of age received a half dose . Substantial system reactions , including temperature increases of 2.2 F-4.9 F , were observed in all children who received whole-virus vaccines . In contrast , ether-extracted , subunit vaccines ( with or without A1PO4 ) were minimally pyrogenic in 185 subjects . Two doses of subunit vaccine in subjects younger than 25 years of age were immunologically equivalent to a single dose in older subjects . We concluded that two doses of ether-extracted , subunit virus vaccine with Hsw1N1 antigen , administered at least four weeks apart , are serologically effective for immunization of seronegative subjects of any age and that this dosage regimen should be used in young children in whom whole-virus vaccines are unacceptably reactive A cold-adapted ( ca ) influenza B reassortant virus vaccine that contained the six internal RNA segments from influenza B/Ann Arbor/1/66 ca virus and the neuraminidase and hemagglutinin genes from wild-type influenza B/Texas/1/84 virus was evaluated in children ranging in age from 8 months to 14 years . The children were vaccinated intranasally with doses ranging from 10(3.2 ) to 10(6.2 ) 50 % tissue culture infective doses ( TCID50 ) . Thirty children were seropositive , and 26 were seronegative . Thirty-three children participated as unvaccinated controls . The vaccine was well tolerated by both seronegative and seropositive children . The amount of virus required to infect 50 % of seronegative children was approximately 10(4.5 ) TCID50 . Vaccine viruses recovered from airway secretions retained temperature-sensitive and cold-adapted characteristics . The results of this study indicate that the vaccine virus , influenza B/Texas/84 ca reassortant virus , is attenuated , immunogenic , and phenotypically stable when given to young seronegative children Although current influenza vaccines have been shown to reduce influenza-related morbidity and mortality , there is a desire to develop more efficacious products . Vaccines which can induce CD8(+ ) cytotoxic T cell ( CTL ) responses in addition to strong antibody responses may be more effective in preventing disease since it has been demonstrated that CTL contribute to protective immunity , even against drift variants of influenza A viruses . The immunogenicity of two types of experimental influenza vaccines , which were based on immune stimulating complexes ( ISCOM ) , were evaluated and compared with a conventional non-adjuvanted inactivated split virion vaccine , after immunization of human volunteers . In this r and omized , double blind study , it was shown that the ISCOM vaccines altered the kinetics of the serum antibody response , result ing in more rapid titer rises against the vaccine strains . This accelerated antibody response coincided with enhanced in vitro proliferative T cell responses , which were observed shortly after vaccination . In addition , CTL responses were observed in a higher proportion of the vaccinees receiving an ISCOM vaccine , than in vaccinees receiving the conventional influenza vaccine CONTEXT A growing proportion of young children in the United States participate in day care , and these children are considered to be at high risk for influenza infection . Whether vaccinating day care children reduces household transmission of influenza is not known . OBJECTIVE To evaluate the effect of  vaccinating day care children  on reducing influenza-related morbidity among their household contacts . DESIGN Single-blind , r and omized controlled trial conducted during the 1996 - 1997 influenza season . SETTING Ten day care centers for children of US Navy personnel in San Diego , Calif. PARTICIPANTS A total of 149 day care attendees ( aged 24 - 60 months ) and their families were r and omized ; 127 children and their 328 household contacts received 2 vaccine doses and were included in the analysis . INTERVENTIONS Inactivated influenza vaccine was administered to 60 children with 162 household contacts , and hepatitis A vaccine as a control was administered to 67 age-matched children with 166 household contacts . MAIN OUTCOME MEASURES Information regarding febrile respiratory illnesses and related morbidity for household contacts of influenza-vaccinated vs control children ( subgrouped by influenza-vaccinated and unvaccinated contacts ) , obtained by telephone interviews with parents every 2 weeks from November 1996 through April 1997 . RESULTS Influenza-unvaccinated household contacts ( n = 120 ) of influenza-vaccinated day care children had 42 % fewer febrile respiratory illnesses ( P = .04 ) compared with unvaccinated household contacts of control children . Among school-aged household contacts ( aged 5 - 17 years ) , there was an 80 % reduction among contacts of vaccinated children ( n = 28 ) vs contacts of unvaccinated children ( n = 31 ) in febrile respiratory illnesses ( P = .01 ) , as well as reductions of more than 70 % in school days missed ( P = .02 ) , reported earaches ( P = .02 ) , physician visits ( P = .007 ) , physician-prescribed antibiotics ( P = .02 ) , and adults who missed work to take care of ill children ( P = .04 ) . CONCLUSIONS These results indicate that vaccinating day care children against influenza helps reduce influenza-related morbidity among their household contacts , particularly among school-aged contacts . Future studies should be conducted in civilian population s to assess the full effect of vaccinating day care children against influenza . JAMA . 2000;284:1677 - 1682 Objective . To determine the safety of cold-adapted trivalent intranasal influenza virus vaccine ( CAIV ) in children and adolescents . Study design . A r and omized , double blind , placebo-controlled safety trial in healthy children age 12 months to 17 years given CAIV ( FluMist ; MedImmune Vaccines , Inc. ) or placebo ( r and omization , 2:1 ) . Children < 9 years of age received a second dose of CAIV or placebo 28 to 42 days after the first dose . Enrolled children were then followed for 42 days after each vaccination for all medically attended events . Prespecified outcomes included 4 prespecified diagnostic groups and 170 observed individual diagnostic categories . The relative risk and the 2-sided 90 % confidence interval were calculated for each diagnostic group and individual category by clinical setting , dose and age . More than 1500 relative risk analyses were performed . Results . A total of 9689 evaluable children were enrolled in the study . Of the 4 prespecified diagnostic categories ( acute respiratory tract events , systemic bacterial infection , acute gastrointestinal tract events and rare events potentially associated with wild-type influenza ) , none was associated with vaccine . Of the biologically plausible individual diagnostic categories , 3 , acute gastrointestinal events , acute respiratory events and abdominal pain , had different analyses that demonstrated increased and decreased relative risks , making their association with the vaccine unlikely . For reactive airway disease a significant increased relative risk was observed in children 18 to 35 months of age with a relative risk of 4.06 ( 90 % confidence interval , 1.29 to 17.86 ) in this age group . The individual diagnostic categories of upper respiratory infection , musculoskeletal pain , otitis media with effusion and adenitis/adenopathy had at least one analysis that achieved a significant increased risk ratio . All of these events were infrequent . Conclusion . CAIV was generally safe in children and adolescents . The observation of an increased risk of asthma/reactive airway disease in children < 36 months of age is of potential concern . Further studies are planned to evaluate the risk of asthma/reactive airway disease after vaccine BACKGROUND Although influenza is usually a mild self-limiting disease it can cause serious complications in high risk groups . The economic costs of influenza are large due to the burden on the health system and absenteeism from work . There is evidence that the vaccine is underused in groups targeted for vaccination . OBJECTIVES To estimate : a ) the compliance rate with the influenza , vaccination in Israel during the winter seasons of 1998/1999 and 1999/2000 , b ) the role of health care personnel and the media in influencing compliance , and c ) the reasons for lack of compliance in the elderly . METHODS Two national population -based r and om telephone surveys of 1,500 households were performed during October 1999 and January 2000 to survey influenza vaccination  compliance prior to the winters of 1998/1999 and 1999/2000 respectively . Each survey was performed during four successive evenings . The response rate was 78.1 % for the first survey and 79.1 % for the second . RESULTS Vaccination compliance was similar in both surveys . The average rate of vaccination was 6 % for the population under 65 years and 50 % for the population of 65 years and above . The overall vaccination rate was around 10 % . The family physician was the main authority to recommend the vaccination , followed by the community nurse . Absence of recommendation and lack of faith in the efficacy of the vaccine were the main reasons for noncompliance . CONCLUSIONS Compliance rates with influenza vaccine in targeted groups in Israel remain relatively low . Health care personnel should be more involved in promoting the vaccine A double-blind r and omized study with bivalent influenza virus vaccines was conducted to compare the local and systemic reactions and immunogenicity of a whole-virus vaccine and a split-product vaccine in children .  Fevers of greater than 100 F were more frequent after vaccination with whole-virus than split-product vaccine especially in children one to four years old ( 69 % vs 22 % ; P less than 0.01 ) . Fevers of greater than or equal to 103 F did not occur in children who previously had been given influenza virus vaccine  , even in the absence of preexisting homologous serum antibody . The immune response to the A/Port Chalmers/1/73 antigen in the vaccine was similar after administration of either whole-virus or split-product vaccine . However , split-product vaccine induced significantly less hemagglutination-inhibiting antibody to B/Hong Kong/5/72 virus in children younger than 10 years who had not been previously immunized ; only 43 % developed detectable antibody vs. 100 % of those vaccinated with whole virus vaccine ( P less than 0.01 ) . These studies indicate that ( 1 ) in young children  whole-virus vaccine causes fever more frequently than split-product vaccine ; ( 2 ) young children previously vaccinated with influenza virus vaccine  are unlikely to experience fever subsequent to immunization with a related antigen ; and ( 3 ) split-product vaccine induces less antibody to B/Hong Kong/5/72 virus than whole-virus vaccine in immunologically unprimed young children These studies indicate that the high-risk and normal pediatric population s can be safely and effectively immunized with a two-dose regimen of the influenza A/New Jersey/76 virus vaccine . In addition , the studies have demonstrated important differences between split-product and whole-virus vaccines in the pediatric age group . Furthermore , reactogenicity from the whole-virus vaccine administered in the schedules employed was acceptable after the first dose and negligible after the second dose . More detailed examination of the data will undoubtedly yield additional information of importance to current and future use of inactivated influenza vaccines in children Cost benefit estimates of immunization programs are critically dependent on an accurate and reliable assessment of the protection offered by the vaccines . Consequently , the selection of appropriate parameters of protection becomes an issue of major importance . The protective efficacy of live influenza virus vaccines has been established for several vaccinal strains used in routine immunization . This was established under conditions of natural and artificial exposure to both homologous and heterologous influenza viruses . Reduction in the incidence of specific disease -- respiratory illness , confirmed by influenza virus isolation and /or four-fold increase in serum HAI titer , was found to be significant . These data will be discussed in relation to available epidemiological models that have been developed for the evaluation of disease modifying properties of immunoprophylactic agents A double-blind trial of influenza virus vaccines was initiated in the fall of 1976 . One dose of 500 chick cell-agglutinating units of subvirion influenza B vaccine gave negligible adverse reactions in schoolchildren and young adults , whereas whole-virus vaccine caused systemic reactions .  Subvirion vaccines induced a complement-fixing antibody response , particularly in children , that returned to near original levels over a two-year period . Levels of hemagglutination-inhibiting ( HAI ) antibodies induced by the vaccine remained elevated for at least 2.5 years in the absence of natural challenge . When a major epidemic of influenza B occurred in the winter of 1979 - 1980 , the youngest children ( originally six to nine years of age ) had the highest infection rate ( 53 % ) ; in this group protection was estimated at 44 % + /- 17 % by serologic evidence of infection . Little vaccine efficacy was demonstrated in older age groups at three years after vaccination , despite the persistence of HAI antibodies induced by the vaccine A new influenza subunit vaccine which contains only hemagglutinin and neuraminidase antigens was investigated for reactogenicity and immunogenicity in children aged between three and 15 years . Children under six years of age received either 500 IU or 1000 IU of the commercial vaccine , those aged from six to 15 years either 1000 IU or 2000 IU . The vaccines contained the virus strains recommended by the World Health Organisation for the vaccination season 1976/77 . In a double blind study the vaccinees were allocated at r and om to the different dosage groups . The children were examined for reactions by the vaccinating physician 24 hours after vaccination . Serum hemagglutination inhibiting antibody titers were determined before vaccination and four weeks after vaccination . In the younger age-group additional antibody determination was made two weeks after a booster injection . A very low rate of side-reactions was observed in all dosage groups . The increase of the antigen content was not associated with a higher rate of side reactions . After the first vaccination a significant rise of antibody titers could be observed in all children . After the booster injection a further increase of these antibody titers was observed . The response of the younger age group to the dosages 500 and 100 IU did not different significantly . In contrast , in the older age group the increase of the dosage from 1000 to 2000 IU was connected with a better immune response . This was especially marked in the antibody titers against the influenza B-strain virus This report summarizes the clinical trials of the A/USSR/77 ( H1N1 ) influenza vaccines  performed in 1978 . A total of 2,091 subjects participated in these trials . The results of these clinical trials indicated that two doses of H1N1 viral antigen were necessary to produce serum titers of hemagglutinin-inhibiting ( HAI ) antibody of greater than 1:40 in 80 % or more of the test subjects younger than 25 years of age , who were unlikely to have experienced natural infection during the earlier period of prevalence of H1N1 virus ( 1947 - 1957 ) . Only one dose of the A/Texas/77 ( H3N2 ) or B/Hong Kong/72 antigen was necessary to stimulate equivalent titers of HAI antibody in serum . Thus , previous natural exposure to H1N1 viruses primed individuals 26 years of age or older to respond to H1N1 antigens . No major differences in antigenicity were noted between whole-virus and split-virus vaccines . No differences in reaction indexes measuring systemic reactions were noted when vaccine types were compared . Only one vaccine was associated with a reaction index appreciably higher than that of placebo . The relatively uniform antibody responses observed were attributed to the newer methods of vaccine st and ardization introduced after the clinical trials in 1976 . No cases of vaccine-related neurological problems , including Guillain-Barré syndrome , were found during these trials . Vaccines containing 7 - 21 micrograms of each viral antigen were antigenic and were well tolerated Two live , attenuated cold-adapted influenza A vaccines representing current H1N1 and H3N2 serotypes were simultaneously administered intranasally to doubly seronegative children . No clinical illness result ed . Characterization of virus shedding demonstrated shedding of both original vaccine strains and of reassortant virus with the H3N1 and H1N2 phenotype . A serum immune response to both serotypes was demonstrated . The successful simultaneous administration of two influenza A vaccine strains enhances the potential usefulness of this approach to influenza prophylaxis Summary In the present vaccination trial , 202 seronegative schoolchildren comprising both sexes and aged 11 to 12 years were vaccinated i.m . in the upper arm with either the subunit vaccine at a dosage of 600 CCA or 200 CCA or with a whole-virus vaccine at a dosage of 200 CCA , using the double-blind procedure . Both vaccines were prepared from the strain A/New Jersey/76 ( x 5 3a-recombinant ) . The vaccination was followed four weeks later by a booster injection . In tests of local and systemic reactogenicity , it was found that at both dosages the subunit vaccine caused a low frequency of minor adverse reactions . The whole-virus vaccine was marked by a significantly higher rate of adverse reactions , whether of the local or systemic variety . The whole-virus vaccine had , however , a higher immunogenicity than the subunit vaccine , and due to the relatively high rate of adverse reactions it causes , it is not recommended for the vaccination of seronegative children . Because of its low reactogenicity , the subunit vaccine can be given at higher dosage , and it is a matter for consideration whether a better antibody response might not result from two booster injections To evaluate the efficacy of an intranasal , inactivated , virosomal subunit influenza vaccine for prevention of new episodes of acute otitis media ( AOM ) in children with recurrent AOM , 133 children aged 1 - 5 years were r and omized to receive the vaccine  ( n=67 ) or  no vaccination  ( n=66 ) . During a 6-month period , 24 ( 35.8 % ) vaccine recipients had 32 episodes of AOM ; 42 ( 63.6 % ) control subjects had 64 episodes . The overall efficacy of vaccination in preventing AOM was 43.7 % ( 95 % confidence interval , 18.6 - 61.1 ; P=.002 ) . Children vaccinated before influenza season had a significantly better outcome than did those vaccinated after the onset of influenza season . The cumulative duration of middle ear effusion was significantly less in vaccinated children than in control subjects . Data suggest that the intranasal virosomal influenza vaccine might be considered among the options for the prevention of AOM in children < 5 years old with recurrent AOM BACKGROUND The efficacy of the intranasal , live-attenuated , trivalent cold-adapted influenza virus vaccine ( CAIV-T ) against influenza A(H3N2 ) and B infections in healthy persons is established , but its effectiveness against natural influenza A(H1N1 ) infection is unknown . OBJECTIVE To assess the effectiveness of CAIV-T in healthy children during the 2000 - 2001 influenza A(H1N1 ) and B epidemic . DESIGN Community-based , nonr and omized , open-label trial from August 1998 through April 2001 . SETTING Intervention and comparison communities in central Texas . PARTICIPANTS Healthy children , aged 1.5 to 18 years , from the intervention communities received a single dose of CAIV-T at least 1 time or more in 1998 , 1999 , and /or 2000 . MAIN OUTCOME MEASURES The incidence of medically attended acute respiratory illnesses during the 2000 - 2001 influenza epidemic was compared in 3794 health plan CAIV-T recipients with age-eligible , health plan nonrecipients in the intervention communities for direct effectiveness ( n = 9325 ) , and with those in the 2 comparison communities for total effectiveness ( n = 16,264 ) . RESULTS The 2281 CAIV-T recipients in 2000 had significant direct protection against medically attended acute respiratory illness of 18 % to 20 % during the biphasic influenza A(H1N1 ) and B epidemic , and 17 % to 26 % during influenza A(H1N1 ) predominance . The 931 recipients of CAIV-T in 1999 containing influenza A/Beijing/262/95(H1N1 ) and B/Beijing/184/93-like viruses had persistent heterovariant protection against the 2000 - 2001 influenza A/New Caledonia/20/99(H1N1 ) and B/Sichuan/379/99 variants . The 616 recipients of a single CAIV-T dose in 1999 only , including those younger than 5 years with no prior natural exposure to influenza A(H1N1 ) viruses , showed persistent protection . CONCLUSION Healthy children who received CAIV-T in 2000 or 1999 were protected against new variants of influenza A(H1N1 ) and B in the 2000 - 2001 influenza epidemic OBJECTIVE Intranasal influenza vaccine has proven clinical efficacy and may be better tolerated by young children and their families than an injectable vaccine . This study determined the potential cost-effectiveness ( CE ) of an intranasal influenza vaccine among healthy children . METHODS We conducted a CE analysis of data collected between 1996 and 1998 during a prospect i ve 2-year efficacy trial of intranasal influenza vaccine , supplemented with data from the literature . The CE analysis included both direct and indirect costs . We enrolled 1602 healthy children aged 15 to 71 months in year 1 , 1358 of whom were enrolled in year 2 . One or 2 doses of intranasal influenza vaccine or placebo were administered to measure the cost per febrile influenza-like illness ( ILI ) day avoided . RESULTS During the 2-year study period , vaccinated children had an average of 1.2 fewer ILI fever days/child than unvaccinated children . In an individual-based vaccine delivery scenario with vaccine given twice in the first year and once each year thereafter at an assumed base case total cost of $ 20 for the vaccine and its administration ( ie , per dose ) , CE was approximately $ 30/febrile ILI day avoided . CE ranged from $ 10 to $ 69/febrile ILI day avoided at $ 10 to $ 40/dose , respectively . In a group-based delivery scenario , vaccination was cost saving compared with placebo and remained so if vaccine cost was < $ 28 ( the break-even price per dose ) . In the individual-based scenario , vaccination was cost saving if vaccine cost was < $ 5 . In this scenario , nearly half of lost productivity in the vaccine group was attributable to vaccine visits , which overshadowed the relatively modest savings in ILI-associated costs averted . CONCLUSIONS Routine use of intranasal influenza vaccine among healthy children may be cost-effective and may be maximized by using group-based vaccination approaches . cost-effectiveness , influenza , vaccine , children BACKGROUND Current laboratory tests often can not distinguish between bacterial and aseptic meningitis rapidly and accurately . The ability to make a prompt diagnosis has important implication s for the management and outcome of children with meningitis . The observation that leukocytes aggregate in the cerebrospinal fluid ( CSF ) has been previously reported , and it has been advocated as a reliable method to distinguish the causes of meningitis in children . OBJECTIVE To investigate the utility of CSF leukocyte aggregation as a screening test to distinguish between bacterial and aseptic meningitis . METHODS We compared the clinical and laboratory indices of 109 prospect ively enrolled patients with meningitis ( 67 bacterial , 23 viral , 19 undefined etiology ) and evaluated the validity of the  CSF leukocyte aggregation test . The predefined leukocyte aggregation scores ( LAS ) were compared among the types of meningitis , and correlations with other markers of inflammation were calculated . RESULTS The median LAS was significantly higher ( P < 0.001 ) in the bacterial ( 32.1 % ; range , 0 to 84.1 % ) than in the viral ( 0 % ; range , 0 to 16.6 % ) or undefined ( 0 % ; range , 0 to 20.7 % ) groups . The optimal sensitivity of the leukocyte aggregation test , 98.5 to 92.5 % , was demonstrated with LAS values of 0 to 3 % . The corresponding specificity was 64.3 to 88.1 % . The peripheral white blood cell ( WBC ) count , serum C-reactive protein , CSF WBC count , blood culture , CSF Gram stain and CSF culture were inferior to the LAS as screening tests when compared individually . The LAS was as effective as CSF protein , TNF-alpha , IL-1-beta , IL-6 and IL-8 to predict bacterial meningitis . In a logistic regression model that included routine laboratory tests , the best predictor of bacterial meningitis was the LAS ( odds ratio , 1.6 to 3.7 ) . Significant correlations were demonstrated between the LAS and CSF protein , CSF WBC count , IL-1-beta , IL-6 and IL-8 . Duration of symptoms before diagnosis , pretreatment with antibiotics , HIV-1 infection status and CSF red blood cell count did not significantly alter the LAS . CONCLUSIONS There is no single test to diagnose the etiology of meningitis in children promptly and accurately . The finding of leukocyte aggregation in CSF might be of value as a sensitive adjunctive screening tool for the timely diagnosis of bacterial meningitis , recognizing that it has low specificity and potential practical limitations In the autumn of 1963 , 1,679 employees at two U.K.A.E.A. establishments were inoculated with a single dose ( 0·25 ml . ) of polyvalent oil-adjuvant influenza vaccine . In a non-epidemic winter , no significant improvement in certified sickness absence could be demonstrated in the vaccinated group when compared with a r and omly selected uninoculated group . In particular , no real protection was shown , in those vaccinated , against influenza and acute upper respiratory tract infections . Once respiratory sickness had occurred the vaccine showed no significant effect on the length of sickness absence . In this trial , unpleasant reactions to the vaccine occurred in about a quarter of the inoculated , and , in particular , a large number of participants complained of general malaise which persisted for more than two weeks . These reactions were thought to be severe enough to induce consumer resistance to routine annual immunization , which is thought to be neither justified nor acceptable in a healthy industrial population at the present stage of vaccine development . This in no way detracts from the suitability or acceptability of the vaccine to high-risk patients . Further research and testing , which is being carried out by pharmaceutical firms , is essential , and so , too , is the need for more controlled trials to evaluate changing vaccines in different population groups Phased clinical trials were undertaken to evaluate the efficacy of neuraminidase specific recombinant ( HEqN2 ) inactivated influenza vaccine in a population of school children . Groups of subjects were immunized under code , with influenza A2 Port Chalmer ( H3N2 ) , Port Chalmer neuraminidase recombinant ( HEqN2 ) , and placebo vaccines ( vaccine diluent ) before the onset of A2 strain influenza epidemic in this population . Preliminary results have provided the following information . Immunization with commercial Port Chalmer ( H3N2 ) or neuraminidase recombinant influenza A2 ( HEqN2 ) vaccines , in a childhood population was safe and without any major adverse effects . Vaccination with H3N2 vaccine regularly induced seronconversion for specific hemagglutination-inhibiting ( HAI ) antibodies in over 60 % of vaccinated subjects . The mean titers of antineuraminidase antibody ( ANAB ) in H3N2 recipients who were seropositive prior to immunization increased five-fold while the ANAB titers of individuals who were seronegative prior to immunization did not rise significantly after immunization . On the other h and , immunization with HEqN2 vaccine result ed in little or no HAI response against H3 , while specific ANAB response was observed in over 70 % of such vaccines . The ANAB titers increased approximately 10 fold in the vaccines who were seropositive prior to immunization , and the titers in subjects seronegative prior to immunization were 5 - 6 fold higher than the post immunization titers observed in seronegative individuals in the H3N2 vaccinated group . Preliminary data on protection against natural reinfection suggested that , although the incidence of serological reinfection was similar in all vaccine groups , the expression of clinical disease was somewhat milder in HEqN2 vaccinees and in individuals with high levels of ANAB . These studies provide tentative support to the potential use of neuraminidase specific vaccine for mass immunoprophylaxis against influenza A2 virus BACKGROUND 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 . METHODS 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 . RESULTS 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 ) . CONCLUSIONS A live attenuated , cold-adapted influenzavirus vaccine was safe , immunogenic , and effective against influenza A(H3N2 ) and B in healthy children STUDY OBJECTIVE --To evaluate new national influenza vaccination practice s which were started in 1987 under a revised law in Japan . DESIGN --This was a three year , nonr and omised cohort study with information collected by question naire between 1989 and 1991 . SETTING --Eight primary schools in the city of Yonago , Tottori , Japan . These schools were selected from 23 schools in the city . PARTICIPANTS --Altogether 4251 pupils ( 1355 boys and 2896 girls ) in years 1 - 4 of the eight primary schools were included in this study , and followed up . Three years later , data for 1619 pupils ( 768 boys and 851 girls ) were obtained and analysed . MAIN RESULTS --The one-winter seasonal incidence rates of influenza-like disease were 13.4 % , 29.9 % , and 10.3 % in 1989 , 1990 , and 1991 respectively . The incidence rate of influenza-like disease in fully vaccinated pupils was significantly lower than that in unvaccinated pupils in 1990 , but not in 1989 or 1991 . Stepwise multiple regression analysis showed that the incidence of influenza-like disease had a statistical relationship with the frequency of vaccination and the school year ( R2 was 0.0148 ) . St and ardised parameters of the frequency of vaccination and the school frequency of vaccination and the school year were -0.089 and -0.080 respectively . CONCLUSIONS --The preventive effects of influenza vaccine are not strong . There must be some unknown factors that affect the incidence of influenza . This vaccine is useful for pupils in the early school years who seem to have less resistance . All pupils should not be inoculated with the vaccine to reduce influenza transmission in the community or school Humoral and cell-mediated immunity ( CMI ) were evaluated in groups of school children after immunization with inactivated influenza virus vaccines .  A conventional biphasic strain ( H3ChN2Ch ) of Port Chalmers influenza virus ( X-41 ) , a recombinant influenza virus specific for the neuraminidase antigen ( Heq1N2Ch ) of Port Chambers influenza A virus ( X-42 ) , and a placebo were employed for immunization . The techniques of hemagglutination inhibition and neuraminidase inhibition were used to determine serum antibody titers . The CMI responses were evaluated by the in vitro lymphocyte transformation assay employing HavN2Ch , Heq1Neq1 , H3ChNeq1 , and H3ChN2Ch influenza A virus strains as stimulants . Specific HAI antibody and CMI responses to H3Ch were observed in X-41 but not in X-42 vaccinees . Specific anti-neuraminidase antibodies and CMI responses to N2Ch were manifested by both X-41 and X-42 vaccinees . Immunization with the placebo result ed in no influenza-specific immune responses . The CMI response was first detectable 10 days after immunization and then declined . These observations demonstrate the induction of CMI responses to the HA and NA influenza surface antigens after immunization . These responses may be important in antiviral immunity and the recovery from influenza infection A live , attenuated , recombinant influenza vaccine ( Alice strain ) administered intranasally was evaluated in high school students and compared with intranasal placebo and subcutaneous , inactivated , bivalent influenza vaccine . The Alice strain was antigenic , increasing the geometric mean titer ( GMT ) from a pre study level of 30.2 to a postvaccine level of 189.6 . The inactivated vaccine increased the GMT from 32.9 to 361.8 . There was no increase in the GMT among the placebo recipients . The Alice strain produced little reaction . With an antigenic , safe , acceptable , live , attenuated influenza vaccine available , immunization on a widespread basis should be considered 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 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 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 . Sample s 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 The authors conducted a 2-year , multicenter , double-blind , placebo-controlled efficacy field trial of live , attenuated , cold-adapted , trivalent influenza vaccine administered by nasal spray to children 15 - 71 months old . Overall , vaccine was 92 % efficacious at preventing culture-confirmed infection by influenza A/H3N2 and influenza B. Because influenza A/H1N1 did not cause disease during the years in which this study was conducted , the authors sought to determine vaccine efficacy and correlates of immune protection against experimental challenge with 107 TCID50 of attenuated H1N1 ( vaccine strain ) by intranasal spray . Prechallenge assessment s included serum hemaglutination-inhibiting ( HAI ) antibody and nasal wash IgA antibody to H1N1 . Vaccine was 83 % efficacious ( 95 % confidence interval , 60%-93 % ) at preventing shedding of H1N1 virus after challenge . Any serum HAI antibody or any nasal wash IgA antibody was correlated with significant protection from H1N1 infection as indicated by vaccine-virus shedding , and high efficacy against H1N1 challenge was demonstrated One hundred thirty-three children in San Antonio , Texas , received intramuscular injections of split-virus or whole-virus preparations of killed , monovalent influenza A/New Jersey/76 virus vaccine or placebo .  Thirty-three children were in the three- to five-year-old age group , and 100 were in the six- to 11-year-old group . A minimal antibody response occurred following injection of the first dose of vaccine . A second or booster dose that was administered approximately four months after the first dose result ed in a significant antibody response , even in children who developed a minimal or no detectable immune response to the initial dose . This improved immune response was observed following administration of two doses of either split-virus or whole-virus vaccines .  Reactions by the vaccine recipients on the whole were minimal . Reaction indices determined in both age groups after administration of the booster dose were usually less than those after the first dose . The high prevalence , 78 % overall , of antibodies to influenza A/Victoria/75 virus demonstrated that this virus was previously prevalent in our area Background . Recent studies indicate that influenza can be clinical ly important in otherwise healthy children . However , the interpretation of many studies is limited because of lack of laboratory confirmation of influenza-like illnesses . Therefore it is difficult to conclude whether the socioeconomic impact of influenza justifies vaccinating all children regardless of age or underlying chronic disorders . Methods . We prospect ively collected data from 3771 children younger than 14 years of age presenting to emergency departments or primary care pediatricians with symptoms of respiratory tract infection during the influenza season of 2001 to 2002 . Influenza infections were verified by virus culture or polymerase chain reaction . We additionally r and omized 303 children age 6 months to 5 years to receive either influenza vaccine ( n = 202 ) or no vaccination ( n = 101 ) before the influenza season . The socioeconomic impact of influenza was assessed for both the participating children and their household contacts . Results . Influenza was documented in 352 ( 9.3 % ) of the 3771 children . Compared with influenza-negative children , children with influenza had longer duration s of fever and absenteeism from day care or school ( P < 0.0001 ) . Further the numbers of medical visits , missed work or school days and the need for help at home to care for the sick children were higher among the household contacts of influenza-positive children ( P < 0.0001 ) . Influenza vaccination reduced significantly the direct and indirect influenza-related costs in healthy children and their unvaccinated family members . Conclusions . The findings of this study support a wider use of influenza vaccine in healthy children of all ages to reduce the socioeconomic burden of influenza on the community 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 r and omly 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 Fifty-two infants seronegative to or without prior infection with influenza type A viruses were enrolled in a study to evaluate reactogenicity and immunogenicity of three bivalent cold recombinant type A ( CRA ) and two trivalent inactivated influenza ( TI ) vaccines .  Controls consisted of infants receiving normal saline by nose drops ( Pli.n . ) or intramuscularly ( Pli.m . ) .  CRA and TI vaccines were monitored for local and systemic reactions after vaccination . Serum specimens obtained prior to and 6 weeks postvaccination were analysed for neutralizing antibody to influenza H1N1 and H3N2 viruses . CRA vaccines and Pli.n . recipients had similar numbers of acute respiratory infections and comparable rates of illnesses during the trial . Significantly fewer CRA vaccinees without an intercurrent viral infection had fever ( 0/16 versus 4/10 , p = 0.04 ) and cough ( 4/16 versus 9/10 , p = 0.002 ) than CRA vaccinees with a confirmed intercurrent viral infection . Recipients of TI vaccine and Pli.m . did not develop reactions at the injection site . For each of the CRA vaccines tested , a dominant CRA virus was identified . The dominant CRA viruses were isolated from a greater number of infants or for a longer duration than the non-dominant CRA viruses . All 14 non-dominant CRA viruses were recovered from infants within the first week after vaccination ; 24 of 77 dominant CRA viruses were recovered more than 7 days after vaccination . The immunogenicity of CRA vaccines was not affected by a confirmed intercurrent viral infection or low titres of influenza-specific antibody . ( ABSTRACT TRUNCATED AT 250 WORDS R and omized , 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 c and i date s for use in healthy infants and young children Respiratory syncytial virus ( RSV ) causes serious respiratory illness in preterm children with bronchopulmonary dysplasia . In a prospect i ve r and omized placebo-controlled trial , 21 children received one dose of PFP-2 ( purified fusion [ F ] protein ) vaccine or influenza vaccine ( placebo ) .  Children were followed for adverse reactions and RSV illness over two respiratory seasons . Sera were obtained for determination of IgG titers to RSV F protein and neutralizing antibody titers before and 1 , 6 , and 12 months after vaccination . Adverse reactions were few . Four-fold F protein rises occurred in 9 of 10 PFP-2 and 0 of 11 placebo recipients . Six PFP-2 recipients had low prevaccination neutralizing antibody titers ( < 1:450 ) ; all had 4-fold rises . By 12 months , F protein and neutralizing antibody titers in all 21 children were similar . RSV illness occurred in 6 of 11 placebo versus 1 of 10 PFP-2 recipients ( P = .06 ) ; 1 placebo child required hospitalization . PFP-2 vaccine appears safe and immunogenic and may protect children with bronchopulmonary dysplasia against serious RSV disease on reinfection 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 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 BACKGROUND Studies of  influenza vaccination in healthy children have not definitely answered the question of their efficacy . METHODS We have carried out a r and omized trial in a well selected population of healthy preschool children in Sardinia , Italy . During October 1995 , 344 children aged 1 to 6 years , were r and omly assigned to receive  influenza vaccine  ( n=177 ) or no treatment ( n=167 ) . Two doses of a trivalent subvirion vaccine , containing 15 mg 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 . RESULTS 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 ) CONCLUSIONS Influenza vaccine is safe and effective in healthy preschool children . However the favourable implication s of vaccination on disease rate in subsequent years have to be evaluated A placebo-controlled influenza vaccination trial was carried out on 374 children in the winter of 1967 - 68 . The children were r and omly vaccinated with 300 CCA of A2/Engl and /1/1966 , 300 CCA of A/equine 2/Miami/1963 , or with a placebo . During this winter an influenza outbreak occurred , caused by A2/Nederl and /1968 . The A2 vaccine yielded a protection rate of 58 % ( P = 0.02 ) and the A/equine 2 vaccine a rate of 19 % ( P = 0.33 ) . Serological data revealed that all influenza infections occurred in subjects who had a pre-epidemic  haemagglutination inhibition titre  below 150 . The antibody response against various human influenza A2 viruses and against the horse strain ( A/equine 2 ) is discussed 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 clinical ly . 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 Background . Influenza is an important cause of respiratory illness in children , but data on virologically confirmed influenza infections in children treated as out patients are limited . Methods . We carried out a prospect i ve cohort study of normal children younger than 13 years ( n = 1338 ) in the winter of 2000 to 2001 . During the study period of 32 weeks , the children were examined at the study clinic whenever they had fever or signs of respiratory infection . Nasal swabs were obtained during each episode of infection for determination of the viral etiology of the illness . Results . The overall attack rate of influenza in the cohort was 18.8 % . Influenza viruses were isolated from the children from the beginning of November 2000 through May 2001 . Virtually in each week between mid-November and the end of April ( a period of 24 weeks ) , influenza viruses accounted for at least 5 % of all respiratory infections in the children . During the peak of the epidemic , the percentage of influenza-positive children exceeded 20 % . Conclusions . This study confirms the important role of influenza as a cause of acute respiratory infections in children , even in winters of mild or moderate influenza activity . The study also shows that influenza viruses may circulate in the community at substantial levels much longer than previously thought We performed r and omized , double-blind , controlled trials to assess the safety and immunogenicity of an inactivated , Madin Darby Canine Kidney (MDCK)-derived cell line produced influenza vaccine in healthy adults ( 19 - 50 years ) , children ( 3 - 12 years ) and the elderly ( > or = 65 years ) . We studied three lots of cell culture-derived vaccine and one lot of licensed egg-derived vaccine in healthy adults ( n=462 ) , two lots of cell culture-derived vaccine and one lot of egg-derived vaccine in seniors ( n=269 ) , and one lot of each vaccine in children ( n=209 ) .  Adverse events were collected during the first 3 days post-immunization ; serum was collected before and 1 month after immunization . Rates of local and systemic adverse reactions were similar with both vaccines . An injection site adverse event rated at least moderate severity was reported by 21.9 % of children who received the egg-derived vaccine and 25.0 % of those who received the cell culture-derived vaccine . In healthy adults the proportions were 12.1 and 15.3 % , respectively and 6.7 and 6.3 % , respectively in seniors . Systemic events of at least moderate severity were 12.4 and 12.5 % in children , 19.8 and 13.6 % in healthy adults , and 14.1 and 9.7 % in seniors ; none of these differences were statistically significant . The antibody response against all three viruses was similar between the two vaccines . From 83 to 100 % of children , healthy adults and seniors achieved hemagglutination inhibition titers in excess of 40 post-immunization . We conclude that the cell culture-derived vaccine was safe and immunogenic in children , healthy adults and seniors Reactivity and immunogenicity of two inactivated , zonally purified , ether-extracted , influenza A/New Jersey/X-53 subunit virus vaccines were studied in 103 children three to 18 years of age . Children aged nine years of younger received doses of 100 or 200 chick cell-agglutinating ( CCA ) units , and those older than nine years received doses of 200 or 400 CCA units . Vaccines were given intramuscularly . Two doses were given at intervals of four weeks . The vaccines were minimally pyrogenic , causing only two instances of temperatures of greater than 100.0 F. Other systemic reactions were observed infrequently . Tenderness at the site of injection occurred relatively frequently but was of no medical consequence . The geometric mean titers of homologous antibody , which ranged from 1:52 to 1:75 after administration of two doses , were statistically equivalent in all treatment groups . Titers of antibody of greater than or equal to 1:40 to the influenza A/New Jersey/8/76 virus strain were achieved by 88 % of the vaccinees . We concluded that two doses of ether-extracted , subunit influenza A/New Jersey/X-53 virus vaccine were well tolerated and , when given at least four weeks apart , were serologically effective for immunization of children aged three to 18 years BACKGROUND 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 . METHODS 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 r and omly 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 . RESULTS 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 . CONCLUSION We conclude that inactivated influenza vaccine reduces the incidence of influenza A virus infection in 2 - 6-year-old children BACKGROUND Trivalent formulations of an experimental , cold-adapted , intranasal influenza ( CAIV ) vaccine have been shown to be safe , immunogenic and efficacious in young children . METHODS We evaluated the safety and immunogenicity of three consistency lots of CAIV in children 12 to 36 months of age r and omized 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 . RESULTS 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 . CONCLUSIONS Each consistency lot of CAIV is as or more immunogenic than a lot used in a large efficacy trial OBJECTIVE To provide additional information on the safety of trivalent , cold-adapted influenza vaccine ( CAIV-T )  in children . METHODS Children 15 to 71 months of age were enrolled in a multicenter , prospect i ve , r and omized , double-blind , and placebo-controlled trial to receive by nasal spray CAIV-T or placebo . In year 1 ( 1996 - 1997 ) , 1314 were enrolled in the 2-dose cohort and 288 were enrolled in the 1-dose cohort . In year 2 ( 1997 - 1998 ) , 1358 of the original participants received 1 dose of vaccine or placebo according to their original treatment group assignment . In year 3 ( 1998 - 1999 ) and year 4 , the trial continued as an open-label safety trial of CAIV-T. A total of 642 and 549 children enrolled in years 3 and 4 , respectively , received their third and fourth sequential annual doses of CAIV-T. Measured were 1 ) the occurrence of specific respiratory , gastrointestinal and systemic symptoms , unexpected symptoms ( not specified in the diary card ) , and use of medications within the first 10 days after vaccination ; 2 ) the occurrence of an acute illness and use of medication within 11 to 42 days after vaccination ; and 3 ) the occurrence of serious adverse events within 42 days after vaccination . RESULTS The adjusted odd ratios of specific respiratory and gastrointestinal symptoms during the 10 days after vaccination were determined in years 1 and 2 . Runny nose or nasal congestion , vomiting , muscle aches , and fever were significantly associated with the first dose of CAIV-T. With the second dose , runny nose was the only symptom that was associated with CAIV-T. In year 2 , CAIV-T did not cause excess in any of the specific respiratory and gastrointestinal symptoms . In years 3 and 4 , specific respiratory and gastrointestinal symptoms were comparable to that observed in year 2 . A  CAIV-T-associated symptom was most likely to occur on day 2 with the first dose of vaccine . The occurrence of unexpected symptoms was primarily of the gastrointestinal system . Approximately 6 % of CAIV-T and 3.6 % of placebo recipients had a gastrointestinal symptom .  CAIV-T seemed to be associated with a mild excess in abdominal pain and vomiting only with the first vaccine dose . A statistically significant increase in the use of analgesics/antipyretics was detected only with the first dose in CAIV-T vaccinees compared with placebo recipients ( 23.5 % vs 16.6 % ) . Between days 11 and 42 , CAIV-T use was not associated with an excess of illness , otitis media , or use of medication . None of the 6 serious adverse events in CAIV-T recipients in years 1 to 4 was attributed to the vaccine . CONCLUSIONS CAIV-T was safe in children . Mild respiratory , gastrointestinal , and systemic symptoms of short duration were observed in a minority of children and primarily with the first vaccine dose . Sequential annual doses of CAIV-T were well tolerated High concentrations of split-product vaccine ( SPV ) are more immunogenic than lower concentrations . These studies were verified with another influenza strain , B/Singapore/22/79 . Two ether-treated SPVs were compared in 80 children and young adults . The vaccine strains were influenza A/Bangkok/79 , A/Brazil/78 , and B/Singapore/79 ;  44 patients received a high-dose SPV containing 7 , 7 and 60 micrograms each of the respective hemagglutinins ( HA ) and 36 received a st and ard dose SPV containing 7 , 7 , and 7 micrograms of HA , respectively . Among persons initially seronegative by hemagglutination inhibition ( HAI ) tests , the geometric mean titer ( GMT ) in 15 recipients of one high dose was 97 vs GMT of 37 in 18 recipients of one st and ard dose ( P less than .05 ) . Furthermore , 87 % of high-dose recipients had HAI titer greater than or equal to 40 vs 44 % of st and ard dose recipients . In initially seropositive persons , GMT in 29 recipients of one high dose was 170 vs GMT of 84 in 18 recipients of one st and ard dose ( P less than .05 ) . Immune response to the other two virus strains was comparable for the two vaccines . The reaction index for the high dose vaccine was 0.70 vs 0.45 for the st and ard dose ( P = NS ) . An A/Bangkok epidemic struck the New York metropolitan area . The attack rate in unvaccinated matched sibling control subjects was 35 % ( 15/43 ) . There were no vaccine failures . In conclusions , in the small number of patients studied , a 60-micrograms HA dose of B/Singapore/79 was significantly more immunogenic than a st and ard 7-micrograms HA dose without an increase in reactogenicity Forty-three high-risk preterm children received either one of three doses of purified hemagglutinin antigen ( HA ) ( 7.5 micrograms/0.25 ml , 22.5 micrograms/0.25 ml or 67.5 micrograms/0.25 ml ) or st and ard split product vaccine ( ST ) ( 22.5 micrograms/ml dose ) over the 1990 - 1991 influenza season . Components for all vaccines included A/Shanghai 16/89 , A/Taiwan 1/86 and B/Yamagata 16.88 . Sera for antibody was drawn before , 6 weeks and 4 months after the first vaccine dose . The study was r and omized and blinded . All children received two 0.25 ml doses of vaccine 4 weeks apart . No significant local or systemic reactions occurred . Six weeks after the first dose , children receiving ST vaccine had significantly higher seroconversion rates to A/Shanghai ( p = 0.03 ) and to A/Taiwan ( p = 0.01 ) than did those receiving equivalent HA vaccine . However , seroconversion rates were significantly higher for those children receiving the highest HA dose . All four vaccine groups responded poorly to B/Yamagata .  Geometric mean titres were low for all groups and declined over 4 months . These results suggest that the equivalent dose of HA vaccine offers no advantage over ST vaccine in the immunization of high-risk preterm children ABSTRACT The objective of this study was to compare the immunogenicity and safety of a single-dose regimen and a two-dose regimen of a trivalent virosome influenza vaccine ( Inflexal Berna V ) with those of a trivalent subunit influenza vaccine ( Influvac ) in children and adolescents with cystic fibrosis ( CF ) . In an open , r and omized , multicenter study with parallel groups , 11 young children with CF ( 1 to 6 years old ) and 53 older children and adolescents with CF ( > 6 years old ) were r and omly assigned to one of the following immunization regimens : virosome vaccine at 0.5 ml on study day 0 or 0.25 ml on days 0 and 28 or a st and ard regimen of subunit vaccine , i.e. , 0.5 ml on day 0 for older children and 0.25 ml on days 0 and 28 for younger children . Safety assessment s , i.e. , recording of systemic and local adverse events ( AEs ) and vital signs , were made for a 5-day observation period after each immunization . Hemagglutination inhibition ( HI ) titers were determined at baseline and 4 weeks after the single-dose and the two-dose immunizations , respectively . Immunogenicity was assessed according to the criteria of the European Agency for the Evaluation of Medicinal Products ( EMEA ) . Both vaccines induced comparable HI antibody titers . Seroconversion ( ≥4-fold rise in HI antibody titers , reaching a titer of ≥1:40 ) was achieved in 41 to 100 % of the participants . Seroprotection ( HI titer , ≥1:40 ) and a > 2.5-fold increase in geometric mean titers were achieved in 100 % of the participants . Thus , all three EMEA requirements for influenza vaccine efficacy were met by all treatment groups and for both vaccines . The virosome vaccine , when administered as a single dose , seemed to induce superior immunogenicity compared with the st and ard pediatric two-dose regimen . Totals of 42 and 57 % of vaccinees receiving virosome and subunit vaccines , respectively , reported at least one local AE ( predominantly pain ) . Totals of 84 and 71 % of subjects receiving virosome and subunit vaccines , respectively , complained in response to questions of at least one systemic AE ( mainly cough , fatigue , coryza , or headache ) . The majority of events were mild or moderate and lasted 1 or 2 days only . No obvious relationship was found between AE reporting rate and vaccine formulation , age group , or dose regimen . The relatively high AE reporting rate seemed to be partly related to the symptomatology of the underlying CF disease . In summary , the virosome and subunit vaccines induced in both age groups and against all three influenza strains an efficient immune response and were well tolerated by the children and adolescents with CF OBJECTIVE To evaluate the efficacy of currently used inactivated influenza vaccine during a severe epidemic caused by antigenically drifted influenza type A(H3N2 ) and well-matched type B viruses during the 1992 - 1993 season . DESIGN Prospect i ve nonr and omized controlled trial . SETTING An urban general hospital pediatric asthma clinic in Japan . PARTICIPANTS A total of 137 children with moderate to severe asthma ( mean age , 7.0 years ; range , 2 to 14 years ) . INTERVENTION Eighty-five children received trivalent split-antigen vaccine containing A/Beijing/352/89 ( H3N2 ) and B/Bangkok/163/90 ( B/Panama/45/90-like strain ) . Fifty-two were unvaccinated . MAIN OUTCOME MEASURES Protection against infection was determined using hemagglutination inhibition test and virus isolation . Clinical efficacy was estimated based on febrile episodes with antibody rise or virus isolation . RESULTS Although marked antigenic drift in hemagglutinin was demonstrated in the epidemic virus ( A/Beijing/32/92-like strain ) , the protection against influenza type A(H3N2 ) infection was 67.5 % ( P < .01 ) . The protection against influenza type B infection was 43.7 % ( P < .01 ) , although the epidemic influenza type B viruses were antigenically almost identical to the vaccine strain . Inactivated vaccine was not effective for protection against influenza type B infection in children younger than 7 years . High clinical effectiveness was demonstrated in children at least 7 years of age during the epidemic . CONCLUSIONS Our data suggest that current inactivated vaccine is highly effective for protection against influenza type A(H3N2 ) virus infection regardless of antigenic drift . In contrast , the protective efficacy obtained by vaccination may not be sufficient against influenza type B virus infection , and especially in young children , it does not offer protection 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 ) BACKGROUND 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 . METHODS 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 r and omly 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 . RESULTS 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 . CONCLUSIONS Inactivated influenza vaccine did not reduce the attack rate of influenza A infection in 6 - 24 month old children A safe and effective influenza vaccine is needed to prevent serious influenza illness in infants younger than 6 months of age . The purpose of this study was to determine whether two doses of the cold‐adapted ( ca ) influenza A reassortant vaccine would be safe and immunogenic in this age group . In the first part of this study , infants received two doses of 105 or 108 50 % tissue culture‐infectious dose ( TCID50 ) of the ca influenza vaccine separately from routine immunizations . In the second part of this study two 106 TCID50 doses of the ca influenza vaccine were given with routine immunizations at 2 and 4 or 2 and 6 months of age . The ca influenza vaccine was well‐tolerated by participants in both parts of this study . Two doses of the ca influenza vaccine were immunogenic in infants who received them separately from routine immunizations ; 83 % of vaccinees developed protective titers of serum hemagglutination‐inhibition ( HAI ) antibody . In contrast , when the ca vaccine was administered with routine immunizations , protective HAI antibody titers were induced in only 20 % of those immunized at 2 and 4 months of age and 50 % of those immunized at 2 and 6 months of age . There were no statistically significant associations between HAI antibody response to  ca influenza vaccination and dose schedule , presence of passively acquired maternal HAI antibody , ethnic group or breast‐feeding status . Young age at the time of first immunization , however , appeared to correlate with decreased response to the hemagglutinin antigen of the influenza A virus . Further studies are needed to determine whether a larger dose of vaccine ( 107 TCID50 ) could be used safely to improve the serum antibody response to influenza in very young infants The boys of Christ 's Hospital experienced outbreaks of influenza A in 1972 ( A/Engl and /42/72 ) , in 1974 ( A/Port Chalmers ) , and in 1976 ( A/Victoria ) . In each outbreak , the protective effect of inactivated influenza-A vaccine was limited to those boys , not already immune , who were vaccinated for the first time with the most up-to- date strain . Revaccination with the same strain did not increase the degree of protection , and revaccination with a later strain did not afford protection against subsequent challenge . The cummulative attack-rate in the three outbreaks was similar in all groups irrespective of vaccination history . These observations suggest that annual revaccination with inactivated influenza-A vaccine confers no long-term advantage CONTEXT 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 . OBJECTIVE To evaluate the effectiveness of inactivated influenza vaccine in preventing AOM in children aged 6 to 24 months . DESIGN , SETTING , AND PATIENTS R and omized , 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 . INTERVENTION Two doses ( 0.25 mL each ) of inactivated trivalent subvirion influenza vaccine or placebo were administered intramuscularly approximately 4 weeks apart . MAIN OUTCOME MEASURES 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 re sources . RESULTS Of the 66 children in the vaccine group from whom serum sample s 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 re sources . 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 . CONCLUSION 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 re sources A r and omized , blinded , pilot study of influenza vaccine administered to children attending day care centers was conducted during the 1996 - 1997 winter . Vaccine efficacy in preventing serologically proven influenza virus infection was 0.45 ( 95 % confidence limit [ CL ] : -0.02 , 0.69 ) for influenza B and 0.31 ( 95 % CL : -0.95 , 0.73 ) for influenza A(H3N2 ) . For both influenza A(H3N2 ) and B , children without preexisting hemagglutination inhibition ( HI ) antibody to these antigens had lower antibody responses to vaccine , were less likely to develop a serological response , and were more likely to develop serological evidence of influenza infection . Although there were no reductions in respiratory or febrile respiratory illnesses among all vaccinated children , there was a trend for reductions in such illnesses among vaccinated children with preexisting HI antibodies to influenza A(H3N2 ) and B. Therefore , immunologic priming in young children may be important for vaccine response and for protection against infection . Larger studies are needed in other influenza seasons to assess vaccine efficacy and clinical effectiveness 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 the spring of 1975 an outbreak of influenza associated with influenza virus A/Scotl and /840/74 virus occurred in a residential college where the previous autumn some students had been immunised with a single intranasal dose of Recombinant WRL 105 ( H3N2 ) ( A/Okuda/57xA/Finl and /4/74 ) strain live attenuated infleunza virus vaccine . During the outbreak none of seven students who had been vaccinated suffered from influenza but an influenzal illness did occur in four of eleven who had received  placebo  nose drops only . Fourfold or greater increases in hemagglutinating inhibiting antibodies between sera collected three weeks after vaccination and those collected three months later following the influenza epidemic were found in one of seven vaccinated and in nine of eleven placebo treated subjects and also in one student who had received neither vaccine nor placebo ; a difference in serological response which is statistically significant ( p less than 0.01 ) . Thus recombinant WRL 105 live attenuated vaccine was found to have conferred substantial protection against a current wild strain of influenza A virus without causing any appreciable untoward reactions 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 r and omly 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 Abstract 98 volunteers were vaccinated with formalin-inactivated influenza-B virus intramuscularly or with living influenza-B virus intranasally . They , and a group of control volunteers , were subsequently challenged with live virus administered intranasally . 71 % of those given killed vaccine developed an antibody response but 15 % were infected on challenge . 51 % of those who had received live virus had an antibody response and 2 % were infected on challenge . Vaccination also reduced the frequency of clinical reactions . The living vaccine used in this trial produced too many reactions to be used on a large scale 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 Immunogenicity and efficacy of aerosol inactivated split influenza virus vaccines , which are threefold the strength of the vaccines for parenteral use , and cold-adapted reassortant live influenza virus vaccines were evaluated . Mucosal immune responses were evaluated by quantifying specific IgA antibody of the nasal swab solution , and systemic immune responses were evaluated by determining serum haemagglutination inhibition antibody levels . Efficacy of the aerosol inactivated vaccine was evaluated by a challenge test using live vaccine virus . It was concluded that mucosally administered inactivated influenza virus vaccine stimulated systemic and mucosal immune responses more strongly than live influenza virus vaccine and manifested a much stronger booster effect than live vaccine . Mucosal administration of inactivated influenza virus vaccine was effective in preventing infection by live vaccine virus Abstract A trial of inactivated influenza vaccine containing the A/Hong Kong/68 strain was made in 800 boys in a boarding-school starting in 1970 . The boys had serum sample s withdrawn for antibody estimations and were allocated at r and om to vaccine and control groups . During an outbreak of influenza A due to the A/Engl and /42/72 strain , all boys with clinical influenza reported to the medical officer and the diagnosis was confirmed by laboratory examination . The vaccine was shown to confer substantial protection against the new virus strain . The presence of haemagglutinating ( H.I. ) antibody to either strain 6 weeks before the outbreak was associated with protection against influenza . In boys with H.I. antibody to A/Hong Kong/68 virus the attack-rate was 6 % , compared with 25 % in boys with no H.I. antibody to either virus strain . No influenza occurred in boys known to have H.I. antibody to the A/Engl and /42/72 strain . Three-quarters of the boys in whom A/Hong Kong/68 H.I. antibody had been naturally acquired developed A/Engl and / 42/72 H.I. antibody after vaccination . In contrast , the development of A/Engl and /42/72 H.I. antibody was less frequent after revaccination of boys in whom the A/Hong Kong/68 H.I. antibody had been induced by vaccination . A vaccine prepared from the A/Hong Kong/68 strain conferred substantial protection despite the recent antigenic shift of the influenza virus Influenza is a major cause of illness . We have assessed the safety , efficacy , and effectiveness of CAIV-T vaccine . A two year , multicenter , double-blind , placebo-controlled , efficacy field trial in pre-school aged children was conducted ; 1602 enrolled in Year One and 1358 ( 85 % ) returned in Year Two . In both study years combined , the overall vaccine efficacy against culture-confirmed influenza was 92 % ( 95 % CI : 88 , 94 ) . The vaccine efficacy was 95 % ( 95 % CI : 62 , 99 ) against lower respiratory illness , 94 % ( 95 % CI : 90 , 96 ) against febrile illness and 96 % ( 95 % CI : 88 , 99 ) against otitis media associated with culture-confirmed influenza . A multicenter , double-blind , placebo-controlled , effectiveness field trial was conducted in 4561 working adults aged 18 to 64 years .  Episodes and days of febrile illness ( FI ) , severe febrile illness ( SFI ) , febrile upper respiratory illness ( FURI ) , work loss , and health care use were assessed . Vaccination significantly reduced the numbers of SFI , 18.8 % reduction ( 95 % CI : 7 , 29 ) , and FURI , 26.3 % reduction ( 95 % CI : 13 , 33 ) ; and led to fewer days of illness ( 22.9 % reduction for FI , 27.3 % reduction for SFI ) , fewer days of work lost ( 17.9 % reduction for SFI , 28.4 % for FURI ) , and fewer days of health care provider visits ( 24.8 % for SFI , 40.9 % for FURI ) . Prescription antibiotics and over-the-counter medications were also reduced . The vaccine was generally safe and well tolerated with no vaccine related serious adverse events . LAIV represents an additional important option for the control of influenza This study was design ed to compare the safety and immunogenicity of a trivalent live-attenuated , cold-adapted influenza vaccine ( CAIV-T ) blended and filled at two different manufacturing facilities ( Medeva and Aviron-PA ) . The vaccines contained approximately 10(7 ) TCID(50 ) ( median tissue culture infectious dose ) of each of the three recommended 1997 - 1998 influenza vaccine components , A/Shenzhen/227/95 ( H1N1 ) ( A/Bayern/7/95 (H1N1)-like strain ) , A/Wuhan/359/95 ( H3N2 ) , and B/Ann Arbor/1/94 ( B/Beijing/184/93-like strain ) . Two hundred and twenty-five healthy Australian children aged 12 - 42 months were enrolled and r and omized in a 3:2 ratio to receive CAIV-T blended and filled either at Medeva or at Aviron-PA . Two doses of CAIV-T were given 4 - 6 weeks apart as an intranasal spray . Three blood specimens were collected ( immediately before doses one and two , and 28 + /- 5 days following dose two ) for measuring hemagglutination inhibition ( HAI ) antibody responses . Adverse events occurring within 10 days and serious adverse events occurring within 42 days were collected . Serum HAI antibody levels were measured against the three vaccine strains . Equivalent immunogenicity between the two vaccine groups was pre-specified as : ( 1 ) within 20 % difference in seroconversion rates ( HAI titers > or = 4-fold rise ) ; and ( 2 ) within 4-fold difference in the 90 % confidence interval of geometric mean titer ratio . Among 10 pre-specified adverse events , only vomiting had significantly different incidence rates in the two vaccine groups following dose one ( 3 % versus 13 % , P = 0.01 ) but the difference disappeared following dose two ( 4 % versus 4 % ) . Differences in seroconversion rates following dose two between the two vaccine groups in pre-vaccination seronegative children were all < 20 % for the three vaccine strains ( 16 % for H1N1 , 0 % for H3N2 , and 0 % for B ) . The results indicate that CAIV-T blended and filled in the two facilities had equivalent profiles of safety and immunogenicity 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 Single doses ( 50 , 100 , or 200 chick cell-agglutinating [ CCA ] units ) of split-product or whole-virus ( 50 or 100 CCA units ) , monovalent inactivated A/New Jersey/8/76 ( Hsw1n1 ) virus vaccine or placebo were given to healthy children aged three to five years in Maryl and . Split-product vaccine was nonreactogenic but also virtually nonimmunogenic . Lower doses of whole-virus vaccine ( 50 CCA units of Merck , Sharp and Dohme [ West Point , Pa. ] and 50 or 100 CCA units of Merrell-National Laboratories [ Cincinnati , Ohio ] vaccine ) were mildly reactogenic ( approximately 25 % of the children had low- grade fevers of 100 F-101 F ) . These dosage levels of whole-virus vaccine  stimulated titers of greater than or equal to 1:20 in 68 % and titers of greater than or equal to 1:40 in 37 % of the children . Two inoculations of whole-virus vaccine ( primary immunization followed by a booster one month later ) were tolerated and induced titers of greater than or equal to 1:80 in 100 % of the children We report the safety and antigenicity of influenza A vaccines  in seronegative children one to seven years of age . A natural H1N1 challenge that occurred shortly after completion of the vaccination program permitted an evaluation of efficacy . Twenty-eight subjects were inoculated with live cold-adapted ( ca ) influenza A/Washington/897/80 ( H3N2 ) , 29 with ca influenza A/California/10/78 ( H1N1 ) , 24 with inactivated whole-virus influenza A/Bangkok/79 ( H3N2 ) , and 30 with a placebo . The ca vaccines were well tolerated , whereas the inactivated vaccine caused adverse reactions in about one-third of the children . Fifty-seven percent of the ca H1N1 recipients showed serological responses , contrasted with 84 % and 100 % of subjects receiving the ca or inactivated H3N2 vaccines , respectively . None of the 16 children with induced H1N1 antibody developed clinical ly apparent influenza-like illness , compared with eleven of the 51 initially seronegative children who did not receive the ca H1N1 vaccine and with four of the 12 who failed to respond . Results of the efficacy field trial suggest protection against infection and symptomatic illness in children inoculated with ca H1N1 , despite its failure to stimulate high levels of hemagglutinin-inhibiting antibody The performance of two doses of cold-adapted live attenuated vaccine versus one dose of whole-virus inactivated vaccine was compared in 8 - 15-year-old schoolchildren in two schools in Moscow , Russia , during the winter of 1987/88 . Both vaccines gave rise to low frequencies of associated febrile or systemic reactions , but the inactivated vaccine , delivered by jet injector , did cause small local reactions in about half of the children . Immunogenicity was higher for both vaccines in antibody-free children , and higher levels of serum antibody were detected following use of inactivated vaccine . During the winter , influenza A ( H3N2 ) and influenza B viruses circulated in Moscow . A clear outbreak of ( H3N2 ) virus occurred in both schools , and infections with type B virus also occurred in one school . The influenza A/Philippines/2/82 ( H3N2 ) component of both vaccines exhibited protective efficacy of about 40 % ( p < 0.05 ) against serologically proven infection caused by the antigenically drifted A/Sichuan/2/87 (H3N2)-like epidemic viruses in one school . In another school where illnesses associated with antibody rise were documented , efficacy was seen for both vaccines in reduction of illnesses , and of illnesses with serological evidence of infection , but statistical significance was not achieved 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 The authors provide an analysis of data from a two-year ( 1996 - 1998 ) , multicenter ( ten US cities ) , double-blinded , placebo-controlled influenza vaccine trial in children . The vaccine was the trivalent cold-adapted influenza vaccine . Estimates are made of the vaccine efficacy for susceptibility to culture-confirmed influenza ( VE(S ) ) while taking inter-center variability in the risk of infection into account . Our overall estimate of VE(S ) against influenza is 0.92 ( 95 % confidence interval ( CI ) 0.89 - 0.94 ) . In addition , for the second year , although the vaccine contained antigen for A/Wuhan-like ( H3N2 ) , the estimated VE(S ) for epidemic variant A/Sydney-like ( H3N2 ) was 0.89 ( 95 % CI 0.81 - 0.94 ) . Thus , the vaccine showed a high degree of protection against a variant not closely matched to the vaccine antigen . With regard to natural immunity , an influenza A infection in the first year reduces the estimated risk of an influenza A infection in the second year by a factor of 0.88 ( 95 % CI 0.21 - 0.98 ) . When comparing year 1 to year 2 , there is a negative correlation of -0.50 in the center-specific attack rates in the placebo groups . This is consistent with the theory that natural immunity provides overall community protection to children . The authors argue that mass vaccination of 70 % of the children with the cold-adapted influenza vaccine  could provide substantial protection to the community at large Influenza epidemics are an important cause of morbidity and mortality throughout the world . Current recommendations from Health Authorities emphasize annual immunization of people who are particularly at risk from an influenza virus infection ; however , vaccination of working adults and of school children also has been shown to provide public health benefits . To give it a more advantageous reactogenicity profile than the diethylether-split influenza vaccines available previously , a split virion influenza vaccine has been produced with TritonX-100 . In a series of clinical trials , Aventis Pasteur ( formerly , Pasteur Mérieux Connaught ) tested both the safety and immunogenicity of this TritonX-100-split virion influenza vaccine in 566 subjects ( 42 children , 296 adults , and 228 elderly adults ) during three influenza seasons ( 1991 , 1993 , and 1995 ) . The TritonX-100-split virion vaccine was well tolerated : no serious adverse events were recorded during the 21 days following immunization . Among the local reactions observed , mild pain , redness , or in duration at the injection site were the most frequently reported . Fever ( 38.0 to 38.5 degrees C ) was noted in five adults or elderly subjects ( 1 % ) , and in two children ( 5 % ) . Immunogenicity was determined by measuring serum haemagglutinin antibody titres specific to each vaccine virus strain . In each of the three vaccination campaigns , the TritonX-100-split virion influenza vaccine fulfilled the Notes for Guidance on Harmonization of Requirements for Influenza Vaccines outlined by the Committee for Proprietary Medicinal Products ( CPMP ) of the European Community for an influenza virus vaccine ( i.e. , seroprotection , seroconversion , or increase of geometric mean titre ) in all age groups Background . Influenza is a common and potentially serious infection in children . Although there is interest in broadening the use of influenza vaccine in healthy children , there are few large , r and omized , controlled trials that evaluate the safety and efficacy of inactivated vaccine in the pediatric population . Methods . From 1985 through 1990 a r and omized , controlled trial of cold-adapted and inactivated vaccines for the prevention of influenza A disease was conducted at V and erbilt University , and the cumulative results from this trial in patients of all ages have been previously published . We reanalyzed the data from this trial in the subset of patients who were younger than 16 years at the time of their participation . We determined vaccine safety , immunogenicity and efficacy , based on culture-positive illness and seroconversion , in this subset of patients . Results . During the 5 years of the study , 791 children younger than 16 years received 1809 doses of either inactivated or cold-adapted vaccine or placebo . The vaccines were well-tolerated , and there were no serious reactions . Inactivated trivalent influenza vaccines were 91.4 and 77.3 % efficacious in preventing symptomatic , culture-positive influenza A H1N1 and H3N2 illness , respectively . The efficacy of the inactivated vaccine based on hemagglutination inhibition assay seroconversion was 67.1 and 65.5 % , respectively , for H1N1 and H3N2 serotypes . Conclusions . Inactivated trivalent influenza A vaccines are well-tolerated and efficacious in the prevention of influenza A disease in children 1 to 16 years old 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 r and omized , 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 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 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 ) 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 Clinical and serologic responses to inactivated influenza virus vaccines were studied in 444 children in Los Angeles under doubld-blind , placebo-controlled protocol s. One- and two-dose regimens employing monovalent ( A/New Jersey/76 ) and bivalent ( A/New Jersey/76-A/Victoria/75 ) vaccine were studied in separate trials . In a single dose , whole-virus vaccines were more potent than split-product vaccines as primary inducers of immunity against influenza A/New Jersey/76 virus . Split-product vaccines were better tolerated clinical ly and , after two-dose regiments , produced rates of seroconversion ( greater than 90 % ) against A/New Jersey/76 virus comparable to those produced by two doses of whole-virus vaccines . Analysis of heterotypic antibody responses induced by monovalent A/New Jersey/76 vaccines revealed only slight increases in antibody against influenza A/Victoria/75 virus . After vaccination with bivalent vaccines , levels of antibody against influenza A/Victoria/75 virus were significantly higher in subjects who received high doses of split-product vaccines than in subjects who received whole-virus vaccines An attenuated influenza virus vaccine ( not sensitive to equine serum ) was administered intranasally by nose drops and was effective in stimulating significant rises in both serum and nasal antibody and in protecting against subsequent challenge with virulent influenza virus . Vaccine virus was not transmitted from immunized volunteers to a control group .  Clinical symptoms after immunization were very mild but were significantly more frequent in vaccinees than in members of the control group Fifty children , 6 months to 2 years of age , were vaccinated intranasally with a trivalent preparation containing 10(6 ) TCID50 each of H1N1 and H3N2 and 10(4 ) ( n = 14 ) or 10(6 ) ( n = 36 ) TCID50 of B live , attenuated , cold-adapted ( ca ) influenza strains . The same doses were administered as monovalent vaccines to 69 comparably aged children . Forty-five controls were given placebo .  No clinical ly significant adverse reactions to vaccines were observed . Of children seronegative to H1N1 or H3N2 , > or = 90 % were infected by these vaccine strains . Trivalent vaccine containing 10(4 ) TCID50 of B infected only 27 % of children seronegative to B ( 3/11 ) , which was markedly reduced from the 88 % infection rate ( 7/8 ) following monovalent B vaccine of the same dose ( P = .02 ) ; increasing the B dose to 10(6 ) TCID50 increased the infection rate to 81 % ( 21/26 ) . Replication of ca influenza viruses in tissue culture matched vaccine responses . Trivalent ca influenza vaccines can be formulated that are safe and immunogenic in young children OBJECTIVE To determine if the use of influenza vaccine in children in day care decreases the incidence of otitis media during the influenza season . DESIGN Prospect i ve cohort study . SETTING Eight day-care centers in North Carolina . PARTICIPANTS One hundred eighty-six children aged 6 to 30 months . INTERVENTION Half the participants received trivalent subvirion influenza virus vaccine . MEASUREMENTS Acute otitis media ( AOM ) and serous otitis media ( SOM ) were assessed biweekly from mid-November 1993 to mid-March 1994 by visual and tympanometric examinations performed by " blinded " observers . The winter season was divided into three periods-before , during , and after influenza season-- and the number of children with AOM or SOM during each period was determined . Unadjusted and adjusted odds ratios ( ORs ) were computed , while controlling for race and sex using logistic regression methods . RESULTS Influenza vaccine was protective against AOM ( OR = 0.69 , 95 % CI , 0.49 - 0.98 ) during the influenza season . Although there may have been some protection against SOM ( OR = 0.75 , 95 % CI , 0.54 - 1.02 ) statistical significance was not achieved . Myringotomy tubes were also significantly protective against AOM and SOM during all three time periods , with ORs between 0.34 and 0.52 , but the greatest protection was seen during the influenza period . CONCLUSIONS Influenza vaccination of 6- to 30-month-old children in day care was associated with a decreased incidence of otitis media during the influenza season . Myringotomy tubes protected against AOM and SOM during all 16 weeks monitored A double-blind , r and omized controlled trial over 5 years compared the safety , immunogenicity , and efficacy of cold-adapted and inactivated influenza A vaccines in 5210 normal subjects . Both vaccines were well tolerated . Inactivated vaccine significantly increased hemagglutination inhibition antibody titers . Significant titer rises were also noted after cold-adapted vaccine but of lesser magnitude than with inactivated vaccine . The efficacy of inactivated vaccine in preventing culture-positive influenza was 76 % ( 95 % confidence interval [ CI ] , 58%-87 % ) for H1N1 disease and 74 % ( 95 % CI , 52%-86 % ) for H3N2 ; for cold-adapted vaccine , 85 % ( 95 % CI , 70%-92 % ) and 58 % ( 95 % CI , 29%-75 % ) , respectively . The efficacy of inactivated  vaccine in preventing a four-fold rise in antibody titer over the influenza season was 69 % ( 95 % CI , 61%-76 % ) for H1N1 and 73 % ( 95 % CI , 65%-79 % ) for H3N2 ; for cold-adapted vaccine , 54 % ( 95 % CI , 44%-62 % ) and 32 % ( 95 % CI , 17%-44 % ) , respectively . Cold-adapted and inactivated influenza vaccines are safe and effective for preventing influenza A disease This paper presents the methodology of the multicenter collaborative clinical trials that evaluated monovalent A/New Jersey/76 influenza virus vaccines in healthy children six months to 18 years of age and describes the experience involving 264 children six months to 10 years of age in Omaha , Nebraska . Results indicated that chidren can be safely and effectively immunized with carefully adjusted two-dose regimens that take into account the differences between split-virus and whole-virus vaccines and between the two whole-virsu vaccines OBJECTIVE To assess the safety of live , attenuated influenza vaccine ( LAIV ) administered to relatively asymptomatic or mildly symptomatic HIV-infected children and non-HIV-infected children . METHODS Twenty-five non-HIV and 24 HIV-infected children ( CDC Class N or A1,2 ) were enrolled into this double blind , placebo-controlled study . Children were r and omized within each HIV status group to one of two dosing regimens : Regimen 1 , Dose 1 = LAIV , Dose 2 = placebo , Dose 3 = LAIV ; or Regimen 2 , Dose 1 = placebo , Dose 2 = LAIV , Dose 3 = LAIV . Study doses were separated by 28 to 35 days . Reactogenicity events within 10 days and adverse events within 28 to 35 days after each study dose were recorded . Blood HIV RNA concentrations , CD4 counts and CD4 % were measured throughout the study on HIV-infected children .  Quantitative influenza cultures were performed on nasal aspirates collected periodically from all children up to 28 to 35 days after each study dose . Influenza isolates were assessed for retention of the temperature-sensitive phenotype . Serum influenza HAI antibodies were measured before and after each LAIV vaccination . RESULTS No significant differences were found in rates of reactogenicity events and vaccine-related adverse events after placebo or the first dose of LAIV within each HIV status group , nor were differences found between HIV-infected and HIV-uninfected children after each dose of LAIV . Overall none of the HIV-infected children experienced a significant  LAIV-related serious adverse event or influenza-like illness , making the one sided 95 % CI of such a serious event occurring after LAIV 0 to 12 % . No significant changes in geometric mean HIV RNA concentrations , CD4 counts or CD4 % or prolonged or increased quantity of LAIV virus shedding occurred in HIV-infected children after receiving either dose of LAIV . All recovered influenza isolates retained the temperature-sensitive phenotype . After two doses of LAIV , 83 % of the non-HIV-infected and 77 % of the HIV-infected children had a > or = 4-fold rise in influenza antibody to at least one of the three LAIV strains . CONCLUSION If relatively healthy HIV-infected children become exposed to LAIV inadvertently , then serious adverse outcomes would not be expected to occur frequently 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 For evaluation of heterologous protection by live attenuated influenza virus vaccine , 42 healthy volunteers with low titers of or no antibody to A/Scotl and /74 ( H3N2 ) and A/Victoria/3/75 ( H3N2 ) influenza viruses were given live attenuated A/Scotl and /74 ( H3N2 ) virus vaccine or placebo by the intranasal route with no result ant vaccine-related illness . Seventeen of 21 vaccine recipients and none of 21 placebo recipients developed antibody conversion . Thirty-seven days after administration of vaccine or placebo , all subjects were challenged intranasally with wild-type A/Victoria/3/75 influenza virus . Five placebo recipients and no vaccine recipients developed moderately severe illness , whereas 10 vaccine recipients and three placebo recipients developed no illness ( p less than 0.025 ) . Although 16 of 21 vaccine recipients fulfilled criteria of infection with the challenge virus , shedding of virus was significantly less frequent , less prolonged , and of significantly lower magnitude than that in the placebo recipients . Thus , live attenuated influenza virus vaccine showed a significant protective effect against illness following challenge with heterologous wild-type virus . The protective effect and the negligible side effects of this vaccine merit consideration of its use in a large-scale field trial In a trial of influenza virus vaccines , 3,103 students ( 13.6 % of a campus population ) were given a st and ard dose of vaccine ( 400 chick-cell agglutination [ CCA ] units of influenza A and 300 CCA units of influenza B ) in October or December 1971 . Fifty-eight percent of the vaccinees received a tri-(n-butyl ) phosphate ( TNBP ) split virus vaccine ; 42 % received inactivated whole virus vaccine . In January , a discrete influenza outbreak occurred . Influenza A/HK virus ( H3N2 ) was recovered as the predominant infecting agent . In a three-week period , 168 students sought medical assistance for febrile influenza . Only eight ( 4.8 % ) of these were vaccinees , representing a 69 % reduction from the attack rate in nonvaccinees . The protection derived from split virus and whole virus vaccine was similar Vaccinations have been discussed as one among many environmental c and i date s contributing to the immune process that later may lead to type 1 diabetes . ABIS ( All Babies in Southeast Sweden ) is a prospect i ve cohort study following a nonselected birth cohort of general population . In a r and omly selected sample collection from 4400 children , GADA and IA-2A have been determined at the age of 1 year . The information on vaccinations was collected from question naires answered by the parents and was related to beta cell autoantibodies . When study ing the induction of autoantibodies using the autoantibody level of 90th percentile as cutoff level , hemophilus influenza B ( HIB ) vaccination appeared to be a risk factor for IA-2A [ OR 5.9 ( CI 1.4 - 24.4 ; p = 0.01 ) ] and for GADA [ OR 3.4 ( CI 1.1 - 10.8 ; p = 0.04 ) ] in logistic regression analyses . Furthermore , the titers of IA-2A were significantly higher ( p < 0.01 in Mann-Whitney test ) in those children who had got HIB vaccination . When 99th percentile was used as cutoff to identify the children at risk of type 1 diabetes , BCG vaccination was associated with increased prevalence of IA-2A ( p < 0.01 ) . We conclude that HIB vaccination may have an unspecific stimulatory polyclonal effect increasing the production of GADA and IA-2A . This might be of importance under circumstances when the beta cell-related immune response is activated by other mechanisms OBJECTIVE To determine the safety , immunogenicity , and efficacy of revaccination of children with live attenuated influenza vaccine .  STUDY DESIGN A 2-year multicenter , double-blind , placebo-controlled , efficacy field trial of live attenuated , cold-adapted trivalent influenza vaccine administered by nasal spray to children . This report summarizes year 2 results , a year in which the epidemic strain of influenza A/Sydney was not well matched to the vaccine strains . Each year , vaccine strains were antigenically equivalent to the contemporary inactivated influenza vaccine . In year 2 , a single intranasal revaccination was administered . Active surveillance for influenza was conducted during the influenza season by means of viral cultures . Influenza cases were defined as illnesses with wild-type influenza virus isolated from respiratory secretions . RESULTS In year 2 , 1358 ( 85 % ) children , 26 to 85 months of age , returned for revaccination . The intranasal vaccine was easily accepted , well tolerated , and immunogenic . Revaccination result ed in 82 % to 100 % of the vaccinated children in a subset studied for immunogenicity being seropositive as compared with 26 % to 65 % of placebo recipients , depending on the influenza strain tested . No serious adverse events were associated with the vaccine . In addition to the strains in the vaccine , antibody was induced to the variant strain A/Sydney/H3N2 . In year 2 , influenza A/Sydney/H3N2 , a variant not contained in the vaccine , caused 66 of 70 cases of influenza A ; nonetheless , intranasal vaccine was 86 % efficacious in preventing A/Sydney influenza . Eight cases of lower respiratory tract disease were associated with A/Sydney influenza ; all cases were in the placebo group . CONCLUSIONS This live attenuated , cold-adapted influenza vaccine was safe , immunogenic , and efficacious against influenza A/H3N2 ( including a variant , A/Sydney , not contained in the vaccine ) and influenza B. The characteristics of this vaccine make it suitable for routine use in children to prevent influenza Groups of schoolchildren were immunized with an inactivated recombinant influenza virus vaccine specific for the neuraminidase antigen of Port Chalmers influenza A virus ( Heq1N2Ch ) , a conventional biphasic Port Chalmers strain of influenza virus vaccine ( H3ChN2Ch ) , or a placebo . Immunization with either virus vaccine was found to be safe and had no major adverse effects . Immunization with the Heq1N2Ch vaccine result ed in no specific hemagglutination-inhibiting antibody response to H3Ch antigen , although a specific neuraminidase antibody response to N2Ch antigen was observed in greater than 90 % of the vaccinees . A subsequent natural outbreak of influenza virus result ed in serologically proven infection with H3Ch virus in 26 % of vaccinees receiving H3ChN2Ch virus vaccine , 47 % of those receiving Heq1N2Ch virus vaccine , and 44 % of those receiving a placebo . However , the protective efficacy against illness was 74.3 % for the H3ChN2Ch vaccine and only 51.4 % for the Heq1N2Ch vaccine . Regardless of the type of vaccine employed , vaccinees with serologic evidence of infection and clinical illness were found to have very low titers of hemagglutination-inhibiting and neuraminidase antibody . However , vaccinees with serologically proved infection but without clinical illness were found to have titers of antibody to neuraminidase before infection that were four- to eightfold higher than titers in vaccinees who were infected and who had clinical illness 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 sample s 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 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 Antigen-specific mucosal immunity is thought to be important for protection against influenza virus infection . Currently licensed parenteral influenza vaccines stimulate the production of serum antibodies , but are poor inducers of mucosal immunity . The adjuvant MF59 has been shown to enhance the humoral immune response to parenteral influenza vaccine in humans and the mucosal immune response to intranasally-administered influenza vaccine in mice . We conducted an open-label safety study followed by an observer-blind , r and omized trial comparing the immune response to intranasally-administered subunit influenza vaccine adjuvanted with MF59 , unadjuvanted subunit influenza vaccine , and placebo .  Adverse reactions did not occur significantly more frequently in vaccinees than placebo recipients . Of 31 subjects receiving 2 doses of MF59-adjuvanted influenza vaccine  , 19 ( 61 % ) , 8 ( 26 % ) , and 11 ( 35 % ) developed a mucosal IgA response to influenza A/H1N1 , A/H3N2 , and B , respectively . The percentage of subjects with a serum antibody response was slightly lower . The immune responses to adjuvanted vaccine were not significantly different from those to unadjuvanted vaccine . Both vaccines gave more frequent responses than seen in placebo recipients , indicating the potential of intranasal inactivated vaccines to stimulate local IgA responses The efficacy and tolerance of S and ovac , a new subunit vaccine , was tested in 104 children and juveniles aged 2 1/4 to 17 years , at five children 's clinics .  S and ovac 1000 was given to 39 children , S and ovac 2000 to 65 . The vaccine was well tolerated , no appreciable side effects -- local or systemic -- having been recorded . The efficacy of S and ovac was checked by determining the antibody titre against haemagglutinin and neuraminidase in 36 children before and 28 days after vaccination with S And ovac 1000 . The conversion rate with haemagglutination-inhibiting antibody titres type A strain Victoria was 100 % and type B strain Hong Kong 86 % . The geometric mean values rose by a factor of 29 for type A and 7.4 for type B. For the neuraminidase-inhibiting antibodies the factors were 3.15 with type A and 5.83 with type B. Titre increases by a factor of at least 1.5 occurred in 75 and 84 % , respectively of vaccinated children 1126 children , 2 months to 3 years old , received a single intranasal dose of 10(4 ) , 10(6 ) , or 10(7 ) TCID50 of cold adapted ( ca ) A/Kawasaki/9/86 ( H1N1 ) and A/Beijing/352/89 ( H3N2 ) or placebo , in a double blind , placebo-controlled , safety and immunogenicity trial . No reactogenicity attributable to vaccine was demonstrated . A single bivalent 10(6 ) or 10(7 ) dose produced high rates of seroconversion to H1N1 ( 77 % ) and H3N2 ( 92 % ) in seronegative children > 6 months old ; serologic responses were lower to H1N1 ( P < 0.001 ) and H3N2 ( P = 0.01 ) in younger infants . A single 10(6 ) dose of bivalent ca influenza A vaccine can be immunogenic in children , but response is age dependent
BACKGROUND In children and adults the consequences of influenza are mainly absences from school and work , however the risk of complications is greatest in children and people over 65 years old .
OBJECTIVES To appraise all comparative studies evaluating the effects of influenza vaccines in healthy children ; assess vaccine efficacy ( prevention of confirmed influenza ) and effectiveness ( prevention of influenza-like illness ) and document adverse events associated with receiving influenza vaccines .