Enhanced Immunogenicity of Seasonal Influenza Vaccines in Young Children Using MF59 Adjuvant [The evaluation of the reactogenicity, harmlessness and prophylactic efficacy of Grippol trivalent polymer-subunit influenza vaccine administered to schoolchildren]. [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]. Efficacy and Safety of 1 and 2 Doses of Live Attenuated Influenza Vaccine in Vaccine-Naive Children Vaccine Effectiveness Against Laboratory-confirmed Influenza in Healthy Young Children: A Case–Control Study Safety, Efficacy, and Effectiveness of Cold-Adapted Influenza Vaccine-Trivalent Against Community-Acquired, Culture-Confirmed Influenza in Young Children Attending Day Care 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. Estimating efficacy of trivalent, cold-adapted, influenza virus vaccine (CAIV-T) against influenza A (H1N1) and B using surveillance cultures. Protective efficacy of seasonal influenza vaccination against seasonal and pandemic influenza virus infection during 2009 in Hong Kong. The efficacy of live attenuated, cold-adapted, trivalent, intranasal influenzavirus vaccine in children. Trivalent Live Attenuated Intranasal Influenza Vaccine Administered During the 2003–2004 Influenza Type A (H3N2) Outbreak Provided Immediate, Direct, and Indirect Protection in Children Efficacy and Safety of a Live Attenuated, Cold-Adapted Influenza Vaccine, Trivalent Against Culture-Confirmed Influenza in Young Children in Asia Clinical and epidemiological evaluation of a live, cold-adapted influenza vaccine for 3-14-year-olds. 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. The effectiveness of trivalent inactivated influenza vaccine in children over six consecutive influenza seasons. Herd immunity in adults against influenza-related illnesses with use of the trivalent-live attenuated influenza vaccine (CAIV-T) in children. 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. Failure of inactivated influenza A vaccine to protect healthy children aged 6-24 months. [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]. Effectiveness of virosomal subunit influenza vaccine in preventing influenza-related illnesses and its social and economic consequences in children aged 3-14 years: a prospective cohort study. Live attenuated and inactivated influenza vaccine in school-age children. Estimation of the efficacy of live, attenuated influenza vaccine from a two-year, multi-center vaccine trial: implications for influenza epidemic control. 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. Efficacy of vaccination with live attenuated, cold-adapted, trivalent, intranasal influenza virus vaccine against a variant (A/Sydney) not contained in the vaccine. Comparison of US inactivated split-virus and Russian live attenuated, cold-adapted trivalent influenza vaccines in Russian schoolchildren. Oil-in-water emulsion adjuvant with influenza vaccine in young children. Influenza vaccine effectiveness in primary school children in Japan: a prospective cohort study using rapid diagnostic test results
Background : Children have high morbidity and hospitalization rates from seasonal influenza . Meta-analyses suggest that conventional inactivated influenza vaccines are of low efficacy in young children , making vaccines that induce greater and broader immune protection in this vulnerable population a medical priority . Adjuvanted influenza vaccines may offer a solution . Subjects and Methods : Unprimed healthy children ( 6 to < 36 months ) were enrolled in an observer-blinded study and r and omly assigned to receive 2 doses of MF59-adjuvanted vaccine ( Sub/MF59 , n = 130 ) or nonadjuvanted split vaccine ( split , n = 139 ) ; subgroups of these ( n = 43 and 46 , respectively ) received a booster dose 1 year later . Safety and clinical tolerability were assessed after each dose . Hemagglutination inhibition antibody titers were measured against influenza A and B strains included in the formulation of the vaccines and against mismatched strains . Results : Clinical tolerability and safety were generally comparable between vaccine groups , though some transient , mild solicited reactions were more frequent in the Sub/MF59 group . Postvaccination hemagglutination inhibition antibody titers to all 3 vaccine strains were significantly higher with Sub/MF59 than with split vaccine ( all comparisons P < 0.001 ) after each of the 3 vaccine doses . In addition , Sub/MF59 induced significantly higher cross-reactivity against A/H3N2 and A/H1N1 mismatched strains . Conclusion : MF59-adjuvanted influenza vaccine was well tolerated in healthy young children after each of 3 doses and induced greater , longer-lasting , and broader immune responses than a nonadjuvanted split vaccine . The enhanced immunogenicity of the adjuvanted vaccine was most evident in very young children and for the B vaccine strain Vaccine " Grippol "-- has been developed at the State Research Center -- Institute of Immunology . The preparation belongs to new generation vaccines and is a trivalent polymer-subunit vaccine containing the sterile conjugate of influenza virus surface proteins , types A and B , bound with copolymer polyoxidonium . The administration of " Grippol " to children of school age ( 6 - 18 years ) demonstrated low reactogenicity of the vaccine , its safety and sufficient prophylactic effectiveness . During observations on total morbidity ( with the exception of influenza and acute respiratory diseases ) no side effects produced by " Grippol " were registered . At the same time the fact that the morbidity rate of upper respiratory tract disease in the group of children immunized with the vaccine decreased in comparison with the control group ( by 2.4 times ) can not be disregarded 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 Background : We investigated the efficacy and safety of 1 versus 2 doses of live attenuated influenza vaccine ( LAIV ) in influenza vaccine – naive children aged 6 to < 36 months . Patients / Methods : Subjects were r and omized to 1 of 4 regimens in year 1 : 2 doses LAIV , 1 dose LAIV , excipient placebo , or saline placebo . In year 2 , LAIV recipients were to receive 1 dose of LAIV and placebo recipients were to receive saline placebo . Because of an unintended treatment allocation error in year 2 , 1 block of subjects who were r and omized to LAIV received saline placebo and 1 block who were r and omized to placebo received LAIV . Results : In year 1 , vaccine efficacy versus placebo among recipients of 2 and 1 doses of LAIV was 73.5 % and 57.7 % , respectively , against antigenically similar strains . In year 2 , absolute efficacy of a single dose of LAIV was 73.6 % and 65.2 % , respectively , in recipients of 2 and 1 doses of LAIV in year 1 . Year 2 efficacy was 57.0 % in subjects who received 2 doses of LAIV in year 1 and placebo in year 2 . Safety and tolerability of LAIV were consistent with previous studies . Reactogenicity was similar between placebo groups . Seroconversion rates were significantly higher in the 2-dose versus the 1-dose LAIV group in year 1 and in both LAIV groups versus placebo in years 1 and 2 . Conclusions : One dose of LAIV provided clinical ly significant protection against influenza in young children previously unvaccinated against influenza ; 2 doses provided additional protection . Protection after 2 doses in year 1 persisted through a second season without revaccination . LAIV excipients were not a major contributor to reactogenicity . These benefits provide support for increased use of LAIV in children ≥2 years of age Background : The Western Australian Influenza Vaccine Effectiveness study commenced in 2008 to evaluate a new program to provide free influenza vaccine to all children aged 6 to 59 months . We aim ed to assess the protective effect of inactivated influenza vaccination in these children . Methods : We conducted a prospect i ve case – control study in general practice s and a hospital emergency department , testing all eligible patients for influenza and a range of other common respiratory viruses .  Influenza vaccine effectiveness ( VE ) against laboratory-confirmed influenza was estimated with cases defined as children with an influenza-like illness who tested positive and controls as those with an influenza-like illness who tested negative for influenza virus . We calculated VE using the adjusted odds ratio from multivariate logistic regression . As a surrogate marker for adequate specimen collection , we explored the difference in VE point estimates defining controls as children in whom another respiratory virus was detected . Results : A total of 75 children were enrolled from general practice s and 214 through the emergency department , with 12 ( 27 % ) and 36 ( 17 % ) , respectively , having laboratory-confirmed influenza . Using all the influenza-negative controls , the adjusted VE was 58 % ( 95 % confidence interval , 9–81 ) . When controls were limited to those with another virus present , the adjusted VE was 68 % ( 95 % confidence interval , 26–86 ) . Conclusions : VE estimates were higher when controls included only those children with another respiratory virus detected . Testing for other common respiratory viruses enables the control group to be restricted to those for whom an adequate sample is likely OBJECTIVE . The goal was to evaluate the safety , tolerability , and efficacy of an investigational , refrigerator-stable formulation of live attenuated influenza vaccine ( cold-adapted influenza vaccine-trivalent ) against culture-confirmed influenza , acute otitis media , and effectiveness outcomes in young children in day care over 2 consecutive influenza seasons . METHODS . Children 6 to < 36 months of age who were attending day care were assigned r and omly in year 1 to receive 2 doses of vaccine or placebo intranasally , 35 ± 7 days apart . In year 2 , subjects received 1 dose of the same treatment as in year 1 . RESULTS . A total of 1616 subjects ( vaccine : 951 subjects ; placebo : 665 subjects ) in year 1 and 1090 subjects ( vaccine : 640 subjects ; placebo : 450 subjects ) in year 2 were able to be evaluated for efficacy . The mean age at first vaccination was 23.4 ± 7.9 months . In year 1 , the overall efficacy of the vaccine against influenza subtypes similar to the vaccine was 85.4 % ; efficacy was 91.8 % against A/H1N1 and 72.6 % against B. In year 2 , the overall efficacy was 88.7 % ; efficacy was 90.0 % against H1N1 , 90.3 % against A/H3N2 , and 81.7 % against B. Efficacy against all episodes of acute otitis media associated with culture-confirmed influenza was 90.6 % in year 1 and 97.0 % in year 2 . Runny nose or nasal discharge after dose 1 in year 1 was the only reactogenicity event that was significantly more frequent with cold-adapted influenza vaccine-trivalent ( 82.3 % ) than placebo ( 75.4 % ) . CONCLUSIONS . Cold-adapted influenza vaccine-trivalent was well tolerated and effective in preventing culture-confirmed influenza illness in children as young as 6 months of age who attended day care 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 The authors report on a community-based , nonr and omized , open-label study , conducted during the 2000 - 2001 influenza season in Temple-Belton , Texas , of the protective effectiveness of trivalent , cold-adapted , influenza virus vaccine ( CAIV-T ) in children aged 18 months-18 years . The dominant circulating strains in 2000 - 2001 were influenza A/New Caledonia/20/99 ( H1N1 ) and influenza B/Sichuan/379/99 . Children had access to CAIV-T  during the 1998 - 1999 , 1999 - 2000 , and 2000 - 2001 influenza seasons . The vaccine included influenza A/Sydney/5/97 ( H3N2 ) and B/Beijing/184/93-like ( B/Ann Arbor/l/94 ) strains in all three seasons . The vaccine included A/Beijing/262/95 ( H1N1 ) in 1998 - 1999 and 1999 - 2000 , which was replaced by A/New Caledonia/20/99 ( H1N1 ) in 2000 - 2001 . When medically attended acute respiratory illness ( MAARI ) was used as the outcome , the protective effectiveness for children vaccinated in 2000 was 18 % ( 95 % confidence interval ( CI ) : 11 , 25 ) . Based on a combination of a validation sample of surveillance cultures and the MAARI outcome , protective efficacy against combined influenza A ( H1N1 ) and B was 79 % ( 95 % CI : 51 , 91 ) . The efficacy estimate , after accounting for missing influenza culture status , against influenza A ( H1N1 ) alone was 92 % ( 95 % CI : 42 , 99 ) and against a new variant of influenza B alone was 66 % ( 95 % CI : 9 , 87 ) . CAIV-T provides substantial protection against a mixture of influenza A ( H1N1 ) and B. Results demonstrate the powerful potential of using validation sets for outcomes in vaccine field studies BACKGROUND The relationship between seasonal influenza vaccine and susceptibility to 2009 p and emic A/H1N1 virus infection is not fully understood . METHODS One child 6 - 15 years of age from each of 119 households was r and omized to receive 1 dose of inactivated trivalent seasonal influenza vaccine ( TIV ) or saline placebo in November 2008 . Serum sample s were collected from study subjects and their household contacts before and 1 month after vaccination ( December 2008 ) , after winter ( April 2009 ) and summer influenza ( September-October 2009 ) seasons . Seasonal and p and emic influenza were confirmed by serum hemagglutinination inhibition , viral neutralization titers , and reverse-transcription polymerase chain reaction performed on nasal and throat swab sample s collected during illness episodes . RESULTS TIV recipients had lower rates of serologically confirmed seasonal A/H1N1 infection ( TIV group , 8 % ; placebo group , 21 % ; P=.10 ) and A/H3N2 infection ( 7 % vs 12 % ; P = A9 ) , but higher rates of p and emic A/H1N1 infection ( 32 % vs 17 % ; [ Formula : see text ] ) . In multivariable analysis , those infected with seasonal influenza A during the study had a lower risk of laboratory-confirmed p and emic A/H1N1 infection ( adjusted odds ratio [ OR ] , 0.35 ; 95 % confidence interval [ CI ] , 0.14 - 0.87 ) , and receipt of seasonal TIV was unassociated with risk of p and emic A/H1N1 infection ( adjusted OR , 1.11 ; 95 % CI , 0.54 - 2.26 ) . CONCLUSIONS TIV protected against strain-matched infection in children . Seasonal influenza infection appeared to confer cross-protection against p and emic influenza . Whether prior seasonal influenza vaccination affects the risk of infection with the p and emic strain requires additional study . CLINICAL TRIALS REGISTRATION Clinical Trials.gov number NCT00792051 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 OBJECTIVE . Live attenuated influenza vaccine may protect against wild-type influenza illness shortly after vaccine administration by innate immunity . The 2003–2004 influenza A ( H3N2 ) outbreak arrived early , and the circulating strain was antigenically distinct from the vaccine strain . The objective of this study was to determine the effectiveness of influenza vaccines for healthy school-aged children when administered during the influenza outbreak . DESIGN / METHODS . An open-labeled , nonr and omized , community-based influenza vaccine trial was conducted in children 5 to 18 years old . Age-eligible healthy children received trivalent live attenuated influenza vaccine . Trivalent inactivated influenza vaccine was given to children with underlying health conditions . Influenza-positive illness was compared between vaccinated and nonvaccinated children . Medically attended acute respiratory illness and pneumonia and influenza rates for Scott and White Health Plan vaccinees were compared with age-eligible Scott and White Health Plan non participants in the intervention communities . Herd protection was assessed by comparing age-specific medically attended acute respiratory illness rates in Scott and White Health Plan members in the intervention and comparison communities . RESULTS . We administered 1 dose of trivalent live attenuated influenza vaccine or trivalent inactivated influenza vaccine to 6569 and 1040 children , respectively ( 31.5 % vaccination coverage ) , from October 10 to December 30 , 2003 . The influenza outbreak occurred from October 12 to December 20 , 2003 . Significant protection against influenza-positive illness ( 37.3 % ) and pneumonia and influenza events ( 50 % ) was detected in children who received trivalent live attenuated influenza vaccine but not trivalent inactivated influenza vaccine . Trivalent live attenuated influenza vaccine recipients had similar protection against influenza-positive illness within 14 days compared with > 14 days ( 10 of 25 vs 9 of 30 ) after vaccination . Indirect effectiveness against medically attended acute respiratory illness was detected in children 5 to 11 and adults 35 to 44 years of age . CONCLUSION . One dose of trivalent live attenuated influenza vaccine was efficacious in children even when administered during an influenza outbreak and when the dominant circulating influenza virus was antigenically distinct from the vaccine strain . We hypothesize that trivalent live attenuated influenza vaccine provides protection against influenza by both innate and adaptive immune mechanisms Background : This study was design ed to evaluate the efficacy and safety of cold-adapted influenza vaccine , trivalent ( CAIV-T ) against culture-confirmed influenza in children 12 to < 36 months of age during 2 consecutive influenza seasons at multiple sites in Asia . Methods : In year 1 , 3174 children 12 to < 36 months of age were r and omized to receive 2 doses of CAIV-T ( n = 1900 ) or placebo ( n = 1274 ) intranasally ≥28 days apart . In year 2 , 2947 subjects were rer and omized to receive 1 dose of CAIV-T or placebo . Results : Mean age at enrollment was 23.5 ± 7.4 months . In year 1 , efficacy of CAIV-T compared with placebo was 72.9 % [ 95 % confidence interval ( CI ) : 62.8–80.5 % ] against antigenically similar influenza subtypes , and 70.1 % ( 95 % CI : 60.9–77.3 % ) against any strain . In year 2 , revaccination with CAIV-T demonstrated significant efficacy against antigenically similar ( 84.3 % ; 95 % CI : 70.1–92.4 % ) and any ( 64.2 % ; 95 % CI : 44.2–77.3 % ) influenza strains . In year 1 , fever , runny nose/nasal congestion , decreased activity and appetite , and use of fever medication were more frequent with CAIV-T after dose 1 . Runny nose/nasal congestion after dose 2 ( year 1 ) and dose 3 ( year 2 ) and use of fever medication after dose 3 ( year 2 ) were the only other events reported significantly more frequently in CAIV-T recipients . Conclusions : CAIV-T was well tolerated and effective in preventing culture-confirmed influenza illness over multiple and complex influenza seasons in young children in Asia 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 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 OBJECTIVE To estimate the effectiveness of two doses of trivalent inactivated influenza vaccine ( TIV ) over six consecutive influenza seasons in a small community in Japan . PATIENTS AND METHODS A prospect i ve , non-r and omized , observational study of TIV effectiveness was performed involving children aged 6 months to 6 years accessing pediatric services in Soma and Shinchi , Japan . The total number of children under observation was 14,788 . Each fall from 2002 to 2007 TIV was offered to all children with an average uptake of 52.9 % . Influenza rapid diagnostic tests were performed to all children with respiratory symptoms and a temperature > 38 ° C during each surveillance period . The efficacy of two doses of TIV was estimated by the relative risk of influenza illness and influenza associated hospitalizations and effectiveness by reduction in all respiratory illness in vaccinated and unvaccinated children . RESULTS Influenza A occurred each year result ing in approximately one in five children in the unvaccinated group having an influenza A related clinic visit . For influenza A , two doses of TIV showed yearly efficacies that ranged from 42 % to 69 % with the highest efficacy during the 2002/2003 influenza season when the vaccine strains were well matched with the circulating viruses . The overall efficacy of two doses of TIV against influenza A and B associated illness was 52 % and 59 % , respectively . TIV also reduced the rate of the influenza associated hospitalizations attributable to both influenza A and B. CONCLUSIONS Vaccination with two doses of TIV was consistently effective in preventing influenza-associated clinic visits and hospitalizations Highest attack rates for influenza occur in children . Immunization of schoolchildren with inactivated influenza vaccine in Michigan and Japan was associated with decreased morbidity and mortality , respectively , in older community contacts . An open-labeled , non-r and omized , community-based trial in children with the cold adapted influenza vaccine , trivalent ( CAIV-T )  was initiated to determine the coverage necessary to reduce spread of influenza in the community . Age-specific baseline rates of medically attended acute respiratory illness ( MAARI ) for Scott and White Health Plan ( SWHP ) members at intervention ( Temple and Belton ) and comparison communities ( Waco , Bryan , and College Station ) were obtained in 1997 - 1998 . During three subsequent vaccination years , 4298 , 5251 and 5150 children received one dose per season of CAIV-T.  Vaccinees represented 20 - 25 % of the age-eligible children .  Age-specific MAARI rates were compared for SWHP members in the intervention and comparison sites during the influenza outbreaks . Baseline age-specific MAARI rates per 100 persons for the influenza season were comparable between the intervention and comparison communities . In the subsequent three influenza seasons , the age groups 35 - 44 , 45 - 54 , 55 - 65 and > 64 years experienced reductions in MAARI rates in the intervention communities . In adults > or = 35 years of age , significant reductions in MAARI of 0.08 ( 95 % CI : 0.04 , 0.13 ) , 0.18 ( 95 % CI : 0.14 , 0.22 ) and 0.15 ( 95 % CI : 0.12 , 0.19 ) , were observed in the influenza seasons for vaccination years 1 , 2 and 3 , respectively . No consistent reduction in MAARI rates was detected in the younger age groups . Vaccination of approximately 20 - 25 % of children , 1.5 - 18 years of age in the intervention communities result ed in an indirect protection of 8 - 18 % against MAARI in adults > or = 35 years of age Three groups of children were immunized with an inactivated Port Chalmers ( H3ChN2Ch ) influenza vaccine ( group A ) , a neuraminidase-specific ( Heq1N2Ch ) influenza vaccine ( group B ) , or a placebo . Immunization induced seroconversion for H3Ch and N2Ch-specific antibody in group A and for N2Ch antibody in group B. The protective efficacies observed against naturally acquired illness with the Port Chalmers strain of influneza A virus were 68.7 % and 37.4 % in groups A and B , respectively , in comparison to the placebo group , and those against illness produced by the subsequent outbreak of the Victoria strain were 80.0 % and 72.7 % . These data support the role of neuraminidase-specific immunization in protection against influenza . Although the degree of protection after vaccination with the Heq1N2Ch vaccine was less than that provided by the biphasic H3ChN2Ch vaccine against the Port Chalmers strain , it appeared to be similar in the two vaccine study groups against the Victoria strain 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 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 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 To evaluate the effectiveness of a virosomal subunit influenza vaccine in preventing influenza-related illnesses and its social and economic consequences in children aged 3 - 14 years , a prospect i ve cohort study was carried out during the 2004 - 2005 influenza season in 11 private pediatric clinics in the Barcelona metropolitan area . One dose of a virosomal subunit inactivated influenza vaccine ( Inflexal V Berna ) was given during September and October 2004 to healthy children aged 3 - 14 years attended in 5 of the 11 clinics . Who comprised the vaccinated cohort ( n=966 ) . The non-vaccinated cohort ( n=985 ) was comprised of children attended in the other six clinics . Informed consent was obtained from all parents . The follow up was performed between 1 November 2004 and 31 March 2005 . Using a self-administered question naire , information was collected from parents or guardians on any type of acute , febrile respiratory illness suffered by their children during the study period , including antibiotic use , and absence from school or work-loss of parents as a result of the illness . RT-PCR ( influenza A+B+C ) was carried out on pharyngeal and nasal sample s obtained from children attended by pediatricians during this period in these clinics with the following symptoms : fever > or = 38.5 degrees lasting at least 72h , cough or sore throat ( influenza-like illness ) . Adjusted vaccination effectiveness was 58.6 % ( 95 % CI 49.2 - 66.3 ) in preventing acute febrile respiratory illnesses , 75.1 % ( 95 % CI 61.0 - 84.1 ) in preventing cases of influenza-like illnesses and 88.4 % ( 95 % CI 49.2 - 97.3 ) in preventing laboratory-confirmed cases of influenza A. The adjusted vaccination effectiveness in reducing antibiotic use ( 18.6 % , 95 % CI -4.2 to 3.64 ) , absence from school ( 57.8 % , 95 % CI 47.9 - 65.9 ) and work-loss of parents ( 33.3 % , 95 % CI 8.9 - 51.2 ) in children affected by an acute febrile respiratory illness was somewhat lower . Vaccination of children aged 3 - 14 years in pediatric practice s with one dose of virosomal subunit inactivated influenza vaccine has the potential to considerably reduce the health and social burdens caused by influenza-related illnesses In 1985 , we enrolled 189 school-age children by family in a double-blind study to determine protection against influenza by a single dose of cold-recombinant bivalent A vaccine or commercial trivalent inactivated vaccine compared with placebo .  All children in school or day care , 3 to 18 years of age , in an enrolled family received the same preparation . Following vaccination , 60 % and 21 % of cold-recombinant bivalent A vaccine recipients and 73 % and 83 % of trivalent inactivated vaccine recipients demonstrated fourfold or greater response in hemagglutination-inhibition antibody titer to A/H1N1 and A/H3N2 , respectively . Sixty-seven percent of all trivalent inactivated vaccine recipients demonstrated a fourfold or greater serologic response to H1N1 , H3N2 , and influenza B following a single dose of vaccine . During the 1985 - 1986 influenza B/Ann Arbor epidemic , heterotypic protection afforded by the influenza B/USSR component of trivalent inactivated vaccine was 62 % compared with placebo . A single dose of trivalent inactivated vaccine protected school-age children , 6 to 19 years of age , from influenza B infection ; the rate of protection was 64 % against infection and 73 % against febrile illness The 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 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 ) 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 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 BACKGROUND The efficacy of inactivated influenza vaccines is known to be poor in infants and young children . METHODS We studied the effect of the adjuvant MF59 , an oil-in-water emulsion , on the efficacy of trivalent inactivated influenza vaccine ( TIV ) in 4707 healthy children 6 to less than 72 months of age who had not previously been vaccinated against influenza . The children were r and omly assigned to three study groups , each of which received the assigned vaccines in two doses , 28 days apart , during two consecutive influenza seasons . Two of the groups were given age-appropriate doses of TIV either with or without the MF59 adjuvant , and the third group was given control ( noninfluenza ) vaccines to assess their absolute and relative efficacy against influenza-like illness , as confirmed by means of polymerase-chain-reaction ( PCR ) assay . RESULTS Attack rates of influenza-like illness across both influenza seasons were 0.7 % , 2.8 % , and 4.7 % in the adjuvant , nonadjuvant , and control vaccine groups , respectively . The absolute vaccine efficacy rates against all influenza strains ( 94 of 110 cases were due to vaccine-matched H3N2 viruses ) were 86 % ( 95 % confidence interval [ CI ] , 74 to 93 ) for the MF59-adjuvant vaccine ( ATIV ) and 43 % ( 95 % CI , 15 to 61 ) for the vaccine without the adjuvant ( TIV ) ; the relative vaccine efficacy rate for ATIV versus TIV was 75 % ( 95 % CI , 55 to 87 ) . The efficacy rates for ATIV were 79 % ( 95 % CI , 55 to 90 ) in children 6 to less than 36 months of age and 92 % ( 95 % CI , 77 to 97 ) in those 36 to less than 72 months of age , as compared with 40 % ( 95 % CI , -6 to 66 ) and 45 % ( 95 % CI , 6 to 68 ) , respectively , for TIV . Antibody responses were higher with ATIV and remained so through day 181 . The rates of systemic and local reactions to the influenza vaccines with and without the adjuvant were similar in the younger age group ( relative risk , 1.04 ; 95 % CI , 0.98 to 1.09 ) , but systemic events in the older age group were more frequent after administration of ATIV ( 63 % ) than after administration of TIV ( 44 % ) or the control vaccine ( 50 % ) . Serious adverse events were distributed evenly across the three vaccine groups . CONCLUSIONS Influenza vaccine with the MF59 adjuvant is efficacious against PCR-confirmed influenza in infants and young children . ( Funded by Novartis Vaccines and Diagnostics ; Clinical Trials.gov number , NCT00644059 . ) A low-cost , prospect i ve cohort study using the results of rapid diagnostic test performed at local clinics was conducted to estimate influenza vaccine effectiveness ( VE ) in school children ( 6–12 year-olds ) . All children in four primary schools in Tsuchiura City , Ibaraki , Japan were enrolled ( n = 2607 ) .  Vaccination status and other risk factors were obtained with a baseline question naire . Participants were encouraged to visit a clinic to have a rapid test when they developed an influenza-like illness during the winter season in 2006–2007 , and 88.6 % of those who reported influenza to the school had been tested . The result of the test was obtained with another question naire . The attack rate of influenza A and B was 5.4 % and 11.9 % , respectively . Logistic regression was used to model the association between influenza vaccination and rapid-test-confirmed influenza after adjusting for potential confounders . Influenza VE was calculated as ( 1– adjusted odds ratio ) × 100 . VE for total influenza was 21 % ( 95 % confidence interval −8 to 42 ) , which was a combination of VE for influenza A ( 44 % , 8–66 ) and VE for influenza B ( 5 % , −37 to 34 ) . Among several possibilities that would account for rather low VE estimates in this study , low sensitivity of the rapid test , and differential propensity to seek vaccination or medical care between the vaccinated and nonvaccinated were considered to be important . This study was able to estimate influenza VE at very low cost with high specificity in case ascertainment by collecting the readily available data on influenza rapid test with question naires
AIM To assess the efficacy and effectiveness of seasonal influenza vaccines in healthy children up to the age of 18 years .