Enhanced Immunogenicity of Seasonal Influenza Vaccines in Young Children Using MF59 Adjuvant Effects of Influenza Plus Pneumococcal Conjugate Vaccination Versus Influenza Vaccination Alone in Preventing Respiratory Tract Infections in Children: A Randomized, Double-Blind, Placebo-Controlled Trial AMSTAR is a reliable and valid measurement tool to assess the methodological quality of systematic reviews. Clinical impact of influenza immunization in patients with liver cirrhosis. Live attenuated versus inactivated influenza vaccine in infants and young children. Prevention of symptomatic seasonal influenza in 2005-2006 by inactivated and live attenuated vaccines. Prevention of antigenically drifted influenza by inactivated and live attenuated vaccines. Clinical efficacy of cell culture–derived and egg‐derived inactivated subunit influenza vaccines in healthy adults. Effect of influenza vaccination of children on infection rates in Hutterite communities: a randomized trial. Evaluation of clinical data and antibody response following influenza vaccination in patients with chronic obstructive pulmonary disease. Influenza vaccination and risk of community-acquired pneumonia in immunocompetent elderly people: a population-based, nested case-control study Influenza Vaccination and Mortality: Differentiating Vaccine Effects From Bias The Efficacy of Live Attenuated and Inactivated Influenza Vaccines in Children as a Function of Time Postvaccination Efficacy, safety, and immunogenicity of a Vero-cell-culture-derived trivalent influenza vaccine: a multicentre, double-blind, randomised, placebo-controlled trial Influenza vaccination and mortality benefits: new insights, new opportunities. Mortality reduction with influenza vaccine in patients with pneumonia outside "flu" season: pleiotropic benefits or residual confounding? Influenza vaccination reduces cardiovascular events in patients with acute coronary syndrome. Efficacy of Injectable Trivalent Virosomal-Adjuvanted Inactivated Influenza Vaccine in Preventing Acute Otitis Media in Children With Recurrent Complicated or Noncomplicated Acute Otitis Media The effect of giving influenza vaccination to general practitioners: a controlled trial [NCT00221676]. Effectiveness of maternal influenza immunization in mothers and infants. Comparative efficacy of inactivated and live attenuated influenza vaccines. Trivalent inactivated influenza vaccine in African adults infected with human immunodeficient virus: double blind, randomized clinical trial of efficacy, immunogenicity, and safety.
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 Objective To evaluate the effects of influenza vaccination with or without heptavalent pneumococcal conjugate vaccination on  respiratory tract infections ( RTIs ) in children . Study design This was a r and omized , double-blind , placebo-controlled trial comprising 579 children age 18 to 72 months with a previous history of physician-diagnosed RTI , recruited between 2003 and 2005 . The children were assigned to 2 doses of parenteral inactivated trivalent subunit influenza plus heptavalent pneumococcal conjugate vaccination ( TIV+PCV7 ) , influenza plus placebo vaccination ( TIV+plac ) , or control hepatitis B virus vaccination plus placebo ( HBV+plac ) . Main outcome measures were febrile RTI and related polymerase chain reaction (PCR)-confirmed influenza , primary care visits , antibiotic prescriptions , and acute otitis media ( AOM ) episodes . Results During influenza seasons , febrile RTI were reduced by 24 % ( 95 % confidence interval [ CI ] = 1 % to 42 % ) in the TIV+PCV7 group and by 13 % ( 95 % CI = -12 % to 32 % ) in the TIV+plac group compared with the control group . The occurrence of PCR-confirmed influenza was reduced by 52 % ( 95 % CI = 7 % to 75 % ) in the TIV+PCV7 group and by 51 % ( 95 % CI = 3 % to 75 % ) in the TIV+plac group . Episodes of AOM were reduced by 57 % ( 95 % CI = 6 % to 80 % ) in the TIV+PCV7 group and by 71 % ( 95 % CI = 30 % to 88 % ) in the TIV+plac group . Outside of the influenza seasons , no significant effects of vaccinations were demonstrated on the studied outcomes . Conclusions During influenza seasons , influenza vaccination with or without pneumococcal conjugate vaccination substantially reduced cases of confirmed influenza and AOM episodes OBJECTIVE Our purpose was to measure the agreement , reliability , construct validity , and feasibility of a measurement tool to assess  systematic review s ( AMSTAR ) . STUDY DESIGN AND SETTING We r and omly selected 30 systematic review s from a data base . Each was assessed by two review ers using : ( 1 ) the enhanced quality assessment question naire ( Overview of Quality Assessment Question naire [ OQAQ ] ) ; ( 2 ) Sacks ' instrument ; and ( 3 ) our newly developed measurement tool ( AMSTAR ) . We report on reliability ( interobserver kappas of the 11 AMSTAR items ) , intraclass correlation coefficients ( ICCs ) of the sum scores , construct validity ( ICCs of the sum scores of AMSTAR compared with those of other instruments ) , and completion times . RESULTS The interrater agreement of the individual items of AMSTAR was substantial with a mean kappa of 0.70 ( 95 % confidence interval [ CI ] : 0.57 , 0.83 ) ( range : 0.38 - 1.0 ) . Kappas recorded for the other instruments were 0.63 ( 95 % CI : 0.38 , 0.78 ) for enhanced OQAQ and 0.40 ( 95 % CI : 0.29 , 0.50 ) for the Sacks ' instrument . The ICC of the total score for AMSTAR was 0.84 ( 95 % CI : 0.65 , 0.92 ) compared with 0.91 ( 95 % CI : 0.82 , 0.96 ) for OQAQ and 0.86 ( 95 % CI : 0.71 , 0.94 ) for the Sacks ' instrument . AMSTAR proved easy to apply , each review taking about 15 minutes to complete . CONCLUSIONS AMSTAR has good agreement , reliability , construct validity , and feasibility . These findings need confirmation by a broader range of assessors and a more diverse range of review BACKGROUND Influenza vaccine is considered to reduce influenza-related morbidity and mortality in patients with underlying chronic medical conditions . Yet in liver cirrhosis , influenza vaccines have received little attention in determining the potential benefits . OBJECTIVES We intended to evaluate the clinical benefits of influenza vaccination and clinical outcomes of influenza in patients with liver cirrhosis . METHODS We performed a controlled , prospect i ve clinical trial of 311 cirrhotic patients , who were enrolled in October 2004 . Among them , 198 patients were vaccinated with a trivalent influenza vaccine and the rest were not vaccinated .  Both groups were followed with respect to the occurrence of influenza-like illness ( ILI ) until May 2005 . RESULTS Overall incidences of ILI ( p=0.064 ) and culture positivity of influenza ( p=0.009 ) were remarkably higher in unvaccinated group compared to the vaccinated group . Most of the cirrhotic patients with influenza had fever ( 91.6 % ) and complained of myalgia ( 83.3 % ) without respiratory symptoms , which were not typical clinical presentations of influenza . Influenza vaccination also decreased influenza-related complication rates in patients with liver cirrhosis . CONCLUSION Influenza vaccination should be recommended to all cirrhotic patients . High suspicion is required for early diagnosis and antiviral treatment , allowing for the frequent hepatic decompensation among cirrhotic patients BACKGROUND Universal vaccination of children 6 to 59 months of age with trivalent inactivated influenza vaccine has recently been recommended by U.S. advisory bodies . To evaluate alternative vaccine approaches , we compared the safety and efficacy of intranasally administered live attenuated influenza vaccine with those of inactivated vaccine in infants and young children . METHODS Children 6 to 59 months of age , without a recent episode of wheezing illness or severe asthma , were r and omly assigned in a 1:1 ratio to receive either cold-adapted trivalent live attenuated influenza vaccine ( a refrigeration-stable formulation of live attenuated intranasally administered influenza vaccine ) or trivalent inactivated vaccine in a double-blind manner . Influenza-like illness was monitored with cultures throughout the 2004 - 2005 influenza season . RESULTS Safety data were available for 8352 children , and 7852 children completed the study according to the protocol . There were 54.9 % fewer cases of cultured-confirmed influenza in the group that received live attenuated vaccine than in the group that received inactivated vaccine ( 153 vs. 338 cases , P<0.001 ) . The superior efficacy of live attenuated vaccine , as compared with inactivated vaccine , was observed for both antigenically well-matched and drifted viruses . Among previously unvaccinated children , wheezing within 42 days after the administration of dose 1 was more common with live attenuated vaccine than with inactivated vaccine , primarily among children 6 to 11 months of age ; in this age group , 12 more episodes of wheezing were noted within 42 days after receipt of dose 1 among recipients of live attenuated vaccine ( 3.8 % ) than among recipients of inactivated vaccine ( 2.1 % , P=0.076 ) . Rates of hospitalization for any cause during the 180 days after vaccination were higher among the recipients of live attenuated vaccine who were 6 to 11 months of age ( 6.1 % ) than among the recipients of inactivated vaccine in this age group ( 2.6 % , P=0.002 ) . CONCLUSIONS Among young children , live attenuated vaccine had significantly better efficacy than inactivated vaccine . An evaluation of the risks and benefits indicates that live attenuated vaccine should be a highly effective , safe vaccine for children 12 to 59 months of age who do not have a history of asthma or wheezing . ( Clinical Trials.gov number , NCT00128167 [ Clinical Trials.gov ] . ) BACKGROUND The efficacy of influenza vaccines may vary annually . In 2004 - 2005 , when antigenically drifted viruses were circulating , a r and omized , placebo-controlled trial involving healthy adults showed that inactivated vaccine appeared to be efficacious , whereas live attenuated vaccine appeared to be less so . METHODS In 2005 - 2006 , we continued our trial , examining the absolute and relative efficacies of the live attenuated and inactivated vaccines in preventing laboratory-confirmed symptomatic influenza . RESULTS A total of 2058 persons were vaccinated in October and November 2005 . Study wide influenza activity was prolonged but of low intensity ; type A ( H3N2 ) virus was circulating , which was antigenically similar to the vaccine strain . The absolute efficacy of the inactivated vaccine was 16 % ( 95 % confidence interval [ CI ] , -171 % to 70 % ) for the virus identification end point ( virus isolation in cell culture or identification through polymerase chain reaction ) and 54 % ( 95 % CI , 4%-77 % ) for the primary end point ( virus isolation or increase in serum antibody titer ) . The absolute efficacies of the live attenuated vaccine  for these end points were 8 % ( 95 % CI , -194 % to 67 % ) and 43 % ( 95 % CI , -15 % to 71 % ) , respectively . CONCLUSIONS With serologic end points included , efficacy was demonstrated for the inactivated vaccine in a year with low influenza attack rates . The efficacy of the live attenuated vaccine was slightly less than that of the inactivated vaccine , but not statistically greater than that of the placebo BACKGROUND The efficacy of influenza vaccines may decline during years when the circulating viruses have antigenically drifted from those included in the vaccine . METHODS We carried out a r and omized , double-blind , placebo-controlled trial of inactivated and live attenuated influenza vaccines in healthy adults during the 2004 - 2005 influenza season and estimated both absolute and relative efficacies . RESULTS A total of 1247 persons were vaccinated between October and December 2004 . Influenza activity in Michigan began in January 2005 with the circulation of an antigenically drifted type A ( H3N2 ) virus , the A/California/07/2004-like strain , and of type B viruses from two lineages . The absolute efficacy of the inactivated vaccine against both types of virus was 77 % ( 95 % confidence interval [ CI ] , 37 to 92 ) as measured by isolating the virus in cell culture , 75 % ( 95 % CI , 42 to 90 ) as measured by either isolating the virus in cell culture or identifying it through real-time polymerase chain reaction , and 67 % ( 95 % CI , 16 to 87 ) as measured by either isolating the virus or observing a rise in the serum antibody titer . The absolute efficacies of the live attenuated vaccine were 57 % ( 95 % CI , -3 to 82 ) , 48 % ( 95 % CI , -7 to 74 ) , and 30 % ( 95 % CI , -57 to 67 ) , respectively . The difference in efficacy between the two vaccines appeared to be related mainly to reduced protection of the live attenuated vaccine against type B viruses . CONCLUSIONS In the 2004 - 2005 season , in which most circulating viruses were dissimilar to those included in the vaccine , the inactivated vaccine was efficacious in preventing laboratory-confirmed symptomatic illnesses from influenza in healthy adults . The live attenuated vaccine also prevented influenza illnesses but was less efficacious . ( Clinical Trials.gov number , NCT00133523 . BACKGROUND More efficient methods are needed to manufacture influenza vaccines . This trial compared the efficacy of cell culture-derived influenza vaccine ( CCIV ) and egg-derived trivalent inactivated vaccine ( TIV ) with placebo against laboratory-confirmed influenza illness in healthy adults in the United States , Finl and , and Pol and during the 2007 - 2008 influenza season . METHODS A total of 11,404 study participants aged 18 - 49 years were r and omized equally to receive CCIV ( Optaflu ; n = 3828 ) , TIV ( Agrippal ; n = 3676 ) , or placebo ( n = 3900 ) . Each participant was observed during a 6-month study surveillance period . Nasal and throat swabs for virus isolation and characterization were collected from all patients with influenza-like illness . Vaccine immunogenicity was evaluated in a subset of 1045 participants . RESULTS Efficacy of CCIV and TIV against vaccine-like ( 83.8 % [ 1-sided 97.5 % confidence interval [ CI ] lower limit , 61.0 % ] and 78.4 % [ 1-sided 97.5 % CI lower limit , 52.1 % ] , respectively ) and all circulating influenza virus strains ( 69.5 % [ 1-sided 97.5 % CI lower limit , 55.0 % ] and 63.0 % [ 1-sided 97.5 % lower limit , 46.7 % ] , respectively ) exceeded the Center for Biologics Evaluation and Research efficacy criteria . Immunogenicity of both vaccines exceeded the Center for Biologics Evaluation and Research licensing criteria . Both vaccines were well tolerated , with similar safety profiles . Most solicited reactions were mild to moderate in severity and transient . No vaccination-related serious adverse events were reported ; no withdrawals result ed from vaccine-related adverse events . CONCLUSIONS Both CCIV and TIV were effective in preventing influenza caused by vaccine-like and by all circulating influenza virus strains , were well tolerated , and had good safety profiles . Both vaccines can be considered for annual influenza vaccination campaigns . CLINICAL TRIALS REGISTRATION NCT00630331 CONTEXT Children and adolescents appear to play an important role in the transmission of influenza . Selectively vaccinating youngsters against influenza may interrupt virus transmission and protect those not immunized . OBJECTIVE To assess whether vaccinating children and adolescents with inactivated influenza vaccine could prevent influenza in other community members . DESIGN , SETTING , AND PARTICIPANTS A cluster r and omized trial involving 947 Canadian children and adolescents aged 36 months to 15 years who received study vaccine and 2326 community members who did not receive the study vaccine in 49 Hutterite colonies in Alberta , Saskatchewan , and Manitoba . Follow-up began December 28 , 2008 , and ended June 23 , 2009 . INTERVENTION Children were r and omly assigned according to community and in a blinded manner to receive st and ard dosing of either inactivated trivalent influenza vaccine or hepatitis A vaccine , which was used as a control . MAIN OUTCOME MEASURES Confirmed influenza A and B infection using a real-time reverse transcriptase polymerase chain reaction ( RT-PCR ) assay and by measuring serum hemagglutination inhibition titers . RESULTS The mean rate of study vaccine coverage among eligible participants was 83 % ( range , 53%-100 % ) for the influenza vaccine colonies and 79 % ( range , 50%-100 % ) for the hepatitis A vaccine colonies . Among nonrecipients , 39 of 1271 ( 3.1 % ) in the influenza vaccine colonies and 80 of 1055 ( 7.6 % ) in the hepatitis A vaccine colonies had influenza illness confirmed by RT-PCR , for a protective effectiveness of 61 % ( 95 % confidence interval [ CI ] , 8%-83 % ; P = .03 ) . Among all study participants ( those who were and those who were not vaccinated ) , 80 of 1773 ( 4.5 % ) in the influenza vaccine colonies and 159 of 1500 ( 10.6 % ) in the hepatitis A vaccine colonies had influenza illness confirmed by RT-PCR for an overall protective effectiveness of 59 % ( 95 % CI , 5%-82 % ; P = .04 ) . No serious vaccine adverse events were observed . CONCLUSION Immunizing children and adolescents with inactivated influenza vaccine significantly protected unimmunized residents of rural communities against influenza . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00877396 The present study investigated the antibody response against influenza vaccine  and also the efficacy of vaccination on clinical findings in patients with Chronic Obstructive Pulmonary Disease ( COPD ) following influenza vaccination .  A total of 82 cases with COPD ( 44 cases as vaccinated and 38 cases as unvaccinated ) were evaluated clinical ly and 21 healthy volunteers were also included in the study as a control group . Influenza ( A and B ) Ig M and Ig G parameters were analyzed quantitatively in blood sample s of the vaccinated group and healthy volunteers by ELISA method once before vaccination and one month and one year after vaccination . The presence of dyspnoea , increased sputum production and /or purulence were accepted as criteria of acute exacerbation . The number of hospital presentations was significantly lower in the vaccinated group and higher in severe cases with COPD in unvaccinated group . Vaccinated cases in the study group experienced significantly fewer episodes of pneumonia , hospitalization and intensive care . Quantitative influenza ( A and B ) antibody IgG levels significantly increased in these patients as well . In conclusion , seasonal influenza vaccination with the trivalent influenza split virion vaccine especially in severe or very severe COPD patients who need hospitalization was evaluated as beneficial in clinical use BACKGROUND Pneumonia is a common complication of influenza infection in elderly individuals and could therefore potentially be prevented by influenza vaccination . In studies with data from administrative sources , vaccinated elderly people had a reduced risk of admission for pneumonia compared with unvaccinated seniors ; however , these findings could have been biased by underlying differences in health between the groups . Furthermore , since most individuals with pneumonia are not treated in hospital , such studies should include both outpatient and inpatient events . We therefore assessed whether influenza vaccination is associated with a reduced risk of community-acquired pneumonia in immunocompetent elderly people after controlling for health status indicators . METHODS We did a population -based , nested case-control study in immunocompetent elderly people aged 65 - 94 years ( cases and controls ) enrolled in Group Health ( a health maintenance organisation ) during the 2000 , 2001 , and 2002 preinfluenza periods and influenza seasons . Cases were individuals with an episode of outpatient or inpatient community-acquired pneumonia ( vali date d by review of medical records or chest radiograph reports ) . We r and omly selected two age-matched and sex-matched controls for each case . The exposure of interest was influenza vaccination . We review ed medical records to define potential confounders , including smoking history , presence and severity of lung and heart disease , and frailty indicators . FINDINGS 1173 cases and 2346 controls were included in the study . After we adjusted for the presence and severity of comorbidities , as defined by chart review , influenza vaccination was not associated with a reduced risk of community-acquired pneumonia ( odds ratio 0.92 , 95 % CI 0.77 - 1.10 ) during the influenza season . INTERPRETATION The effect of influenza vaccination on the risk of pneumonia in elderly people during influenza seasons might be less than previously estimated . FUNDING Group Health Center for Health Studies internal funds and Group Health Community Foundation fellowship grant It is widely believed that influenza ( flu ) vaccination of the elderly reduces all-cause mortality , yet r and omized trials for assessing vaccine effectiveness are not feasible and the observational research has been controversial . Efforts to differentiate vaccine effectiveness from selection bias have been problematic . The authors examined mortality before , during , and after 9 flu seasons in relation to time-varying vaccination status in an elderly California population in which 115,823 deaths occurred from 1996 to 2005 , including 20,484 deaths during laboratory-defined flu seasons .  Vaccine coverage averaged 63 % ; excess mortality when the flu virus was circulating averaged 7.8 % . In analyses that omitted weeks when flu circulated , the odds ratio measuring the vaccination-mortality association increased monotonically from 0.34 early in November to 0.56 in January , 0.67 in April , and 0.76 in August . This reflects the trajectory of selection effects in the absence of flu . In analyses that included weeks with flu and adjustment for selection effects , flu season multiplied the odds ratio by 0.954 . The corresponding vaccine effectiveness estimate was 4.6 % ( 95 % confidence interval : 0.7 , 8.3 ) . To differentiate vaccine effects from selection bias , the authors used logistic regression with a novel case-centered specification that may be useful in other population -based studies when the exposure- outcome association varies markedly over time Background : In the United States , more children are being vaccinated against influenza in August and September , months before peak influenza activity . Sustained vaccine efficacy through 12 months postvaccination has been demonstrated in children for live attenuated influenza vaccine ( LAIV ) but not trivalent inactivated influenza vaccine ( TIV ) . Three large , r and omized studies compared LAIV and TIV efficacy in children , providing the opportunity to examine the impact of time on the relative efficacy of the 2 vaccines . Methods : For each study , the relative efficacy of LAIV versus TIV was analyzed by time interval ( 0–4 and > 4–8 months postvaccination ) for matched and mismatched strains . Results : LAIV recipients had less influenza than TIV recipients during both intervals ; the relative efficacy of LAIV versus TIV for matched strains in each study increased from 0 to 4 months ( range , 25%–60 % ) to > 4 to 8 months ( range , 49%–89 % ) . Analysis of the incidence of individual types/subtypes revealed the same pattern for the predominant matched strain in each study ; no consistent pattern was seen for lower-incidence matched strains . For mismatched strains , similar relative efficacy was seen in each time interval . Conclusions : For matched strains , data suggest that the relative efficacy of LAIV versus TIV in young children increases over time . Consistent with previous studies of TIV-induced immunity , this analysis suggests that the absolute efficacy of TIV against matched strains in children may be lower at > 4 to 8 versus 0 to 4 months postvaccination . Relative efficacy against mismatched strains was similar over time , consistent with previous estimates of the absolute efficacies of the vaccines against mismatched strains . Further research is needed to confirm these findings and to characterize the duration of protection provided by TIV in children BACKGROUND The use of cell-culture technologies for the manufacture of influenza vaccines might contribute to improved strain selection and robust vaccine supplies . We investigated the safety , immunogenicity , and protective efficacy of a Vero-cell-culture-derived influenza vaccine , and assessed the correlation between vaccine efficacy and haemagglutination inhibition antibody titre . METHODS In a double-blind , placebo-controlled  , phase 3 trial undertaken in 36 centres in the USA , healthy adults ( aged 18 - 49 years ) were r and omly assigned in a 1:1 ratio to one injection of either placebo or Vero-cell-culture-derived influenza vaccine during the 2008 - 09 season . R and omisation was done in blocks by use of the r and om number generator algorithm , and participants were allocated by use of a central ised telephone system . The primary objective was the efficacy of the vaccine in preventing cell-culture-confirmed influenza infection with viruses that were antigenically matched to one of the vaccine strains . Analysis was by intention to treat . The study is registered with Clinical Trials.gov , number NCT00566345 . FINDINGS 7250 participants were r and omly assigned to vaccine ( n=3626 ) and placebo ( n=3624 ) . 7236 were analysed for the primary outcome ( n=3619 and n=3617 , respectively ) . Overall protective efficacy for antigenically matched influenza infection was 78·5 % ( 95 % CI 60·8 - 88·2 ) . The vaccine was well tolerated with no treatment-related serious adverse events . Adverse events were mainly mild and transient . An HI titre of at least 1:15 provided a reliable correlate of cell-culture-derived influenza vaccine-induced protection ; no additional benefit was noted with titres greater than 1:30 . INTERPRETATION The data indicate that existing correlates of protection afforded with egg-derived seasonal influenza vaccines also apply to this vaccine . FUNDING Federal ( US Government ) funds from the Office for Preparedness and Response , Biomedical Advanced Research and Development Authority , under contract to DynPort Vaccine Company Influenza vaccination control strategies in most countries rely on vaccination of seniors and other high risk groups . Although placebo-controlled r and omized trials show influenza vaccine is effective in younger age groups , few seniors > 70 years were studied even though they suffer > 90 % of influenza-related deaths . Excess mortality studies could not confirm a national decline in influenza-related mortality while vaccine coverage quadrupled . Cohort studies have consistently reported that vaccination reduces all-cause winter mortality by approximately 50 % , an astonishing cl aim given only approximately 5 % of all winter deaths are attributable to influenza . This VE overestimation has now been attributed to profound confounding frailty selection bias . A way forward includes a new generation of unbiased studies with laboratory endpoints , and requires an agreement that the evidence base was flawed . The latter may clear the way for more immunogenic vaccines for seniors and exploration of other influenza control strategies RATIONALE Observational studies suggest a 50 % mortality reduction for older patients receiving influenza vaccination ;  some deem this magnitude of benefit implausible and invoke confounding by the " healthy user effect " as an alternate explanation . OBJECTIVES To evaluate unrecognized confounding by hypothesizing the presence of a 50 % mortality reduction with vaccination for patients with pneumonia outside of influenza season . METHODS Clinical , laboratory , and functional data were prospect ively collected on 1,813 adults with community-acquired pneumonia admitted to six hospitals outside of influenza season in the Capital Health region ( AB , Canada ) . Vaccination status was ascertained by interview and chart review . Outcome was in-hospital mortality .  Influenza-vaccinated patients were matched to a nonvaccinated control using propensity scores , and then multivariable regression was used to determine the independent association between vaccination and mortality . MEASUREMENTS AND MAIN RESULTS The cohort consisted of 352 vaccine recipients and 352 matched control subjects . Most ( 85 % ) patients were 65 years or older , 29 % had severe pneumonia , and 12 % died .  Influenza vaccination was associated with a 51 % mortality reduction ( 28 of 352 [ 8 % ] died vs. 53 of 352 [ 15 % ] control subjects ; unadjusted odds ratio [ OR ] , 0.49 ; 95 % confidence interval [ CI ] , 0.30 - 0.79 ; P = 0.004 ) outside influenza season . Adjustment for age , sex , and comorbidities did not alter these findings ( adjusted OR , 0.45 ; 95 % CI , 0.27 - 0.76 ) . More complete adjustment for confounding ( e.g. , functional and socioeconomic status ) markedly attenuated these benefits and their statistical significance ( adjusted OR , 0.81 ; 95 % CI , 0.35 - 1.85 ; P = 0.61 ) . CONCLUSIONS The 51 % reduction in mortality with vaccination initially observed in patients with pneumonia who did not have influenza was most likely a result of confounding . Previous observational studies may have overestimated mortality benefits of influenza vaccination AIMS Influenza infection has been shown to accentuate the progression of atherosclerosis and precipitate the occurrence of acute coronary syndrome ( ACS ) . However , the protective effects of the influenza vaccine on cardiovascular events are still inconclusive . METHODS AND RESULTS The study was a prospect i ve r and omized open with blinded endpoint ( PROBE ) study . The 439 patients who had been admitted due to ACS within 8 weeks were enrolled and r and omly allocated to receive inactivated influenza vaccine in the vaccine group and no treatment in the control group . All patients were treated with the st and ard therapy including revascularization according to primary cardiologists . The primary endpoint , which was the combined major cardiovascular events , including death , hospitalization from ACS , hospitalization from heart failure , and hospitalization from stroke , occurred less frequently in the vaccine group than the control group [ 9.5 vs. 19.3 % , unadjusted HR 0.70 ( 0.57 - 0.86 ) , P = 0.004 ] . There was no significant difference in the incidence of cardiovascular death between the vaccine and control groups [ 2.3 vs. 5.5 % , unadjusted HR 0.39 ( 0.14 - 1.12 ) , P = 0.088 ] . CONCLUSION The influenza vaccine reduced major cardiovascular events in patients with ACS . Therefore , it should be encouraged as a secondary prevention in this group of patients Background : Most cases of acute otitis media ( AOM ) follow an upper respiratory infection due to viruses , including influenza viruses . As effective and safe influenza vaccines are available , their use has been considered among the possible measures of AOM prophylaxis . Objectives : To evaluate the efficacy of an inactivated virosomal-adjuvanted influenza vaccine in preventing AOM in children with a history of noncomplicated recurrent AOM ( rAOM ) or rAOM complicated by spontaneous perforation . Methods : In this prospect i ve , r and omized , single-blinded , placebo-controlled study , 180 children aged 1 to 5 years with a history of rAOM and previously unvaccinated against influenza were r and omized to receive the inactivated virosomal-adjuvanted subunit influenza vaccine ( n = 90 ) or no treatment ( n = 90 ) , and AOM-related morbidity was monitored every 4 to 6 weeks for 6 months . Results : The number of children experiencing at least 1 AOM episode was significantly smaller in the vaccinated group ( P < 0.001 ) , as was the mean number of AOM episodes ( P = 0.03 ) , the mean number of AOM episodes without perforation ( P < 0.001 ) , and the mean number of antibiotic courses ( P < 0.001 ) ; the mean duration of bilateral OME was significantly shorter ( P = 0.03 ) . The only factor that seemed to be associated with the significantly greater efficacy of influenza vaccine  in preventing AOM was the absence of a history of recurrent perforation ( crude odds ratio , P = 0.01 ; adjusted odds ratio , P = 0.006 ) . Conclusions : The intramuscular administration of injectable trivalent inactivated virosomal-adjuvanted influenza vaccine in children with a history of rAOM significantly reduces AOM-related morbidity . However , the efficacy of this preventive measure seems to be reduced in children with rAOM associated with repeated tympanic membrane perforation BACKGROUND No efficacy studies of influenza vaccination given to GPs have yet been published . Therefore , our purpose was to assess the effect of an inactivated influenza vaccine given to GPs on the rate of clinical respiratory tract infections ( RTIs ) and proven influenza cases ( influenza positive nose and throat swabs and a 4-fold titre rise ) , while adjusting for important covariates . METHODS In a controlled trial during two consecutive winter periods ( 2002 - 2003 and 2003 - 2004 ) we compared ( 77 and 100 ) vaccinated with ( 45 and 40 ) unvaccinated GPs working in Fl and ers , Belgium .  Influenza antibodies were measured immediately prior to and 3 - 5 weeks after vaccination , as well as after the influenza epidemic . During the influenza epidemic , GPs had to record their contact with influenza cases and their own RTI symptoms every day . If they became ill , the GPs had to take nose and throat swabs during the first 4 days . We performed a multivariate regression analysis for covariates using Generalized Estimating Equations . RESULTS One half of the GPs ( vaccinated or not ) developed an RTI during the 2 influenza epidemics . During the two influenza periods , 8.6 % of the vaccinated and 14.7 % of the unvaccinated GPs had positive swabs for influenza ( RR : 0.59 ; 95%CI : 0.28 - 1.24 ) . Multivariate analysis revealed that influenza vaccination  prevented RTIs and swab-positive influenza only among young GPs ( ORadj : 0.35 ; 95%CI : 0.13 - 0.96 and 0.1 ; 0.01 - 0.75 respectively for 30-year-old GPs ) . Independent of vaccination , a low basic antibody titre against influenza ( ORadj 0.57 ; 95%CI : 0.37 - 0.89 ) and the presence of influenza cases in the family ( ORadj 9.24 ; 95%CI : 2.91 - 29 ) were highly predictive of an episode of swab-positive influenza . CONCLUSION Influenza vaccination was shown to protect against proven influenza among young GPs . GPs , vaccinated or not , who are very vulnerable to influenza are those who have a low basic immunity against influenza and , in particular , those who have family members who develop influenza BACKGROUND Young infants and pregnant women are at increased risk for serious consequences of influenza infection . Inactivated influenza vaccine is recommended for pregnant women but is not licensed for infants younger than 6 months of age . We assessed the clinical effectiveness of inactivated influenza vaccine administered during pregnancy in Bangladesh . METHODS In this r and omized study , we assigned 340 mothers to receive either inactivated influenza vaccine ( influenza-vaccine group ) or the 23-valent pneumococcal polysaccharide vaccine ( control group ) . Mothers were interviewed weekly to assess illnesses until 24 weeks after birth . Subjects with febrile respiratory illness were assessed clinical ly , and ill infants were tested for influenza antigens . We estimated the incidence of illness , incidence rate ratios , and vaccine effectiveness . RESULTS Mothers and infants were observed from August 2004 through December 2005 . Among infants of mothers who received influenza vaccine  , there were fewer cases of laboratory-confirmed influenza than among infants in the control group ( 6 cases and 16 cases , respectively ) , with a vaccine effectiveness of 63 % ( 95 % confidence interval [ CI ] , 5 to 85 ) . Respiratory illness with fever occurred in 110 infants in the influenza-vaccine group and 153 infants in the control group , with a vaccine effectiveness of 29 % ( 95 % CI , 7 to 46 ) . Among the mothers , there was a reduction in the rate of respiratory illness with fever of 36 % ( 95 % CI , 4 to 57 ) . CONCLUSIONS Inactivated influenza vaccine reduced proven influenza illness by 63 % in infants up to 6 months of age and averted approximately a third of all febrile respiratory illnesses in mothers and young infants . Maternal influenza immunization is a strategy with substantial benefits for both mothers and infants . ( Clinical Trials.gov number , NCT00142389 . BACKGROUND The efficacy of influenza vaccines may vary from year to year , depending on a variety of factors , and may differ for inactivated and live attenuated vaccines . METHODS We carried out a r and omized , double-blind , placebo-controlled trial of licensed inactivated and live attenuated influenza vaccines in healthy adults during the 2007 - 2008 influenza season and estimated the absolute and relative efficacies of the two vaccines . RESULTS A total of 1952 subjects were enrolled and received study vaccines in the fall of 2007 . Influenza activity occurred from January through April 2008 , with the circulation of influenza types A ( H3N2 ) ( about 90 % ) and B ( about 9 % ) . Absolute efficacy against both types of influenza , as measured by isolating the virus in culture , identifying it on real-time polymerase-chain-reaction assay , or both , was 68 % ( 95 % confidence interval [ CI ] , 46 to 81 ) for the inactivated vaccine and 36 % ( 95 % CI , 0 to 59 ) for the live attenuated vaccine . In terms of relative efficacy , there was a 50 % ( 95 % CI , 20 to 69 ) reduction in laboratory-confirmed influenza among subjects who received inactivated vaccine as compared with those given live attenuated vaccine . The absolute efficacy against the influenza A virus was 72 % ( 95 % CI , 49 to 84 ) for the inactivated vaccine and 29 % ( 95 % CI , -14 to 55 ) for the live attenuated vaccine , with a relative efficacy of 60 % ( 95 % CI , 33 to 77 ) for the inactivated vaccine . CONCLUSIONS In the 2007 - 2008 season , the inactivated vaccine was efficacious in preventing laboratory-confirmed symptomatic influenza A ( predominately H3N2 ) in healthy adults . The live attenuated vaccine also prevented influenza illnesses but was less efficacious . ( Clinical Trials.gov number , NCT00538512 . BACKGROUND Data on the efficacy of trivalent , inactivated influenza vaccine ( TIV ) in HIV-infected adults , particularly in Africa , are limited . This study evaluated the safety , immunogenicity , and efficacy of TIV in HIV-infected adults . METHODS In Johannesburg , South Africa , we undertook a r and omized , double-blind , placebo-controlled trial involving 506 HIV-infected adults . Subjects included 157 individuals who were antiretroviral treatment ( ART ) naive and 349 on stable-ART . Participants were r and omly assigned to receive TIV or normal saline intramuscularly . Oropharyngeal swabs were obtained at illness visits during the influenza season and tested by shell vial culture and RT PCR assay for influenza virus . Immune response was evaluated by hemagglutinin antibody inhibition assay ( HAI ) in a nested cohort . The primary study outcome involved vaccine efficacy against influenza confirmed illness . This trial is registered with Clinical Trials.gov , number NCT00757900 . RESULTS The efficacy of TIV against confirmed influenza illness was 75.5 % ( 95 % CI : 9.2%-95.6 % ) ; with a risk difference of 0.18 per 100 person-weeks in TIV recipients . Among TIV recipients , seroconversion , measured by HAI titers , was evident in 52.6 % for H1N1 , 60.8 % for H3N2 , and 53.6 % for influenza B virus . This compared with 2.2 % , 2.2 % , and 4.4 % of placebo recipients ( P < .0001 ) . The frequency of local and systemic adverse events post-immunization was similar between study groups . CONCLUSIONS TIV immunization is safe and efficacious in African HIV-infected adults without underlying co-morbidities . Further evaluation of effectiveness is warranted in severely immunocompromized HIV-infected adults and those with co-morbidities such as tuberculosis
PURPOSE To systematic ally review the evidence regarding the efficacy , effectiveness and risks of the use of inactivated influenza vaccines in children , healthy adults , elderly individuals and individuals with co-morbidities such as diabetes , chronic lung disease , cardiovascular disease , kidney or liver disease and immune suppression .