Pneumococcal disease after pneumococcal vaccination: an alternative method to estimate the efficacy of pneumococcal vaccine. Field evaluation of vaccine efficacy. Increased Risk of Noninfluenza Respiratory Virus Infections Associated With Receipt of Inactivated Influenza Vaccine Effect of influenza vaccination of children on infection rates in Hutterite communities: a randomized trial. Publication Delay of Randomized Trials on 2009 Influenza A (H1N1) Vaccination Effectiveness of inactivated influenza vaccine in preventing acute otitis media in young children: a randomized controlled trial. Controlled trial of inactivated influenza vaccine containing the a-Hong Kong strain during an outbreak of influenza due to the a-England-42-72 strain. Clinical trials with inactivated monovalent (A/New Jersey/76) and bivalent (A/New Jersey/76-A/Victoria/75) influenza vaccines in Los Angeles children. [Results of coded trials of the activity of the trivalent subunit influenza vaccine Grippovak in Moscow kindergartens in December 1983 through the 1st quarter of 1984]. Correlation of Cellular Immune Responses with Protection against Culture-Confirmed Influenza Virus in Young Children
Trials of pneumococcal vaccine in healthy young adult population s suggest 75 to 95 per cent type-specific efficacy . Trials have not been done , however , in groups for which pneumococcal vaccine is currently recommended in the United States . To assess efficacy in the immunocompromised groups now receiving the vaccine , we compared serotypes of 35 isolates of Streptococcus pneumoniae isolated from blood or cerebrospinal fluid one month or longer after the patient had received commercially available pneumococcal vaccine with serotypes of 392 isolates  from unvaccinated persons surveyed in a study of the nationwide distribution of pneumococcal serotypes . Proportions of infections with vaccine serotypes were unexpectedly similar . An alternative approach to estimation of vaccine efficacy suggested an average efficacy of 36 per cent in persons of all ages . The estimated efficacy was lowest in children two to 10 years old ( less than or equal to 0 per cent ) and in persons with preexisting diseases that are thought to predispose to pneumococcal disease ( less than or equal to 0 per cent ) , and highest in the group over 10 years old ( 60 per cent ) . The possibility that efficacy is low in high-risk , immunocompromised population s makes it important to evaluate clinical efficacy and not just serum antibody responses in such groups This paper describes the epidemiological techniques available for measuring vaccine  efficacy and recommends a practical approach to their use . The efficacy of vaccines in clinical use can be determined by a variety of means , including screening , outbreak investigations , secondary attack rates in families or clusters , vaccine coverage assessment , and case-control studies . They all offer a means of monitoring vaccine programs under conditions of day-to-day vaccine use . A table summarizes the different techniques for measuring efficacy . The screening technique is the most useful and rapid means of determining whether there is a problem with a vaccine . All that is required is a reliable estimate of the proportion of cases occurring in vaccinated individuals and an estimate of the vaccine coverage in the population at risk . If the estimated efficacy is within expected limits , more detailed studies are not warranted . If the results suggest low efficacy , more rigorous methods are necessary to assess the efficacy more accurately . Of the more accurate methods available , outbreak investigation offers the simplest means of measuring vaccine efficacy and is the preferred technique if the situation permits . The biases inherent in the method can be minimized , particularly if the disease incidence rate is high during the outbreak and accurate records exist . In large population s , the underlying immunization status prior to the outbreak can be estimated using the same cluster sampling method used in coverage assessment s. Calculation of secondary attack rates in families is also an excellent and accurate means of measuring vaccine efficacy and is an acceptable alternative to the outbreak investigation . Vaccine coverage methods in endemic areas are best suited to urban areas where the measles incidence rate is high after age 11 months and low before 12 months , and maternal histories of disease are thought to be accurate . Case-control studies are best suited to areas where reliable personal immunization records may be difficult to find but other information , such as clinic records , may be available . No epidemiological method is perfect because it can not exactly duplicate the experimental conditions of a prospect i ve r and omized clinical trial . The most accurate results will be obtained when biases are anticipated and corrective measures are taken whenever possible . Clinical vaccine efficacy determinations are carried out in order to assess whether the observed pattern of illness is consistent with the proper use of a highly effective vaccine . The components of a vaccine efficacy evaluation -- case definition , case ascertainment , and vaccination status determination -- apply to studies on all vaccines Abstract We r and omized 115 children to trivalent inactivated influenza vaccine ( TIV ) or placebo . Over the following 9 months , TIV recipients had an increased risk of virologically-confirmed non-influenza infections ( relative risk : 4.40 ; 95 % confidence interval : 1.31 - 14.8 ) . Being protected against influenza , TIV recipients may lack temporary non-specific immunity that protected against other respiratory viruses 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 Background R and omized evidence for vaccine immunogenicity and safety is urgently needed in the setting of p and emics with new emerging infectious agents . We carried out an observational survey to evaluate how many r and omized controlled trials testing 2009 H1N1 vaccines were published among those registered , and what was the time lag from their start to publication and from their completion to publication . Methods PubMed , EMBASE and 9 clinical trial registries were search ed for eligible r and omized controlled trials . The units of the analysis were single r and omized trials on any individual receiving influenza vaccines  in any setting . Results 73 eligible trials were identified that had been registered in 2009–2010 . By June 30 , 2011 only 21 ( 29 % ) of these trials had been published , representing 38 % of the r and omized sample size ( 19905 of 52765 ) . Trials starting later were published less rapidly ( hazard ratio 0.42 per month ; 95 % Confidence Interval : 0.27 to 0.64 ; p<0.001 ) . Similarly , trials completed later were published less rapidly ( hazard ratio 0.43 per month ; 95 % CI : 0.27 to 0.67 ; p<0.001 ) . R and omized controlled trials were completed promptly ( median , 5 months from start to completion ) , but only a minority were subsequently published . Conclusions Most registered r and omized trials on vaccines for the H1N1 p and emic are not published in the peer- review ed literature CONTEXT Acute otitis media ( AOM ) frequently complicates influenza infection . Previous studies have found influenza vaccine effective in reducing the occurrence of AOM in children mainly older than 2 years . OBJECTIVE To evaluate the effectiveness of inactivated influenza vaccine in preventing AOM in children aged 6 to 24 months . DESIGN , SETTING , AND PATIENTS R and omized , double-blind , placebo-controlled trial of 786 children aged 6 to 24 months enrolled at Children 's Hospital of Pittsburgh before the 1999 - 2000 ( 411 children ) and 2000 - 2001 ( 375 children ) respiratory seasons ( defined as December 1 through March 31 of the respective following year ) . Children received influenza vaccine or placebo in a 2:1 ratio . The first cohort was observed for 1 year and the second cohort until the end of the ensuing respiratory season . INTERVENTION Two doses ( 0.25 mL each ) of inactivated trivalent subvirion influenza vaccine or placebo were administered intramuscularly approximately 4 weeks apart . MAIN OUTCOME MEASURES Proportion of children who developed AOM , monthly occurrence rate of AOM , estimated proportion of time with middle ear effusion , and utilization of selected health care and related re sources . RESULTS Of the 66 children in the vaccine group from whom serum sample s were collected , seroconversion against strains in the vaccine formulations developed in 88.6 % to 96.8 % , depending on the specific strain . The efficacy of the vaccine against culture-confirmed influenza was 66 % ( 95 % confidence interval [ CI ] , 34%-82 % ) in 1999 - 2000 and -7 % ( 95 % CI , -247 % to 67 % ) in 2000 - 2001 ; however , influenza attack rates differed between these 2 periods ( in the placebo group , 15.9 % and 3.3 % , respectively ) . Compared with placebo , influenza vaccine did not reduce the proportion of children who had at least 1 episode of AOM during the respiratory season ( in the first cohort : vaccine , 49.2 % vs placebo , 52.2 % ; P = .56 ] ; in the second cohort : vaccine , 55.8 % vs placebo , 48.3 % ; P = .17 ) . The vaccine also did not reduce the monthly rate of AOM ; the estimated proportion of time with middle ear effusion ; or the utilization of selected health care and related re sources . There were also no differences between the vaccine and placebo groups regarding any of these outcomes during peak influenza periods . The vaccines administered to both cohorts of children were well tolerated . CONCLUSION Administration of inactivated trivalent influenza vaccine to children aged 6 to 24 months did not reduce their burden of AOM or their utilization of selected health care and related re sources Abstract A trial of inactivated influenza vaccine containing the A/Hong Kong/68 strain was made in 800 boys in a boarding-school starting in 1970 . The boys had serum sample s withdrawn for antibody estimations and were allocated at r and om to vaccine and control groups . During an outbreak of influenza A due to the A/Engl and /42/72 strain , all boys with clinical influenza reported to the medical officer and the diagnosis was confirmed by laboratory examination . The vaccine was shown to confer substantial protection against the new virus strain . The presence of haemagglutinating ( H.I. ) antibody to either strain 6 weeks before the outbreak was associated with protection against influenza . In boys with H.I. antibody to A/Hong Kong/68 virus the attack-rate was 6 % , compared with 25 % in boys with no H.I. antibody to either virus strain . No influenza occurred in boys known to have H.I. antibody to the A/Engl and /42/72 strain . Three-quarters of the boys in whom A/Hong Kong/68 H.I. antibody had been naturally acquired developed A/Engl and / 42/72 H.I. antibody after vaccination . In contrast , the development of A/Engl and /42/72 H.I. antibody was less frequent after revaccination of boys in whom the A/Hong Kong/68 H.I. antibody had been induced by vaccination . A vaccine prepared from the A/Hong Kong/68 strain conferred substantial protection despite the recent antigenic shift of the influenza virus Clinical and serologic responses to inactivated influenza virus vaccines were studied in 444 children in Los Angeles under doubld-blind , placebo-controlled protocol s. One- and two-dose regimens employing monovalent ( A/New Jersey/76 ) and bivalent ( A/New Jersey/76-A/Victoria/75 ) vaccine were studied in separate trials . In a single dose , whole-virus vaccines were more potent than split-product vaccines as primary inducers of immunity against influenza A/New Jersey/76 virus . Split-product vaccines were better tolerated clinical ly and , after two-dose regiments , produced rates of seroconversion ( greater than 90 % ) against A/New Jersey/76 virus comparable to those produced by two doses of whole-virus vaccines . Analysis of heterotypic antibody responses induced by monovalent A/New Jersey/76 vaccines revealed only slight increases in antibody against influenza A/Victoria/75 virus . After vaccination with bivalent vaccines , levels of antibody against influenza A/Victoria/75 virus were significantly higher in subjects who received high doses of split-product vaccines than in subjects who received whole-virus vaccines During the autumn-winter epidemic of influenza-like diseases in December , 1983 - -first quarter , 1984 , in Moscow commissioned coded observations on the effectiveness of  prophylactic vaccination against influenza of 3 - 7-year-old children with a preparation " Grippovak SE-AZh "  were carried out in day-care centers . In the previous large-scale trials , 1981 - 1984 , the " Grippovak " had been evaluated positively as a completely harmless , serologically and immunologically active preparation reducing 3 - 3.5-fold the number of laboratory-verified cases of viral type A and B influenza in the vaccinees . In 1986 , however , the " Journal of Microbiology , Epidemiology , Immunology " ( JMEI , 2 : 49 - 54 ) published a paper whose authors , on behalf of the Commission which had checked the preparation in the day-care centers ( Z.A. Bashliaeva , A.A. Sumarokov , et al. ) , came to a conclusion that " Grippovak " was ineffective in children . Other members of the above Commission disagreeing with this conclusion made a repeat analysis of the decoded material s of the observations in the day-care centers using computer methods and demonstrated that because of significant prevalence of non-influenza ARD cases and recurrent ( up to 44 % ) ARD cases in children in the 4 months of observation , it was impossible to judge the effectiveness of the vaccine by comparison of the total incidence of influenza and ARD from the clinical data alone in the vaccinees and controls . ( ABSTRACT TRUNCATED AT 250 WORDS ABSTRACT The highly sensitive gamma interferon ( IFN-γ ) enzyme-linked immunosorbent spot ( ELISPOT ) assay permits the investigation of the role of cell-mediated immunity ( CMI ) in the protection of young children against influenza . Preliminary studies of young children confirmed that the IFN-γ ELISPOT assay was a more sensitive measure of influenza memory immune responses than serum antibody and that among seronegative children aged 6 to < 36 months , an intranasal dose of 107 fluorescent focus units ( FFU ) of a live attenuated influenza virus vaccine ( CAIV-T ) elicited substantial CMI responses . A commercial inactivated influenza virus vaccine elicited CMI responses only in children with some previous exposure to related influenza viruses as determined by detectable antibody levels prevaccination . The role of CMI in actual protection against community-acquired , culture-confirmed clinical influenza by CAIV-T was investigated in a large r and omized , double-blind , placebo-controlled dose-ranging efficacy trial with 2,172 children aged 6 to < 36 months in the Philippines and Thail and . The estimated protection curve indicated that the majority of infants and young children with ≥100 spot-forming cells/106 peripheral blood mononuclear cells were protected against clinical influenza , establishing a possible target level of CMI for future influenza vaccine development . The ELISPOT assay for IFN-γ is a sensitive and reproducible measure of CMI and memory immune responses and contributes to establishing requirements for the future development of vaccines against influenza , especially those used for children
BACKGROUND The consequences of influenza in children and adults are mainly absenteeism from school and work .
However , the risk of complications is greatest in children and people over 65 years of age .
This is an up date of a review published in 2011 .
OBJECTIVES To assess the effects ( efficacy , effectiveness , and harm ) of vaccines against influenza in healthy children .