Immunologic Considerations for the Timing of the Booster Dose of 7-Valent Pneumococcal Conjugate Vaccine in Young Children The immunogenicity and safety of Haemophilus influenzae type b-tetanus toxoid conjugate vaccine in Gambian infants. Enhanced surveillance of invasive Haemophilus influenzae disease in England, 1990 to 1996: impact of conjugate vaccines. Combination of direct and indirect evidence in mixed treatment comparisons. Safety and immunogenicity of a combined diphtheria-tetanus-acellular pertussis-inactivated polio vaccine-Haemophilus influenzae type b vaccine administered at 2-4-6-13 or 3-5-12 months of age. The efficacy in Navajo infants of a conjugate vaccine consisting of Haemophilus influenzae type b polysaccharide and Neisseria meningitidis outer-membrane protein complex. Effect of neonatal immunization with diphtheria and tetanus toxoids on antibody responses to Haemophilus influenzae type b conjugate vaccines. Efficacy in infancy of oligosaccharide conjugate Haemophilus influenzae type b (HbOC) vaccine in a United States population of 61 080 children Serologic responses to an Haemophilus influenzae type b polysaccharide-Neisseria meningitidis outer membrane protein conjugate vaccine in very young Gambian infants. Immunogenicity of a Fourth Dose of Haemophilus influenzae Type b (Hib) Conjugate Vaccine and Antibody Persistence in Young Children from the United Kingdom Who Were Primed with Acellular or Whole-Cell Pertussis Component-Containing Hib Combinations in Infancy Response to conjugate Haemophilus influenzae B vaccine among infants in Niamey, Niger. Economisation of vaccination against Haemophilus influenzae type b: a randomised trial of immunogenicity of fractional-dose and two-dose regimens Randomised trial of Haemophilus influenzae type-b tetanus protein conjugate vaccine [corrected] for prevention of pneumonia and meningitis in Gambian infants. Priming effect, immunogenicity and safety of an Haemophilus influenzae type b-tetanus toxoid conjugate (PRP-T) and diphtheria-tetanus-acellular pertussis (DTaP) combination vaccine administered to infants in Belgium and Turkey. Immunogenicity of Haemophilus influenzae type b polysaccharide-Neisseria meningitidis outer membrane protein conjugate vaccine in 2- to 6-month-old infants. Fall in Haemophilus influenzae serotype b (Hib) disease following implementation of a booster campaign CONSORT 2010 Statement: updated guidelines for reporting parallel group randomised trials
Background : The booster ( fourth ) dose of 7-valent pneumococcal conjugate vaccine ( PCV7 ) is recommended to be given at 12–15 months but in Canada it better fits the national schedule at 18 months , prompting this comparison of the safety and immunogenicity of booster immunization at 15 or 18 months . Methods : Children who had completed a study of primary PCV7 immunization ( with final serology at 7–8 months of age ) were enrolled at 12 months , bled and r and omly assigned to receive a PCV7 booster at age 15 or 18 months , with serologic testing before and 4 weeks afterward . Adverse events were documented for 3 days postbooster . Antibody concentrations were measured for the 7 pneumococcal serotypes and Haemophilus influenzae type b at 7–8 , 12 , 15 or 18 months and after boosting . Results : Three hundred thirty-one children were boosted , 167 at 15 months and 164 at 18 months . Pneumococcal geometric mean antibody concentrations declined by 15 months to 23.4 % of peak geometric mean concentrations at age 7–8 months and to 19.8 % by 18 months . Spontaneous increases in 1 or more antibody concentrations were noted in 195 subjects ( 61.7 % ) , most commonly with types 6B and 19F . Antibody responses to PCV7 were similarly brisk at 15 and 18 months . Mild injection-site redness and swelling were significantly more frequent at 15 than 18 months but no other differences in reactogenicity were observed . Conclusions : Residual antibody concentrations differed minimally between 15 and 18 months . Spontaneous antibody increases often occurred before boosting , possibly from colonization . PCV7 booster vaccination at 18 months appears to be safe and provides comparable immunogenicity to 15 months vaccination In developing countries , Haemophilus influenzae type b is a major cause of meningitis and pneumonia in the 1st year of life . The safety and immunogenicity of a Haemophilus influenzae type b polysaccharide-tetanus toxoid conjugate vaccine ( PRP-T ) were evaluated in two studies of Gambian infants . In the first study , 131 infants were recruited and r and omized into three groups to receive PRP-T at 1 and 3 months ( group A ) , PRP-T at 2 and 4 months ( group B ) or no PRP-T ( group C ) . The liquid form of PRP-T was used . The geometric mean titre ( GMT ) of anti-PRP antibody 1 month after the second dose was 0.26 microgram/ml in group A and 0.41 microgram/ml in group B. In the second study , 66 infants were given PRP-T in the lyophilized form at 2 , 3 and 4 months of age . The GMT 1 month after the first dose was 0.09 microgram/ml , after the second 0.74 microgram/ml and after the third 2.32 micrograms/ml . After the third dose , 72 % of children had antibody levels greater than 1.0 microgram/ml and 93 % greater than 0.15 microgram/ml . No serious side-effects were observed and the rate of adverse reactions was consistent with the concurrent administration of diphtheria-tetanus-pertussis ( DPT ) vaccine We report an enhanced prospect i ve survey of invasive Haemophilus influenzae infections that has defined the pattern of invasive disease in five English regions for 2 years before and 4 years after the introduction of the H. influenzae type b ( Hib ) vaccination program .  During the prevaccination period the majority of cases of invasive H. influenzae were caused by type b ; most ( 89 % ) of these infections occurred in children < 5 years of age and the most common presentation was meningitis . Since the introduction of routine immunization of infants with conjugate Hib vaccine , there has been a 16-fold reduction in the annual attack rate of invasive Hib disease recorded in children < 5 years of age . This reduction is of a magnitude similar to that observed in other countries with Hib vaccination programs . The number of infections caused by non-type b H. influenzae has shown a small but progressive increase over the same period , emphasizing the need for continued surveillance . There was no increase in the number of infections caused by other serotypes . Diagnostic category varied with both age and serotype but was not affected by vaccine introduction ; meningitis was the most common presentation overall but pneumonia and bacteremia were more common in adults and with noncapsulated isolates Mixed treatment comparison ( MTC ) meta- analysis is a generalization of st and ard pairwise meta- analysis for A vs B trials , to data structures that include , for example , A vs B , B vs C , and A vs C trials . There are two roles for MTC : one is to strengthen inference concerning the relative efficacy of two treatments , by including both ' direct ' and ' indirect ' comparisons . The other is to facilitate simultaneous inference regarding all treatments , in order for example to select the best treatment . In this paper , we present a range of Bayesian hierarchical models using the Markov chain Monte Carlo software WinBUGS . These are multivariate r and om effects models that allow for variation in true treatment effects across trials . We consider models where the between-trials variance is homogeneous across treatment comparisons as well as heterogeneous variance models . We also compare models with fixed ( unconstrained ) baseline study effects with models with r and om baselines drawn from a common distribution . These models are applied to an illustrative data set and posterior parameter distributions are compared . We discuss model critique and model selection , illustrating the role of Bayesian deviance analysis , and node-based model criticism . The assumptions underlying the MTC models and their parameterization are also discussed METHODS In an open r and omized study we compared the safety and immunogenicity of two schedules for priming and booster vaccinations of infants . A pentavalent combination vaccine , including a lyophilized Haemophilus influenzae type b-tetanus toxoid conjugate vaccine reconstituted with a liquid diphtheria , tetanus , acellular pertussis ( pertussis toxoid and filamentous hemagglutinin ) and inactivated polio vaccine ( DTaP-IPV/Act-HIB ; Pasteur Mérieux Connaught , Lyon , France ) was administered to 236 Swedish infants either at 2 , 4 and 6 months or at 3 and 5 months , and a booster dose was administered 7 months after the last primary dose . Adverse events were monitored by diaries for 3 days after each vaccination and by questions at the ensuing visits . Antibodies against the different vaccine components were analyzed after the primary series of vaccinations , before and after the booster injections . RESULTS There were no serious adverse reactions , and the rates of febrile events and local reactions were low in both groups . The three dose primary schedule induced higher geometricmean concentrations for all antigens than did the two dose schedule , but there were no differences between the groups in proportions with protective antibody titers against diphtheria , tetanus , Hib and polio or in proportions with certain defined levels of pertussis antibodies . Prebooster results showed a similar pattern , with the exception that the group primed with three injections showed higher proportions of infants with detectable antibodies against polio-virus types 1 and 3 . After booster vaccinations there were no differences between the two schedules in geometric mean or in proportions with antibodies above defined antibody concentrations , indicating effective priming from both primary series of vaccinations . Conclusion . The combined vaccine DTaP-IPV/ Act-HIB vaccine was equally safe and immunogenic when administered according to both time schedules studied BACKGROUND AND METHODS Several conjugate vaccines against Haemophilus influenzae type b have been developed in the search for one that induces protection even in young infants . We evaluated the safety and efficacy of a conjugate vaccine that links the H. influenzae type b capsular polysaccharide to the outer-membrane protein complex ( OMPC ) of Neisseria meningitidis serogroup B. We conducted a double-blind , placebo , controlled trial in Navajo infants , who are at high risk for systemic infections caused by H. influenzae type b. The infants were r and omly assigned to receive the first dose of vaccine or placebo at 42 to 90 days of age and the second at 70 to 146 days of age . RESULTS Of the infants in the trial , 2588 were assigned to receive the vaccine and 2602 to receive placebo .  The mean follow-up was 269 days in the vaccine group and 267 days in the placebo group . Before the age of 18 months , there was 1 systemic H. influenzae type b infection in the vaccine group , as compared with 22 in the placebo group ( P less than 0.001 ; point estimate of efficacy , 95 percent ; 95 percent confidence interval , 72 to 99 percent ) . Of the 22 H. influenzae type b infections in the placebo group , 13 were meningitis . Among the children who received both doses , there was 1 H. influenzae type b infection in the vaccine group ( n = 2056 ) and 14 in the placebo group ( n = 2105 ) ( P less than 0.001 ; point estimate of efficacy , 93 percent ; 95 percent confidence interval , 53 to 98 percent ) . The single infection in the vaccine group occurred at 15 1/2 months of age in an infant with osteomyelitis . Between the first and second doses there were no H. influenzae type b infections in the vaccine group and eight in the placebo group ( P less than 0.005 ; point estimate of efficacy , 100 percent ; 95 percent confidence interval , 41 to 100 percent ) . CONCLUSIONS The H. influenzae type b OMPC vaccine , administered at 2 and 4 months of age , is safe and induces a high rate of protection against invasive disease caused by H. influenzae type b in infants under the age of 18 months . Protection begins after the first dose We r and omly assigned 150 newborn infants to receive diphtheria and tetanus toxoids ( DT ) or Hib oligosaccharide conjugate ( HbOC ) at birth to determine whether exposure to the Haemophilus influenzae type b ( Hib ) conjugate vaccines ' carrier proteins would enhance immune responses to subsequent administrations of HbOC or PRP-tetanus toxoid conjugate ( PRP-T ) at 2 , 4 , and 6 months of age . Their antibody responses were compared with those of 100 children immunized with HbOC or PRP-T beginning at 2 months of age . No serious adverse reactions were associated with neonatal vaccination . Administration of HbOC at birth did not lead to earlier or higher antibody levels . Newborn immunization with DT did not prime children for enhanced antibody responses . Moreover , Hib antibody levels were lower in DT-primed children than in children immunized beginning at 2 months of age . Diphtheria antibody levels , but not tetanus antibody levels , were also lower in children immunized with DT at birth . We conclude that neonatal immunization with Hib conjugate vaccines is not a means to provide earlier protection against invasive Hib disease . Newborn DT administration does not enhance subsequent antibody responses to Hib conjugate vaccines , and may lead to suppression of Hib and diphtheria antibody responses The efficacy of the HbOC conjugate Haemophilus influenzae type b vaccine was evaluated in a study population of 61 080 infants in the Northern California Kaiser Permanente Medical Care Program . Between February , 1988 , and June , 1990 , the HbOC vaccine was given as part of a three-dose series at 2 , 4 and 6 months of age to 20 800 infants . The study population included children with a well-care visit at a study center during the first 6 months of life . There were 25 cases of Haemophilus influenzae type b disease in the study population : 22 in unvaccinated children and 3 in children who received only one dose of HbOC vaccine .  The efficacy of the full three-dose series was evaluated by several methods : a primary analysis comparing fully vaccinated children with unvaccinated children from 7 to 18 months of age ; a stratified exact analysis adjusted for age and seasonality ; and a case-control analysis which further adjusted for known risk factors . The efficacy of three doses of vaccine was 100 % with the lower bound of the 95 % confidence interval for the three analyses at 68 , 71 , and 64 % , respectively . There were no cases of disease result ing from two doses of HbOC vaccine yielding an estimate of 100 % efficacy ( 95 % confidence interval , 47 to 100 ) for two doses of HbOC vaccine . However , for children who had received only one dose of HbOC vaccine , vaccine efficacy was estimated to be 26 % and the possibility that one dose of HbOC vaccine had no efficacy could not be excluded . An intent-to-treat analysis and supplementary analyses of possible sources of bias supported the conclusion that immunization with HbOC vaccine was effective in preventing H. influenzae type b disease in infancy Recent studies in the United States and Europe have shown that Haemophilus influenzae type b polysaccharide-protein conjugate vaccines can induce protective antibody levels in young infants , but it was not clear that this would be the case in African infants , to whom  H influenzae vaccines must be given at a very early age to prevent disease caused by H influenzae . Therefore , antibody responses to an H influenzae type b polysaccharide-Neisseria meningitidis outer membrane protein conjugate vaccine were measured in very young Gambian infants . In the first group ( n = 85 ) , to whom the vaccine was given at the ages of 1 and 3 months , the geometric mean antibody level rose from a prevaccination level of 0.23 microgram/mL to a postvaccination level of 1.27 micrograms/mL , and in the second group ( n = 56 ) , vaccinated at the ages of 2 and 4 months , the prevaccination level of 0.16 microgram/mL rose to a postvaccination level of 1.59 micrograms/mL. These two final postvaccination levels did not differ significantly , and interpolation suggests that similar antibody levels were present in both groups of infants at the age of 3 months . This is the age by which protection would need to be achieved to protect against H influenzae meningitis in The Gambia and in other countries where the infection has similar epidemiologic characteristics . No significant side effects of vaccination were noted ABSTRACT In response to the rising incidence of Haemophilus influenzae type b ( Hib ) disease in the United Kingdom , a national campaign to give a booster dose of single-antigen Hib conjugate vaccine to children aged 6 months to 4 years was undertaken in 2003 . Children ( n = 386 ) eligible for Hib vaccine in the campaign were recruited .  Hib antibody concentrations were measured before boost and at 1 month , 6 months , 1 year , and 2 years after boost and were analyzed according to children 's ages at booster dose and whether a Hib combination vaccine containing acellular pertussis ( aP ) or whole-cell pertussis ( wP ) components was given in infancy . The geometric mean antibody concentrations ( GMCs ) before the booster declined as the time since primary immunization increased ( P < 0.001 ) , and GMCs were threefold higher in recipients of wP-Hib than aP-Hib combination vaccines ( P < 0.001 ) . GMCs 1 month after the booster increased with age ( P < 0.001 ) as follows : 6 to 11 months ; 30 μg/ml ( 95 % confidence interval [ CI ] , 22 to 40 ) ; 12 to 17 months , 68 μg/ml ( 95 % CI , 38 to 124 ) ; and 2 to 4 years , 182 μg/ml ( 151 to 220 ) , with no difference according to the type of priming vaccine received . Antibody levels declined after the booster , but 2 years later , GMCs were more than 1.0 μg/ml for all age groups . By extrapolating data for the decline in antibody levels , we found the GMCs 4 years after boosting were predicted to be 0.6 , 1.4 , and 2.6 μg/ml for those boosted at 6 to 11 months , 12 to 17 months , and 2 to 4 years , respectively , with levels of at least 0.15 μg/ml in about 90 % of individuals . A booster dose of Hib vaccine given after the first year of life should provide long-lasting protection Despite near elimination of Haemophilus influenzae b ( Hib ) meningitis from several industrialized countries following introduction of conjugate Hib vaccines into infant immunization schedules , Hib remains a major cause of meningitis and pneumonia in re source -poor countries . In Niger , Hib causes nearly 200 cases of meningitis per 100,000 children < one year of age , and > 40 % of cases are fatal . We evaluated the immunogenicity of Hib polysaccharide-tetanus toxoid conjugate vaccine ( PRP-T ) administered in the same syringe as diphtheria-tetanus-pertussis ( DTP ) vaccine among infants in Niger . Infants were r and omized into group 1 ( PRP-T at six , 10 , and 14 weeks ) , group 2 ( PRP-T at 10 and 14 weeks ) , or a control group ( meningococcal A/C polysaccharide vaccine ) . By 14 weeks of age , all subjects in groups l and 2 had > or = 0.15 microg/ml of anti-PRP antibody , and 82 % versus 76 % had > or = 1.0 microg/ml of antibody ( P = not significant ) . By nine months of age the proportion of infants with > or = 0.15 and > or = 1.0 microg/ml was group I=97 % and 76 % ; group 2=93 % and 67 % ; controls=10 % and 2.6 % . Four weeks after the first , second , and third doses of PRP-T , infants in group 1 showed geometric mean titers ( GMTs ) of 0.19 , 3.97 , and 6.09 microg/ml while infants in group 2 had GMTs of 2.40 and 4.41 microg/ml four weeks after the delayed first and second doses . Both PRP-T groups had significantly higher GMTs at 18 weeks and nine months of age than infants in the control group . The Hib PRP-T vaccine was immunogenic in infants in Niger . The strong response after PRP-T was initiated one month after the first DTP vaccination may reflect carrier priming . Two dose schedules of PRP-T should be given serious consideration , particularly if their reduced cost permits vaccine introduction that would be otherwise unaffordable BACKGROUND The cost of Haemophilus influenzae type b ( Hib ) conjugate vaccines has limited their use in non-industrialised countries . To identify more economical vaccination schedules , we carried out a r and omised trial of the immunogenicity of alternative regimens to the st and ard three-dose series . METHODS 627 Chilean infants were r and omly allocated to one of four regimens with either Hib polysaccharide-tetanus toxoid conjugate vaccine ( PRP-T ) or Hib oligosaccharide-diphtheria mutant toxoid conjugate vaccine ( PRP-CRM197 ) , for a total of eight groups . All infants receive diphtheria-tetanus-pertussis ( DTP ) vaccine at ages 2 , 4 , and 6 months . The regimens included three full doses , three fractional doses consisting of one half or one third of the full dose , and a regimen of two full doses ( at age 4 and 6 months ) . The primary outcome was the proportion of infants with serum anti-polyribosylribitol phosphate ( PRP , the type b capsular polysaccharide ) concentrations of 0.15 microg/mL or more at age 8 months . FINDINGS 93 % ( 95 % CI 85 - 98 ) of infants vaccinated with three full doses of PRP-T or PRP-CRM197 ( 95 % CI 84 - 98 ) achieved anti-PRP concentrations of 0.15 microg/mL or more at age 8 months , compared with 91 % ( 83 - 96 ) to 100 % ( 95 - 100 ) of infants immunised with any fractional-dose regimen . Of the infants vaccinated with two doses of PRP-T or PRP-CRM197 , 99 % ( 93 - 100 ) and 87 % ( 77 - 93 ) developed anti-PRP concentrations of 0.15 microg/mL or more , respectively . INTERPRETATION 91 % ( 83 - 96 ) to 100 % ( 95 - 100 ) of infants immunised with one-half or one-third of a full dose of Hib conjugate developed protective antibody concentrations . Carrier priming with DTP may make two-dose schedules an option in some places . These alternative regimens could bring the cost of Hib vaccines within reach of countries that currently can not afford them BACKGROUND In developing countries , pneumonia and meningitis due to Haemophilus influenzae type b ( Hib ) are common in children under age 12 months and the mortality from meningitis is high . Protein-polysaccharide conjugate vaccines have brought Hib disease under control in industrialised countries . We did a double-blind r and omised trial in The Gambia to assess the efficacy of a Hib conjugate vaccine for the prevention of meningitis , pneumonia , and other invasive diseases due to Hib . METHODS Between March , 1993 , and October , 1995 , 42,848 infants were r and omly allocated the conjugate vaccine Hib polysaccharide tetanus protein ( PRP-T ) mixed with diphtheria-tetanus-pertussis vaccine ( DTP ) , or DTP alone at age 2 months , 3 months , and 4 months . Children who presented with signs of invasive Hib were investigated by blood culture and , where appropriate , by lumbar puncture , chest radiograph , or percutaneous lung aspirate . Children were followed up for between 5 and 36 months . FINDINGS The median ages at which children received the study vaccine were 11 weeks , 18 weeks , and 24 weeks . 83 % of children enrolled received all three doses of vaccine . 17 cases of culture-positive Hib pneumonia , 28 of Hib meningitis , and five of other forms of invasive Hib disease were detected amongst the study children . The efficacy of the vaccine for the prevention of all invasive disease after three doses was 95 % ( PRP-T vaccinees 1 , controls 19 [ 95 % CI 67 - 100 ] ) , for the prevention of Hib pneumonia after two or three doses , 100 % ( vaccinees 0 , controls 10 [ 55 - 100 ] ) , and for the prevention of radiologically defined pneumonia at any time after enrollment , 21.1 % ( PRP-T vaccinees 198 , controls 251 [ 4.6 - 34.9 ] ) . INTERPRETATION PRP-T conjugate Hib vaccine prevented most cases of meningitis and pneumonia due to Hib in Gambian infants . The reduction in the overall incidence of radiologically defined pneumonia in PRP-T vaccinees suggests that about 20 % of episodes of pneumonia in young Gambian children are due to Hib . The introduction of Hib vaccines into developing countries should substantially reduce childhood mortality due to pneumonia and meningitis To evaluate the priming effect , immunogenicity and safety of an Haemophilus influenzae type b ( Hib ) tetanus toxoid conjugate ( PRP-T ) and diphtheria-tetanus-acellular ( two component ) pertussis ( DTaP ) combination vaccine , a r and omized , comparative study was conducted in two centers , one in Belgium and one in Turkey . A total of 410 healthy infants , 160 in Belgium and 250 in Turkey , r and omly received DTaP and PRP-T vaccines  in one of three fashions . One group ( N = 138 ) received DTaP and PRP-T vaccines reconstituted immediately prior to injection at 3 , 4 and 5 months of age , and are referred to as the combined , short schedule group ( Co-S ) . A second group ( N = 135 ) received DTaP + PRP-T simultaneously but injected at different sites according to the same schedule , and are referred to as the associated , short schedule group ( As-S ) . The third group ( N = 137 ) also received DTaP + PRP-T at separate sites , but at 2 , 4 and 6 months , and are referred to as the associated , long schedule group ( As-L ) . The As-L group allowed for serological bridging with a Senegalese two-component pertussis vaccine efficacy trial , using the same batch of DTaP vaccine . Children of both short-schedule groups ( Co-S and As-S ) received , at the age of 12 - 14 months , a booster dose of DTaP vaccine associated with unconjugated PRP vaccine . Mixing of the vaccines did not affect the immune response to the antigens included in the DTaP vaccine . The immune response to Hib capsular polysaccharide , however , was significantly lower after combined administration ( Co-S group ) than after associated ( As-S group ) administration ( P < 0.0001 ) , with a similar trend among both countries ( GMTs , 1.78 microg/ml and 6.19 microg/ml in Belgium , and 5.02 microg/ml and 11.67 microg/ml in Turkey ) . Booster vaccination with the unconjugated PRP induced a vigorous and similar anamnestic response in both groups . Belgian infants showed a significantly lower immune response to all antigens than Turkish infants ( P < or = 0.001 for all antigens ) , with a similar trend among each study group . In all groups , the incidence of adverse events was lower than that usually reported after DTwP(whole-cell ) vaccine . Higher rates of systemic reactions were observed in the Belgian population , possibly due to differences in reporting practice . Our results indicate ( 1 ) that the combination vaccine , DTaP//PRP-T , represents an important improvement over the existing uncombined vaccines ; ( 2 ) that immunogenicity studies should include at least one booster injection to evaluate priming effects by combined vaccines ; and ( 3 ) that it is feasible and valuable to co-r and omize combination vaccine studies in sufficiently different geographical areas and child population Fifty infants , 2 to 6 months of age , were vaccinated with Haemophilus influenzae type b capsular polysaccharide covalently linked to an outer membrane protein from Neisseria meningitidis group B. Subjects were given two injections and were r and omly assigned to receive the injections separated by 1 or 2 months . Each dose contained 15 micrograms of polysaccharide and 51 micrograms of protein , or approximately twice the amount of polysaccharide as used in our previous trial ( Lancet 1986;2:299 ) . Fevers of 38.0 degrees to 38.8 degrees C developed in three infants ( 6 % ) within 24 hours after vaccination , but there were no other notable reactions . Following one injection , the geometric mean antibody concentration increased from 0.13 micrograms/mL in preimmune serum to 1.50 micrograms/mL in serum obtained 1 to 2 months later ( P less than .001 ) . After a second injection , there was a further increase in serum antibody ( geometric mean = 3.11 micrograms/mL , P less than .007 ) . The geometric mean antibody concentration of the group reimmunized 2 months after the first injection was higher than that in the group reimmunized after 1 month ( 3.95 v 2.32 micrograms/mL , P = .05 , by analysis of covariance with age as the covariant ) . These data confirm our previous preliminary observations on the safety and immunogenicity of this new conjugate vaccine in infants 2 to 6 months of age . The data suggest that a 2-month interval between the first and second injections results in higher levels of serum antibody than a 1-month interval Objective : To assess the impact of a Hib vaccination booster campaign targeting children aged 6 months to 4 years between May and September 2003 , following a nationwide increase in the number of invasive Haemophilus influenzae serotype b ( Hib ) cases in all age groups after 1999 . Design : The Health Protection Agency Centre for Infections prospect ively monitors all cases of H influenzae disease in Engl and and Wales and collects data from primary care trusts ( PCTs ) on coverage for vaccines in the childhood programme . Population : Adults and children in Engl and and Wales ( January 1991 to December 2006 ) Results : Data on vaccine coverage during the Hib booster campaign were available for 288/303 ( 95 % ) PCTs in Engl and and revealed coverage of 71.8 % for the 6–12-month age group and 63.2 % for the 13–48-month age group . The Hib booster campaign result ed in a dramatic reduction in cases within 12 months in the age groups targeted for the booster . This decline was followed by a reduction in the number of cases reported among older children and adults . Since the campaign , however , there has been an increase in the number of cases reported among 1–3-year-old children ( 13 cases in 2004 , 26 cases in 2005 and 32 cases in 2006 ) , primarily in children who were too young to be vaccinated in the booster campaign . This group of children will be targeted in the pre-school catch-up programme that began in September 2007 . Conclusions : The Hib booster campaign has helped to re-establish herd immunity in the UK . The increase in Hib disease among toddlers after 2004 supports the decision to introduce routine boosting for Hib at 12 months of age The CONSORT statement is used worldwide to improve the reporting of r and omised controlled trials . Kenneth Schulz and colleagues describe the latest version , CONSORT 2010 , which up date s the reporting guideline based on new method ological evidence and accumulating experience . To encourage dissemination of the CONSORT 2010 Statement , this article is freely accessible on bmj.com and will also be published in the Lancet , Obstetrics and Gynecology , PLoS Medicine , Annals of Internal Medicine , Open Medicine , Journal of Clinical Epidemiology , BMC Medicine , and Trials
BACKGROUND The optimal schedule and the need for a booster dose are unclear for  Haemophilus influenzae type b ( Hib ) conjugate vaccines  .
We systematic ally review ed relative effects of Hib vaccine schedules .