A new DTPw-HB/Hib combination vaccine for primary and booster vaccination of infants in Latin America. A combined liquid Hib (PRP-OMPC), hepatitis B, diphtheria, tetanus and whole-cell pertussis vaccine: controlled studies of immunogenicity and reactogenicity. The immunogenicity and reactogenicity of DTPw-HBV/Hib 2.5 combination vaccine: results from four phase III multicenter trials across three continents. Primary vaccination of infants with diphtheria-tetanus-acellular pertussis-hepatitis B virus- inactivated polio virus and Haemophilus influenzae type b vaccines given as either separate or mixed injections. Primary and booster vaccination with DTPw-HB/Hib pentavalent vaccine in Costa Rican children who had received a birth dose of hepatitis B vaccine. Assessment of the immunogenicity and reactogenicity of a quadrivalent diphtheria, tetanus, acellular pertussis and hepatitis B (DTPa-HBV) vaccine administered in a single injection with Haemophilus influenzae type b conjugate vaccine, to infants at 2, 4 and 6 months of age. Developing optimal search strategies for detecting clinically sound treatment studies in EMBASE. Immunogenicity and reactogenicity of DTPw–HB/Hib vaccine administered to Colombian infants after a birth dose of hepatitis B vaccine Assessment of the compatibility of co-administered 7-valent pneumococcal conjugate, DTaP.IPV/PRP-T Hib and hepatitis B vaccines in infants 2-7 months of age. Feasibility study of the immunogenicity and safety of a novel DTPw/Hib (PRP-T) Brazilian combination compared to a licensed vaccine in healthy children at 2, 4, and 6 months of age. Immunogenicity and safety in infants of a DTwPHib full liquid vaccine
OBJECTIVES In 1998 the World Health Organization ( WHO ) recommended the inclusion of Haemophilus influenza type B ( Hib ) conjugate vaccines in infant immunization programs , whenever in accordance with national priorities . GlaxoSmithKline Biologicals has developed a new pentavalent combined diphtheria-tetanus-whole cell pertussis-hepatitis B/Hib ( DTPw-HB/Hib ) vaccine containing 5 microg of polyribosylribitol phosphate ( PRP ) , and we assessed the immunogenicity and reactogenicity of primary and booster vaccination of healthy children with this new vaccine compared with a reference regimen consisting of the licensed DTPw-HB ( Tritanrix ) and Hib ( Hiberix ) vaccines given as simultaneous concomitant injections . METHODS We performed a r and omized , double-blind study from September 1998 to August 1999 to establish the immunogenicity and reactogenicity of primary and booster vaccination of healthy children with the new pentavalent combined DTPw-HB/Hib vaccine  given as a single injection , compared with the reference regimen . RESULTS Both vaccination regimens elicited excellent immune responses , with all subjects in both groups achieving seroprotective anti-PRP antibody concentrations of > or = 0.15 microg/mL one month after primary vaccination . The combined DTPw-HB/Hib vaccine was non-inferior to the licensed vaccines in terms of seroprotection/seropositivity/vaccine response rates for all antigen components . Persistence of antibodies against all study vaccine antigens up to the time of booster vaccination was comparable between groups , and a marked increase of all antibody concentrations was observed after the booster dose . Both vaccine regimens were similar in terms of their overall reactogenicity profiles . CONCLUSIONS Our results indicate that the new DTPw-HB/Hib pentavalent combination vaccine provides an efficient and reliable way of implementing WHO recommendations for controlling hepatitis B and Hib infections on a worldwide basis We evaluated the immunogenicity and reactogenicity of a new liquid pentavalent combination vaccine , which incorporates a diphtheria , tetanus and whole-cell pertussis vaccine ( DTP ) with Hib ( PRP-OMPC ) and hepatitis B vaccine ( HB ) , in a series of three studies involving 2156 infants . The vaccination schedule was 2 , 4 , 6 and 18 months for all studies . In addition , subjects in the third study also received a dose of monovalent hepatitis B vaccine  at birth . The principal study was a r and omised double blind trial of two separate , but concurrently administered vaccines in each of three groups : pentavalent vaccine [ DTP-Hib-HB ] plus placebo ( Group A , n=619 ) ; quadrivalent vaccine [ DTP-HB ] plus Hib vaccine ( Group B , n=620 ) ; and bivalent vaccine [ Hib-HB ] plus DTP ( Group C , n=226 ) . The second study ( Group D , n=231 ) was an open trial of three separate , but concurrently administered licensed control vaccines ( DTP , Hib and HB ) . The third study ( Group E , n=460 ) administered a dose of monovalent hepatitis B vaccine at birth followed by pentavalent vaccine as for Group A. Subjects were bled prior to the 2- and 18-month vaccinations , and a month after the 6- and 18-month vaccinations . A diary card was used to record subject temperatures and other systemic and local clinical signs for 7 days after each vaccination . The pentavalent vaccine , whether or not preceded by a birth dose of hepatitis B vaccine , was generally well tolerated at all administration times , and had a reactogenicity profile similar to that observed for licensed vaccine controls . Diphtheria and tetanus antibody levels were substantially above protective levels in all study groups . The anti-HBs responses ( % > or = 10 mIU/ml ) following the 6-month dose of vaccines were , respectively , for Groups A-E : 83.2 , 91.7 , 96.5 , 98.8 and 93.9 % , and following the 18-month doses : 87.9 , 97.5 , 98.8 , 98.8 and 92.8 % . Anti-PRP responses ( % > or = 1.0 microg/ml ) following the 6-month dose for Groups A-D were 86.0 , 90.5 , 91.2 , and 74.4 % , and after the 18-month dose for Groups A-E were 97.3 , 98.3 , 98.1 , 97.0 , and 99.5 % . Consistently higher geometric mean titres ( GMTs ) for pertussis antibodies to agglutinogens ( Agg2 , Agg3 ) and pertactin were recorded for the pentavalent vaccine compared to the licensed control vaccine , though they were somewhat lower for pertussigen ( PT ) . Except for the hepatitis B response , antibody responses induced by the pentavalent vaccine to all antigens with a schedule commencing at 2 months of age and completed at 18 months were equivalent to responses to the same antigens induced by the separate , but concurrently administered licensed control vaccines . A regimen of a birth dose of hepatitis B vaccine followed by pentavalent vaccine at 2 , 4 , 6 and 18 months was not countered by any clinical ly significant decrease in seroresponses This paper presents the results of four separate phase III trials , which assessed the immunogenicity and reactogenicity of DTPw-HBV/Hib 2.5 in comparison with licensed Tritanrix-Hep B ( GlaxoSmithKline Biologicals ) and Hiberix ( 10 microg PRP ) , given as separate or mixed injections ( 3 trials ) or with or without hepatitis B vaccine at birth ( 1 trial ) . The immunogenicity of DTPw-HBV/Hib 2.5 was non-inferior to the reference vaccine regimen in terms of seropositivity rates . The overall reactogenicity profile of DTPw-HBV/Hib 2.5 was also similar to that of the reference vaccine regimen . These results confirm the previously established immunogenicity and safety of reduced dose PRP conjugated vaccine regimens OBJECTIVE The aim of this open , multicenter , r and omized trial was to evaluate the immunogenicity and reactogenicity of a c and i date combined diphtheria-tetanus-acellular pertussis-hepatitis B virus-inactivated polio virus ( DTaP-HBV-IPV ) vaccine when given as either a mixed or as separate concomitant injections with Haemophilus influenzae type b ( Hib ) vaccine . STUDY DESIGN A total of 359 subjects were r and omized to receive either DTaP-HBV-IPV/Hib ( mixed administration - 180 subjects ) or DTaP-HBV-IPV + Hib ( separate administration in opposite limbs - 179 subjects ) at 2 , 3 , and 4 months of age . RESULTS After vaccination , seroprotective antibody concentrations against diphtheria , tetanus , hepatitis B , and polio viruses and a high ( > or = 97 % ) pertussis vaccine response were seen in almost all study participants . All subjects except one in the mixed administration group had postvaccination Hib anti-PRP antibody concentrations > or = 0.15 microg/mL. Of subjects in the mixed and separate group , 77.2 % ( geometric mean antibody concentration , 2 . 62 microg/mL ) and 88.6 % ( geometric mean antibody concentration , 4.45 microg/mL ) had Hib anti-PRP concentrations > or = 1 microg/mL , respectively . The addition of the Hib component to the 5-component vaccine did not increase the incidence of local or general reactions . CONCLUSION Both administrations of the c and i date vaccine were found to be safe , immunogenic , and well tolerated . Although anti-PRP geometric mean antibody concentrations and the percent of subjects achieving the 1 microg/mL seroprotective level were lower after the mixed administration , they were in the range seen with monovalent Hib vaccines or with other DTaP-based/Hib combinations licensed in some European countries . Therefore both administrations have the potential to simplify childhood immunization OBJECTIVE The DTPw-HB/Hib pentavalent combination vaccine has been developed following recommendations of the World Health Organization for the introduction of hepatitis B ( HB ) and Haemophilus influenzae type b ( Hib ) vaccines into routine childhood vaccination programs . The objectives of this study were to : 1 ) analyze the immunogenicity and the reactogenicity of the DTPw-HB/Hib pentavalent combination vaccine in comparison to separate injections of DTPw-HB and Hib vaccines as primary vaccination in a group of children who had received a dose of HB vaccine at birth and 2 ) in the second year of life to assess the antibody persistence as well as the response to a DTPw-HB/Hib or DTPw/Hib booster . METHODS In the first part of the study ( primary -vaccination stage ) , conducted in 1998 - 1999 , we analyzed the immunogenicity and reactogenicity of the DTPw-HB/Hib combination vaccine in comparison to separate injections of DTPw-HB and Hib vaccines as primary vaccination at 2 , 4 , and 6 months of age in 207 Costa Rican children who had received a dose of HB vaccine at birth . Later , in the booster-vaccination stage of the study , in 1999 - 2000 , in a subset of the children ( 69 toddlers , now 15 - 18 months old ) , antibody persistence was measured , and response to a DTPw-HB/Hib or DTPw/Hib booster was also assessed . RESULTS In both primary -vaccination groups , at least 97.5 % of the infants reached protective levels of antibodies ( seropositivity ) against the antigens employed in the vaccines . The DTPw-HB/Hib pentavalent combination vaccine did not result in more local reactions than did the DTPw-HB vaccine alone , and , in terms of general reactions , there was no clinical ly significant difference between the combination or separate injections , and with the pentavalent vaccine having the benefit of needing one less injection . Nine months after the third dose of the primary -vaccination course , antibody persistence was similar in both groups , with over 93 % of children still having protective/seropositive titers for Hib , HB , and tetanus and about 50 % for diphtheria and Bordetella pertussis . At 15 months of age , virtually all the toddlers responded with a strong boost response to all the vaccine antigens , whether they received the DTPw-HB/Hib pentavalent vaccine or the DTPw/Hib vaccine as a booster . Both booster regimens were equally well tolerated , indicating that up to five doses of the HB vaccine can be given without impact on safety . CONCLUSIONS Our study confirms that the DTPw-HB/Hib pentavalent vaccine is highly immunogenic as a primary vaccination in children who received an HB vaccine at birth , with the pentavalent combination inducing both persisting immunity and boostable memory . The pentavalent vaccine was safe both for primary and booster vaccinations . Thus , this study in Costa Rican infants supports the routine use of the pentavalent DTPw-HB/Hib vaccine as part of childhood vaccination programs in Latin America and the Caribbean This double-blind , r and omised study was performed to assess the immunogenicity and reactogenicity of three lots of a quadrivalent diphtheria-tetanus-acellular pertussis-hepatitis B vaccine ( DTPa-HBV ) co-administered with three lots of Haemophilus influenzae type b conjugate ( Hib ) vaccine in one injection , as a primary vaccination course in healthy infants at 2 , 4 and 6 months of age . 269 infants ( 8 - 11 weeks of age ) were r and omly allocated to three groups to receive DTPa-HBV/Hib vaccines , concomitantly with oral polio vaccine .  Blood sample s for antibody determinations were taken before vaccination and 1 month after the third dose in 262 subjects . Local and general symptoms were recorded by parents on diary cards . All vaccinees had post-vaccination protective anti-D and anti-T ( > or = 0.1 IU ml-1 ) antibodies , and 98 % had protective anti-HBs antibody titres ( > or = 10 mIU ml-1 ) . There were no statistically significant differences between groups in post-vaccination anti-D , anti-T , anti-HBs antibody geometric mean titres ( GMT ) , these being 3.49 IU ml-1 , 5.92 IU ml-1 and 1109 mIU ml-1 , respectively . All subjects responded to three pertussis components , i.e. pertussis toxin ( PT ) , filamentous haemagglutinin ( FHA ) and pertactin ( PRN ) . Although statistically significant differences in GMTs of anti-PT , anti-FHA and anti-PRN were found between groups , these were not believed to be of any clinical relevance as the minimum GMTs were 60 , 193 and 230 EL.U ml-1 for anti-PT , anti-FHA and anti-PRN , respectively . There were no statistically significant differences in anti-PRP antibody GMT ( 4.05 micrograms ml-1 ) between groups , 100 % and 85 % of subjects having titres > or = 0.15 and 1.0 microgram ml-1 , respectively . No symptoms were reported for one third of the subjects . Fever ( > 38 degrees C ) was reported after 16 % of doses , with < 1 % having > 39.5 degrees C. Almost all local and general symptoms were mild or moderate , and lasted less than 48 h. No subject dropped out due to a severe adverse reaction . The administration of an experimental mix of DTPa-HBV and Hib vaccines in a single injection is safe , well-tolerated and immunogenic for all vaccine components OBJECTIVE The ability to accurately identify articles about therapy in large bibliographic data bases such as EMBASE is important for research ers and clinicians . Our study aim ed to develop optimal search strategies for detecting sound treatment studies in EMBASE in the year 2000 . METHODS H and search es of journals were compared with retrievals from EMBASE for c and i date search strategies . Six trained research assistants review ed fifty-five journals indexed in EMBASE and rated articles using purpose and quality indicators . C and i date search strategies were developed for identifying treatment articles and then tested , and the retrievals were compared with the h and - search data . The operating characteristics of the strategies were calculated . RESULTS Three thous and eight hundred fifty articles were original studies on treatment , of which 1,256 ( 32.6 % ) were method ologically sound . Combining search terms revealed a top performing strategy ( r and om:.tw . OR clinical trial:.mp . OR exp health care quality ) with sensitivity of 98.9 % and specificity of 72.0 % . Maximizing specificity , a top performing strategy ( double-blind:.mp . OR placebo:.tw . OR blind : .tw . ) achieved a value over 96.0 % , but with compromised sensitivity at 51.7 % . A 3-term strategy achieved the best optimization of sensitivity and specificity ( r and om:.tw . OR placebo:.mp . OR double-blind:.tw . ) , with both these values over 92.0 % . CONCLUSION Search strategies can achieve high performance for retrieving sound treatment studies in EMBASE Objective : To evaluate , in an open study , the immunogenicity , safety and reactogenicity of a birth dose of hepatitis B vaccine followed by a three-dose course of diphtheria – tetanus whole-cell pertussis – hepatitis B vaccine , extemporaneously mixed with Haemophilus influenzae b ( Hib ) vaccine . Methods : At 2 , 4 and 6 months of age , a single group of 120 Colombian infants were enrolled in this study to receive a regimen consisting of three doses of the combination vaccine following a dose of hepatitis B vaccine at birth . Results : Seroprotection/vaccine response rates to all vaccine antigens was 98–100 % 1 month after completion of the full vaccination course . The vaccine had an acceptable reactogenicity profile and the incidence of reported local and general symptoms decreased with the administration of subsequent vaccine doses . Conclusion : The mixed DTPw – HB/Hib vaccine  was safe and well-tolerated , with high immunogenicity against all component antigens . Compared with previous studies , reactogenicity did not increase with the additional dose of hepatitis B vaccine given at birth . The DTPw – HB/Hib combination can be used to provide primary vaccination of infants who have already received a first dose of hepatitis B vaccine at birth This study assessed compatibility of concurrently administered 7-valent pneumococcal conjugate ( PCV7 ) , hepatitis B ( HB ) and DTaP.IPV/Hib vaccines .  Infants were given DTaP.IPV/Hib and HB at 2 , 4 , 6 months and r and omly assigned ( 2:1 ) to receive PCV7 concurrently or sequentially ( at 3 , 5 , 7 months ) . Antibody levels were compared in 246 concurrent and 122 sequential vaccinees .  Responses to  PCV7 , DTaP.IPV/Hib and HB were generally unaltered with concurrent administration except that Hib responses were increased ( p=0.008 ) and HB responses were reduced ( p=0.006 ) with concurrent dosing , the latter possibly from same thigh injection with DTaP.IPV/Hib . We conclude that PCV7 , DTaP.IPV/Hib and HB are compatible with concurrent , separate injections Vaccination of infants with conjugated Haemophilus influenzae type b ( Hib ) vaccines has been proven to reduce Hib meningitis by 95 % and pneumoniae by 20 % . The routine use of Hib vaccine is facilitated by the introduction of combination vaccines into the EPI ( Exp and ed Plan of Immunization ) . The objective of this study was to compare the immunogenicity and reactogenicity of an extemporaneously mixed DTPw/Hib ( diphtheria-tetanus-whole cell pertussis ) combination , using the technology of two Brazilian manufacturers , against a licensed DTPw/Hib European combination in 108 infants vaccinated at 2 , 4 and 6 months according to the local national schedule . The Brazilian combination was highly immunogenic with Hib seroprotection rates ( anti-PRP > 0.15 mg /ml of 98 % after 2 doses and 100 % after 3 ) . Also for tetanus and pertussis the new Brazilian combination was as immunogenic as the European counterpart , except the diphtheria seroprotection rates and titers were lower . There was also no clinical ly relevant difference in reactogenicity . If these feasibility results are confirmed , the Brazilian DTPw/Hib combination should help to boost the uptake of Hib vaccination in Brazil Aim : Combining paediatric vaccines is a rational solution to reduce the number of injections during a single clinical visit , to maintain parents ' compliance and to extend vaccine coverage . Different diphtheria , tetanus and whole cell pertussis (DTwP)‐containing combination vaccines are licensed and used world‐wide . This study assessed the immunogenicity and safety in infants of a combined diphtheria‐tetanus‐whole cell pertussis‐Haemophilus influenzae type b‐CRM197  conjugate full liquid vaccine .  Methods : The safety and efficacy of a combined ready‐to‐use liquid vaccine containing diphtheria and tetanus toxoids , cell suspension of Bordetella pertussis and H. influenzae type b‐CRM197 conjugate vaccine ( DTwPHib ) were assessed in infants eligible for the local Exp and ed Programme on Immunization ( EPI ) in Valencia , Spain . The comparative group received separate injections of reference vaccines DTwP + Hib . Results : Local and systemic reactions and adverse events were generally mild and similar in the two groups . DTwPHib elicited anti‐PRP antibody titres ±0.15 μg ml−1 in 97 % and DTwP + Hib in 94 % of infants . Furthermore , 89 % of DTwPHib and 78 % of DTwP + Hib recipients attained anti‐PRP antibody titres ±1.0 μg ml−1 , signifying long‐term protection . The anti‐PRP geometric mean titre was significantly higher in the combined DTwPHib vaccine group ( 6.65 vs 3.57 μg ml−1 ) . In both groups , 99 % of infants achieved protective ( ±0.01 IU ml−1 ) anti‐diphtheria antibody levels and all children achieved protective ( ±0.1 IU ml−1 ) anti‐tetanus antibody levels . DTwPHib caused a ±2‐fold increase in anti‐pertactin antibody titres in 91 % and a ±4‐fold increase in 82 % of recipients . The corresponding proportions in the DTwP + Hib group were 95 % and 90 % . DTwPHib induced a ±2‐fold increase in anti‐Agg 12 and 3 antibody levels in 79 % and a ±4‐fold increase in 73 % of recipients . The corresponding proportions among DTwP + Hib infants were 85 and 82 % . Conclusion : Overall , the combined liquid vaccine DTwPHib is a safe and effective immunogenic vaccine for EPI use in infants
BACKGROUND Advantages to combining childhood  vaccines include reducing the number of visits , injections and patient discomfort , increasing compliance , and optimizing prevention .
The World Health Organization recommends that routine infant immunization programs include a vaccination against Haemophilus influenza type B ( HIB ) in the combined diphtheria , tetanus , pertussis (DTP)-hepatitis B ( HBV ) vaccination .
The effectiveness and safety of the combined vaccine should be carefully and systematic ally assessed to ensure their acceptability by the community .
OBJECTIVES To compare the effectiveness of combined DTP-HBV-HIB vaccine with DTP-HBV and HIB vaccinations .