Incidences of vaccine-preventable Haemophilus influenzae type b pneumonia and meningitis in Indonesian children: hamlet-randomised vaccine-probe trial [Absence of meningitis caused by Haemophilus influenzae type b in The Netherlands following twofold vaccination]. Efficacy of Haemophilus influenzae type b polysaccharide-diphtheria toxoid conjugate vaccine in infancy. The efficacy in Navajo infants of a conjugate vaccine consisting of Haemophilus influenzae type b polysaccharide and Neisseria meningitidis outer-membrane protein complex. Efficacy in infancy of oligosaccharide conjugate Haemophilus influenzae type b (HbOC) vaccine in a United States population of 61 080 children Efficacy of Haemophilus influenzae type b conjugate vaccine PRP-T Clinical comparison of the Haemophilus influenzae type B polysaccharide-diphtheria toxoid and the oligosaccharide-CRM197 protein vaccines in infancy. Defining the burden of pneumonia in children preventable by vaccination against Haemophilus influenzae type b. A randomized, prospective field trial of a conjugate vaccine in the protection of infants and young children against invasive Haemophilus influenzae type b disease. Limited efficacy of a Haemophilus influenzae type b conjugate vaccine in Alaska Native infants. The Alaska H. influenzae Vaccine Study Group.
BACKGROUND Most studies of Haemophilus influenzae type b ( Hib ) disease in Asia have found low rates , and few Asian countries use Hib vaccine in routine immunisation programmes . Whether Hib disease truly is rare or whether many cases remain undetected is unclear . METHODS To estimate incidences of vaccine-preventable Hib pneumonia and meningitis among children younger than 2 years in Lombok , Indonesia , during 1998 - 2002 , we undertook a hamlet-r and omised , controlled , double-blind vaccine-probe study ( 818 hamlets ) . Children were immunised ( WHO schedule ) with diphtheria , tetanus , pertussis ( DTP ) or DTP-PRP-T ( Hib conjugate ) vaccine . Vaccine-preventable disease incidences were calculated as the difference in rates of clinical outcomes between DTP and DTP-PRP-T groups . Analyses included all children who received at least one vaccine dose . FINDINGS We enrolled 55073 children : 28147 were assigned DTP-PRP-T and 26926 DTP . The proportion of pneumonia outcomes prevented by vaccine ranged from less than 0 to 4.8 % . Calculated incidences of vaccine-preventable Hib disease ( per 10(5 ) child-years of observation ) for outcome categories were : substantial alveolar consolidation or effusion , less than zero ( -43 [ 95 % CI -185 to 98 ] ) ; all severe pneumonia , 264 ( 95 % CI less than zero to 629 ) ; all clinical pneumonia , 1561 ( 270 to 2853 ) ; confirmed Hib meningitis , 16 ( 1.4 to 31 ) ; meningitis with cerebrospinal-fluid findings consistent with a bacterial aetiology , 67 ( 22 to 112 ) ; and admission for suspected meningitis or presenting to a clinic with convulsions , 158 ( 42 to 273 ) . INTERPRETATION Hib vaccine did not prevent the great majority of pneumonia cases , including those with alveolar consolidation . These results do not support a major role for Hib vaccine in overall pneumonia-prevention programmes . Nevertheless , the study identified high incidences of Hib meningitis and pneumonia ; inclusion of Hib vaccine in routine infant immunisation programmes in Asia deserves consideration OBJECTIVE To determine the two-year results of nationwide vaccination with Haemophilus influenzae type b ( Hib ) vaccine on the occurrence of Hib meningitis in the Netherl and s. DESIGN Retrospective controlled study . SETTING The Netherl and s. METHOD Children born since April 1 , 1993 are vaccinated at the age of 3 , 4 , 5 and 11 months to protect them from infections with Hib . The number of Hib meningitis patients in the period 1 April , 1993 to 1 April , 1995 , among infants born in this period who were offered the Hib vaccine  ( study group ) , was compared with the number of Hib meningitis patients in the period 1 April , 1991 to 1 April , 1993 among children born in last-mentioned period ( control group ) . RESULTS Twenty-one cases of meningitis by Hib were observed in the study group . Twelve children who , as a consequence of their age , had only been vaccinated once or not at all ; 7 children were not vaccinated for several reasons . In addition one patient was infected by H. influenzae type f strain and one by a non-typable strain . In the control group 185 cases of Hib meningitis occurred . CONCLUSION Hib meningitis was not observed among infants who had been vaccinated at least twice Haemophilus influenzae type b capsular polysaccharide-diphtheria toxoid conjugate vaccine has recently been shown to be capable of inducing antibodies to H. influenzae in infants . In an evaluation of its clinical efficacy , 60,000 children were enrolled in an open trial in Finl and . Children born on odd-numbered days between October 1 , 1985 , and September 30 , 1986 , received the vaccine at 3 , 4 , 6 , and 14 months ; those born on even-numbered days served as controls . The geometric mean antibody titer measured in a cohort of 99 children rose from a prevaccination level of 0.08 microgram per milliliter at three months of age to 0.42 microgram per milliliter at seven months . Only minor adverse reactions were reported . Up to February 1987 , two cases of invasive H. influenzae infection had occurred among the children who had received three doses of vaccine , whereas 12 cases had occurred among the controls ( P = 0.0005 by Poisson one-tailed test ) . The rate of short-term ( average follow-up time , five months ) protection provided by this conjugate vaccine in infancy was thus 83 percent 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 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 Efficacy of the Haemophilus influenzae type b ( Hib ) conjugate vaccine PRP-T ( Pasteur-Merieux ) was evaluated in a controlled community intervention study in the Oxford region , UK .  PRP-T was offered to infants from May 1 , 1991 in three of the region 's eight districts and from July 1 , 1991 , in a fourth district . It was given by separate injection in addition to the st and ard diphtheria , tetanus , and pertussis vaccine according to an accelerated 2 , 3 , and 4 month schedule without a booster dose in the second year of life . By October 1 , 1992 , more than 90 % of infants in vaccine districts had received at least one dose of PRP-T. None of the infants given three doses had developed Hib infection , whereas 11 infections occurred in the control population ( vaccine efficacy 100 % , 95 % CI 80 - 100 % ) . Intention-to-treat analysis also showed a high estimate of efficacy for the vaccine ( 90 % , 50 - 99 % ) . Follow-up of study children until November 1 , 1993 , has shown only 1 vaccine failure in an infant , and no invasive infections in those older than 1 year ( average age 22 months ) . PRP-T vaccine had high protective efficacy with an accelerated immunisation schedule . Furthermore , the vaccine appears to remain protective through the second year of life without a booster dose . These findings provide encouragement for use of PRP-T in the Exp and ed Programme of Immunisation OBJECTIVE To compare two Haemophilus influenzae type B ( HiB ) conjugate vaccines , a polysaccharide-diphtheria toxoid conjugate ( PRP-D ) vaccine and an oligosaccharide-CRM197 protein conjugate ( HBOC [ PRP-CRM ] ) vaccine , in the same population . DESIGN One hundred twenty-five thous and infants were r and omized to receive the PRP-D or HBOC vaccine . Primary immunization consisted of two doses of either vaccine administered at 4 and 6 months and a booster dose was given at 14 to 18 months . Protection was assessed by recording episodes of invasive disease with HiB isolated from the blood or another normally sterile body site . SETTING One thous and thirty-six child health care centers in Finl and . PARTICIPANTS Infants born in Finl and during the 24-month period from 1987 to 1989 . INTERVENTION Each vaccine dose was injected intramuscularly in a volume of 0.5 mL. At the same time , a separate site was injected with the diphtheria and tetanus toxoids and pertussis vaccine at 4 months of age , with inactivated poliovirus vaccine at 6 months of age , and with measles-mumps-rubella vaccine at 14 to 18 months of age . MAIN RESULTS The mean anticapsular antibody concentration 1 month after the second dose was 0.63 micrograms/mL and 4.32 micrograms/mL in the PRP-D and HBOC vaccine recipients , respectively . The booster dose result ed in a high antibody concentration : 33.3 micrograms/mL and 58.3 micrograms/mL for PRP-D and HBOC vaccine recipients , respectively . At 36 months of age , the antibody concentration declined to 2.5 micrograms/mL and 5.6 micrograms/mL for PRP-D and HBOC vaccine recipients , respectively . After two doses of the vaccine , there were five episodes ( 39 were expected based on historical controls ) of invasive HiB disease in the PRP-D group and two episodes ( 35 were expected ) in the HBOC group . Hence , an 87 % ( 95 % confidence limit [ CL ] , 69 , 96 ) protection rate in the PRP-D group and a 95 % ( 95 % CL , 76 , 99 ) protection rate in the HBOC group were achieved . No episodes occurred after the booster dose in either group . CONCLUSIONS Both the PRP-D and HBOC vaccines are safe and effective . A two-dose primary vaccination schedule seems appropriate , at least in circumstances prevailing in Finl and and probably in other areas with similar epidemiological effects of HiB disease OBJECTIVES To determine the burden of pneumonia requiring hospitalization in infants and young children preventable by vaccination against Haemophilus influenzae type b ( Hib ) .  DESIGN Vaccination centers in Santiago , Chile , were r and omly selected to administer PRP-T , an Hib conjugate vaccine , combined with diphtheria-tetanus toxoids-pertussis ( DTP ) vaccine or DTP alone . SUBJECTS Infants who received > or = 2 doses of DTP or DTP and Hib conjugate vaccine combined .  MAIN OUTCOME MEASURES Pneumonia episodes leading to hospitalization accompanied by indicators of likely bacterial infection including radiologic evidence of alveolar consolidation or pleural effusion , an elevated erythrocyte sedimentation rate ( > or = 40 mm/h ) or bronchial breath sounds on auscultation . RESULTS In participants age 4 to 23 months , PRP-T reduced the incidence of pneumonia associated with alveolar consolidation or pleural effusion by 22 % ( 95 % confidence interval , -7 to 43 ) from 5.0 to 3.9 episodes per 1000 children per year . When the pneumonia case definition included any of the following , alveolar consolidation , pleural effusion , erythrocyte sedimentation rate > or = 40 mm/h or bronchial breath sounds , PRP-T provided 26 % protection ( 95 % confidence interval , 7 to 44 ) and prevented 2.5 episodes per 1000 children per year . CONCLUSIONS Hib vaccine provides substantial protection against nonbacteremic pneumonia , particularly those cases with alveolar consolidation , pleural effusion or other signs of likely bacterial infection . Hib vaccination prevented approximately 5 times as many nonbacteremic pneumonia cases in infants as meningitis cases , thus indicating that the largest part of the effect of Hib vaccination might be undetectable by routine culture methods BACKGROUND Haemophilus influenzae type b is the leading cause of invasive bacterial disease in young children . The capsular polysaccharide vaccine does not protect children at greatest risk ( those under the age of 18 months ) , but a polysaccharide-protein conjugate vaccine has proved to be more immunogenic in this age group . METHODS We enrolled 114,000 infants in Finl and in an open , prospect i ve , r and omized trial of a H. influenzae type b capsular polysaccharide-diphtheria toxoid conjugate vaccine ( polyribosylribitol phosphate-diphtheria toxoid [ PRP-D ] ) .  Children born on odd-numbered days were vaccinated at the ages of 3 , 4 , 6 , and 14 to 18 months ; those born on even-numbered days formed the control group and received the same vaccine at the age of 24 months . RESULTS After three doses of the vaccine there were 4 cases of verified bacteremic H. influenzae type b disease in the group receiving early vaccination , as compared with 64 cases in the control group , between the ages of approximately 7 and 24 months . The protective efficacy of the vaccine was thus 94 percent ( 95 percent confidence interval , 83 to 98 ) . No serious adverse effects were reported . The immune response to the conjugate vaccine was characteristic of a T-cell-dependent response when studied in a cohort of 120 infants . The primary immunization series result ed in a geometric mean concentration of anticapsular antibody of 0.53 micrograms per milliliter at the age of seven months , and the fourth dose evoked an anamnestic response , with a mean antibody concentration of 45.22 micrograms per milliliter . CONCLUSIONS A new conjugate vaccine consisting of the capsular polysaccharide of H. influenzae type b covalently linked to a protein carrier ( PRP-D ) , administered to infants beginning at the age of 3 months , is highly effective in protecting young Finnish children ( 7 to 24 months old ) against invasive H. influenzae type b infections BACKGROUND The prevention of invasive Haemophilus influenzae type b disease requires a vaccine that is effective when administered during the first six months of life . The infants of Alaska Natives are at particularly high risk of invasive H. influenzae type b disease . METHODS To evaluate the protective efficacy of a H. influenzae type b polysaccharide-diphtheria toxoid conjugate vaccine ( polyribosylribitol phosphate-diphtheria toxoid [ PRP-D ] ) , we enrolled 2102 Alaska Native infants in a r and omized , double-blind , placebo-controlled trial in which either the vaccine or a saline placebo was administered at approximately two , four , and six months of age . RESULTS After 3969 subject-years of follow-up and 32 episodes of H. influenzae type b disease , the overall incidence of invasive disease was not reduced significantly in the vaccinated subjects ( 6.0 cases per 1000 patient-years ) , as compared with the placebo controls ( 9.6 ) or with other Alaska Native infants ( 6.0 ) . After one , two , or three doses there was no significant protective efficacy with the vaccine ; after three doses the efficacy was only 35 percent ( 95 percent confidence interval , -57 to 73 ) . The lack of efficacy was not related to the age at onset of disease , age at immunization , type of disease , degree of Alaska Native heritage , time after immunization , or year of the study . Levels of H. influenzae type b anticapsular antibody in recipients of the vaccine became significantly higher than levels in those who received placebo only after the second and third doses . Even after the third dose , only 48 percent of the vaccinated infants had antibody levels of more than 0.1 microgram per milliliter ( geometric mean titer , 0.18 ) . Antibody responses did not vary with the level of maternally acquired antibody , degree of Alaska Native ancestry , or age at time of the first or second immunizations , but they increased with increasing age at time of the third dose ( P less than 0.001 ) . CONCLUSIONS We found no evidence that the PRP-D vaccine provides significant protection , at least for Alaska Native infants , against invasive diseases caused by H. influenzae type b. The ineffectiveness of the vaccine paralleled its limited immunogenicity
BACKGROUND Haemophilus influenzae ( H. influenzae ) is an important cause of meningitis and pneumonia in children , causing an estimated three million cases of serious disease and hundreds of thous and s of deaths annually worldwide .
The introduction of H. influenzae type b ( Hib ) vaccines into routine immunisation schedules in developed countries has been followed by a rapid decline in disease occurrence , but vaccine cost is a significant barrier to use in developing countries .
There is a need to determine the size of the effects of the vaccine , to enable cost-effectiveness comparisons with competing priorities in developing countries .
To determine the effects of conjugate Hib vaccine in preventing Hib disease or death in children under five years.2 .
To determine any serious adverse outcomes .