Antibody persistence and Haemophilus influenzae type b carriage after infant immunisation with PRP-T

OBJECTIVES: To assess the persistence of serum Haemophilus influenzae type b antibodies and the prevalence of H influenzae type b carriage in a group of preschool age children previously vaccinated in infancy. DESIGN: Names were randomly selected from immunisation records. Families were visited on five occasions over a period of 12 months and throat swabs were taken from all family members present, with blood obtained from children at the first and last visits. RESULTS: One hundred and fifty three children at a median age of 3.6 years had a geometric mean titre (GMT) of 1.06 micrograms/ml (95% CI 0.80 to 1.38). Eight per cent had an undetectable antibody concentration, received a booster dose of plain PRP vaccine, and responded with concentrations > 2 micrograms/ml. GMT at 4.5 years of age was 0.89 microgram/ml (0.69 to 1.16). Twelve children who had been exposed to H influenzae had a GMT of 4.7 v 0.8 micrograms/ml for those without exposure. CONCLUSIONS: Accelerated immunisation against H influenzae without a second year booster results in persistence of satisfactory serum concentrations of antibody to 4.5 years of age. In those with undetectable antibody, immunological memory may still be present.     

Immunogenicity of Haemophilus b conjugate vaccine (meningococcal protein conjugate) in children with prior invasive Haemophilus influenzae type b disease

Children younger than 2 years of age with previous invasive Haemophilus influenzae (Hib) type b disease may not develop protective antibodies to antigens of Hib and may be at risk of developing a second episode of Hib disease. Twenty-three children with prior Hib disease were immunized with Haemophilus b conjugate vaccine (meningococcal protein conjugate). Children 12 to 24 months of age were given one dose of vaccine and children younger than 12 months of age were given 2 doses 2 months apart. Antibody to the polysaccharide capsule of Hib (PRP) was measured by radioimmunoassay. Eighteen children had preimmunization serum antibody concentrations less than 0.150 micrograms/ml. All 18 children responded with greater than 0.150 micrograms/ml of antibody after a single dose of vaccine. Only 1 of the 23 children had a preimmunization serum antibody concentration greater than 1.000 micrograms/ml. Seventeen children ultimately responded with greater than 1.000 micrograms/ml of antibody (P less than 0.0001), concentrations of antibody thought to correlate with protection. Haemophilus b conjugate vaccine (meningococcal protein conjugate) is immunogenic in children with invasive Hib disease. Children younger than 2 years of age with invasive Hib disease should be subsequently immunized with a Hib conjugate vaccine.     

IgG subclass response to immunization with Haemophilus influenzae type b polysaccharide-outer membrane protein conjugate vaccine

We immunized 117 children with either Haemophilus influenzae type b polysaccharide vaccine or type b polysaccharide coupled to an outer membrane protein of group B Neisseria meningitidis (conjugate vaccine), and measured the IgG, IgG1, and IgG2 subclass composition of antibody to type b polysaccharide in postimmunization sera by ELISA. The IgG responses of 51 children, 24-83 months of age, immunized for the first time with the conventional type b vaccine consisted of both IgG1 and IgG2 antibody (respective geometric means of 2.24 and 0.77 micrograms/ml). In contrast, the IgG responses of 28 infants, 2-17 months of age, immunized with conjugate vaccine were predominantly or exclusively IgG1 (genometric mean IgG1 and IgG2 antibody concentrations of 1.92 and 0.19 micrograms/ml). A total of 38 children was primed with conjugate vaccine between 2 and 17 months of age and boosted approximately 1 yr later. The 28 children boosted with type b polysaccharide vaccine showed memory antibody responses consisting of both IgG1 and IgG2 (respective geometric means of 12.7 and 4.8 micrograms/ml); the 10 children boosted with conjugate vaccine showed a similar pattern of IgG subclass responses (respective geometric means of 20.8 and 5.1 micrograms/ml, p greater than 0.4 compared to the respective geometric mean IgG1 and IgG2 values of the group boosted with polysaccharide). Thus, in children 24-83 months of age, immunization with conventional type b polysaccharide vaccine generally elicits both IgG1 and IgG2 responses, with a slight predominance of IgG1.(ABSTRACT TRUNCATED AT 250 WORDS)     

Immunogenicity of Haemophilus influenzae oligosaccharide-protein and polysaccharide-protein conjugate vaccination of children at 4, 6, and 14 months of age

At 4 and 6 months of age, 118 infants were vaccinated with either one of two Haemophilus influenzae type b capsular polysaccharide-protein conjugate vaccines: 72 infants received the polysaccharide coupled to diphtheria toxoid (PRP-D group), and 46 infants received polysaccharide-derived oligosaccharides coupled to CRM197 protein, a nontoxic mutant form of diphtheria toxin (HbOC group). A third dose of the same vaccine was given to 40 children in the PRP-D group and 25 children in the HbOC group at 14 months of age. Antibodies to the H influenzae type b capsular polysaccharide were measured by Farr-type radioimmunoassay in serum samples taken before each vaccination and 1 month after the second and the third doses. Adverse reactions monitored by a questionnaire were mild. After two vaccine doses, the geometric mean concentration of antibodies to H influenzae type b polysaccharide increased from 0.07 micrograms/mL in the prevaccination samples to 0.63 micrograms/mL in the PRP-D group and to 4.32 micrograms/mL in the HbOC group. In the following 7 months, the geometric mean concentrations declined to 0.38 and 1.12 micrograms/mL, respectively. The booster dose given at 14 months elicited a strong antibody response in both groups (to geometric mean concentrations of 29.7 and 58.3 micrograms/mL, respectively). Both vaccines appear to be capable of immunologic priming by immunization in infancy.     

Haemophilus influenzae type b conjugate vaccine trial in Oxford: implications for the United Kingdom.

The safety and immunogenicity of a Haemophilus influenzae type b conjugate vaccine was investigated in 103 infants immunised at 3, 5, and 9 months of age; the infants also received diphtheria, pertussis, and tetanus and polio vaccines. Side effects were compared with 99 matched infants receiving diphtheria, pertussis, and tetanus and polio vaccines only. No serious side effects were observed and the incidence of minor side effects was no greater in the recipients of H influenzae type b conjugate vaccine. Two doses of the vaccine (standard and low) were compared: geometric mean titres of serum anticapsular antibody rose from 0.11 microgram/ml before immunisation to 26.4 micrograms/ml after three immunisations with the standard dose and 14.6 micrograms/ml with the low dose. The geometric mean titre among 21 unimmunized infants at this age was 0.06 micrograms/ml. Both doses therefore generated antibody concentrations likely to be protective after three immunisations. There were no non-responders. Incorporation of an H influenzae type b conjugate vaccine into the primary immunisation schedule has the potential for preventing over 1000 cases of systemic H influenzae type b disease and 50 deaths each year in the United Kingdom.     

Immunogenicity of Haemophilus influenzae type b polysaccharide-tetanus protein conjugate vaccine in children with sickle hemoglobinopathy or malignancies, and after systemic Haemophilus influenzae type b infection.

To determine the immunogenicity of Haemophilus influenzae type b polysaccharide-tetanus protein conjugate vaccine in specific populations at risk, we administered vaccine to children with sickle cell anemia (n = 19; mean age, 18.3 months, malignancies (n = 18; mean age, 43.1 months), or a recent history of systemic H. influenzae type b infection (n = 17; mean age, 11.9 months). After one dose of polyribosylribitol phosphate-tetanus toxoid conjugate vaccine the geometric mean titers for polyribosylribitol phosphate antibody were 4.8 micrograms/ml (14/19 greater than 1 microgram/ml), 1.4 micrograms/ml (9/18 greater than 1 microgram/ml), and 5.6 micrograms/ml (15/17 greater than 1 microgram/ml) in these three groups, respectively. Children with sickle cell anemia or a recent history of systemic H. influenzae type b infection had polyribosylribitol phosphate antibody levels comparable to those of normal children of similar age after one or two doses of polyribosylribitol phosphate-tetanus toxoid conjugate vaccine. We conclude that this vaccine is immunogenic in children with underlying conditions associated with an increased risk of H. influenzae type b infection.     

Immunogenicity of the Haemophilus influenzae type b capsular polysaccharide conjugate vaccine in children after systemic Haemophilus influenzae type b infections

We immunized 24 patients (mean age 15.2 +/- 9.3 months) with polyribosylribitol phosphate-diphtheria toxoid conjugate vaccine (PRP-D) 2 months after a systemic Haemophilus influenzae type b infection. Children less than 24 months of age were immunized twice. Serum was obtained for antibody to PRP before and 1 or 2 months after immunization. Three of five children greater than 24 months of age and three of six children 18 to 24 months of age developed greater than 1 microgram/ml of antibody after immunization, and geometric mean postimmunization levels were significantly greater than preimmunization levels for both groups. However, two children who failed to respond to conventional PRP vaccine did not respond as expected to one dose of PRP-D. For children 7 to 17 months of age, the geometric mean PRP antibody levels increased as follows: preimmunization, 0.05 micrograms/ml; after the first dose, 0.28 micrograms/ml (p = 0.003); and after the second dose, 3.39 micrograms/ml (p = 0.001). Of 13 children, 10 developed antibody values greater than 1.0 micrograms/ml. PRP conjugate vaccines are immunogenic in young children who have not developed protective PRP antibody levels after a systemic H. Influenzae type b infection.     

Factors influencing immunogenicity and safety of two Haemophilus influenzae type b polysaccharide vaccines in children 18 and 24 months of age

The purpose of this study was to evaluate differences in the safety and immunogenicity of Haemophilus influenzae type b (Hib) capsular polysaccharide vaccine produced by two manufacturers (Connaught and Praxis) in children 18 and 24 months of age. Eighty-five children were evaluated in a prospective, double-blind, randomized fashion. Postvaccination antibody concentrations (measured by radioimmunoassay) and response rates were not significantly different between the two manufacturers' vaccines but immunogenicity was significantly less in 18-month-old children (antibody concentration, 0.149 microgram/ml) compared with 24-month-old children (0.838 microgram/ml) (P = 0.001). No significant differences were noted in the safety of the two vaccines. This study suggests that previously observed differences of immunogenicity data between various type b capsular polysaccharide vaccines are due to differences in antibody assays, not in vaccines. Eighteen-month-old children appear to have a relatively poor immune response to type b capsular polysaccharide. Therefore to optimize the benefits of immunization, we suggest children receive this vaccine at 24 months of age.     

Immunogenicity of Haemophilus influenzae type B vaccines in children with hepatoportoenterostomies

To assess the immunogenicity of HIB vaccines in patients in whom hepatoportoenterostomies were performed for biliary atresia, eight such children received Haemophilus influenzae type b-polyribosylribitol phosphate (HIB-PRP) vaccine and had pre- and postvaccination total serum anti-PRP antibody concentrations determined by radioimmunoassay. Preimmunization anti-PRP antibody levels ranged from less than 0.125 to 0.40 microgram/ml [geometric mean antibody titer (GMT) 0.106 microgram/ml], while postvaccination levels ranged from 0.161 to 1.192 micrograms/ml (GMT = 0.489 microgram/ml). Five children who did not achieve postimmunization anti-PRP antibody levels greater than 1.0 microgram/ml received 15 micrograms of either PRP coupled to diphtheria toxoid (PRP-D) or PRP coupled to an outer membrane protein complex of Neisseria meningitidis group B (PRP-NOMP) conjugate vaccine. Anti-PRP antibody levels 1 month after immunization with HIB conjugate vaccines ranged from 1.51 to 10.35 micrograms/ml (GMT = 3.386 micrograms/ml). Patients with extrahepatic biliary atresia and hepatoportoenterostomies who previously received the HIB-PRP vaccine should be revaccinated with PRP protein conjugate vaccines to ensure adequate protection against H. influenzae type b disease.     

Immunologic priming to capsular polysaccharide in infants immunized with Haemophilus influenzae type b polysaccharide-Neisseria meningitidis outer membrane protein conjugate vaccine

Thirty children vaccinated at 2 to 17 months of age with Haemophilus influenzae type b polysaccharide linked to a partially purified 40,000 dalton outer membrane protein of Neisseria meningitidis were revaccinated 10 to 14 months later with conventional H. influenzae type b polysaccharide vaccine. The geometric mean anti-type b antibody concentration before reimmunization was 0.68 micrograms/mL, and rose to 31 micrograms/mL in sera obtained 1 month later. The mean level after immunization was not significantly different than that in sera from 12 adults immunized with type b polysaccharide vaccine (51 micrograms/mL, P = 0.3), and was 10-fold higher than that of 13 control children immunized with type b polysaccharide for the first time (2.7 micrograms/mL, P less than 0.001). The IgG responses of the children first given conjugate vaccine and then conventional type b polysaccharide vaccine were of a similar magnitude as those in the immunized adults. Further, the children maintained high levels of serum antibody 6 to 8 months later. Ten other children vaccinated in infancy with conjugate vaccine, and again with conjugate vaccine 10 to 15 months later, showed similar antibody responses to those of the group given conjugate vaccine in infancy, and booster with conventional polysaccharide vaccine. Thus vaccination with H. influenzae type b polysaccharide-outer membrane protein conjugate vaccine primes the immune system to an IgG memory antibody response to either type b polysaccharide or conjugate vaccine. Post-booster sera from all children tested showed high titers of functional activity in a complement-mediated bactericidal assay. These data suggest that protection of most infants from type b Haemophilus disease may be achieved by a combination of immunization at 2 to 4 months of age with this conjugate vaccine, and reimmunization 1 year later with conjugate or conventional type b polysaccharide vaccine.     

Haemophilus influenzae b polysaccharide revaccination: a continued role for the unconjugated vaccine

In a study of the issue of revaccination with Haemophilus influenzae b polysaccharide vaccine, 36 children who had been vaccinated with polysaccharide vaccine at age 18 to 20 months were stratified according to their 3-week postvaccination anticapsular antibody concentration determined by radioantigen binding assay, then sequentially assigned to one of three groups so as to have comparable distributions of peak antibody concentrations. These children were revaccinated with polysaccharide vaccine at 24 to 27, 30 to 33, or 36 to 39 months of age. The post-reimmunization geometric mean antibody concentrations in these three groups were 3.1, 3.0 and 7.8 micrograms/ml, respectively, and the percentages rising to greater than 1 microgram/ml were 75, 80 and 93%. The geometric means and antibody response rates were nearly identical to age-matched control groups not previously vaccinated. Thus there was no evidence of priming (memory induction) or of tolerance induction by the early (18 months old) primary vaccination.     

Immunogenicity and reactogenicity of four Haemophilus influenzae type b capsular polysaccharide vaccines in Finnish 24-month-old children

Stimulated by questions raised on potential differences between the Haemophilus influenzae type b capsular polysaccharide (PRP) vaccines on the market and the applicability of the efficacy data of a similar PRP vaccine obtained in a large field study in 1974 in Finland, we wished to compare the immunogenicity of all these preparations in 24-month-old Finnish children. In our study 137 children received the now recommended 25-micrograms dose of 1 of 4 H. influenzae type b PRP vaccines currently available, and an additional 86 children received half this dose corresponding to the 12.7 micrograms used in 1974. Anti-PRP antibodies were measured in blood samples taken before and 4 weeks after vaccination by the same radioimmunoassay and in the same laboratory as in 1974. The vaccines were equally immunogenic. Furthermore the now recommended dose of 25 micrograms did not give results (geometric mean concentrations, 2.38 to 3.45 micrograms/ml) differing from those after a 12.5-micrograms (2.01- to 3.45-micrograms/ml) dose which was used in 1974. Antibody concentrations of 0.15 and 1.0 micrograms/ml were achieved in 91 to 95 and 66 to 84% of the children, respectively. The corresponding values after 1974 vaccinations were 3.53 micrograms/ml and 100 and 82% of children, respectively. The percentage of those responding with concentrations greater than or equal to 1 microgram/ml was somewhat higher in these Finnish children than reported for children of the same age receiving the same vaccine lots in the United States. Adverse reactions were mild or moderate and transient.     

Priming and induction of Haemophilus influenzae type b capsular antibodies in early infancy by Dpo20, an oligosaccharide-protein conjugate vaccine

A conjugate vaccine (Dpo20) was made by direct coupling of diphtheria toxoid and oligosaccharides obtained by periodate oxidation of Haemophilus influenzae type b capsular polysaccharide. This approach gave a higher multiplicity of saccharides per protein and greater immunogenicity in infancy than our previously studied conjugates. Thirty-three healthy infants received three sequential injections, and no serious side effects were observed. When Dpo20 was given with diphtheria-tetanus-pertussis vaccine at ages 2, 4, and 6 months, the geometric mean titer of anticapsular antibody rose to 5.9 micrograms/ml at age 7 months. Dpo20 given at 3, 5, and 7 months raised the mean to 3.2 micrograms/ml at 7 months (after two injections) and 15.4 micrograms/ml at 10 months. The antibodies included IgG and were bactericidal in vitro. Thus, antibody activities potentially protective against invasive H. influenzae b infections were induced in the most susceptible age range. The infants also became primed for mature-for-age responses to (unconjugated) polysaccharide vaccine given as a booster at age 12 months.     

Immunization of children with sickle cell disease with Haemophilus influenzae type b polysaccharide vaccine

There are limited data concerning safety and immunogenicity of Haemophilus influenzae type b polysaccharide vaccine in children with sickle cell disease. Ninety-eight patients with sickle cell disease (65 with SS phenotype, 23 with SC phenotype, and 10 with S beta-thalassemia) 1.5 to 20 years of age were given 25 micrograms of vaccine subcutaneously. The vaccine was well tolerated; mild side effects were observed in 6 of 98 (6.1%) children. In addition, one patient with a recent vasoocclusive crisis was hospitalized because of fever and vasoocclusive crisis 8 hours after vaccination. Prevaccination anticapsular antibody concentrations (by radioimmunoassay) were less than 0.15 microgram/mL in 7 of 11 children 18 to 24 months of age (geometric mean 0.17 microgram/mL), in 10 of 25 children 2 to 5 years of age (geometric mean 0.36 microgram/mL), and in 3 of 50 patients 6 to 20 years of age (geometric mean 1.03 microgram/mL). Inadequate response (1- to 2-month postvaccination antibody level less than 1 microgram/mL) was found in 3 of 5 children 18 to 24 months of age (geometric mean 1.74 microgram/mL), in 8 of 21 children 2 to 5 years of age (geometric mean 2.20 micrograms/mL), and in 2 of 49 patients 6 to 20 years of age (geometric mean 18.03 micrograms/mL). Six months after vaccination, greater than 1 microgram/mL of antibody was present in the 2 children 6 to 20 years of age with inadequate response but not in the 7 children 2 to 5 years of age with inadequate response.(ABSTRACT TRUNCATED AT 250 WORDS)     

Immunogenicity of Haemophilus influenzae type b polysaccharide-outer membrane protein conjugate vaccine in patients who acquired Haemophilus disease despite previous vaccination with type b polysaccharide vaccine

To investigate the basis of the immune defect in children who acquire invasive Haemophilus disease despite previous vaccination with Haemophilus influenzae type b (Hib) polysaccharide vaccine, we determined the ability of vaccine failure patients with low levels of serum anticapsular antibody (less than 1 microgram/ml) to respond to reimmunization. Thirty-four patients, ranging in age from 27 to 61 months, were vaccinated with either Hib polysaccharide (n = 20) or Hib polysaccharide-outer membrane protein conjugate vaccine (n = 14). All but three of the children had normal serum concentrations of immunoglobulins, including IgG2. The geometric mean serum anticapsular antibody concentration of the group given polysaccharide vaccine increased from 0.27 microgram/ml before vaccination to 0.65 microgram/ml 1 month later (p less than 0.05), but the magnitude of the response was nearly 10-fold less than that of 31 age-matched control children given polysaccharide vaccine (6.3 micrograms/ml, p less than 0.001). In contrast, all 14 patients with vaccine failure who were given conjugate vaccine showed increases of fivefold or more in serum anticapsular antibody (geometric means 0.35 and 12.8 micrograms/ml, respectively; p less than 0.001). All patients with vaccine failure who did not respond to polysaccharide vaccine were subsequently given conjugate vaccine, and all had high antibody responses. Most patients tested showed increases in complement-mediated serum bactericidal activity. These data suggest that immunization with conjugate vaccine confers protection against Hib disease to children who, because of genetic or other reasons, cannot respond to the unconjugated form of the polysaccharide vaccine.     

Haemophilus influenzae type b capsular polysaccharide vaccine in children: a double-blind field study of 100,000 vaccinees 3 months to 5 years of age in Finland.

A recently developed Haemophilus influenzae type b capsular polysaccharide vaccine was given to 48,977 children 3 months to 5 years of age; an equal number of children receiving group A meningococcal vaccine served as controls. The protection as well as serum antibody response was strongly age-dependent. Among children who had received the H. influenzae type b vaccine when 18 months of age or older, there were no cases of bacteremic disease caused by H. influenzae type b in the first year after vaccination. At the same time 11 such cases were seen in the control group of the same age, a highly significant difference. In the second year after vaccination two cases occurred in the H. influenzae type b-vaccinated group, five in the meningococcal-group A vaccinated group. No protection was seen among children who had been younger than 18 months when vaccinated, even if they received a booster dose of the vaccine. The serum antibody response to the H. influenzae type b polysaccharide, measured by radioimmunoassay, was poor in children below 18 months of age and good in those above it. No effect of the vaccine could be seen on the nasopharyngeal carriage of H. influenzae type b, which was approximately 6% in this age group. Adverse effects of the vaccine were mild.     

Persistence of serum antibodies elicited by Haemophilus influenzae type b-tetanus toxoid conjugate vaccine in infants vaccinated at 3, 5 and 12 months of age

Eighty-five children received three injections of a vaccine consisting of Haemophilus influenzae type b (Hib) capsular polysaccharide (CPS) conjugated to tetanus toxoid (TT) (Hib-TT) at 3, 5 and 12 months of age according to the vaccination schedule for Swedish children. Diphtheria-tetanus toxoid vaccine was concurrently injected at another site. Two dosages, 7.5 and 15 micrograms, of Hib CPS were studied. No serious reactions occurred. Hib-TT elicited fewer local reactions than diphtheria-tetanus toxoid vaccine. Significant increases in Hib CPS serum antibodies occurred after all injections in both dosage groups with virtually no differences between the two groups. After the first and second injections geometric mean serum antibody concentrations of both dosage groups combined increased to 0.49 and 3.71 micrograms/ml and 81 and 99% of the vaccinees, respectively, had concentrations greater than 0.15 micrograms/ml. After the third dose geometric mean concentrations increased to 13.7 micrograms/ml and all had concentrations greater than 0.15 micrograms/ml. The geometric mean Hib CPS antibody concentrations decreased to 1.24 micrograms/ml 18 months after the third injection, but 97% still had concentrations greater than 0.15 micrograms/ml. The rise of Hib CPS antibodies was mostly in the IgG class. The most pronounced increase was seen in the IgG1 subclass but there were also increase in IgG2 and IgG3. Protective concentrations of TT antibodies were found in all postimmunization sera. In conclusion Hib-TT is safe and immunogenic in infants and should be protective from 6 to 30 months and probably longer thereafter.     

Antibody responses to four Haemophilus influenzae type b conjugate vaccines

Serum antibody responses to four Haemophilus influenzae type b capsular polysaccharide-protein conjugate vaccines (PRP-D, HbOC, C7p, and PRP-T) were studied and compared in 175 infants, 85 adults and 140 2-year-old children. Antibodies to the H influenzae type b polysaccharide vaccines were determined with a Farr-type radioimmunoassay. The infants received two doses of vaccine at the ages of 4 and 6 months. After the first dose of vaccine, the geometric mean antibody concentration measured at the age of 6 months was 0.09 to 0.10 mg/L, only marginally higher than that measured before immunization in all infants who had received PRP-D, HbOC, or C7p but increased to 0.82 mg/L in those who had received PRP-T. One month after the second dose, the geometric mean antibody concentration was increased in all vaccine groups. No significant differences were noted between recipients of HbOC, C7p, or PRP-T (geometric mean antibody concentrations, 4.32, 3.10, and 6.10 mg/L, respectively), whereas the PRP-D recipients had a significantly lower geometric mean antibody concentration (0.63 mg/L). In contrast, PRP-D, HbOC, C7p, and PRP-T were all highly immunogenic in adults, with no differences noted among them. The 2-year-old children also responded to one dose of these vaccines with a high antibody concentration.     

Invasive Haemophilus influenzae type b disease in the Oxford region (1985-91)

For a seven year period (1985-91) clinical and epidemiological data were prospectively collected on children aged < 10 years with microbiologically confirmed invasive Haemophilus influenzae type b infection in the Oxford region to study the epidemiology of the disease and determine the potential impact of early primary immunisation in infants. Computer records of primary immunisations given to these cases were retrospectively analysed and, where necessary, hospital and general practitioner records were searched to determine the immunisation history. Over the seven year period, 416 cases of invasive H influenzae type b disease were reported. Widescale immunisation against H influenzae type b began in 1991 as part of a regional trial. The estimated annual incidence for invasive disease between 1985 and 1990 was 35.5 cases per 100,000 children aged less than 5 years; for H influenzae type b meningitis it was 25.1 per 100,000 children aged less than 5 years. The cumulative risks for invasive disease and meningitis by the fifth birthday were one in 560 and one in 800 respectively. The majority of disease (71%) occurred in children less than 2 years of age with the peak monthly incidences at 6 and 7 months of age. The overall mortality was 4.3% and 50% of these deaths occurred suddenly. Most (91%) of the children had received at least one primary immunisation against diphtheria, tetanus, and pertussis before H influenzae type b infection and there was only one case of parental refusal of immunisation. None had received H influenzae type b immunisation. Given a vaccine uptake of 90% by 5 months of age it is estimated that at least 82% of the H influenzae type b infections could have been prevented. Extrapolated nationally, 1150 cases of infection and 50 deaths could be prevented each year by routine primary immunisation.     

Invasive Haemophilus influenzae type b disease in the Oxford region (1985-91).

For a seven year period (1985-91) clinical and epidemiological data were prospectively collected on children aged < 10 years with microbiologically confirmed invasive Haemophilus influenzae type b infection in the Oxford region to study the epidemiology of the disease and determine the potential impact of early primary immunisation in infants. Computer records of primary immunisations given to these cases were retrospectively analysed and, where necessary, hospital and general practitioner records were searched to determine the immunisation history. Over the seven year period, 416 cases of invasive H influenzae type b disease were reported. Widescale immunisation against H influenzae type b began in 1991 as part of a regional trial. The estimated annual incidence for invasive disease between 1985 and 1990 was 35.5 cases per 100,000 children aged less than 5 years; for H influenzae type b meningitis it was 25.1 per 100,000 children aged less than 5 years. The cumulative risks for invasive disease and meningitis by the fifth birthday were one in 560 and one in 800 respectively. The majority of disease (71%) occurred in children less than 2 years of age with the peak monthly incidences at 6 and 7 months of age. The overall mortality was 4.3% and 50% of these deaths occurred suddenly. Most (91%) of the children had received at least one primary immunisation against diphtheria, tetanus, and pertussis before H influenzae type b infection and there was only one case of parental refusal of immunisation. None had received H influenzae type b immunisation. Given a vaccine uptake of 90% by 5 months of age it is estimated that at least 82% of the H influenzae type b infections could have been prevented. Extrapolated nationally, 1150 cases of infection and 50 deaths could be prevented each year by routine primary immunisation.