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.     

Haemophilus influenzae type b disease in the Oxford region.

A prospective survey of children in the Oxford region identified 200 cases of systemic Haemophilus influenzae type b disease in the first three and a half years of the study. The annual incidence in children less than 5 years of age was 33.4/100,000. This represents a cumulative incidence of one systemic infection in 600 children before their 5th birthday. The mortality was 5.0%. The risk of H influenzae type b meningitis was one in 850 with a mortality of 5.6%, and substantial morbidity among survivors. From the total live birth rate, about 1300 cases of systemic H influenzae type b disease, over 900 cases of H influenzae type b meningitis, and 65 deaths would be predicted annually in children in the United Kingdom.     

Non-type b Haemophilus influenzae disease: clinical and epidemiologic characteristics in the Haemophilus influenzae type b vaccine era

BACKGROUND: As a result of the decline in Haemophilus influenzae type b (Hib) disease caused by the widespread use of conjugate vaccines, non-type b H. influenzae will become a more important cause of H. influenzae (Hi) disease. Characterization of the clinical and epidemiologic features of non-b Hi disease is needed in the Hib vaccine era. METHODS: A prospective active surveillance study of invasive Hi disease involving pediatricians in the United Kingdom and Republic of Ireland. For the first phase of the study (October 1, 1992, to October 31, 1995) pediatricians were asked to report any child who had invasive Hi disease and who had received Hib conjugate vaccine. For the second phase of the study (November 1, 1995. To December 31, 1998) pediatricians were asked to report any child with invasive Hi disease regardless of vaccination status. RESULTS: During the study period 102 cases of invasive non-type b Hi disease and 106 cases of invasive Hib disease were reported in children who had been fully vaccinated against Hib. Children with non-type b disease were younger (16 vs. 22 months of age, P = 0.08), less likely to have meningitis and epiglottitis (P < or = 0.001) and more likely to have pneumonia and bacteremia (P < or = 0.001) than children with type b disease. For the last 2 years of the study invasive Hi disease occurring in a fully vaccinated child was more likely to be caused by a non-b strain than by a type b strain (58 vs. 38). In 1998 the incidence of non type-b Hi disease in all children <5 years of age in the UK was 1.3/100,000 as compared with an incidence of Hib disease of 0.6/100,000. The majority (88%) of non-b strains isolated in children were nontypable strains. CONCLUSIONS: Non-b Hi is a rare cause of disease in children, but in the Hib vaccine era it has become more common than type b as a cause of Hi disease in fully vaccinated children.     

Epidemiology of invasive Haemophilus influenzae type b disease among children in Finland before vaccination with Haemophilus influenzae type b conjugate vaccine

On the basis of intensified surveillance in Finland we report the epidemiology of invasive Haemophilus influenzae type b disease based on 333 consecutive culture-proved cases recorded during 1985 and 1986. The annual incidence rate among children younger than 5 years of age was 52/100,000; 46% of patients had meningitis, 29% had epiglottitis and 25% had other forms of invasive disease. The median age of patients was 27 months, with 45% younger than 2 years of age. Meningitis and epiglottitis were found more often among boys than among girls, whereas the opposite was found among patients with other types of invasive disease (P = 0.015). Among the latter 68% of children with pneumonia or septicemia were 2 years or older compared with 32% of patients with arthritis, cellulitis or pyelonephritis (P = 0.009). These background data are essential for correct interpretation and application of results from trials with H. influenzae type b conjugate vaccines that are currently ongoing in Finland.     

Haemophilus influenzae type b infections in Victoria, Australia, 1985 to 1987

Invasive Haemophilus influenzae type b (HIB) infections occurring from 1985 to 1987 in children younger than 16 years of age living in the state of Victoria were reviewed. There were 547 cases which fulfilled the case definition, including 231 cases of meningitis, 219 of epiglottitis and 97 other infections; 14 (2.6%) children died, 8 with meningitis, 5 with epiglottitis and 1 with pneumonia. Ninety-five percent of cases occurred in children younger than 5 years of age, in whom the case attack rate was 58.5/100,000/annum. Nearly two-thirds of cases (46% of meningitis; 91% of epiglottitis; 45% of other infections) occurred in children more than 18 months of age (the age at which vaccine is presently given in the United States). Compared with the United States, the case attack rate for HIB disease in Victoria is lower, the mean age of affected children higher and the proportion with epiglottitis is greater. However, the incidence, age distribution and clinical manifestations of HIB disease in Victoria are similar to those described in Scandinavia before the successful introduction of vaccines. Effective conjugate vaccines against HIB disease are now available and the majority of cases are preventable (depending on the immunization schedule used). These data suggest that immunization of Victorian children against HIB infection should be cost-effective.     

Recurrent invasive Haemophilus influenzae type b disease in Alaskan Natives

Alaskan Natives (Indians and Eskimos) have an extraordinary incidence of invasive Haemophilus influenzae type b (Hib) disease (500 cases/100,000 children younger than 5 years of age) and also an increased incidence of recurrent disease. However, the incidence of primary Hib disease and recurrent disease are not excessive in non-Native children in Alaska (mainly Caucasian). Twelve recurrent cases in Alaskan Natives were studied, 10 of which were detected in surveillance activities between 1971 and 1984. These recurrent episodes occurred 23 to 197 days after the initial episodes (median, 51 days); the overall rate of recurrent disease was 3.5%. The ages of the patients with recurrent disease were significantly younger than single episode cases. To determine if disease recurrence was a manifestation of the high disease incidence and earlier age at onset of disease, we calculated an expected number of recurrent cases for our study population, based on the incidence observed in children with first episodes and the period of observed follow-up. The expected number of recurrent cases was only 1.9, significantly fewer than the 10 observed, indicating that age and the high incidence of disease alone were not the only factors contributing to the recurrent disease. No other significant clinical or epidemiologic risk factors could be identified. Patients who develop recurrent invasive Hib disease may represent a subset of this population with unusual disease susceptibility.     

Invasive Haemophilus influenzae type b infections in Singapore children: a hospital-based study

OBJECTIVE: A 6-year (1990-95) hospital-based retrospective study was carried out to investigate the pattern of invasive Haemophilus influenzae type b (Hib) disease. METHODOLOGY: Cases with Hib isolated from sterile sites (blood, cerebrospinal fluid, or joint aspirate) were identified from the hospital's microbiological records, and their reviewed case records. Patients with pyogenic meningitis in the same study period were also identified to estimate the incidence of Hib meningitis. RESULTS: Twelve patients had positive cultures from sterile sites, of whom nine children were less than 5 years of age. These included seven cases of meningitis, one patient with acute epiglottitis, and one case of pneumonia. Three of the seven patients with meningitis had significant long-term sequelae. Our data also suggests a relatively low proportion of ethnic Chinese children with invasive disease. It was estimated that 18.4% to 41.1% of pyogenic meningitis in children admitted to the National University Hospital were due to Hib. The estimated annual attack rate of invasive Hib disease was at most 3.3 per 100 000 children aged less than 5 years (95% confidence interval: 2.6-3.5/100 000). CONCLUSION:: Invasive Hib infections are relatively uncommon in our community. This justifies the need for a cost effectiveness study before a universal Hib vaccination program is implemented.     

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.     

Haemophilus influenzae type b pneumonia.

Thirteen patients with Haemophilus influenzae type b pneumonia are reported to emphasise the clinical, radiographic, and therapeutic aspects of this illness. All but one patient was under 2 1/2 years of age. The presenting complaint was a variable duration of upper respiratory infection and fever in most cases. One-third of patients had radiographic evidence of pleural involvement; one-third showed a patchy bronchopneumonia on roentgenogram; and the remainder had segmental or lobar infiltrates. Clinical response to antibiotic therapy was prompt in patients without pleural involvement.