Haemophilus influenzae type b still remains a leading cause of meningitis among unvaccinated children--a prospective CSF analysis study

A prospective, hospital-based cerebrospinal fluid (CSF) analysis study was undertaken in 65 children who had diagnostic lumbar puncture on admission for suspected central nervous system infections. Twenty-three children were clinically diagnosed to have had sepsis and/or meningitis. CSF bacterial culture grew Haemophilus influenzae type b (Hib) in four cases and Streptococcus pneumonia (SP) was cultured in another child. Bacterial antigen was detected in 13 other CSF specimens and the pathogens were Hib (n = 9), SP (n = 3) and Group B Streptococcus (n = 1). No etiologic cause was identified to explain the abnormal CSF pleocytosis and biochemistry in the remaining five cases. In contrast, the CSF analysis was normal in 42 other children with probable viral and non-infectious neurological condition, mostly febrile convulsions. The overall frequency rate for all types of meningitis and especially for Hib meningitis were 43 and 31 cases per 100,000 children < 5 years of age, respectively. These findings support our earlier observations that Hib meningitis still remains the leading cause of childhood meningitis in our region. Also it reaffirms the observation that bacterial meningitis may often be under-reported if CSF positive culture alone is considered for the diagnosis.     

Epidemiology of invasive Haemophilus influenzae type b infections in Bedouins and Jews in southern Israel

We report the epidemiology of invasive Haemophilus influenzae type b disease requiring hospital intervention in Southern Israel, an area that contains two ethnic populations, Bedouins and Jews. The study is based on 107 blood or cerebrospinal fluid culture-positive cases during the years 1984 to 1988. The annual incidence rate among children younger than 5 years of age was 51/100,000 (48/100,000 for Jews and 58/100,000 for Bedouins). Thirty-nine percent of patients had meningitis, 32% had pneumonia and 31% had otitis media. Epiglottitis was present in only one case (less than 1%). The median age was 8 months. Twenty-six percent of the cases were 6 months old or younger, 75% were 1 year old or younger and 87% were 18 months old or younger. Ninety-five percent of all meningitis cases occurred during the first 18 months of life. A projected number of 2938 hospitalization days and 9.8 deaths/year for a population in which 100,000 births occur yearly was calculated. The major impact of invasive H. influenzae type b infections and the very young age involved justify initiation of H. influenzae vaccine studies in our region.     

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.     

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.     

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.     

Bacterial meningitis following introduction of Hib conjugate vaccine in northern Uganda

BACKGROUND: St Mary's Hospital, Lacor is in Gulu district in northern Uganda. Owing to conflict and insurgency, the majority of the hospital population live in internally displaced people's camps. There is ongoing public health surveillance of paediatric bacterial meningitis by the hospital. Before the introduction of Haemophilus influenza type b (Hib) conjugate vaccine in June 2002, Hib was the leading cause of bacterial meningitis in the area. METHODS: All patients with suspected bacterial meningitis between April 2003 and August 2006 were recruited. Meningitis was confirmed by isolation of bacteria. RESULTS: During the study period, 4986 cases of suspected bacterial meningitis were identified, 395 of whom had purulent cerebrospinal fluid (CSF). A culture was obtained from 259 (65%): Streptococcus pneumoniae 132 (51%), H. influenzae 22 (8.5%), salmonella spp 85 (32.8%), Neisseria meningitidis 9 (3.5%) and others 11 (4.2%). Over the surveillance period, there was a remarkable decline in the prevalence of H. influenza meningitis to only three cases or fewer per year compared with 42 in 2001. The minimum incidence of Streptococcus pneumoniae meningitis among children under 5 years of age was 33.7/100,000 of population and it was more prevalent during the dry season. The minimum incidence of non-typhoidal salmonella spp meningitis was 22.7/100,000, making it the second most common cause of paediatric bacterial meningitis with a case fatality rate of 18.2%. CONCLUSION: Hib conjugate vaccine delivered through the national immunisation programme is very effective in reducing Hib meningitis in children under 5 years of age. Continued laboratory-based surveillance of bacterial meningitis in Africa is needed to assess the effectiveness of vaccination programmes and detect other vaccine-preventable pathogens.     

Epidemiology of bacterial meningitis.

This 10 year retrospective study of all causes of bacterial meningitis for children resident in Nottingham District Health Authority area reports an annual incidence rate per 100,000 children aged 0-16 years of 16.0 (95% confidence interval 14.0 to 18.1). There was a steady increase in incidence from 9.6/100,000 in 1980 to 24.3/100,000 in 1989. This was mainly due to an increase in the incidence of meningococcal infections in the age group 1 month to 5 years. Incidence rates varied with age being: 37.2/100,000 (25.9 to 53.5) for 0-28 days of age, 115.5/100,000 (93.9 to 141.9) for 1-11 months of age, 28.5/100,000 (23.1 to 35.3) for 12-59 months of age, and 2.8/100,000 (1.9 to 4.1) for 5-16 years of age. Overall annual mortality incidence per 100,000 was 1.8 (1.2 to 2.8). For the different age groups this was: 10.1 (4.8 to 21.1) for 0-28 days, 11.5 (6.0 to 22.2) for 1-11 months, 1.0 (0.3 to 3.1) for 12-59 months, and 0.4 (0.1 to 1.2) for 5-16 years of age. There were interactions between the type of meningitis and the year of the infection on the mortality rate. Mortality decreased in those with infections caused by bacteria other than Neisseria meningitidis and Haemophilus influenzae.     

Incidence of invasive pneumococcal disease in Sydney children, 1991-96

OBJECTIVE: Few data are available on invasive disease due to Streptococcus pneumoniae in representative Australian childhood populations. This study aimed to determine the age-specific incidence of invasive pneumococcal disease in Sydney children. METHODOLOGY: Population-based prospective study where isolates of Streptococcus pneumoniae from normally sterile sites were identified through an established laboratory surveillance network. Isolates came from children aged under 15 years living within the boundaries of Central, Eastern. Southern, Western and South-western Sydney Area Health Services from 1 July 1991 to 30 June 1996. RESULTS: Invasive pneumococcal disease was identified in 320 children during a 5-year period, of whom 193 (60%) were under 2 years of age. The incidence per 100,000 children was 12.7 per 100,000 (95% CI: 11.4-14.2/100,000) under 15 years; 31.7 (95% CI 28.1-35.7) under 5 years, and 45.5 (95% CI 38.9-53.3) under 2 years. The incidence of pneumococcal meningitis in children aged under 2 years was 10.5 per 100,000 (95% CI: 7.4-14.5/100,000). CONCLUSIONS: The incidence of childhood invasive pneumococcal disease in Sydney was stable during 1991-96 and comparable to rates reported from other industrialized countries. There was no evidence of any change in pneumococcal disease incidence with reduction in invasive Haemophilus influenzae type b (Hib) disease following introduction of Hib immunization.     

The epidemiology of Haemophilus influenzae type b meningitis in Burkina Faso

BACKGROUND: Haemophilus influenzae type b (Hib) disease burden studies are important to conduct in African countries that plan to introduce vaccine so that vaccine impact can be documented. METHODS: We implemented population-based meningitis surveillance in 3 districts of Burkina Faso for 12 months each during 2002-2003 and 2004-2005 using polymerase chain reaction, culture and antigen detection. RESULTS: Lumbar puncture was performed on 1686 patients and 112 had Hib identified. Persons <1, <5, 5-14 and 15+ years of age had annual Hib meningitis incidences of 97, 34, 2.1 and 0.55 per 100,000, respectively; overall case fatality proportion was 25%. During the historic meningitis epidemic season months of December through April, the proportion of purulent cerebrospinal fluid among children aged <5 years that yielded Hib was 27% compared with 30% during other months. Twenty-five of 98 persons with information available were treated with only one or 2 doses of oily chloramphenicol. Among children age <5 years with Hib meningitis, 28% were pretreated with antimalarials and antimalarial pretreatment was associated with delay in hospitalization. CONCLUSIONS: In Burkina Faso, Hib meningitis incidence and case fatality proportion are high and thus vaccine could have a substantial impact. While awaiting well-implemented routine infant Hib vaccination, empiric case management for pediatric meningitis in sub-Saharan Africa must recognize that Hib is likely even during the epidemic season. In malaria-endemic areas, pediatric Hib meningitis case management may be adversely affected by the similar presentation of these 2 diseases.     

Sequelae of Haemophilus influenzae type b meningitis in Aboriginal and non-Aboriginal children under 5 years of age

Between 1984 and 1990, 257 cases of Haemophilus influenzae type b (Hib) meningitis occurred in children under five years of age in Western Australia. We obtained information on possible sequelae in 131 cases (all non-Aboriginal) by medical record review and parental interview, and in a further 116 cases (60 non-Aboriginal, 56 Aboriginal) by medical record review only; no follow-up information was available for ten children (nine non-Aboriginal, 1 Aboriginal). The incidence of Hib meningitis in children under five years of age was 26.3 per 100000 for non-Aboriginal and 152.2 per 100000 for Aboriginal children. The case fatality rate was 3.5% for non-Aboriginal children and 14.0% for Aboriginal children. Sequelae were recorded for 17.1% of non-Aboriginal and 22.4% of Aboriginal children who survived Hib meningitis. Surviving Aboriginal children experienced severe sequelae following Hib meningitis almost three times more frequently than surviving non-Aboriginal children (10.5%vs 3.6%), although mild and moderate sequelae were not more common in Aboriginal children. The information on incidence and severity of sequelae in this study was obtained by chart review and parental interview, and hence may be subject to error or bias, particularly for mild and moderate disabilities. Outcomes like death and severe sequelae, such as cerebral palsy and profound intellectual and physical disability, are less subject to bias. Of Aboriginal children who contracted Hib meningitis in Western Australia over the study period, 22.8% either died or had severe sequelae, while only 7.0% of non-Aboriginal children experienced these severe outcomes.     

Effectiveness of Haemophilus influenzae B-diphtheria conjugate vaccination in German children]

BACKGROUND: In 1990 the Haemophilus influenzae b-Diphtheria conjugate vaccine (Hib-D) was introduced in Germany. In addition, most children under 18 months of age failed to develop protective levels of Hib antibodies in response to systemic infections. METHODS: To evaluate the protective efficacy of the Hib-D vaccine in Germany a post marketing case-control study was performed during 1.5. 1990-30.4. 1992. Surveillance for invasive Hib-infections was maintained by pediatricians of 8 hospitals in the Rhein-Main area. The antibody responses to Hib were evaluated by ELISA at the onset (days 0-3) and during remission of disease. RESULTS: During the first year of the study 23 cases per 100,000 children of invasive Hib-infections were recorded. Of these children, 15 suffered from meningitis, 6 from epiglottitis and one from cellulitis and pericarditis respectively. None of these patients had been vaccinated except for one, who received two injections of Hib-D. Due to increased acceptance of the Hib-D vaccine we found a significant reduction of invasive Hib-infections (6 cases per 100,000 children) in the second year of the study. Again, of these children only one child was vaccinated. As expected, in all patients investigated the initial Hib antibody level was below 1 microgram/ml. The development of Hib specific immunity to invasive disease was clearly age dependent: 10 of 11 children below 18 months failed to produce any Hib antibodies (> 0.15 microgram/ml) in response to their infection. In contrast 8 of 10 children older than 18 months developed protective antibody levels to Hib. CONCLUSIONS: The incidence of serious Hib-disease has significantly decreased in Germany since the introduction of the Hib-D vaccine. Because no other Hib vaccine was licensed in Germany our data confirm efficacy and safety of Hib-D reported previously. In addition, children, who contracted disease before 18 months of age, remain susceptible to Hib and require active immunization for protection.     

Value of pneumococcal vaccination in infants and young children]

Streptococcus pneumoniae is a common cause of meningitis, sepsis, pneumonia, acute otitis media, and sinusitis in children. Children younger than 24 months have the highest rates of invasive pneumococcal infections (Germany 1997-1999: 19.5/100,000/year). Pneumococcal infections cause in Germany 220-250 cases of meningitis, about 50,000 of pneumonia (children younger than 5 years) and more than 1 million cases of otitis media (children) annually. The case-fatality rate for invasive pneumococcal diseases is high (1997-1999 5.5%, meningitis 8.3%). 20-30% of survivors from meningitis suffer from CNS-related sequelea. In children up to 2 years vaccination with the heptavalent pneumococcal conjugate vaccine can reduce invasive pneumococcal diseases by about 80% and otitis media and recurrent otitis media by 6% and 9-16%, respectively. Due to the increased risk of pneumococcal infections in the first two years of live all children of this age group should be vaccinated. The high rate of resistance of pneumococci against macrolides in Germany, the high rate of non-licensed antibiotics in infants and the inefficacy of the 23-valent vaccine in children younger than 2 years makes the new vaccine to a necessary alternative.     

Haemophilus influenzae type b meningitis in the state of Paraná, Brazil

OBJECTIVE: During the second half of 1996, the municipalities of Londrina and Curitiba (State of Paraná, Brazil) included Haemophilus influenzae type b (Hib) vaccine into their routine vaccination regimen, approximately 30 months before its introduction into the National Immunization Program. The present study aimed at verifying the incidence of meningitis caused by Hib among children in Londrina, Curitiba, and in the remaining municipalities of the State, before and after the introduction of this vaccine into the immunization program. METHODS: An observational and retrospective study was carried out. The study included all cases of Haemophilus influenzae type b meningitis recorded by the epidemiological surveillance system in Londrina and by the State of Paraná Health Secretariat between 1992 and 1999 among children aged less than 5 years. The incidence rates of Hib meningitis were calculated per 100,000 children aged less than five years. RESULTS: After the introduction of Hib vaccine, an important reduction in the incidence rate of Haemophilus influenzae type b meningitis was observed in Londrina (from 23.91 in 1996 to 2.79 in 1999). A Similar decrease was observed in Curitiba. In the remaining localities of the state, which had not introduced the vaccine till mid-1999, the incidence rate remained almost unchanged. CONCLUSION: Regular vaccination against Hib was effective in reducing the incidence rate of meningitis amongst children younger than five years in Londrina and Curitiba. In order to maintain this low incidence rate, adequate vaccination coverage and strict epidemiological surveillance should be guaranteed.     

Haemophilus influenzae type b unsuspected bacteremia

To further define the clinical features and natural history of unsuspected Haemophilus influenzae type b (Hib) bacteremia, we retrospectively reviewed the records of 322 Hib infections observed during a 45-month period at Children's Hospital, Boston. We identified 31 patients with unsuspected Hib bacteremia and 19 with unsuspected Hib antigenemia and sterile blood cultures. Bacteremic patients were typically under two years of age (81%), had high fevers (mean = 39.5 degrees C), and frequently had otitis media (65%) diagnosed as their only focus of infection at presentation. Nineteen of 31 were empirically treated with oral antibiotics. Ten of 31 (32%) developed focal infectious complications consisting of meningitis (n = 7), cellulitis (n = 2), and pneumonia (n = 1). Children with focal infectious complications differed from those without infectious complications in having a significantly higher mean fever of 40.3 degrees C compared to 39.7 degrees C (P less than 0.05). Five of 19 (26%) empirically treated patients developed focal complications (all meningitis) compared to five of 12 (42%) untreated patients. Blood cultures at follow-up visit were positive in three of 19 (9%) treated patients and seven of 12 (42%) untreated patients (P less than 0.05). Of the 19 children with antigenemia and sterile blood cultures, 16 (84%) were empirically treated with antibiotics, and none had positive blood cultures or focal infections on follow-up evaluation. Children with occult Hib bacteremia are at high risk for developing serious focal infections, particularly meningitis, despite empiric antibiotic therapy. Once Hib bacteremia is suspected, strong consideration should be given to parenteral in hospital antibiotic therapy. The utility of rapid antigen detection for identifying high-risk patients requires further evaluation.     

A population-based retrospective assessment of the disease burden resulting from invasive Haemophilus influenzae in infants and young children in Santiago, Chile

Clinical discharge and laboratory records were reviewed in the seven government hospitals that provide care for 93% of the pediatric population of Santiago, Chile, to detect cases of meningitis and other invasive (bacteremia-associated) infections caused by Haemophilus influenzae. infections that occurred in children less than five years of age from January, 1985, through December, 1987, were recorded and matched with census data to calculate incidence rates. The incidence of meningitis and non-meningitis syndromes peaked in the 6- to 11-month age group and tapered sharply after 12 months of age. The city-wide incidence (ca. 21.6 cases/10(5) children less than 5 years of age) is one-third to one-half that reported for the general pediatric population in the United States. However, there is much evidence for under-reporting in Santiago. In Area Norte, served by Roberto del Rio Children's Hospital where H. influenzae has been a subject of research by pediatricians for years, the incidence of invasive H. influenzae infections (42.5/105) is approximately two-fold higher than the rest of Santiago. The cumulative proportions of episodes of H. influenzae disease occurring in successively older age groups closely parallel the pattern seen in the general United States pediatric population. Although only ca. 20% of all episodes occur during the first 6 months of life, nearly 80% of episodes are seen by 18 months of age. Based on the observed incidence rates, the apparent underreporting and the high city-wide case fatality of Hib meningitis (16%), invasive H. influenzae infections represent an important public health problem in Santiago, Chile.     

Haemophilus influenzae meningitis in Sweden 1981-1983.

Four hundred and seventy cases of meningitis caused by Haemophilus influenza in children and 30 cases in adults were identified in Sweden between 1981 and 1983. The age specific incidence in the most susceptible age group (0-4 years) was 31/100,000/year (440 cases), which is higher than previously reported from Europe. A further 30 cases were seen in children aged 5-14. The risk of developing H influenzae meningitis before the age of 15 was 1 in 669. There were 11 deaths (2%) and five cases of serious neurological sequelae among the children. Only 18 children (4%) had predisposing diseases. All but one of the 294 strains of H influenzae from children that had been serotyped were type b. Infections in adults differed from infections in children. Five of the adults died (17%), 12 had important predisposing diseases, and at least six of the infections were caused by non-typable strains. It is concluded that research into the prevention of invasive H influenzae infections in children should have high priority.     

Effectiveness of Haemophilus influenzae type B conjugate vaccine on prevention of pneumonia and meningitis in Bangladeshi children: a case-control study

BACKGROUND: Few Asian countries have introduced Haemophilus influenzae type b (Hib) conjugate vaccine because of its cost and uncertainty regarding disease burden. METHODS: To estimate the effectiveness of Hib conjugate vaccine in preventing pneumonia and meningitis in children age <2 years, an incident case-control study was conducted in a birth cohort of about 68,000 infants in Dhaka city, Bangladesh. DPT vaccine was systematically replaced by a combined Hib-DPT vaccine in selected immunization centers of the study area. Four matched community- and 2 hospital-controls were randomly selected for each confirmed case of pneumonia and meningitis from the study area. RESULTS: About 35% of the infants received each of the 3 doses of Hib-DPT vaccine. There were 2679 children who had a chest roentgenogram. For 475 children, a radiologist and a pediatrician independently identified substantial alveolar consolidation. Following at least 2 doses of Hib vaccine, the preventable fractions [95% confidence intervals (CI)] using community and hospital controls were 17% (-10% to 38%) and 35% (13% to 52%) respectively. Of these 475 cases, 2 radiologists with the World Health Organization concurred with the findings for 343 patients, yielding preventable fractions of 34% (6% to 53%) and 44% (20% to 61%). Fifteen confirmed Hib meningitis cases were identified; the preventable fractions (95% CI) using community and hospital controls, respectively, were 89% (28% to 100%) and 93% (53% to 100%). CONCLUSIONS: The study documented that significant fractions of pneumonia and meningitis in Bangladeshi children age <2 years can be prevented by the Hib conjugate vaccine.     

Safety evaluation of PRP-D Haemophilus influenzae type b conjugate vaccine in children immunized at 18 months of age and older: follow-up study of 30,000 children

We evaluated the safety of the PRP-D conjugate Hib vaccine (ProHIBit, Connaught) in 29,309 children vaccinated at 18-60 months of age in the Southern California Kaiser Permanente medical clinics during the period April 1, 1988, to July 31, 1989. Surveillance for potential reactions involved postcard questionnaires, telephone surveys, reports of Kaiser staff and review of hospitalizations and covered two periods following immunization: (1) the first 48 hours and (2) days 2 through 30. Surveillance for invasive Hib disease involved the above methods in addition to systematic reviews of laboratory and hospital records through January 31, 1990. Rates of local and systemic reactions within 48 hours of vaccination with PRP-D alone were low (less than or equal to 2% for fever greater than 102 degrees F, local redness or swelling) and similar to those previously reported after vaccination with PRP. Hospitalization and seizures (0.15% and 0.09% of vaccinated children, respectively) occurring within 1 month of immunization appeared to be unrelated to vaccination. One 29-month-old child had onset of a fatal episode of Hib sepsis/meningitis within 48 hours of vaccination. Also, a 30-month-old child developed Hib meningitis 10 months after PRP-D vaccination. We conclude that PRP-D is safe when given alone or in combination with other childhood vaccines between 18 and 60 months of age.     

Epidemiology of Haemophilus influenzae type b infections among children in Denmark in 1985 and 1986

A retrospective epidemiological study of invasive Haemophilus influenzae type b infections among children in Denmark 1985 and 1986 was carried out and 226 cases were identified. Of these 93% occurred in patients younger than five, corresponding to an annual incidence of 40 cases per 100,000 children aged 0-4 years, 68% occurred in patients younger than two years of age, and 6% in patients younger than six months. The annual incidences of meningitis and epiglottis were 27 and 8 cases, respectively, per 100,000 children aged 0-4 years. Of the 156 cases with meningitis four patients died and seven had severe neurological sequelae. Only 67% of the cases of meningitis had been notified.     

Impact of vaccination against Haemophilus influenzae on the incidence of invasive infections from Haemophilus influenzae type B in the Nord-Pas-de-Calais region]

BACKGROUND: In industrialized countries where immunization against Haemophilus influenzae b (Hib) is largely used, the incidence of invasive Hib infections has dramatically decreased. The aim of this study was to analyse the impact of immunization against Hib on the incidence of invasive Hib infections in the Nord-Pas-de-Calais area in France. PATIENTS AND METHODS: This retrospective multicenter study enrolled 11 of the 18 hospitals in the Nord-Pas-de-Calais area, comparing two periods: 1991-1993 (before immunization), and 1994-1996 (during immunization). All children less than 60 months of age and having an invasive Hib infection were included. The Pasteur-Mérieux Company was asked to provide the number of vaccines sold in the Nord-Pas-de-Calais area during the study period. RESULTS: The number of vaccines sold in 1992 was 56,208; this reached 189,173 in 1996, corresponding to an immunization ratio higher than 90%. One hundred and two children representing 155 invasive Hib infections were studied. The annual incidence was 42 during the first period (meningitis: 18.6; septicemia: 14.6; epiglottitis: 5.6), and nine (meningitis: 5; septicemia: 2.6; epiglottitis: 0.3) during the second period, that is a 78% decrease. CONCLUSION: These results confirm previous data in the literature by demonstrating that immunization in the Nord-Pas-de-Calais area has dramatically decreased the incidence of invasive Hib infections.