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.     

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.     

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.     

Nasopharyngeal colonization with Haemophilus influenzae type b among infants and children in Japan

Healthy carriers of Haemophilus influenzae type b (Hib) play an important role in the spread of invasive Hib disease. The aim of the present study was to estimate Hib colonization among infants and children in Japan. Specimens from throat and nasopharyngeal cultures were obtained by thorough swabbing of both tonsils and the posterior pharynx. Specimens were inoculated on Hib antiserum agar. This was prepared with Levinthal base and Hib antiserum. Conventional methods were used concomitantly. Four of 474 infants from 1–48 months of age (0.84%) had Hib cultured from their nasopharynx. The carriage rate in 1–12 month old infants was 0.62% (2/322 cases), and that in 13–48 month old children was 1.32% (2/152 cases). Five of 167 (3.0%) 13-year-old children, and five of 154 (3.2%) 9-year-old children were asymptomatic carriers. Thirty-five of 104 household contacts of a patient with invasive Hib disease (33.6%) had Hib colonization. The carriage rate in healthy Japanese children may not be different from that in the USA prior to the availability of the conjugate Hib vaccine. The Hib carriage rate in household contacts of patients with invasive Hib disease was higher than in healthy children (P < 0.005). Our results suggest the possibility of an outbreak of invasive Hib disease in Japan.     

Reduced effectiveness of Haemophilus influenzae type b conjugate vaccine in children with a high prevalence of human immunodeficiency virus type 1 infection

BACKGROUND: Haemophilus influenzae type b (Hib) conjugate vaccines have successfully reduced the burden of invasive Hib disease in developed countries; however, their effectiveness in countries with a high incidence of pediatric HIV-1 is unknown. METHODS: The effectiveness of Hib conjugate vaccine was prospectively evaluated in South African children. The burden of invasive Hib disease in children < 1 year old was compared in 2 cohorts. The first cohort included 22,000 African children born in 1997 [969 (4.45%) of whom were estimated to be HIV-1-infected] who were not vaccinated with Hib conjugate vaccine. This group was compared with 19,267 children [1162 (6.03%) of whom were estimated to be HIV-1 infected] vaccinated at 6, 10 and 14 weeks of age with an Hib conjugate vaccine [TETRAMUNE (polyribosylribitol phosphate-CRM(197)-diphtheria-tetanus toxoids-whole cell pertussis)] between March, 1998, and June, 1999. RESULTS: The estimated burden of invasive Hib disease in nonimmunized HIV-1-infected children < 1 year of age was 5.9-fold [95% confidence interval (95% CI), 2.7 to 12.6] higher than in HIV-1-uninfected children. The overall estimated effectiveness of Hib conjugate vaccine in fully vaccinated children <1 year of age was 83.2% (95% CI 60.3 to 92.9). Vaccine effectiveness was significantly reduced in HIV-1-infected [43.9% (95% CI -76.1 to 82.1)] compared with uninfected children [96.5% (95% CI 74.4 to 99.5); P < 10(-5)]. Among three of the fully vaccinated HIV-1-infected children who developed invasive Hib disease, the anti-Hib polyribosylribitol phosphate serum antibody concentrations were 0.23, 0.25 and 0.68 microg/ml. CONCLUSION: Although the Hib conjugate vaccine was less effective among HIV-1-infected than among uninfected children, it was 83% effective in preventing overall invasive Hib disease and therefore should be considered for inclusion in the routine vaccination schedule by other African countries.     

Haemophilus influenzae type b disease: impact and effectiveness of diphtheria-tetanus toxoids-acellular pertussis (-inactivated poliovirus)/H. influenzae type b combination vaccines.

BACKGROUND: Since 1996 in Germany primary infant immunization against Haemophilus influenzae has been most commonly given in the form of diphtheria-tetanus toxoids-acellular pertussis/H. influenzae type b (DTaP/Hib) or diphtheria-tetanus toxoids-acellular pertussis (-inactivated poliovirus)/H. influenzae type b (DTaP-IPV/Hib) combination vaccines. These combination vaccines elicit lower anti-Hib antibody concentrations than the equivalent Hib conjugate administered as a separate injection, but the clinical relevance of this phenomenon is unknown. METHODS AND FINDINGS: To assess the impact of DTaP/Hib combination vaccines on the incidence of invasive Hib disease in Germany, two independent surveillance systems, one hospital- and one laboratory-based, were used during 1998 and 1999 for detection of cases. Vaccination histories of all cases detected were obtained by telephone contact with parents or health care providers. During the 2-year study period invasive H. influenzae disease in the <5-year age group continued to fall, with a mean annual incidence of 1.01/100 000 children. National vaccination coverage rates revealed that only 70% of children given DTaP/Hib or DTaP-IPV/Hib received the recommended three doses in their first year of life, but the overall effectiveness of these vaccines was high at 97.5% (95% confidence interval, 96.3 to 98.4) for those who had received at least one dose. In subjects who received the full 3-dose schedule, effectiveness was 98.8% (95% confidence interval, 98.2 to 99.3). CONCLUSION: Although it is well-documented that DTaP/Hib vaccines elicit lower anti-Hib titers than separate vaccines, such combinations are effective in reducing the incidence of invasive H. influenzae type b disease.     

Experience with the prevention of invasive Haemophilus influenzae type b disease by vaccination in Alaska: the impact of persistent oropharyngeal carriage

OBJECTIVES: To report the epidemiology of invasive Haemophilus influenzae type b (Hib) disease in high-risk Alaska Native infants before and after universal infant Hib vaccination and evaluate an increase in invasive Hib disease in 1996 after changing Hib vaccine type. STUDY DESIGN: Statewide laboratory surveillance for invasive Hib disease has been conducted since 1980. Three cross-sectional Hib carriage studies were conducted in 1997 and 1998. RESULTS: The invasive Hib disease rate in Alaska Natives decreased from 332 cases per 100,000 children <5 years old in 1980-1991 to 17:100,000 in 1992-1995 but increased primarily in rural areas to 57.9:100,000 after a switch in Hib vaccine types. Carriage studies in 5 rural Alaska Native villages showed oropharyngeal Hib carriage as high as 9.3% in children aged 1 to 5 years; in contrast, carriage in urban Alaska Native children was <1%. CONCLUSIONS: Although Hib disease has decreased in Alaska, the rate of Hib disease and carriage in rural Alaska Natives did not decrease to the same extent as in non-Natives and urban Alaska Natives. Use of polyribosylribitol phosphate-outer-membrane protein conjugate vaccine for the first vaccine dose is critical to disease control in this population with continued transmission in infants <6 months of age. The ability to eliminate Hib carriage and disease may be affected by population characteristics, vaccination coverage, and Hib vaccine type used. This may pose a challenge to global elimination of Hib.     

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.     

Aetiology and clinical signs of bacterial meningitis in children admitted to Goroka Base Hospital, Papua New Guinea, 1989-1992

Children aged 1-59 months admitted to Goroka Base Hospital with signs suggestive of meningitis were recruited to determine what proportion of such children have clinical or bacterial meningitis and to investigate the bacterial aetiology. A laboratory classification of definite, probable, possible, indeterminate and no meningitis was established. Thirty per cent of 697 children had a final clinical diagnosis of meningitis, 12% had culture-proven bacterial meningitis (case fatality rate 34%) and 10% had probable or possible meningitis. Inability to feed, vomiting, drowsiness, "staring eyes" and haemoglobin < 9 g/dl in addition to the classical signs of meningitis were associated with increased mortality. Isolates from cerebrospinal fluid were 62 pneumococci, 22 Haemophilus influenzae type b (Hib) and one Neisseria meningitidis. Including blood culture-proven and antigen-proven Hib disease, Hib and pneumococci accounted for 44% and 46% of bacterial meningitis, respectively, and 23% of pneumococci were intermediately resistant to penicillin. Inability to feed, bulging fontanelle, convulsions in young children, neck stiffness, fever and "staring eyes" were all independently associated with bacterial meningitis. Conjugate Hib vaccine must be given to infants as early as possible. Conjugate pneumococcal vaccines, maternal immunization with 23-valent vaccine and pneumococcal protein vaccines are under investigation for prevention of pneumococcal disease.     

Natural immunity to Haemophilus influenzae type B in children of Ankara, Turkey

BACKGROUND: Haemophilus influenzae type b (Hib) infection has a high morbidity and mortality rate especially in children under 5 years of age. The incidence of Hib disease in Turkey is not known, and Hib vaccine is not included in the National Immunization Program. The aim of this study was to determine the natural immunity to Hib of children 6-60 months of age living in the Park Health Center region of Ankara, Turkey. METHODS: A total of 270 children were selected by layered random sampling method, and 242 of them (89.6%) participated in the study. A questionnaire was given to the parents of the children who were included in the study and blood samples were taken from those children. Anti-Hib IgG antibody (anti-PRP) level was determined in the serum by using anti-Haemophilus influenzae IgG EIA kit and anti-PRP antibody levels of 0.15 microg/mL and over were accepted as the natural immunity. RESULTS: Natural immunity was determined in 65.3% of the children. A relationship was determined statistically between the history of disease with possible Hib agent and with natural immunity. CONCLUSIONS: The exposure rate of children with Hib was higher than expected, even in children who were just a few months old. Our data revealed that multicentric, national studies should be done to define the burden of Hib disease before making a decision for Hib vaccine to be included in the National Immunization Program.     

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.     

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.     

Outbreak of Haemophilus influenzae type b disease among fully vaccinated children in a day-care center

BACKGROUND: Two cases of invasive Haemophilus influenzae type b (Hib) infection were reported in immunized children in a day nursery within 1 week. Both cases were younger than 18 months of age, cared for in the same room. We aimed to characterize carriage of Hib and response to eradication therapy in this setting. METHODS: Ninety-four children were enrolled in the nursery, cared for by 21 staff in 4 rooms, divided by age. Two children of a part time teacher also attended. Oropharyngeal swabs were taken to detect Hib carriage before introduction of rifampin prophylaxis (20 mg/kg/day for 4 days). A questionnaire addressing risk factors for colonization was administered to parents and staff. Carriage was reassessed in children and carers from the same room as the index cases 1 month later. RESULTS: Eighty-nine children and all 21 staff were swabbed. Two additional Hib carriers, 1 child and 1 staff member, were identified from the same room as the cases. These isolates appeared identical with those causing invasive disease. Given the small numbers no clear risk factors for carriage could be confirmed. Compliance with rifampin prophylaxis was 97.4%. One month later no carriers were found among the 7 children and 3 staff tested from the room in which the cases were originally identified. CONCLUSIONS: Although immunization against Hib has resulted in a reduction in the incidence of this disease in the UK, individual protection cannot be assumed to be infallible. The importance of timely chemoprophylaxis of close contacts of a child with invasive Hib disease is reinforced.     

Management of the febrile child without a focus of infection in the era of universal pneumococcal immunization

Should strategies of management of invasive disease in the febrile child without focus of infection (occult bacteremia) be reconsidered in communities with universal immunization of infants with the conjugate vaccines for Haemophilus influenzae type b and Streptococcus pneumoniae (PCV7)? The incidence of occult bacteremia is likely to decrease with the virtual elimination of H. influenzae type b and vaccine serotype pneumococcal invasive diseases. The number of children with fever coming to physicians' offices, however, is unlikely to change. The challenge of distinguishing the febrile child with invasive bacterial disease who requires aggressive therapy from the febrile child who has a viral infection and requires only symptomatic therapy will persist. The bacteriology of invasive disease in infants and young children in 2002 will include pneumococcal serotypes not in PCV7; serotypes in PCV7 that occur in the unimmunized, partially immunized or fully immunized child (vaccine failures); Neisseria meningitidis; Salmonella spp., group A Streptococcus, Staphylococcus aureus and gram-negative enteric bacilli. Management plans published in the 1990s suggested an aggressive diagnostic approach to the febrile child 3 to 36 months old who was toxic or had a temperature of >39 degrees C. Diagnostic tests included white blood cell counts, cultures of blood and urine and chest radiograph and lumbar puncture as indicated by clinical signs and administration of parenteral ceftriaxone. Although PCV7 was extraordinarily effective in prevention of serotype-specific invasive pneumococcal disease in clinical trials, pediatricians need to know whether the results based on 38,000 enrollees will be maintained as millions of children are immunized. In addition questions about change in serotype of pneumococci causing invasive disease (serotype switching), herd immunity and durability of protection after immunization need to be answered. Until more experience is available to answer these questions, the febrile child without focus of infection should be managed without consideration of immunization with PCV7. Evaluation of the organism (serotype) and the host (acute and convalescent sera) should be undertaken for each case of invasive pneumococcal disease in this era of universal pneumococcal immunization.     

Population-based surveillance for hospitalized and ambulatory pediatric invasive pneumococcal disease in Santiago,Chile

BACKGROUND: Nine- and 11-valent pneumococcal conjugate vaccines under development may control pediatric pneumococcal disease in nonindustrialized countries. Because these vaccines are expensive, population-based surveillance of pneumococcal disease in children <36 months of age was undertaken in Santiago, Chile to provide health authorities with reliable data on the burden of invasive pneumococcal disease and causative serotypes, including those in outpatients with high fever. METHODS: Automated blood culture machines were introduced into 9 hospitals that admit 85% of all hospitalized children in Santiago. Acutely ill pediatric febrile ambulatory patients are attended at 8 emergency rooms (ERs) and 36 urgent primary care services. After a 12-month pilot study in 3 ERs, health authorities collected blood cultures from children <36 months of age with high fever seen in the ER as standard practice. isolates were serotyped. RESULTS: Blood cultures of 18 (1.2%) of 1,503 outpatients 6 to 35 months of age with high fever in the pilot study yielded S. In the ensuing 24 months 236 children <36 months old were hospitalized with invasive pneumococcal disease (incidence, 33.9 cases/10(5) children), and 188 bacteremias were detected among ambulatory ER patients with high fever (incidence, 27.0 cases/10(5) children). Although serotypes were similar among hospitalized and ambulatory cases (except 18C, which was more common in the latter), case fatality was 9.5% in hospitalized (21 of 236) 0% in ambulatory cases (0 of 188) (P = <0.0001). High level resistance to penicillin (25.8% vs 10.1%) and cefotaxime (19.5% vs 6.2%) was observed more often among pneumococcal isolates from hospitalized than among ambulatory cases (P < 0.001). CONCLUSIONS: ER surveillance detected approximately one case of pneumococcal bacteremia among febrile ambulatory patients for each hospitalized invasive case. Because 71% of cases were caused by vaccine serotypes (and 87% by vaccine serogroups), 9- and 11-valent pneumococcal conjugate vaccines could prevent most invasive pediatric pneumococcal disease in Chile.     

Pharyngeal colonization with Haemophilus influenzae type b among healthy Turkish infants and children

BACKGROUND: An absence of Haemophilus influenzae type b (Hib) disease surveillance and epidemiological data on the pharyngeal carriage of Turkish children causes delay in the introduction of conjugated Hib vaccination into proposed national vaccination programs. METHODS: Oropharyngeal cultures were obtained from 1404 healthy infants and children. Six healthy child clinic (HCC), 11 day-care centers (DCC) and seven elementary schools (ES) were randomly selected in seven different counties at the Anatolian side of Istanbul between January and April 2000. RESULTS: Haemophilus influenzae was isolated from 315 (22.8%) of all participants and 98 (31%) isolates were serotype b. The carriage rate for Hib was higher in children at DCC (43 out of 448, 9.6%) and ES (46 out of 504, 9.1%) compared to infants 0-24 months of age (nine out of 430, 2.1%) presented to HCC. All Hib isolates were susceptible to azithromycin, chloramphenicol and cefotaxime. Beta-lactamase production was detected in only one isolate. Trimethoprim-sulfamethoxazole resistance was found in 8.5% of Hib isolates. Multivariate analysis showed that DCC and ES attendance were independent predictors of Hib carriage. CONCLUSION: A significant proportion of healthy Turkish children was shown to be colonized with Hib. The burden of invasive Hib infections should be determined in order to evaluate the Hib conjugated vaccine as a part of a routine immunization program in Turkey.     

Four and one-half-year follow-up of the effectiveness of diphtheria-tetanus toxoids-acellular pertussis/Haemophilus influenzae type b and diphtheria-tetanus toxoids-acellular pertussis-inactivated poliovirus/H. influenzae type b combination vaccines in Germany

BACKGROUND: Recently an increase in the number of invasive Haemophilus influenzae type b (Hib) cases was observed in the United Kingdom, which coincided with a temporary change from diphtheria-tetanus toxoids-wild-type pertussis to diphtheria-tetanus toxoids-acellular pertussis (DTaP) Hib vaccines. A study in Germany based on approximately 2 years of follow-up, estimated vaccine effectiveness (VE) of DTaP/Hib and DTaP-inactivated poliovirus/Hib combination vaccines against invasive Hib disease to be high. OBJECTIVES: To assess VE of DTaP-containing Hib vaccines against Hib in Germany with the use of extended follow-up of case surveillance and vaccine uptake. SUBJECTS AND METHODS: Cases with confirmed systemic Hib infections in children born between June 1, 1996 and December 31, 1998 were ascertained by a nationwide active surveillance system from January 1998 through June 2002. A representative subcohort of 667 children born in the same time frame was randomly sampled in a nationwide vaccine coverage survey. VE was determined with a case-cohort approach of Cox regression with time-dependent covariates. RESULTS: Thirty-six cases of Hib disease were reported. Of these, 10 were vaccinated with DTaP-containing Hib vaccines only and 20 were not vaccinated. Of the 10 vaccinated cases, 4 had received an incomplete primary series (1-2 doses), and 6 had received the full primary series (3 doses), 3 of whom also received the booster dose. VE of combination vaccines against invasive Hib infection was 89.6% [95% confidence interval (CI), 67.0-96.7] for an incomplete primary series, 96.7% (95% CI 87.7-99.1) for a full primary series and 98.5% (95% CI 94.5-99.6) for a booster dose (irrespective of priming). CONCLUSION: Hib combination vaccines containing acellular pertussis antigens continue to be highly effective in Germany.     

Estimation de la couverture vaccinale chez les enfants de 10 mois, 2 ans et 4 ans, venus consulter en centre de bilan de santé de l'enfant à Paris durant l'année 1997

In France, the vaccination program has changed through the last years. We report a study on immunization rates of children who underwent a complete health checkup at a Well Child Clinic in Paris. We studied three groups of children (children at the ages of 10 months, 2 years and 4 years) regarding types of daycare and medical care. PATIENTS AND METHODS: Nine hundred children who underwent a health checkup between April and June 1997 were included in the study. Data were collected from immunization records and parents' interviews. RESULTS: In 10-month-old children, prevalence rates of immunization against diphtheria, tetanus, poliomyelitis and pertussis (DTPP) and immunization against Haemophilus influenzae type b (Hib) disease were 98% and 96%, respectively. Only 1.7% were immunized against measles. Forty-two percent of children had complete or ongoing immunization against hepatitis B. The vaccination coverage for BCG was 94%. In two-year-old children, boostering for DTPP vaccine had been performed by 90%, more than 90% were immunized against measles and 50% had received at least one shot to prevent hepatitis B. At the age of 4 years, 99% were immunized against DTPP, 78% were immunized against Hib disease, 98% against measles and 48% for hepatitis B. All children were immunized with BCG, and 98% were BCG-controlled (22% had tuberculin intradermal reaction). The highest immunization rates were observed in children who had preventive care in 'Maternal and Infantile Protection Centres.' Immunization rates were not influenced by the type of daycare, except for measles in two-year-old children managed by private pediatricians. CONCLUSION: We observed high immunization rates of children who underwent health checkups. Late immunization against measles and low immunization rates against hepatitis B reflect the difficulties encountered in mobilising physicians and families for these vaccinations.     

Immunization with oligosaccharide conjugate Haemophilus influenzae type b (HbOC) vaccine on a large health maintenance organization population: extended follow-up and impact on Haemophilus influenzae disease epidemiology. The Kaiser Permanente Pediatric Vaccine Study Group.

Between February, 1988, and June, 1990, the safety, immunogenicity and efficacy of the HbOC (oligosaccharide conjugate Haemophilus influenza type b) vaccine was evaluated in a prelicensure trial performed in a study population of 61,080 children within the Northern California Kaiser Permanente Medical Care Program. In this evaluation the HbOC vaccine was found to be safe, immunogenic and efficacious in infancy. Since licensure an estimated 162,000 additional doses of HbOC vaccine have been given to 75,000 additional children. In addition to reporting on extended follow-up of this population, this publication reports on the impact of immunizing a high proportion of the Northern California Kaiser Permanente Medical Care Program population in infancy and early childhood on the epidemiology of invasive disease caused by H. influenzae type b (Hib) and invasive disease caused by non-type b H. influenzae. As of January 31, 1992, six cases of Hib invasive disease have been identified in vaccinated children. Of these five occurred in children who had received only one dose of vaccine in infancy. One case of Hib meningitis occurred in a 3 1/2-year-old child who had received doses of HbOC at 2, 4 and 6 months of age but no further doses of any Hib vaccines. During 1991 a total of three cases of invasive disease caused by Hib were observed in children younger than 18 months of age within the Northern California Kaiser Permanente Medical Care Program. This represents a 94% reduction in disease incidence in this age group from that observed in the years 1984 to 1987.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.