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.     

Invasive infections caused by haemophilus influenzae serotypes in twelve Canadian IMPACT centers, 1996-2001

BACKGROUND: Haemophilus influenzae type b (Hib) immunization has changed the epidemiology of pediatric bacterial invasive disease. We describe the epidemiology of H. influenzae invasive infections in 12 Canadian pediatric tertiary care [Immunization Monitoring Program, ACTive (IMPACT)] centers during the era of universal immunization against this pathogen. METHODS: Children with positive cultures for H. influenzae serotypes a to f (Hia to Hif) and nontypable H. influenzae from sterile sites were identified from the laboratory records at 12 IMPACT centers from January 1, 1996 to December 31, 2001. Hospital records were retrospectively reviewed for demographic and clinical information. RESULTS: Of 166 H. influenzae cases, 58 (35%) were caused by Hib, 89 (54%) by non-b serotypes, and 19 (11%) were not serotyped. The non-b serotypes included: 25 Hia (28%), 4 Hid (4%), 2 Hie (2%), 11 Hif (12%), and 47 were nontypable isolates (53%). For patients with Hib and Hia infection, meningitis was the most common presentation, accounting for 40% and 52% respectively, whereas the most common presentation for nontypable serotypes was pneumonia, seen in 43% of cases. Epiglottitis was associated mainly with Hib. Aboriginal ethnicity was an important risk factor for Hia cases, accounting for 76% of patients with infections caused by this serotype. Mean duration of hospitalization, need for admission to a pediatric intensive care unit, and case fatality rates were similar for the cases because of Hib, Hia, Hif, and nontypable serotypes. CONCLUSIONS: In 1996-2001, two-thirds of H. influenzae invasive disease in the 12 IMPACT centers was caused by non-b serotypes, which were associated with significant morbidity and mortality.     

Invasive Haemophilus influenzae type B diseases in Bangladesh, with increased resistance to antibiotics

OBJECTIVE: To determine the prevalence, age-group distribution, serotype, and antibiotic susceptibility patterns of invasive Haemophilus influenzae type b (Hib) isolates in Bangladeshi children because data regarding Hib diseases in developing countries are scarce, which has led to delay of the introduction of Hib vaccine in these countries. METHODS: Children diagnosed with meningitis (n = 1412) and pneumonia (n = 2434) were enrolled in this surveillance study for Hib invasive diseases. Cerebrospinal fluid (CSF) and blood specimens, and the subsequent isolates, were processed using standard procedures. RESULTS: During 1993 to 2003, 455 H influenzae strains were isolated from patients with meningitis (n = 425) and pneumonia (n = 30), and an additional 68 Hib meningitis cases were detected by latex agglutination (LA) testing. Overall, 35% of pyogenic meningitis cases were a result of H influenzae, 97.1% of which were Hib. Most (91.4%) cases occurred during the first year of life. Resistance to ampicillin, chloramphenicol, and cotrimoxazole was 32.5%, 21.5%, and 49.2%, respectively. There was a trend toward increasing resistance for all three drugs. Resistance to ampicillin and chloramphenicol was almost universally coexistent and was associated with increased sequelae compared with the patients infected with susceptible strains (31% [23/75] vs 11% [21/183]; P <.001). CONCLUSION: Hib is the most predominant cause of meningitis in young Bangladeshi children. Resistance to ampicillin and chloramphenicol and the high cost of third-generation cephalosporin highlight the importance of disease prevention through vaccination against Hib.     

Haemophilus influenzae causing conjunctivitis in day-care children

The role of Haemophilus influenzae in acute purulent conjunctivitis was studied during an outbreak among children in day care. Five day-care centers contributed 20 cases and 35 controls. All the children were subjected to culture of the nasopharynx and the eyes. H. influenzae was carried in the nasopharynx of 53% of the children (range between day care centers, 20 to 91%). Of the 20 children with acute conjunctivitis 8 had eye cultures positive for H. influenzae, 2 had Moraxella and the remaining were culture-negative. Ten colonies of H. influenzae were isolated from each positive culture and identified by capsular type, biotype and multi-locus enzyme electrophoresis. All but one of the isolates were nonencapsulated. They belonged to 4 biotypes and 8 electrophoretic types. The same strain was recovered from the eyes and nasopharynx of the symptomatic children, suggesting that the H. influenzae in the eyes originated from the nasopharynx. There was no evidence for spread of the same H. influenzae strains between day-care centers. Even within each center the Haemophilus strains recovered from the eyes varied among the symptomatic children. The in vitro capacity to attach to oropharyngeal epithelial cells was not increased among the H. influenzae recovered from the eyes. The results question if the majority of conjunctivitis cases were caused by H. influenzae and suggested that eyes were colonized with the nasopharyngeal carrier strain rather than infected by an isolate with special virulence for the eye.     

Pharyngeal colonization with Haemophilus influenzae type b in children in a day care center without invasive disease

During an 18-month period, monthly pharyngeal cultures for Haemophilus influenzae type b (Hib) were obtained from 66 children and their caretakers in a day care center in which no systemic disease caused by Hib occurred. The average colonization rate for Hib was 10%, and ranged from 0% to 23% for a single month. Infants housed in a separate building with a cohorted staff were not colonized by Hib. However, 71% of the toddler group and 48% of the preschool group became colonized by Hib at some time during the 18-month-study. Of 89 Hib isolates, 93% were biotype 1 (Kilian), and 90% of these had a similar outer membrane protein profile, designated subtype 1L. This strain was recovered from children at the center for 15 of 18 months. No invasive disease occurred. Thus, Hib may be widespread among preschool children in a day care center and persist for longer than a year without resulting in systemic disease.     

The UK Hib vaccine experience.

Haemophilus influenzae type b (Hib) is an important pathogen in children <5 years of age. The Hib conjugate vaccines were the first polysaccharide-protein conjugate vaccines to be used in routine childhood schedules. Their introduction in the UK in 1992 has resulted in the near elimination of Hib disease. The UK Hib vaccine programme has a number of unique features including an accelerated schedule, absence of a booster dose, and the inclusion of a catch up component at the beginning of the programme. Collaboration between UK paediatricians, microbiologists, and public health physicians has allowed active national surveillance of Haemophilus influenzae disease and enabled important conclusions to be drawn. These include high vaccine effectiveness, the presence of herd immunity, and the frequency of risk factors in cases of vaccine failure and in cases of invasive disease due to non-b H influenzae. Parallel studies have shown the immunogenicity, induction of immunological memory, and persistence of immunity following vaccination at the UK schedule, as well as measuring the impact of vaccination on pharyngeal Hib carriage. Cases continue to occur and complacency is ill advised, particularly as other vaccines and combinations are introduced. Surveillance of H influenzae disease in the UK remains important.     

The UK Hib vaccine experience

Haemophilus influenzae type b (Hib) is an important pathogen in children <5 years of age. The Hib conjugate vaccines were the first polysaccharide-protein conjugate vaccines to be used in routine childhood schedules. Their introduction in the UK in 1992 has resulted in the near elimination of Hib disease. The UK Hib vaccine programme has a number of unique features including an accelerated schedule, absence of a booster dose, and the inclusion of a catch up component at the beginning of the programme. Collaboration between UK paediatricians, microbiologists, and public health physicians has allowed active national surveillance of Haemophilus influenzae disease and enabled important conclusions to be drawn. These include high vaccine effectiveness, the presence of herd immunity, and the frequency of risk factors in cases of vaccine failure and in cases of invasive disease due to non-b H influenzae. Parallel studies have shown the immunogenicity, induction of immunological memory, and persistence of immunity following vaccination at the UK schedule, as well as measuring the impact of vaccination on pharyngeal Hib carriage. Cases continue to occur and complacency is ill advised, particularly as other vaccines and combinations are introduced. Surveillance of H influenzae disease in the UK remains important.     

Fifteen years of experience with bacterial meningitis.

BACKGROUND: Introduction of Haemophilus influenzae type b (Hib) vaccines has dramatically altered the epidemiology of bacterial meningitis in children. The goal of this study was to describe these changes in a pediatric teaching hospital. METHODS: Patient charts at Children's Hospital and Regional Medical Center, Seattle, were identified by diagnosis codes and reviewed retrospectively. The 1981 to 1995 time period was chosen to incorporate three distinct 5-year periods: before the use of unconjugated Hib vaccine; between the unconjugated and conjugate vaccines; and after the conjugate vaccines were available for routine immunization of infants. RESULTS: Bacterial meningitis was identified in 806 cases. In 13 premature infant cases Escherichia coli was most frequently isolated (6 cases). Group B Streptococcus, E. coli and Listeria monocytogenes were the most common pathogens in 87 neonatal cases. The most common pathogens in 706 cases of childhood meningitis were H. influenzae, Streptococcus pneumoniae and Neisseria meningitidis. H. influenzae was the most common pathogen in the first two time periods (73 and 69% of childhood cases, respectively), but not so in the third period (16%). CONCLUSIONS: A changing pattern in childhood meningitis was observed during the study period. H. influenzae cases dramatically declined, altering the relative proportions of other pathogens, S. pneumoniae and N. meningitidis. However, the number of cases caused by these latter pathogens remained steady.     

Rifampin for eradicating carriage of multiply resistant Haemophilus influenzae b

We studied the efficacy of rifampin prophylaxis in reducing the prevalence of ampicillin- and chloramphenicol-resistant Haemophilus influenzae type b in four day care facilities after each center had individual cases of invasive infections (two meningitis, one pneumonia and one cellulitis) caused by multiply resistant organisms. Rifampin was given in a single daily dose of 20 mg/kg for 4 days. Cultures were taken pretreatment and 10 days after the last dose of rifampin. Included in the study were 174 children and 27 adults. We identified a total of 55 nasopharyngeal carriers; 45 received rifampin and 10 refused treatment. On the 10-day follow-up culture in the second sample, 95.5 and 20%, respectively, of treated and untreated children were no longer colonized with H. influenzae (P less than 0.001, Fisher's exact test). We conclude that rifampin can successfully reduce the prevalence of multiply resistant H. influenzae type b carriers attending day care centers.     

Direct detection of the multidrug resistance genome of Haemophilus influenzae in cerebrospinal fluid of children: implications for treatment of meningitis

BACKGROUND: Multidrug resistance (MDR), specifically to ampicillin and chloramphenicol, has complicated the treatment of Haemophilus influenzae type b (Hib) meningitis. This is worsened by use of prior antibiotics, which limits identification of the causative agent by culture and increases reliance on antigen detection. OBJECTIVE: We aimed to develop a PCR assay for detecting the family of Haemophilus integrating and conjugative elements (ICEs) represented by ICEHin1056 among antibiotic resistant Hib, and then apply this directly to CSF to diagnose Hib meningitis and predict organism susceptibility, irrespective of culture results. STUDY DESIGN: Primers specific for orf 51 of ICEHin1056 were designed and multiplexed with Bex primers, specific for H. influenzae, and tested on culture positive and negative cases. RESULTS: Of 73 Hib isolates, orf 51 PCR amplicons, predicting the presence of ICEs, were found in all 33 MDR isolates while only in 1 of 33 sensitive strains. The remaining 7 ampicillin susceptible, chloramphenicol and tetracycline resistant strains did not produce a PCR product to orf 51. PCR amplification from CSF specimens of these culture positive cases produced identical results with 100% and 97% positive and negative predictive values, respectively. Multiplex PCR to detect Bex and orf 51 identified another 16 MDR Hib cases among 81 culture-negative CSF samples. CONCLUSIONS: Direct PCR for orf 51 in CSF identified resistance pattern of 51% more Hib strains than culture alone (110 versus 73). The ability to detect MDR, in culture negative Hib meningitis cases has significant implications for better directing antibiotic treatment of meningitis cases and thus for preventing disability and death.     

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 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.     

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.     

Severity and frequency of sequelae of bacterial meningitis in Alaska Native infants. Correlation with a scoring system for severity of sequelae.

OBJECTIVES--To (1) determine the frequency and severity of sequelae of Haemophilus influenzae type b and Streptococcus pneumoniae meningitis in Alaska Native children, (2) compare morbidity and mortality of H influenzae b and S pneumoniae meningitis, and (3) evaluate the applicability of the Herson-Todd prognostic score (HTPS) to both H influenzae b and S pneumoniae meningitis in this population. DESIGN--A retrospective study of all cases of H influenzae b and S pneumoniae meningitis in Alaska Native children younger than age 5 years. Data on meningitis sequelae, obtained from medical charts and records of the Infant Learning Program, were collected, and incidence of sequelae tabulated. Data obtained on admission to the hospital were used to calculate HTPS. SETTING--Indian Health Service facility for the Yukon-Kuskokwin Delta region of southwest Alaska. STUDY SUBJECTS--51 of 63 Alaska Native children with H influenzae b meningitis and 13 of the same 63 Alaska Native children with S pneumoniae meningitis occurring between 1980 and 1988. One child was infected with both organisms, producing a total of 64 cases for study. SELECTION PROCEDURES--Cases were identified by surveillance for these diseases between January 1, 1980, and December 31, 1988, maintained by the Arctic Investigations Program, Centers for Disease Control. MEASUREMENTS AND RESULTS--Sequelae of bacterial meningitis caused by H influenzae b were equal to or exceeded rates of sequelae described in other children in the United States. After H influenzae b meningitis, motor abnormalities (29%) and hydrocephalus (7%) occurred two to four times more often in Alaska Native children than in children in other parts of the United States. Differences in severity of H influenzae b sequelae could not be accounted for by microbiologic markers of the H influenzae b strain, including ampicillin sensitivity, biotype, outer membrane protein type, or electropherotype. Numbers of cases of S pneumoniae meningitis were too small for statistically valid comparison, but sequelae of S pneumoniae meningitis occurred in roughly equal proportion as sequelae of H influenzae b meningitis. The HTPS was applied to Alaska Native children with H influenzae b meningitis and was found to be very accurate in predicting children with major sequelae. Analysis of the prognostic factors used in deriving the HTPS revealed a unique set of predictors for sequelae in Alaska Native children: seizures at admission, glucose levels in cerebrospinal fluid of less than 1.1 mmol/L; and male gender, with a significant predictive interaction between male gender and age less than 6 months at admission. CONCLUSIONS--Alaska Native children suffer greater neurologic morbidity as a result of H influenzae b meningitis than do their non-Native counterparts. The HTPS was a good predictor of major sequelae in Alaska Native children with H influenzae b or S pneumoniae meningitis and could be useful in determining which patients need referral to a tertiary care center.     

Prospective surveillance of Haemophilus influenzae type b disease in Dallas County, Texas, and in Minnesota

Among children less than 12 years of age residing in Dallas County, Texas, and in the state of Minnesota we conducted prospective, active surveillance of invasive Haemophilus influenzae disease. During 18 months, 616 cases were identified, of which 600 were caused by type b organisms. The annual incidence of disease was significantly greater in Dallas than in Minnesota (109 v 68/100,000 children younger than 5 years of age, P less than .001) and was greater in Dallas, even when rates for white children in the two regions were compared (P less than .001). Other regional differences were observed. In Dallas, a larger proportion of cases were in children attending day-care centers (27% compared with 12% in Minnesota, P less than .001) and more patients attended day care for greater than 40 h/wk (56% compared with 30% in Minnesota, P less than .001). Outer membrane protein subtyping of isolates revealed that in Dallas 6U isolates were associated significantly with cases in black children who attended day care. In Minnesota, but not in Dallas, isolates with subtype 1H were associated significantly with cases in children in day care. These data indicate that there are regional differences in the epidemiology of type b Haemophilus disease that may relate to differences in strains, day-care practices, or other unknown cultural or environmental factors. Finally, because only 15% of systemic Haemophilus disease in these regions occurred in children in the age groups recommended for vaccination (24 to 59 months), the new Haemophilus type b polysaccharide vaccine is expected to have a limited impact on the overall incidence of disease.     

Frequent Haemophilus influenzae type B colonization in rural Thailand

In Asia, there is uncertainty regarding whether the burden of Haemophilus influenzae type b (Hib) disease is great enough to warrant vaccination. In this nasopharyngeal carriage study in rural Thailand, 7% of children younger than 5 years of age carried Hib, a prevalence similar to that found in countries with high rates of Hib disease before vaccine introduction.     

Incidences of nasopharyngeal colonization of respiratory bacterial pathogens in Japanese children attending day-care centers

BACKGROUND: In Japan, many younger children attending day-care centers tend to frequently experience acute respiratory infections and prolonged otitis media. OBJECTIVES: To evaluate the carriage rate of respiratory bacterial pathogens in children attending day-care centers in our district. METHODS: Nasopharyngeal cultures of 156 healthy children between the ages of 1 month and 5 years were conducted at two day-care centers in Japan, in April 1999. The carriage rates of four major pathogens (Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and Staphylococcus aureus) and the antibiotic susceptibilities of the isolates were examined. RESULTS: Streptococcus pneumoniae, H. influenzae, M. catarrhalis and S. aureus were detected in 94 (60.3%), 83 (53.2%), 54 (34.6%) and 28 (17.9%) children, respectively. A total of 141 (90.4%) children carried at least one pathogen among these four pathogens and 87 (55.8%) children carried more than one pathogen. Fifty-seven of the 94 (60.6%) S. pneumoniae isolates were penicillin-intermediately or highly resistant strains of S. pneumoniae (PISP/PRSP). Beta-lactamase producing H. influenzae was not detected. Twelve of the 28 (42.9%) S. aureus isolates were methicillin-resistant. The incidence of colonization by PISP/PRSP in children younger than 3 years (43/69, 62.3%) was significantly higher than that in children aged 3-5 years (14/87, 16.1%) (P < 0.0001). CONCLUSIONS: We conclude that the rates of colonization by respiratory bacterial pathogens, especially by antibiotic-resistant strains, were high in children attending day-care centers in our district, suggesting their horizontal spread among children in day-care centers. Considering that the majority of children attending day- care centers carried one or more of the bacterial pathogens, the judicious use of antimicrobials will be required to prevent the increase of antibiotic-resistant rates among the colonizing pathogens.     

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 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.     

Effectiveness of haemophilus influenzae type B conjugate vaccine for prevention of meningitis in Senegal

A total of 24 cases of hospitalized, laboratory-confirmed Haemophilus influenzae type b (Hib) meningitis were identified through a regional pediatric bacterial meningitis surveillance system. Each case was matched by age and residence to 4 neighborhood controls. The adjusted vaccine effectiveness for ≥ 2 doses was 95.8% (95% confidence interval, 67.9%-99.4%). Hib vaccine appears to be highly effective in preventing Hib meningitis in Senegal.