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.     

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.     

Clinical manifestations and outcome of Haemophilus influenzae type b disease

Objectives: To document clinical manifestations, laboratory findings and outcome of childhood Haemophilus influenzae type b (Hib) infections.
Methodology: Medical records of 235 children with Hib disease admitted to hospital during a 2 year period were reviewed; additional information was obtained by questionnaire and follow up 6 weeks after discharge.
Results: Three-quarters of patients presented with either meningitis or epiglottitis. Children with epiglottitis were older, had shorter illnesses and were less likely to have had antibiotics before admission than those with meningitis; 38% of the latter had been given some antibiotic therapy, with no apparent effect on the outcome. Fever persisted for 7 days or more in 23% of patients with meningitis. Death from meningitis occurred in 3.8% of patients and was due to fulminating disease.
Conclusions: These data will assist in recognition and appropriate management of Hib disease as the clinical manifestations become less familiar following the introduction of immunization. Specific laboratory diagnosis is required for accurate surveillance, which should be maintained in order to ensure high immunization rates.     

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.     

Epidemiology and prevention of invasive Haemophilus influenzae type b infection

The use of rifampicin prophylaxis is recommended in dose contacts of individuals with invasive Haemophilus influenzae type b infection if they include a child less than 4 years old in whom the risk of secondary infection is relatively high. In practice, delays in administration of rifampicin, contra-indications to its use and the difficulty of identifying all contacts at risk can reduce significantly its efficacy. Only 1–2% of cases of H. influenzae type b disease are attributable to known contact and, at best, rifampicin prophylaxis can have little impact on the incidence, in the USA, one in 200 children less than 5 years old is affected. The incidence is probably similar in Australia but there are local differences which could affect the value of preventative measures. The vaccine recently licensed in the USA is not effective in children less than 18–24 months of age in whom the incidence of invasive H. influenzae type b infection, other than epiglottitis, is highest. Nevertheless, it could prevent more than 30% of cases if given to children at the age of 24 months. Vaccines effective in younger infants should become available soon. The best chance of prevention is by the optimal use of both rifampicin prophylaxis and immunization.     

Immune response to Haemophilus influenzae type b conjugate vaccine in preterm infants

Background: Haemophilus influenzae type b (Hib) vaccine became available for use in Japan in December 2008. The aim of the present study was to evaluate the immunogenicity of Hib vaccine in Japanese preterm infants. Methods: Serum samples were obtained from 54 preterm infants before the first vaccination and 1 month after the third. Anti‐polyribosylribitol phosphate (PRP) antibodies were measured using an enzyme‐linked immunosorbent assay method. Antibody positivity was defined as levels >1 µg/mL. Results: Of the 54 preterm infants, 46 (85.2%) achieved antibody levels >1 µg/mL. This compares with the 92.4% reported in full‐term infants. The antibody seroconversion rate of infants starting vaccination at 2 months of age was close to being significantly lower than when vaccination was started at 3 months of age (P= 0.060). In addition, the percentage of infants achieving a positive response in the group with a history of antenatal steroid exposure was significantly higher than in those not exposed (P= 0.046). Thus, risk factors for lower Hib antibody concentrations after three doses of vaccine were age at first vaccination and lack of use of antenatal steroids. Conclusions: There is a possibility that perinatal factors and the environment unique to preterm infants are related to their lower antibody positivity rates compared to full‐term infants. It may therefore be preferable to modify the proposed immunization schedule.     

Invasive Haemophilus influenzae type b infections in children hospitalized in Hong Kong, 1986–1990

A 5-year territory-wide retrospective survey of invasive Haemophilus influenzae type b diseases was conducted in Hong Kong. Between 1986 and 1990, 57 cases (28 male) were recorded in children less than 12 years old (37 cases of meningitis, 9 of septicaemia and 11 of bacteraemic pneumonia). The annual incidence for children less than 5 years old was 2.7 per 10⁵ (95% confidence interval (CI) 2.0–3.5). Of the 57 cases, 39 were Chinese and 18 non-Chinese (7 Vietnamese refugees, 6 Caucasians, 5 others). The annual incidence in Vietnamese refugees less than 5 years old was 42.7 per 10⁵ (95% CI 17.2–87.9), giving a relative risk of 18.5 (95% CI 8.3–41.0). Chinese patients (68%) were under-represented as Chinese accounted for at least 94% of the population. Moreover, 14 of the 39 Chinese patients had pre-existing medical problems, compared with only 1 of the 18 non-Chinese patients (p = 0.022).     

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.     

Osteomyelitis and septic arthritis due to Citrobacter freundii and Haemophilus influenzae type b

This report describes dual infection with Citrobacter freundii and Haemophilus influenzae type b causing septic arthritis and osteomyelitis of the elbow in a previously healthy 5-year-old boy. The patient was treated successfully with intravenous fosfomycin for 4 weeks. Infections with Citrobacter beyond the neonatal period are rare in paediatric patients. When Citrobacter spp. is isolated, coinfection with other bacterial pathogens should be considered.     

Antibody response of 18 month old children 1 month and 18 months following Haemophilus influenzae type b vaccine administered singly or with DTP vaccine

Seventy-six children (aged 17-19 months) received 10 micrograms of Haemophilus influenzae type b polyribosyl-ribitol phosphate (PRP) vaccine, diluted with either phosphate-buffered saline (PBS) or diphtheria-tetanus-pertussis (DTP) vaccine, in a single-blind randomized trial. There were few side effects when PRP was administered alone. Before vaccination 37 of 76 children (49%) had non-protective antibody levels (less than 0.15 micrograms/mL); 26 of these 37 (70%) achieved antibody levels of greater than 0.15 micrograms/mL 1 month after vaccination. Before vaccination 16 of 76 (21%) had antibody levels of greater than 1.0 micrograms/mL; 1 month after vaccination 39 of 76 children (51%) achieved levels of greater than 1.0 micrograms/mL. Of 12 infants who had antibody levels less than 0.15 micrograms/mL 1 month after immunization, 10 had protective levels 18 months later. Administration of PRP mixed with DTP did not affect antibody response to PRP. The potential use and limitations of PRP vaccine are discussed.     

Quantitative measurements of Hemophilus influenzae type b capsular polysaccharide antibodies in Japanese children

BACKGROUND: Hemophilus influenzae type b (Hib) infection has a high morbidity and mortality rate in children. The frequency of natural immunity against Hib in Japanese children is not known, and Hib vaccine has not yet been introduced in Japan. METHODS: Anti-capsular polysaccharide-specific IgG (anti-CP) antibody titers were examined in serum samples from 100 children and 107 young adults who were not vaccinated against Hib, in serum samples from eight patients with Hib systemic infection and in 10 commercially available human immune globulin preparations on enzyme-linked immunosorbent assay. RESULTS: A total of 44% (44/100) of Japanese children and all patients with Hib systemic infection in the acute phase did not have the minimum protective level of anti-CP antibodies (>0.15 microg/mL). The rate of natural Hib immunity was lowest in children under 1 year of age and gradually increased with age. Only 3.74% (4/107) of Japanese young adults did not have the minimum protective level of anti-CP antibodies. Analysis of 10 commercially available human immune globulin preparations indicated an average level of 28.25 microg anti-CP antibody/mL immune globulin (range 14.96-44.17 microg/mL). CONCLUSIONS: Approximately half of Japanese children are not protected against Hib infection. Therefore, Hib vaccine should immediately be included as part of the routine immunization program in Japan. It was also found that all tested commercially available immune globulin preparations had high anti-CP titers. Well-controlled clinical trials of i.v. immune globulin administration for prevention and treatment of Hib systemic infection are needed in Japan.     

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.     

Immunogenicity and safety of Haemophilus influenzae type b capsular polysaccharide tetanus conjugate vaccine (PRP-T) presented in a dual-chamber syringe with DTP

Separate injections of Haemophilus influenzae type b capsular polysaccharide-tetanus conjugate (PRP-T) vaccine and diphtheria-tetanus-pertussis (DTP) reconstitution of freeze-dried PRP-T vaccine with liquid DTP vaccine have been shown to be safe and immunogenic in infants. The present study was conducted to test the safety and immunogenicity of the liquid combination vaccine administered to young infants in the dual-chamber syringe. The study was a monocenter, open clinical trial of 3 month-old infants receiving PRP-T and DTP vaccines in the dual-chamber syringe reconstituted prior to injection. Healthy infants were immunized according to a 3, 4 and 5 months-of-age schedule. The vaccine was administered in a dual-chamber syringe, ready to use with two chambers. The proximal chamber contained freeze-dried PRP-T and the distal chamber contained liquid combination-vaccine DTP. The freeze-dried PRP-T vaccine was reconstituted with the liquid DTP vaccine in the same unidose dual-chamber syringe (0.5 mL) and was injected intramuscularly into the deltoid region. Blood sampling was performed prior to vaccination at 3 months of age and after the third vaccination at 6 months. The primary end-point was the serological response to PRP-T vaccine as expressed by the percentage of infants with an antibody titer greater than or equal to 1 μg/mL. The reactogenicity was expressed as the percentage of reported local and systemic reactions. A total of 108 infants were included in the study and received the dual-chamber syringe vaccine. After the third injection, all the infants had a PRP antibody titer greater than or equal to 0.15 μg/mL and 94.4% of infants had a PRP antibody titer greater than or equal to 1 μg/mL; the pertussis agglutinin titers were over the threshold 40 and 80 in all infants and 98.1% were over the threshold 320. After the third injection, all the infants had diphtheria antibody titers greater than 0.1 IU/mL and 83.3% had titers greater than 1 IU/mL; all the infants had tetanus antibody titers greater than 0.1 IU/mL and 97.2% had results over 1 IU/mL. Thirty-seven infants (34.6%) had local reactions and 64.5% had systemic reactions. The dual-chamber syringe may reduce the cost of vaccine delivery, as well as the workload, and increase the vaccine acceptability and coverage rate of vaccines.     

Effect of aluminum adjuvants on safety and immunogenicity of Haemophilus influenzae type b-CRM197 conjugate vaccine

OBJECTIVE: The present study was carried out to evaluate the safety and immunogenicity of the Haemophilus influenzae type b-CRM197 (Hib-CRM197) conjugate vaccine in relation to the change of adjuvant from aluminum hydroxide to aluminum phosphate (AlPO4). METHODS: The present study was a clinical phase II, observer-blind, randomized, multicenter, controlled study. Subjects were healthy infants aged 6-12 weeks, eligible for expanded program of immunization (EPI) routine vaccination and admitted to Hacettepe University Department of Social Pediatrics and Gülveren Health Center, Ankara. A total of 520 healthy infants were randomized in a 2:2:1 ratio to receive at either Chiron Hib/AlPO4 vaccine or VaxemHib (aluminum hydroxide adjuvant) vaccine or HibTiter (no adjuvant). Vaccines were administered simultaneously with routine diphtheria, tetanus and pertussis (DTaP) and oral polio vaccine (OPV) vaccines at 2, 4 and 6 months of age. Blood samples for anti-plain polysaccharide (PRP) antibody measurement were collected before the first vaccination and 1 month after the last vaccination. After each vaccination parents filled out a diary for 7 days. RESULTS: Out of 520 subjects enrolled, 514 received three doses and were included for safety analysis. Local and systemic reactions occurred with low and similar frequencies in all groups. Only erythema was more common in Chiron Hib/AlPO4 vaccine (19, 10, 11% in Chiron Hib/AlPO4, VaxemHib and HibTiter, respectively, P < 0.05). Nine serious adverse events were reported in seven cases of which none were related to vaccines. A total of 504 subjects were included in the immunogenicity analysis. The three vaccines were highly immunogenic and equivalent in terms of percentage of acquisition of long-term protective levels. The anti-PRP geometric mean titers were 9.9, 8.3 and 5.14 micro g/mL, respectively (P < 0.05). CONCLUSIONS: The use of aluminum compounds adjuvants in Hib-CRM197 conjugate vaccines does not impact the safety profile, while it does increase the magnitude of anti-PRP antibody titers.     

流感嗜血杆菌b型与急性呼吸道感染关系的研究

目的进一步了解急性呼吸道感染中流感嗜血杆菌（ＨＩ）感染的发病情况。方法采用单克隆抗体夹心酶联免疫吸咐法，对３６例上呼吸道感染、３２例支气管炎、７０例肺炎患儿及４５例健康对照组的血、尿进行ｂ型ＨＩ外膜蛋白（ＨｉｂＯＭＰ）抗原的检测，并对７０例肺炎患儿的血清进行ＨｉｂＯＭＰ抗体检测。结果３６例上呼吸道感染患儿中有４例为ＨｉｂＯＭＰ抗体阳性，３２例支气管肺炎患儿中有４例阳性，７０例肺炎患儿中有１８例为阳性；４５例健康对照组中仅１例为ＨｉｂＯＭＰ抗原阳性。肺炎组抗原检出率高于对照组（χ２＝１０．９６０，Ｐ＜０．０１）。７０例肺炎中１８例ＨｉｂＯＭＰ抗体阳性。抗原、抗体检测共有２４例（包括抗原、抗体均阳性１２例，仅抗原或抗体阳性各６例）肺炎获得阳性结果。结论１１．１％的上呼吸道感染、１２．５％支气管炎和３４．３％的肺炎患儿为Ｈｉｂ感染；抗原、抗体联合检测可使Ｈｉｂ检出率提高。