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.     

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.     

Acute osteomyelitis in children. Reassessment of etiologic agents and their clinical characteristics

One hundred thirty-five children with acute osteomyelitis were identified by chart review during a 7-year period, January 1, 1980, through December 31, 1986. Bacteriologic causes were detected in 75 (55%) of the patients. Staphylococcus aureus, Haemophilus influenzae type b, and Pseudomonas aeruginosa were identified in 34 (25%), 16 (12%), and eight (6%) children, respectively. Staphylococcus aureus occurred in all age groups, H influenzae type b occurred only in children younger than 3 years and was the number one cause of disease in this group. Pseudomonas aeruginosa occurred exclusively in children older than 9 years. Children with H influenzae type b had clinical and laboratory findings that were almost indistinguishable from a matched group of children with osteomyelitis due to other known bacteria, although children with H influenzae type b tended to have more joint effusions (63% vs 27%), less lower extremity disease (22% vs 70%), and fewer positive cultures from bone or joint aspirates (41% vs 89%). Unlike most pediatric cases of osteomyelitis, the ones due to P aeruginosa did not represent the hematogenous route of infection; penetrating injury to the foot was present in every case. Children with P aeruginosa infections were older than 9 years (100%), predominantly male (88%), often afebrile (83%), and never bacteremic. These data provide guidelines for the initial work-up and management of osteomyelitis in children.     

Sequelae of acute bacterial meningitis in children treated for seven days

The sequelae of acute bacterial meningitis in children who were treated with ampicillin or chloramphenicol for seven days during the period January 1979 to June 1983 were assessed prospectively. The 235 patients (117 boys and 118 girls) ranged in age from four days to 18 years (mean 26.4 months). Haemophilus influenzae type b was isolated in 70% of patients, Streptococcus pneumoniae in 20%, and Neisseria meningitidis in 10%. The mortality rate was 6.4%. No relapses occurred. Of the 220 survivors, 171 had neurologic psychometric, audiologic, and ophthalmologic assessments performed for a minimum of 1 year following their illness. One hundred thirty-six (80%) children had no detectable sequelae; 20% had mild to severe handicaps. The frequency of sequelae was greatest among children with S pneumoniae meningitis (57%) and least among children with N meningitidis (0%). The sequelae observed included: sensorineural hearing loss (12.9%), developmental delay (5.3%), speech defect (4.7%), motor defect (3.0%), hydrocephalus (1.7%), and seizure disorder (1%). The frequency of observed sequelae among these patients is similar to that previously reported in children treated for ten to 14 days. Our findings indicate that seven days of intravenous antibiotic therapy is adequate for the treatment of bacterial meningitis in children.     

Moxalactam therapy of Haemophilus influenzae type b meningitis in children

Thirty-four children with Haemophilus influenzae type b meningitis were given prospectively either moxalactam (200 mg/kg/day) or ampicillin (400 mg/kg/day) plus chloramphenicol (75 mg/kg/day). One patient in each group died. The mean duration of fever, clinical response, sequential cerebrospinal fluid findings, and incidence of neurologic sequelae were similar between groups. Moxalactam cerebrospinal fluid bioactivity was significantly greater than that of ampicillin or chloramphenicol throughout therapy. Neutropenia, liver enzyme abnormalities, and diarrhea were not significantly different. In eight of 11 patients given moxalactam (versus one of 14 controls) there was complete elimination of gram-negative aerobic flora in the stools by day 10 (P = 0.002); however, none acquired Clostridium difficile. Moxalactam in effective therapy for H. influenzae type b meningitis.     

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.     

Endotoxin concentrations in cerebrospinal fluid correlate with clinical severity and neurologic outcome of Haemophilus influenzae type B meningitis

Endotoxin concentrations were measured in paired samples of cerebrospinal fluid from 38 patients with Haemophilus influenzae type b meningitis. On admission, the median concentration of endotoxin in cerebrospinal fluid was 104 ng/mL and decreased rapidly in follow-up samples. From 17 to 48 hours after admission, 50% of the patients had concentrations of less than 1 ng/mL. Endotoxin concentrations correlated significantly with concentrations of interleukin 1 beta, protein, and glucose in cerebrospinal fluid, duration of secondary fever, and neurologic abnormalities during hospitalization and on follow-up examinations. Twenty-eight percent of patients with endotoxin concentrations of 100 ng/mL or more on admission had long-term complications, compared with none of those with lower endotoxin concentrations (relative risk, 2.31; 95% confidence interval, 1.53 to 3.48). These results indicate that quantitation of endotoxin in cerebrospinal fluid could be a valuable aid in identifying those children at increased risk of complications during Haemophilus influenzae type b meningitis and provide additional evidence that the Haemophilus influenzae type b meningitis lipo-oligosaccharide is important in the pathogenesis of meningitis.     

Moxalactam treatment of serious infections primarily due to Haemophilus influenzae type b in children

Thirty-eight children completed therapy with moxalactam for a variety of non-CNS infections. Haemophilus influenzae type b (seven ampicillin-resistant strains) was the etiologic agent for 32 children. Doses of moxalactam ranged from 113 to 200 mg/kg/d in three or four divided doses administered parenterally. All children with infections due to H influenzae type b had excellent responses to moxalactam therapy. Children treated for infections due to other agents also responded satisfactorily to moxalactam therapy. Moxalactam concentrations in joint and pleural fluids greatly exceeded the minimal bactericidal concentrations of moxalactam for H influenzae type b. Adverse reactions included neutropenia, eosinophilia, thrombocytosis, and transient elevation of transaminase levels. Moxalactam administered parenterally, at a dose of 113 to 150 mg/kg/d in three or four divided doses is effective therapy for serious infections in children due to H influenzae type b and selected other organisms.     

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.     

Bacteriology of middle ear fluid specimens obtained by tympanocentesis from 111 Colombian children with acute otitis media

We cultured middle ear fluid specimens obtained by tympanocentesis from 111 Colombian infants and children, ages 11 days to 11 years, with acute otitis media. Bacteria were isolated in 82 patients (74%). Haemophilus influenzae, the most common isolate, was present in 40 cases (36%); 32 were nontypable strains and 8 were type b. Streptococcus pneumoniae, identified in 26 cases (22%), was the second most common pathogen. All H. influenzae and S. pneumoniae strains were susceptible to ampicillin and penicillin, respectively. We conclude that amoxicillin remains the drug of choice for treatment of acute otitis media in our country.     

Endemic bacterial meningitis in Sudanese children: aetiology, clinical findings, treatment and short-term outcome.

During the period April 1985 to November 1986 (18 months), 196 children (of age greater than 1 month) admitted to the Children's Emergency Hospital in Khartoum, Sudan, with clinical suspicion of meningitis/meningoencephalitis were followed up prospectively. Bacterial meningitis was diagnosed by culture, direct microscopy and/or antigen-detecting assays (co-agglutination and enzyme immunoassay) in 44 infants (25 Haemophilus influenzae type b, 8 Neisseria meningitidis, 7 Streptococcus pneumoniae, 3 enterobacteria and one mixed infection), aseptic meningitis in 52, cerebral malaria in 4 and febrile convulsions in 96. The majority of cases of bacterial meningitis were boys and 57% of those in whom H. influenzae was the commonest isolate were less than 1 year old. The presenting signs and symptoms are described as well as the transient and permanent short-term sequelae. The total mortality from bacterial meningitis was 19%, permanent neurological sequelae were seen in 26% of survivors. Prospective follow-up, including audiometry, of 35 children 1-2 months after discharge showed that 11% had hemiplegia and 20% had hearing impairment. The potential impact of vaccination against invasive H. influenzae infections is discussed.     

Chloramphenicol or ceftriaxone, or both, as treatment for meningitis in developing countries?

AIMS: To determine in children with meningitis whether there is any difference in mortality and neurological sequelae using chloramphenicol as first line treatment, with a change to ceftriaxone if chloramphenicol resistance is shown in vitro, compared to using ceftriaxone as first line treatment, with a change to chloramphenicol if there is no evidence of in vitro resistance. METHODS: An observational study with a retrospective control group nested within a randomised trial of fluid management for bacterial meningitis where clinical care was standardised. Chloramphenicol is standard treatment for bacterial meningitis in Papua New Guinea. In the first 150 cases we used chloramphenicol and only changed treatment to ceftriaxone if chloramphenicol resistance for cerebrospinal fluid isolates was proved. After finding 20% of Haemophilus influenzae were resistant to chloramphenicol, and that most affected children had poor outcomes, we changed to an alternative strategy. In the next 196 cases first line treatment was ceftriaxone and treatment was changed to chloramphenicol if the isolated bacteria were found to be susceptible. RESULTS: When chloramphenicol was used as first line treatment for meningitis followed by ceftriaxone when in vitro resistance was shown, there was invariably a very poor outcome in chloramphenicol resistant disease (71% of children died or had severe neurological complications). Using ceftriaxone as first line treatment was effective in reducing mortality and neurological sequelae from chloramphenicol resistant Haemophilus influenzae type (71% v 9%, relative risk 0.13; 95% CI 0.02 to 0.87; p = 0.013). Changing to chloramphenicol if there was no evidence of in vitro resistance was less than half the cost of empirical use of ceftriaxone for a full course for all children with meningitis. CONCLUSIONS: Using a third generation cephalosporin as first line treatment is effective in dealing with the problem of poor outcomes from meningitis due to Haemophilus influenzae that is resistant to chloramphenicol, and a strategy of changing to chloramphenicol if in vitro susceptibility is shown will reduce the use of expensive third generation cephalosporins without comprising on clinical outcomes. This highlights the urgent need to reduce the costs of third generation cephalosporins, to improve bacteriological services in developing countries, and to introduce effective and affordable vaccines against H influenzae and Streptococcus pneumoniae.     

Epidemiology of Haemophilus influenzae Type b Infections among Children in Denmark in 1985 and 1986

ABSTRACT. 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 epiglottitis were 27 and 8 cases, respectively, per 100000 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.     

Countercurrent immunoelectrophoresis in the evaluation of childhood infections

Samples of CSF, serum, and urine from 162 children with a clinical diagnosis of possible bacterial infection were examined by CIE within 1 hr of admission to the hospital. Results obtained were compared to information derived from gram stain and bacterial cultures of these specimens. Thirty-eight of 59 patients with culturally proved bacterial infections had positive CIE determinations at the time of admission. Highest correlation between culture and CIE results was in patients with meningitis due to Hemophilus influenzae type b while poorest correlation was obtained in children with pneumococcal septicemia. PRP within serum or CSF was quantitated on 21 occasions in patients with H. influenzae meningitis. Patients who experienced sequelae of their meningitis had significantly (p less than 0.005-0.025) higher levels of PRP within CSF and serum than those whose recovery was uneventful.     

Antibody response to outer membrane of noncapsulated Haemophilus influenzae isolated from the nasopharynx of children with pneumonia

In a prospective study aimed at determining the etiology of community-acquired pneumonia in children nasopharyngeal cultures and paired serum samples were obtained from 336 consecutive children ages 6 weeks to 15 years with pneumonia, 167 hospitalized and 169 outpatients. Results regarding Haemophilus influenzae are reported here. Blood cultures obtained from 127 of the hospitalized patients did not yield growth of H. influenzae. H. influenzae was isolated from the nasopharynx of 88 children. Seventy-three strains were noncapsulated, 2 were type b, 2 were type f and 11 were not serotyped. Paired serum samples were available from 38 children with growth of noncapsulated H. influenzae in the nasopharynx as the only potential pathogen. Sixteen of them responded with significant increases in serum antibodies against outer membrane preparations prepared from their own nasopharyngeal isolates. Thirty-eight age- and sex-matched control children with pneumonia without growth of H. influenzae in the nasopharynx served as controls. Sera from each control patient were tested for antibodies against two strains of noncapsulated H. influenzae. Of those, 4 had significant increases in antibodies against one or both outer membrane preparations. The increases in serum antibodies against the outer membrane of noncapsulated strains of H. influenzae indicate that this organism might be a cause of pneumonia in some children.     

Haemophilus influenzae type b in respiratory secretions

Oral and respiratory secretions of 31 children who were healthy or had mild upper respiratory infection, and who had a positive throat culture for Haemophilus influenzae type b, were cultured to determine which secretions contain this organism and how long it can be recovered from fomites. Rhinorrhea was present in 11 of 31 (34%) children and nasal mucus was positive for H. influenzae type b in 10 (91%). In 5 of these children the concentration of H. influenzae type b in nasal mucus was 10(4) to 10(7) colony-forming units/ml3. H. influenzae type b in nasal mucus applied to fomites were recovered for 12 hours. Cultures of saliva and cough secretions compared with nasal mucus were less often positive (3 of 31, P less than 0.001; 3 of 25, P less than 0.001, respectively) and contained fewer H. influenzae type b (5 and 15 colony-forming units, respectively). H. influenzae type b was recovered from the hand of 2 of 27 (7%) children; both children had positive cultures of saliva. These data indicate that H. influenzae type b can be found in oral and respiratory secretions of pharyngeal carriers and can contaminate children's hands. Nasal mucus was the most consistently positive secretion and contained the largest number of bacteria. Careful management of nasal mucus secretions is warranted in settings where transmission could occur to susceptible children.     

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.     

Septic arthritis in childhood

BACKGROUND: The purpose of the present study was to determine whether there was a difference between septic arthritis (SA) combined with osteomyelitis and SA alone with regard to clinical and laboratory findings, such as symptoms on admission, age, sex, joint involvement and isolated micro-organisms, and a relationship between age and joint involvement in SA. In addition, we also aimed to determine the prognostic factors in SA. METHODS: The clinical and laboratory findings of 40 patients who were diagnosed with SA in our hospital were reviewed retrospectively. The diagnosis of SA was made according to the following criteria: immediate joint fluid aspiration (culture and Gram's stain positive, leukocyte count markedly elevated and glucose level low), blood culture positive and positive cultures from other possible sites of infection. RESULTS: Of the 40 patients, 22 were boys, 18 were girls and the male to female ratio was 1.2/1. Patient ages ranged from 6 months to 14 years (mean (+/- SD) 8.44 +/- 4.18 years). The most observed symptoms were fever (52.5%), arthralgia (50%) and joint swelling (45%). Thirty-four (85%) patients had only one joint and six patients (15%) had more than one joint involved. In total, arthritis was diagnosed in 49 joints. The joints diagnosed as having arthritis were the following: knee (n = 18), hip (n = 12), ankle (n = 12), elbow (n = 3), shoulder (n = 2), wrist (n = 1) and interphalangeal joint (n = 1). Of the 40 patients, 21 (52.5%) had SA alone and 19 (47.5%) had arthritis together with osteomyelitis. While arthritis was diagnosed in 27 joints in the group of patients with SA, it was diagnosed in 22 joints in the group of patients with SA combined with osteomyelitis; in the latter, an increase was not observed in the number of joints involved. Joint fluid culture was positive in 22 (55%) patients; the growth of Staphylococcus aureus was observed in 20 cases and Pseudomonas aeruginosa and Staphylococcus epidermidis were isolated in each patient. In contrast, in one patient, arthritis occured during meningococcal meningitis (in this patient, Gram-negative diplococci was isolated from a cerebrospinal fluid culture). Patients with SA combined with osteomyelitis and those with SA alone were compared for symptoms on admission, the history of trauma and antibiotic use, sex, age, fever, joint involvement, anemia, leukocytosis and micro-organisms isolated from joint fluid and blood; there were no significant differences for these parameters between the two groups (P > 0.05). In addition, we found that there was no relationship between age and joint involvement in SA and there was no effect of micro-organisms on mortality. Three of 40 patients died; the mortality rate was 7.3%. Of the three patients who died, two had SA alone and one had SA combined with osteomyelitis. The primary disease was sepsis in these three patients; S. aureus was cultured from blood in two patients and Gram-positive cocci was observed following examination of the joint fluid in the other patient. CONCLUSIONS: We would like to emphasize that SA is mono-articular, frequently localized in the knee, hip and ankle in 85% of patients, joint fluid culture was positive in 55% of patients, bacteria was isolated from one or more cultures of blood, joint fluid, pus or bone in 70% of patients and the most common isolated micro-organism was S. aureus. In addition, it must be pointed out that children younger than 2 years of age with fever, a positive trauma history and/or abnormal joint findings should be carefully examined for SA because the rate of SA was lower (7.5%) than expected in this age group. We also found that the mortality of SA was not influenced by age, joint involvement and bacterial agents, and there was no significant difference in symptoms on admission, the history of trauma and antibiotic use, sex, age, fever, joint involvement,anemia, leukocytosis and micro-organisms isolated from joint fluid and blood between patients with SA     

Immunogenicity of Haemophilus influenzae type b conjugate vaccine in children with sickle cell disease.

OBJECTIVE--To determine the safety and immunogenicity of Haemophilus influenzae type b conjugate vaccine in children with sickle cell disease. RESEARCH DESIGN--Prospective, nonrandomized, nonblinded study. SETTING--Hospital-based, comprehensive sickle cell center. PATIENTS--Children with sickle cell disease aged 18 months to 18 years who were previously unvaccinated or had an inadequate or waning response to H influenzae type b polysaccharide vaccine. SELECTION PROCEDURES--Consecutive eligible patients. INTERVENTIONS--Vaccination and observation for adverse effects. Blood samples were taken before and 1 to 2 and 6 months after vaccination to measure anticapsular antibody levels. MEASUREMENTS AND RESULTS--Vaccination was well tolerated. One hundred percent and 96% of the 31 immunized children had postvaccination anticapsular antibody concentrations of greater than 0.15 and 1.0 mg/L, respectively. Six months after vaccination, 100% and 89% of children had these antibody concentrations. CONCLUSIONS--H influenzae type b conjugate vaccines are safe and highly immunogenic in children with sickle cell disease. It is likely that these vaccines will be protective against invasive H influenzae type b disease.     

Successful treatment of epiglottitis with two doses of ceftriaxone.

Epiglottitis in childhood is caused by Haemophilus influenzae type b. The usual antibiotic treatment at the Royal Children's Hospital, Parkville, Victoria is a five day course of chloramphenicol. Increasingly, third generation cephalosporins are being used to treat invasive H influenzae type b infections and preliminary data suggest that they can be used successfully for epiglottitis. In a prospective, randomised trial, the efficacy of a short course (two days) of ceftriaxone was compared with that of five days of chloramphenicol for the treatment of epiglottitis. The ability of these treatment regimens to eradicate H influenzae type b from the throat was also studied. Fifty five children were enrolled over an 18 month period. Epiglottitis was diagnosed clinically and confirmed on inspection of the epiglottis at direct laryngoscopy. Fifty three (96%) of 55 patients had H influenzae type b detected from at least one site: 44/52 (85%) from blood cultures, 41/47 (87%) from throat swab, and 6/8 (75%) as H influenzae type b urinary antigen. Children were randomised to receive either ceftriaxone 100 mg/kg intravenously followed by a single dose of 50 mg/kg 24 hours later (28 patients), or chloramphenicol 40 mg/kg intravenously, then 25 mg/kg eight hourly for five days, intravenously then by mouth (27 patients). All household contacts and patients receiving chloramphenicol received rifampicin 20 mg/kg daily for four days. Index patients randomised to ceftriaxone were not treated with rifampicin. There was no significant difference in outcome between the two groups with respect to the mean duration of fever, the duration of intubation, or the length of hospital admission. The proportion of patients colonised with H influenzae type b four weeks after discharge was not significantly different between the two groups: ceftriaxone 5/22 (23%) versus chloramphenicol and rifampicin 3/23 (13%). A short course of ceftriaxone was successful in treating all patients with no significant side effects and no relapses. A short course of ceftriaxone is a safe, efficacious, and economic alternative to the standard treatment in children with epiglottitis.