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Acute otitis media (AOM) has been associated with respiratory syncytial virus (RSV) infection; AOM develops in up to one third of children with RSV illness. A masked multicenter trial used an immune globulin enriched with RSV-neutralizing antibodies (RSVIG) to prevent RSV infection of the lower respiratory tract in 249 children with either bronchopulmonary dysplasia, congenital heart disease, or prematurity. To determine whether monthly RSVIG therapy might decrease the incidence of AOM, we retrospectively analyzed the records of 109 children in two of the centers. RSVIG was administered during RSV season of a high dose of 750 mg/kg monthly or a low dose of 150 mg/kg monthly; control children received no RSVIG. Children were examined for AOM by masked observers using pneumatic otoscopy. No difference in sex, race, underlying diagnosis, number of persons in the home, exposure to smoking, or atopy was found between groups studied. In recipients of high doses of RSVIG, significantly less AOM developed per season than in control children (mean episodes, 0.15 vs 0.78; p = 0.003), and fewer episodes of RSV-related AOM occurred (0 vs 5; p = 0.047). Low doses of RSVIG did not have a clinically significant impact. High doses of RSVIG appeared to have a significant impact on preventing AOM (both RSV- and non-RSV-related AOM) in these-high risk populations. This finding may have important implications in the development of improved preventive modalities for AOM.

We evaluated the prevention of recurrences of acute otitis media (AOM) by bacterial polysaccharide immune globulin (BPIG), a hyperimmune human immune globulin prepared by immunizing donors with bacterial polysaccharide vaccines. We used a randomized, stratified, double-blind, placebo-controlled design. Children < or = 24 months of age with 1 to 3 prior episodes of AOM received BPIG, 0.5 ml/kg, or saline placebo intramuscularly at entry and 30 days later. During the 120-day follow-up period, AOM was diagnosed by using clinical criteria and was confirmed with tympanocentesis and culture of the middle ear exudates. Eighty-eight episodes of AOM were observed in 76 patients who completed the study. The incidence of AOM during the entire 120-day study period was similar in BPIG and placebo recipients. Pneumococcal AOM was significantly less frequent in BPIG recipients (0.21 episode per patient) than in placebo recipients (0.45 episode per patient; p = 0.05). Time spent free of AOM was significantly prolonged in recipients of BPIG, in comparison with placebo recipients (51 vs 35 days; p = 0.034). This study demonstrated that circulating antibody, even without stimulation of specific local immunity, may prevent infection of the middle ear. The use of immune globulin preparations for longer periods or at a higher dosage might decrease the incidence of recurrent AOM in otitis-prone children, and deserves further evaluation.

Passively acquired antibody may interfere with the active antibody response to live viral vaccines such as measles and rubella. To evaluate the duration of this inhibitory effect, we measured the measles and rubella antibody responses of Apache children immunized with measles, mumps, and rubella vaccine at varying intervals after administration of an immune globulin termed bacterial polysaccharide immune globulin (BPIG). This specific immune globulin contained measles and rubella antibody titers similar to those in standard intramuscularly and intravenously administered immune globulins. Antibody responses to measles vaccine were inhibited for up to 5 months after a BPIG dose of 80 mg IgG per kilogram of body weight, but responses to rubella vaccine were inhibited for only 2 months. Most children who had a decreased measles antibody response to primary measles, mumps, and rubella immunization given 1 1/2 to 4 months after BPIG administration responded to a booster immunization given 6 months after their last BPIG dose. We conclude that high doses of immune globulin (> 10 mg/kg) may inhibit the antibody response to measles for more than 3 months. We propose that the interval between administration of immune globulin and measles and rubella immunization be adjusted on the basis of the dose of immune globulin.

Study Objective: To evaluate measurement of interleukin-6 as a diagnostic test for the presence and severity of invasive bacterial disease., Design: Prospective measurement of interleukin-6 in children with signs of sepsis. (Controls, retrospective from serum bank.), Setting: Emergency department of an urban children's hospital., Participants: Twenty children with clinical signs of sepsis and 50 other febrile infants and toddlers with negative blood cultures., Results: Eleven of the 20 patients had bacteriologically documented infections: four with meningitis and two with bacteremia caused by Neisseria meningitidis, three with meningitis caused by Haemophilus influenzae type b, and one each with meningitis and bacteremia caused by Streptococcus pneumoniae. Ten of these 11 had detectable interleukin-6. The geometric mean interleukin-6 level in these culture-positive patients was 407 pg/mL (95% confidence interval, 108 to 1,545); all three children with levels of more than 300 pg/mL developed septic shock, and one died. One of nine culture-negative patients with clinical signs of sepsis had detectable serum interleukin-6 (166 pg/mL), but none of 50 other febrile children without occult bacteremia did. The detection of interleukin-6 had a sensitivity of 91% and a specificity of 98% for invasive bacterial disease., Conclusion: High levels of interleukin-6 occur in children with septic shock, and the presence of interleukin-6 in serum is predictive for the isolation of bacteria from blood and/or spinal fluid.

Because we have noted discordant results in the measurement of IgG subclass concentrations by means of a widely available commercial radial immunodiffusion (RID) kit in comparison with an enzyme-linked immunosorbent assay (ELISA) developed at the Centers for Disease Control (CDC), we conducted in a blinded manner a comparison of the two assays, using sera from 48 healthy children. The correlation coefficients between the assays were 0.92, 0.82, 0.93, and 0.86 for the IgG1, IgG2, IgG3, and IgG4 assays, respectively. However, the RID assay assigned lower values for IgG1 and IgG4 determinations than the ELISA did. Furthermore, the "normal lower range values" provided by the RID assay were higher for each IgG subclass. When the sera from the healthy control subjects were analyzed with the RID assay, 12 (25%) of 48 subjects had values below the normal range for at least one subclass measurement. In contrast, with the CDC ELISA, all values were within the 95% confidence limits determined for the CDC ELISA. We suggest that age-specific normal limits be established with the use of sera from many healthy subjects for any assay measuring IgG subclass concentrations. As new groups of immunodeficiencies are defined and potential therapies are advocated, careful attention to assay standardization will result in a clearer delineation of these disease groups and of their response to treatment.

We studied Haemophilus influenzae type b meningitis in 68 patients to evaluate whether quantitative determination of PRP in body fluids obtained at admission or measurement of the duration of its presence helped identify patients at risk for complications. Geometric mean admission PRP concentrations in CSF, blood, and urine increased with severity of disease, but individual values varied greatly. Measurements of the duration of antigenemia and antigenuria also varied widely and were best predicted by the admission or peak PRP concentration. The mean duration of both antigenemia and antigenuria increased with severity of disease. In contrast, the elimination half-life of PRP did not differ significantly with severity of hospital course, peak PRP concentration in blood or urine, or patient age. Clearance from CSF could not be accurately assessed, but PRP was detectable in only six of 41 patients in whom spinal fluid was obtained after the eighth day of hospitalization; all had complicated courses. Although latex particle agglutination assay is a valuable aid in rapid diagnosis of invasive Hib infections, the predictive value of antigen quantitation at admission and the determination of its duration in body fluids is limited by the wide range of observed values.

To evaluate the possibility that immunization with a capsular polysaccharide vaccine decreases immunity in the immediate postvaccination period and renders an animal susceptible to invasive Haemophilus influenzae type b disease, we passively immunized infant rat pups with an immune globulin preparation, vaccinated them with an H. Influenzae type b capsular polysaccharide vaccine at a wide range of doses, and challenged them with H. influenzae type b given intraperitoneally. Bacteremia occurred in 89% of protected, vaccinated pups compared with 17% of protected, unvaccinated pups (p = 0.0001). In protected, vaccinated pups the rate of bacteremia resembled that in unprotected, unvaccinated control pups and did not vary with the dose of vaccine administered. The magnitude of bacteremia and the incidence of meningitis in protected, vaccinated pups exceeded that occurring in the protected, unvaccinated control animals, but these effects diminished with the dose of vaccine. Diminution of anticapsular antibody occurred in association with the largest doses of vaccine. We conclude (1) that the administration of H. influenzae type b capsular polysaccharide vaccine in infant rats is associated with a diminution of passively acquired anticapsular antibody immediately after vaccination and (2) that experimental challenge with H. influenzae type b at this time produces disease resembling that in animals not passively given protection.

We studied 15 children with recurrent infections and normal serum IgG, IgM, IgA, and IgG-subclass levels. After immunization, the geometric mean serum IgG antibody concentration to Haemophilus influenzae type b (Hib) was eightfold lower than that of age-matched control subjects (p = 0.002). The patients also had a lower geometric mean concentration of serum IgM and IgA directed to Hib, although these differences did not reach significance. However, the groups did not differ in their response to diphtheria toxoid and pneumococcal polysaccharides. To confirm these findings, an additional 11 patients were identified and immunized. The geometric mean serum IgG anti-Hib concentration for this group of patients was also significantly lower than of normal subjects (p = 0.004). We propose that the defect in the antibody response to Hib may be a marker for a poor antibody response to a variety of bacterial and viral antigens that results in an increased propensity to recurrent infections. The defect was not associated with IgG-subclass deficiency. The identification of children with selective antibody deficiency and recurrent infections is important for diagnostic and therapeutic reasons.

Latex particle agglutination and counterimmunoelectrophoresis techniques were compared in a clinical trial to demonstrate their sensitivity, specificity, and usefulness in the rapid diagnosis of invasive Hemophilus influenzae type b disease. LPA, a simplified LPA performed by house officers, and CIE used in this study detected 0.2, 0.5, and 1 to 10 ng/ml of Hib capsular antigen, respectively. One hundred-six illnesses suspected of being caused by Hib were evaluated prospectively by these assays. A total of 39 of these were confirmed by culture or detection of antigen or both. LPA and simplified LPA were more sensitive and specific than CIE in the diagnosis of Hib disease (P less than 0.01), especially in invasive disease other than meningitis. LPA is inexpensive, can be performed quickly, and detects all invasive Hib infections. The results emphasize the usefulness of antigen detection in the rapid diagnosis of Hib infections, demonstrate that LPA is more sensitive and specific than CIE, and can be conveniently performed by physicians.

We examined gentamicin dosage based on body surface area (60 mg/m2 intravenously every eight hours) as a means of attaining therapeutic but nontoxic serum concentrations in 58 patients ranging in age from 0.7 to 73 years. All but one patient had peak serum levels between 3.4 and 8.0 microgram/ml. The mean serum gentamicin half-life was shorter in patients less than 10 years of age (76 minutes) than in patients aged 10 to 50 years (116 minutes) and in patients aged 50 to 63 years (184 minutes) (all significant at P less than 0.01). We conclude that gentamicin dosage based on body surface area produces uniform peak serum gentamicin concentrations in both children and adults, and that the safety and efficacy of a shorter dosage interval for children deserves investigation.

Serum gentamicin concentrations were measured 30 minutes after 140 intravenous doses in 60 children and nine adults with normal renal function. Distinct interpatient variation was observed but individual patients tended to have similar pharmacokinetics with repeated doses. Age had a significant effect in that mean peak serum concentrations were 1.58 mug/ml per 1 mg/kg dose in children between 6 months and 5 years, 2.03 mug/ml per 1 mg/kg in those between 5 and 10, and 2.86 mug/ml per 1 mg/kg in children 10 to 15 years of age. The mean calculated single dose of gentamicin necessary to achieve a peak serum concentration between 4 and 5 mug/ml is 2.5 mg/kg for ages 0.5 to 5 years, 2.0 mg/kg for ages 5 to 10 years, and 1.5 mg/kg for individuals over 10 years of age.