Meningococcal disease among children who live in a large metropolitan area, 1981-1996.

Neisseria meningitidis is an important cause of serious bacterial infections in children. We undertook a study to identify meningococcal infections of the blood, cerebrospinal fluid, or both of children in a defined geographic area to describe the burden of disease and the spectrum of illness. We reviewed the medical records of all children aged <18 years who had meningococcal infections at the 4 pediatric referral hospitals in Boston, Massachusetts, from 1981 through 1996. We identified 231 patients with meningococcal disease; of these 231 patients, 194 (84%) had overt disease and 37 (16%) had unsuspected disease. Clinical manifestations included meningitis in 150 patients, hypotension in 26, and purpura in 17. Sixteen patients (7%) died. Although meningococcal disease is devastating to a small number of children, we found that the burden of pediatric disease that it caused at the 4 pediatric referral centers in this geographic region was limited; that patients with overt meningococcal disease are most likely to have meningitis; and that individual practitioners are unlikely to encounter a patient with unsuspected meningococcal disease.

Respiratory syncytial virus immunoprophylaxis: impact on epidemiology.

OBJECTIVE: To better understand the spectrum of disease among hospitalised children infected with respiratory syncytial virus (RSV) and to assess the potential impact of passive immunoprophylaxis on RSV hospitalisation rates, we analysed all patients infected with RSV who were admitted to a paediatric teaching hospital over a 3-year period. DESIGN: We performed a retrospective chart review of all paediatric patients from whom RSV was isolated between October 1, 1994 and April 30, 1997. RESULTS: A total of 255 children infected with RSV were hospitalised during this 3-year period. 246 (96%) patients had community acquired infections and 9 (4%) had nosocomial infections. Excluding patients with nosocomial infections, the mean length of hospital stay was 4.7 days. 70 (28%) children were admitted to the intensive care unit, 32 (13%) were intubated and there was a total of 4 deaths (1.6%). 48% of hospitalised patients were in 1 of 4 previously recognised high risk groups. Of the 52% of patients not in a defined high risk category, 42% were otherwise healthy infants (>6 weeks of age) and 10% had chronic underlying illnesses generally not associated with an increased risk of severe RSV disease. Patients not in a defined high risk category accounted for 46% of total hospital days. CONCLUSION: In order to reduce overall RSV hospitalisation rates and the economic burden to society, programmes for disease prevention must be directed at healthy infants as well as children in recognised high risk categories. Even if all currently eligible candidates were to have received passive immunoprophylaxis, which yields about a 50% reduction in hospitalisation rates, the number of RSV hospitalisations in our 3-year study would have been reduced by no more than 9%. Without development and widespread use of an effective RSV vaccine, a major impact on RSV-induced hospitalisation is unlikely.

Rapid molecular epidemiologic studies of human parainfluenza viruses based on direct sequencing of amplified DNA from a multiplex RT-PCR assay.

Sequencing studies of limited regions of the human parainfluenza viruses (HPIVs) genomes have helped describe patterns of virus circulation and characterize institutional outbreaks of HPIVs-associated respiratory illness. In this study, we sequenced reverse transcription polymerase chain reaction (RT-PCR)-amplified HPIVs RNA obtained from a multiplex RT-PCR assay described previously for simultaneous detection of HPIV-1, 2 and 3. Differences in the nucleotide sequences of limited regions of the HN gene allowed us to distinguish temporally and geographically diverse HPIV isolates (43 HPIV-1, 7 HPIV-2, 12 HPIV-3 isolates from this and previously published studies). In addition, an outbreak of HPIV-3-associated illness among infants on a pediatric ward was investigated by comparing sequences of three ward isolates with three matched community controls. Sequences of all ward isolates were identical and differed from those of the community controls, suggesting a single introduction and nosocomial transmission of the virus. Combining multiplex reverse transcription polymerase chain reaction (RT-PCR) assays with direct sequencing of the PCR products can provide an integrated system for rapid diagnosis and characterization of HPIVs.

Enzyme-linked immunosorbent assay to assess respiratory syncytial virus concentration and correlate results with inflammatory mediators in tracheal secretions.

OBJECTIVE: We developed an enzyme-linked immunosorbent assay (ELISA) for the quantitation of respiratory syncytial virus (RSV) in respiratory secretions in intubated patients infected with RSV. METHODS: We compared the quantitative ELISA and a standardized plaque assay in intubated children <2 years of age who were mechanically ventilated for severe RSV disease and enrolled in a randomized double blind placebo-controlled treatment trial of a monoclonal antibody to the F protein of RSV (palivizumab; Synagis). We also examined the relationship between the concentrations of virus as measured by ELISA and of three inflammatory indices in respiratory secretions (white blood cell count, myeloperoxidase and eosinophilic cationic protein). RESULTS: Quantitative ELISA and plaque assay were highly correlated for both tracheal aspirates (r = 0.67, P = 0.001) and nasal wash specimens (r = 0.75, P = 0.001). Treatment with palivizumab significantly neutralized RSV in tracheal aspirates as measured by plaque assay. In contrast quantitation of RSV by ELISA was not affected by palivizumab treatment. This finding is consistent with results that were obtained in preliminary studies of RSV-containing media treated with monoclonal antibody, where we found that the ELISA measured virus whether antibody-bound or not. The inflammatory indices were not correlated with RSV concentration measured by ELISA or plaque assay. CONCLUSIONS: We conclude that this quantitative ELISA is a potentially useful tool for measurement of RSV concentration in respiratory secretions that may help elucidate the pathophysiology of acute RSV infection. Specific antiviral strategies for the treatment of RSV disease could be evaluated by this method.

The many faces of Kawasaki syndrome.

The clinical challenge lies in recognizing cases not fully meeting the syndrome's diagnostic criteria and those that strongly resemble a variety of infectious and reactive disorders. Prompt treatment with high-dose intravenous immune globulin in combination with aspirin can significantly reduce the frequency and severity of cardiovascular complications.

Anti-human cardiac myosin autoantibodies in Kawasaki syndrome.

Kawasaki syndrome (KS) is the major cause of acquired heart disease in children. Although acute myocarditis is observed in most patients with KS, its pathogenesis is unknown. Because antimyosin autoantibodies are present in autoimmune myocarditis and rheumatic carditis, the purpose of the current study was to determine whether anticardiac myosin Abs might be present during the acute stage of KS. Sera from KS patients as well as age-matched febrile controls and normal adults were compared for reactivity with human cardiac myosin in ELISAs and Western blot assays. A total of 5 of 13 KS sera, as compared with 5 of 8 acute rheumatic fever sera, contained Ab titers to human cardiac myosin that were significantly higher than those found in control sera. Both cardiac and skeletal myosins were recognized in the ELISA by KS sera, although stronger reactivity was observed to human cardiac myosin. Only IgM antimyosin Abs from KS sera were significantly elevated relative to control sera. KS sera containing antimyosin Abs recognized synthetic peptides from the light meromyosin region of the human cardiac myosin molecule and had a different pattern of reactivity than acute rheumatic fever sera, further supporting the association of antimyosin Ab with KS. These Abs may contribute to the pathogenesis of acute myocarditis found in patients with KS.

Safety and pharmacokinetics of an intramuscular monoclonal antibody (SB 209763) against respiratory syncytial virus (RSV) in infants and young children at risk for severe RSV disease.

We conducted a multicenter, double-blind, placebo-controlled, randomized trial of a humanized monoclonal antibody against a respiratory syncytial virus (RSV) fusion protein (SB 209763) to evaluate its safety, pharmacokinetics, and fusion inhibition and neutralization titers. Forty-three infants who were either delivered prematurely (

Report of the National Institutes of Health Workshop on Kawasaki Disease.

The National Institute of Allergy and Infectious Disease, National Institutes of Health convened a workshop on Kawasaki disease, May 1997, co-chaired by Drs. Karyl Barron and Stanford Shulman. The goal of the workshop was to review the latest scientific advances relating to the epidemiology, etiology, pathogenesis, treatment, and complications of Kawasaki disease, along with future therapeutic options and proposed future research directions.

Reduction of respiratory syncytial virus (RSV) in tracheal aspirates in intubated infants by use of humanized monoclonal antibody to RSV F protein.

Thirty-five children <2 years of age mechanically ventilated for respiratory syncytial virus (RSV) infection were randomized to receive an intravenous infusion of 15 mg/kg MEDI-493 or placebo. RSV concentration was measured in tracheal secretions by plaque assay before and at 24-h intervals after treatment. The reduction in tracheal RSV concentration from day 0 to day 1 (-1.7+/-0.28 vs. -0. 6+/-0.21 log10 pfu/mL; P=.004) and from day 0 to day 2 (-2.5+/-0.26 vs. -1.0+/-0.41 log10 pfu/mL; P=.012) was significantly greater in the MEDI-493 group than in the placebo group. RSV concentration in nasal aspirates did not differ significantly between the groups. No significant differences were observed in the tracheal aspirate white blood cell count, or myeloperoxidase or eosinophilic cationic protein concentration, or in measures of disease severity between the groups. Thus, treatment with 15 mg/kg MEDI-493 intravenously was well-tolerated and significantly reduced RSV concentration in tracheal aspirates of children with respiratory failure due to RSV.

Respiratory syncytial virus immune globulin for prophylaxis against respiratory syncytial virus disease in infants and children with congenital heart disease. The Cardiac Study Group.

OBJECTIVE: To examine the effectiveness of respiratory syncytial virus immune globulin administered intravenously (RSV-IGIV) in reducing hospitalization for treatment of RSV in children with congenital heart disease (CHD). METHODS: Children younger than 4 years of age were randomly assigned to a treatment group receiving RSV-IGIV, 750 mg/kg, monthly or to a control group not receiving infusions. Surveillance for respiratory tract infections was carried out and management decisions were made by physicians blinded to treatment group. RESULTS: Hospitalization for treatment of an RSV infection occurred in 32 of 214 (15%) of control children and 21 of 202 (10%) of the children receiving RSV-IGIV, a 31% reduction (P = .16). However, in infants younger than 6 months of age at study entry, 20 of 82 (24%) in the control group and 10 of 96 (10%) in the RSV-IGIV group had RSV hospitalizations (58% reduction, P = .01). The incidence of hospitalization for any respiratory tract symptomatology was lower in the RSV-IGIV group (34 of 202, 17%) than in the control group (57 of 214, 27%; P = .02). There was a significantly higher frequency of unanticipated cyanotic episodes and of poor outcomes after surgery among children with cyanotic CHD in the RSV-IGIV group (22 of 78, 28%) than in the control group (4 of 47, 8.5%; P = .009). CONCLUSION: RSV-IGIV should not be used for prophylaxis of RSV disease in children with cyanotic CHD. RSV-IGIV did not reduce RSV hospitalization in all children with CHD, but it was effective in preventing RSV hospitalization in infants younger than 6 months of age. Further studies in these children are indicated.

Neurocognitive abnormalities in children after classic manifestations of Lyme disease.

BACKGROUND: In adults a subtle encephalopathy characterized primarily by memory impairment, irritability and somnolence may occur months to years after classic manifestations of Lyme disease. However, only limited information is available about whether there is an equivalent disorder in children. METHODS: Case series of five children seen in a Lyme disease clinic in a university referral center for evaluation of neurocognitive symptoms that developed near the onset of infection or months after classic manifestations of Lyme disease. The diagnosis was based on clinical symptoms, serologic reactivity to Borrelia burgdorferi and intrathecal antibody production to the spirochete. Evaluation included detailed neuropsychologic testing. After evaluation the children were treated with intravenous ceftriaxone for 2 or 4 weeks. Follow-up was done in the clinic and a final assessment was made by telephone 2 to 7 years after treatment. RESULTS: Along with or months after erythema migrans, cranial neuropathy or Lyme arthritis, the five children developed behavioral changes, forgetfulness, declining school performance, headache or fatigue and in two cases a partial complex seizure disorder. All five patients had IgG antibody responses to B. burgdorferi in serum as well as intrathecal IgG antibody production to the spirochete. Two patients had CSF pleocytoses and three did not. Despite normal intellectual functioning the five children had mild to moderate deficits in auditory or visual sequential processing. After ceftriaxone therapy, the four children in whom follow-up information was available experienced gradual improvement in symptoms. CONCLUSIONS: Children may develop neurocognitive symptoms along with or after classic manifestations of Lyme disease. This may represent an infectious or postinfectious encephalopathy related to B. burgdorferi infection.