RESUMO
OBJECTIVE: To determine the utility of polymerase chain reaction (PCR) assay of cerebrospinal fluid (CSF), serum, and urine for rapid diagnosis of enteroviral meningitis in infants 3 months of age and younger. STUDY DESIGN: We identified prospectively infants 3 months of age and younger coming to the emergency department with fever whose examination included a lumbar puncture, blood culture, or both. Samples of CSF, serum, urine, throat, and stool specimens were collected for viral culture and, with the exception of stool, for PCR assay. Those infants who had not received prior antibiotic therapy and had sterile bacterial cultures of CSF, blood, and urine were selected for the present analysis. RESULTS: A total of 259 specimens for viral culture and 203 specimens for PCR assay were collected from 64 infants. Comparison of results of PCR assay of CSF with viral culture, the gold standard for diagnosis of enteroviral meningitis, demonstrated a sensitivity of 100% and a specificity of 90%. Because enteroviruses are not always detectable by culture, the following modified standard was established to define enteroviral meningitis: either CSF pleocytosis, sterile bacterial cultures and detection of an enterovirus in stool culture or positive viral culture of CSF, or both. With this modified definition, the sensitivity and specificity of the PCR assay of CSF were 92% and 94%, respectively. PCR assay of serum and urine offered no benefit over PCR assay of CSF alone for diagnosis of meningitis. CONCLUSION: PCR assay of CSF is useful for the rapid and reliable diagnosis of enteroviral meningitis. Application of this technique in the clinical setting can potentially diminish unnecessary hospitalization and use of antibiotics.
Assuntos
DNA Viral/sangue , DNA Viral/líquido cefalorraquidiano , DNA Viral/urina , Infecções por Enterovirus/metabolismo , Enterovirus/genética , Meningite Viral/metabolismo , Reação em Cadeia da Polimerase/métodos , Infecções por Enterovirus/diagnóstico , Humanos , Lactente , Recém-Nascido , Meningite Viral/diagnóstico , Estudos Prospectivos , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: In experimental models of meningitis and in children with meningitis, dexamethasone has been shown to reduce meningeal inflammation and to improve the outcome of disease. METHODS: We conducted a placebo-controlled, double-blind trial of dexamethasone therapy in 101 infants and children admitted to the National Children's Hospital, San José, Costa Rica, who had culture-proved bacterial meningitis or clinical signs of meningitis and findings characteristic of bacterial infection on examination of the cerebrospinal fluid. The patients were randomly assigned to receive either dexamethasone and cefotaxime (n = 52) or cefotaxime plus placebo (n = 49). Dexamethasone (0.15 mg per kilogram of body weight) was given 15 to 20 minutes before the first dose of cefotaxime and was continued every 6 hours thereafter for four days. RESULTS: The demographic, clinical, and laboratory profiles were similar for the patients in the two treatment groups. By 12 hours after the beginning of therapy, the mean opening cerebrospinal pressure and the estimated cerebral perfusion pressure had improved significantly in the dexamethasone-treated children but worsened in the children treated only with cefotaxime (controls). At 12 hours meningeal inflammation and the concentrations of two cytokines (tumor necrosis factor alpha and platelet-activating factor) in the cerebrospinal fluid had decreased in the dexamethasone-treated children, whereas in the controls the inflammatory response in the cerebrospinal fluid had increased. At 24 hours the clinical condition and mean prognostic score were significantly better among those treated with dexamethasone than among the controls. At follow-up examination after a mean of 15 months, 7 of the surviving 51 dexamethasone-treated children (14 percent) and 18 of 48 surviving controls (38 percent) had one or more neurologic or audiologic sequelae (P = 0.007); the relative risk of sequelae for a child receiving placebo as compared with a child receiving dexamethasone was 3.8 (95 percent confidence interval, 1.3 to 11.5). CONCLUSIONS: The results of this study, in which dexamethasone administration began before the initiation of cefotaxime therapy, provide additional evidence of a beneficial effect of dexamethasone therapy in infants and children with bacterial meningitis.
Assuntos
Infecções Bacterianas/tratamento farmacológico , Dexametasona/uso terapêutico , Meningite/tratamento farmacológico , Adolescente , Cefotaxima/administração & dosagem , Pressão do Líquido Cefalorraquidiano , Criança , Pré-Escolar , Dexametasona/administração & dosagem , Método Duplo-Cego , Feminino , Transtornos da Audição/etiologia , Humanos , Lactente , Masculino , Meningite/líquido cefalorraquidiano , Meningite/complicações , Meningite por Haemophilus/tratamento farmacológico , Meningite Meningocócica/tratamento farmacológico , Meningite Pneumocócica/tratamento farmacológico , Doenças do Sistema Nervoso/etiologia , Fator de Necrose Tumoral alfa/líquido cefalorraquidianoRESUMO
Because interleukin-1 beta (IL-1 beta) and cachectin (tumor necrosis factor) are thought to mediate the body's response to microbial invasion, we measured IL-1 beta and tumor necrosis factor concentrations in paired cerebrospinal fluid (CSF) samples (on admission to the hospital, CSF1; 18 to 30 hours later, CSF2) from 106 infants and children with bacterial meningitis. In CSF1, IL-1 beta was detected in 95% of samples; the mean (+/- 1 SD) concentration was 944 +/- 1293 pg/ml. Patients with CSF1 IL-1 beta concentrations greater than or equal to 500 pg/ml were more likely to have neurologic sequelae (p = 0.001). Tumor necrosis factor was present in 75% of CSF1 samples; the mean concentration was 787 +/- 3358 pg/ml. In CSF2 the mean IL-1 beta concentration was 135 +/- 343 pg/ml, and IL-1 beta concentrations correlated significantly with CSF2 leukocyte count, with glucose, lactate, protein, and tumor necrosis factor concentrations, and with neurologic sequelae. Tumor necrosis factor was detected in CSF2 specimens of 53 of 106 patients, with a mean concentration of 21 +/- 65 pg/ml. Of the 106 patients, 47 received dexamethasone therapy at the time of diagnosis. These patients had significantly lower concentrations of IL-1 beta and higher glucose and lower lactate concentrations in CSF2, and they had a significantly shorter duration of fever compared with the values in patients not treated with steroids (p less than or equal to 0.002). Our data suggest a possible role of IL-1 beta and tumor necrosis factor as mediators of meningeal inflammation in patients with bacterial meningitis, and might explain, in part, the beneficial effect of dexamethasone as adjunctive treatment in this disease.
Assuntos
Infecções Bacterianas/líquido cefalorraquidiano , Interleucina-1/líquido cefalorraquidiano , Meningite/líquido cefalorraquidiano , Fator de Necrose Tumoral alfa/líquido cefalorraquidiano , Infecções Bacterianas/tratamento farmacológico , Pré-Escolar , Dexametasona/uso terapêutico , Método Duplo-Cego , Feminino , Humanos , Lactente , Masculino , Meningite/tratamento farmacológico , Prognóstico , Estudos ProspectivosRESUMO
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.