Faculty Bibliography

Permanent neurologic disabilities are seen in up to a quarter of survivors of bacterial meningitis despite major improvements in therapy. Experimental studies have demonstrated that most of the pathology in meningitis is mediated by inflammatory cytokines such as tumor necrosis factor (TNF) and interleukin-1 (IL-1), which are produced by host cells in response to bacterial invasion of the meninges. Dexamethasone has been used in a number of clinical trials to moderate the host response and to improve neurologic outcome of meningitis. Results of six randomized, placebo controlled trials are summarized in this review. Dexamethasone treatment did not lower mortality. Only a moderate, but not a significant reduction in the neurologic and audiologic sequelae was seen in dexamethasone recipients when Haemophilus influenzae type b (Hib) was the causative agent of meningitis. Following routine use of Hib vaccine, meningitis caused by this agent has virtually disappeared in the USA. Hence, findings from these trials may no longer be applicable in countries with high rates of immunization against Hib. Presently, there is little or no evidence showing a benefit of dexamethasone therapy in meningitis caused by S. pneumoniae or N. meningitidis. Global emergence of penicillin and cephalosporin resistant S. pneumoniae has raised new concerns about the use of dexamethasone in pneumococcal meningitis. Since dexamethasone significantly decreases the penetration and concentration of vancomycin and ceftriaxone in the CSF and delays CSF sterilization, adjunctive dexamethasone therapy may increase the risk of treatment failure in meningitis caused by antibiotic resistant pneumococci. An antibiotic combination should be used in the treatment of meningitis caused by antibiotic resistant pneumococci, particularly if dexamethasone is also being administered concurrently

BACKGROUND: Cytomegalovirus (CMV) is a frequent opportunistic infection in human immunodeficiency virus type 1 (HIV-1)-infected children. The interactions of CMV and HIV-1 in coinfected children are not well-characterized. OBJECTIVE: To evaluate the prevalence of asymptomatic CMV infection and symptomatic CMV disease and to assess the influence of CMV on clinical and laboratory markers of HIV disease progression in CMV-coinfected children. METHODS: Serial urine CMV cultures were performed on 500 children (131 HIV-1-infected (HIV+), 129 seroreverters born to HIV-infected mothers, and 240 HIV-uninfected (HIV-)). The clinical, immunologic and virologic data of 131 HIV+ children were analyzed. RESULTS: CMV was recovered in 40 of 131 HIV+ (31%), 22 of 129 seroreverters (17%) and 30 of 240 HIV- (13%) children. Of the 40 HIV+ children with CMV coinfection, 7 developed symptomatic CMV disease (17.5%) including chorioretinitis (3), colitis (2) and pneumonitis (2). The HIV+ children with symptomatic CMV disease had significantly lower mean CD4+ T lymphocyte proportions (17% vs. 26%; age-adjusted P = 0.013) and greater HIV p24 antigen concentrations (329 pg/ml vs. 57 pg/ml; age-adjusted P = 0.13) than HIV+ children with asymptomatic CMV infection. In a subset of children coinfected with CMV before 6 months of age (n = 11), 5 (45%) developed symptomatic CMV disease, and 4 of these 5 children died within 10 months of diagnosis of CMV disease. At the time of the first positive CMV culture in these children, mean CD4+ T lymphocyte proportions did not differ according to the presence or absence of CMV-related symptoms (symptomatic CMV+, 21% vs. asymptomatic CMV = 38%; P = 0.14). In HIV+ children with symptomatic CMV disease, p24 antigen concentrations were greater than in those with asymptomatic CMV infection (461 vs. 190 pg/ml, P = 0.06). CONCLUSIONS: Symptomatic CMV disease occurred in young CMV-coinfected children with low CD4+ lymphocytes and elevated HIV p24 antigen concentrations. Whether progressive immunodeficiency allows the emergence of CMV disease or CMV infection causes more rapidly progressive HIV-1 disease or whether there is a more complex relationship remains to be determined

The purpose of this study was to characterize systemic Streptococcus pneumoniae disease in human immunodeficiency virus type 1 (HIV-1)-infected children. All cases of bacteremia and meningitis caused by S. pneumoniae among children less than 18 years old were collected by review of the Microbiology Laboratory records at the Bellevue Hospital Center during the period August 1, 1978, through July 31, 1993. There were 31 bouts of systemic S. pneumoniae disease in 19 of 235 HIV-1-infected children cared for by the Pediatric Infectious Disease staff and 116 bouts in 113 children not known to be HIV-1-infected. Four of the 19 HIV-1-infected children had multiple episodes of S. pneumoniae bacteremia as compared with 3 of 113 in the general population (P = 0.008). The frequency of serotypes and distribution of infections by season of the year did not differ between the 2 groups. The median ages at the time of the S. pneumoniae infection were 1.8 and 1.1 years for the HIV-1-infected children and the general population of children, respectively, when those children with multiple episodes were included for their initial episode only (P = 0.06). In the HIV-1-infected patients, 10 episodes were associated with pneumonia, 5 with pneumonia and otitis media, 5 with otitis media only, 1 with pneumonia and meningitis, 1 with meningitis only and 1 with periorbital cellulitis; 5 had no apparent focus of infection. One episode of pneumonia was complicated by lung abscess and there were 2 deaths. Most HIV-1-infected patients recovered without significant sequelae, and the clinical course of their systemic infections did not appear to be markedly different than that of healthy children

A distinct clinical syndrome of cholestasis and hepatitis occurred during early infancy in seven infants with perinatally acquired human immunodeficiency virus 1 infection. In five infants hepatitis was the first manifestation of human immunodeficiency virus 1 infection. The median age of onset of hepatitis was 7 months (range, 5 to 10 months). The mean total bilirubin concentration at presentation was 7.4 mg/dl (range, 3.9 to 11 mg/dl), the mean aspartate aminotransferase was 1512 IU/liter (range, 782 to 2960 IU/liter) and the mean alanine amino-transferase 512 IU/liter (range, 92 to 1247 IU/liter). The absolute CD4 count at the time of onset of hepatitis ranged from 191 to 2298 cells/mm3 (mean, 766 cells/mm3). Six of the seven children died within 12 weeks of onset of hepatitis, three as a result of complications of Pneumocystis carinii pneumonia, and two died of complications secondary to cytomegalovirus. In only one infant was the cause of death the direct consequence of liver failure. The seventh infant died 17 months after the onset of hepatitis of dilated cardiomyopathy. No specific etiologic agent has been identified as the cause of cholestatic hepatitis in these infants. In situ hybridization studies to detect human immunodeficiency virus 1 messenger RNA was negative in the liver tissue obtained at biopsy and autopsy in five of the samples tested

Thirty-two (18%) of 181 children cared for at our institution who were infected with the human immunodeficiency virus type 1 (HIV-1) were first seen, and HIV was diagnosed, when they were 4 years of age and older. Initial complaints or diagnoses for these children included the following: hematologic disorders (5) (3 idiopathic thrombocytopenic purpura, 1 neutropenia, 1 anemia); recurrent bacterial infections (10); Pneumocystis carinii pneumonia (3); developmental delay (1); skin disorders (2) (1 genital wart, 1 chronic zoster); weight loss (3); malignancy (1); and nephropathy (1). Eight children were referred for evaluation because of maternal HIV-1 infection. The risk factors for HIV-1 infection included maternal/perinatal exposure (22), perinatal blood transfusion (6), blood transfusion during infancy (2), and sexual abuse (2). Ten (31%) of the 32 children have subsequently died. The longest survival from perinatal infection was 12 years. HIV-1 infection in children can result in a prolonged clinical latency and can masquerade as other pathologic conditions. The absence of clinical symptoms in older children at risk for HIV-1 infection should not deter HIV testing