Faculty Bibliography

Initial symptoms of Rocky Mountain spotted fever (RMSF), a tick-borne illness caused by Rickettsia rickettsii, are nonspecific and include headache, gastrointestinal disturbances, malaise, and myalgias, followed by fever and rash. The classic triad of fever, rash, and history of tick exposure is uncommon at presentation. Clinical manifestations of RMSF range from virtually asymptomatic to severe. Because of the potentially fatal outcome of RMSF, presumptive clinical diagnosis and empiric antimicrobial therapy can be critical. We present the case of a 3-year-old girl from New York State who presented with fever and rash

The effect of highly active antiretroviral therapy (HAART) in 85 children infected with human immunodeficiency virus type 1 (HIV-1) was compared retrospectively among Centers for Disease Control and Prevention (CDC) immunologic groups 1-3. The duration of HAART did not vary significantly among the immunologic groups (median, 39.07 months). The CD4 cell percentage increased in 39.1%, 58.3%, and 90% of patients in CDC groups 1-3, respectively (P <.001). HAART resulted in the suppression of HIV-1 below detectable levels in 34.8%, 25%, and 32% of patients in the 3 CDC groups, respectively, and in a frequent switch from syncytium-inducing to nonsyncytium-inducing virus. Thymic excision circles increased in a subset of patients with increases in CD4 cell percentage independently of HIV RNA level. The results support the option of delaying HAART in early asymptomatic HIV-1 disease in children and the use of other markers of disease progression, in addition to virus load

OBJECTIVE: To determine the long-term immunologic and virologic effects of highly active antiretroviral therapy (HAART) in children with AIDS. DESIGN: A prospective observational study. SETTING: Two pediatric HIV clinics. PARTICIPANTS: Twenty-five protease-inhibitor naive HIV-infected children (aged 2-18 years) with advanced disease (CD4 < or =6%). INTERVENTION: HAART (one protease inhibitor and one or more nucleoside analogs). Diphtheria and tetanus immunization in six patients after 18 months of therapy. MAIN OUTCOME MEASURES: Changes in percentage of CD4 cells and plasma HIV-1 RNA levels; post-treatment assays of lymphoproliferative responses to recall antigens; CD4 cell memory phenotype. RESULTS: Median duration of follow-up was 18.8 months (range, 7.5-28 months). At baseline the CD4 cell percentage was 2% (range, 0-6%), this increased significantly to 16% (range, 3-48%) above baseline at 12 months (P = 0.002). The mean maximum CD4 cell increase was 20.7% (range 4-48%) which corresponds to 657x10(6) cells/l (range, 30-2240x10(6) cells/l) above baseline. By contrast, the median viral load was not significantly lower at 12 months than at baseline (P = 0.34), and only 25% of the patients had sustained undetectable viral load. Of the reconstituted CD4 cells 70% were naive, and none of the subjects had lymphoproliferative responses to tetanus and diphtheria although 40% did develop responses to Candida, an environmental antigen. A single immunization with diphtheria and tetanus toxoid produced lymphoproliferative responses to tetanus in three out of six patients. CONCLUSIONS: HAART was associated with sustained increases in CD4 cell counts, despite a high incidence of 'virologic failure'. CD4 counts and the proportion of naive cells were higher than have been reported in adults, which may be a reflection of greater thymic activity in children. Memory cell clones for antigens encountered in the past which are not prevalent before therapy could not be expanded without additional antigenic exposure

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. Although trimethoprim-sulfamethoxazole is the preferred chemoprophylaxis against Pneumocystis carinii pneumonia, there are frequent IgE-mediated reactions among children infected with the human immunodeficiency virus (HIV). Oral desensitization allows more patients to receive chemoprophylaxis, but it has been studied in only a limited number of children. METHODS. We desensitized five children infected with the HIV using a rapid, 4-h oral protocol. RESULTS. Three children (including two infants) successfully completed desensitization and started maintenance therapy, but the other two experienced reactions that precluded further administration of trimethoprim-sulfamethoxazole. CONCLUSIONS. We conclude that a rapid, oral trimethoprim-sulfamethoxazole desensitization protocol is safe and, in some instances, effective among HIV-infected children and infants with a history of non-life-threatening, IgE-mediated reactions to trimethoprim-sulfamethoxazole

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

Four methods of estimating mother-to-child transmission rates of human immunodeficiency virus type 1 (HIV-1), based on the 1992 Ghent workshop, were compared in a multicenter New York City prospective cohort study in 1986-1992. Of 833 infants born to women at risk of HIV-1 infection, 388 were born HIV-1 seropositive and 445 were HIV-1 seronegative. The four methods, the Antibody Only, Indirect, Direct, and Virologic Methods, yielded transmission rate estimates of 19-25%, classifying 59-89% of the cohort. Estimation based on persistence of HIV-1 antibody and clinical assessment yielded transmission rates similar to those methods that incorporated virologic testing

OBJECTIVE: To determine whether the amount of p24 antigenemia in the first 6 months of life is a predictor of survival in children infected vertically with human immunodeficiency virus type 1. METHODS: A retrospective study of vertically infected infants and children who were followed prospectively from early infancy and who had quantitation of plasma p24 antigen concentration in the first 6 months of life. Infants were first stratified by duration of survival as infants who died before 2 years of age (short-term survivors) and infants who survived to 2 years of age (intermediate-term survivors). The median p24 antigen concentration and the proportion of infants in each group with high concentrations of antigen were compared. Analyses with and excluding all p24 determinations made after the use of antiretroviral agents were compared Kaplan-Meier product limit analysis was used to compare survival in infants with low and high antigenemia during the first 6 months of life. RESULTS: The median p24 antigen concentration in 15 short-term survivors was 228 pg/ml, compared with 14 pg/ml in 26 intermediate-term survivors (p < 0.05). The proportion of children with > 100 pg/ml of p24 was higher in short-term than in intermediate-term survivors (p = 0.01). Survival to 2 years of age in infants in whom all p24 antigen values during the first 6 months of life were 100 pg/ml or less was 91%, in comparison with 39% in infants with values greater than 100 pg/ml (p = 0.0017). CONCLUSIONS: Elevated p24 antigenemia in the first 6 months of life is associated with shorter survival and may be a useful predictor of outcome