Faculty Bibliography

To minimize the exposure of health care workers to aerosolized ribavirin, we designed a double tent containment system with circulating mist and suction applied between the tents and we evaluated the ability of this system to contain and evacuate aerosolized ribavirin. While the drug was administered with this system at three institutions, three air sampling pumps at different locations in the room and one worn by the investigator (personal breathing zone) collected air samples onto filters for assay of ambient ribavirin. Ribavirin determinations were made by high performance liquid chromatography. A 5- to greater than 20-fold decrease in ambient ribavirin concentrations was observed with the containment system compared with those detected with a single oxyhood in use. The personal breathing zone concentration was 566.0 micrograms/m3 with the oxyhood alone and fell to a mean concentration of 43.81 +/- 33.40 micrograms/m3 with the containment system. Though the risk to exposed health care workers is unknown, this system offers a simple way to decrease significantly occupational exposure to ribavirin.

A 10-year-old boy presented with nuchal rigidity and cerebrospinal fluid (CSF) leukocytosis initially and again on day 6 of intravenous cefuroxime therapy (200 mg/kg/day). Both CSF specimens yielded nontypable beta-lactamase-negative Haemophilus influenzae that were susceptible by disk tests but relatively resistant to cefuroxime (MIC, 8- to 16-fold greater than that of control isolates). To define the mechanism of resistance, the cefuroxime resistance marker was transformed to a susceptible H. influenzae recipient; inactivation and permeability of beta-lactam substrate were tested and the penicillin-binding protein (PBP) profiles were examined. Inactivation of beta-lactam substrate was not detected and reduced permeability was not found. However, reduced beta-lactam binding to PBPs 4 and 5 was observed; 18- to 27-fold more penicillin and 2.5-to 4-fold more cefuroxime was required to saturate or block 50% of the binding sites of these PBPs, respectively. Thus, reduced affinity of PBPs 4 and 5 for beta-lactam substrate appears to be the mechanism of cefuroxime resistance in this strain. The reduced affinity of these targets appears to have contributed to the bacteriologic and clinical failure in this patient.

Disseminated adenovirus infection with fatal hepatic necrosis has been reported in 16 patients, 15 of whom had immunocompromising conditions. Herein we report three patients with AIDS and fatally disseminated adenovirus infection with hepatic necrosis. The median age of these 16 patients was 4.7 years, and their illness was characterized by fever (13 of 16 patients), coagulopathy (10 of 16), lower respiratory tract disease (10 of 16), and gastrointestinal hemorrhage (five of 16) in addition to clinical evidence of hepatitis. The adenoviruses isolated were the commonly found serotypes 1, 2, 3, 5, and 7 for 13 of the 15 cases for which this determination was available. With the high frequency of adenovirus infection in humans and the increasing prevalence of human immunodeficiency virus infection in children, it seems likely that this syndrome will continue to be seen.

Serum samples from 28 children with symptomatic human immunodeficiency virus (HIV) infection were studied for the presence of HIV antigen. Their humoral immune response profile, including anti-HIV specific isotypic responses and neutralizing titers, was characterized. Additionally, serum specimens from 12 of these children were tested for their ability to mediate antibody-dependent cellular cytotoxicity (ADCC) against HIV envelope antigens. Analysis of our results showed that children with acquired immunodeficiency syndrome (AIDS) were much more likely to have serum antigenemia and an absence of anti-p24 antibodies than those with AIDS-related complex (ARC). A significant association was also noted between a more stable clinical status and a strong anti-p24 antibody response with detectable antibodies to other HIV antigens in multiple antibody subclasses. This suggests that the longitudinal evaluation of antigen/antibody profiles may aid in the assessment of prognosis for children with HIV infection. Sera from 6/6 patients with ARC and 4/6 patients with AIDS were able to mediate ADCC. No correlation was found between clinical status and the titers of neutralizing antibodies.

Monoclonal antibodies (MAbs) specific for two surface glycoproteins of respiratory syncytial virus (RSV) were found to enhance RSV infection in two macrophagelike cell lines (P388D1 and THP-1). MAbs to an irrelevant antigen (pneumococcal polysaccharide) and to the nucleocapsid of RSV did not enhance infection. Blocking either the Fc segment of the monoclonal antibody of the Fc receptor on the cells diminished the enhancement, suggesting that this phenomenon involves attachment of the monoclonal antibody to the virus followed by attachment of the Fc of this complex to the Fc receptor on the cells. These data indicate that antibody-mediated enhancement of RSV infection can occur in vitro in macrophages. This enhancement may contribute to the pathogenesis of RSV bronchiolitis and the more severe RSV disease seen in recipients of formalin-inactivated RSV vaccine.