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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 (

Respiratory syncytial virus (RSV) causes serious illness (lower respiratory illness) in preterm infants. RSV antibody-enriched immunoglobulin (RSVIG) that was lyophilized (LYO) protected against RSV lower respiratory illness. The Food and Drug Administration now requires an additional viral inactivation step (VI). We compared LYO, LYO-VI, and a more convenient liquid RSVIG (LIQ-VI) in 30 preterm infants (median age, 7 months; median weight, 5.4 kg). Infants were randomized to receive LYO (n = 10), LYO-VI (n = 10), or LIQ-VI (n = 10) in monthly infusions of 750 mg/kg of body weight per dose (December to March). Children were monitored closely for adverse reactions to RSVIG and for RSV illness.

The recent isolation of human herpesvirus 7 (HHV-7) from activated CD4+ T lymphocytes of a healthy individual raises questions regarding the prevalence of this virus in humans and its immunological relationship to previously characterized human herpesviruses. We report that HHV-7 is a ubiquitous virus which is immunologically distinct from the highly prevalent T-lymphotropic HHV-6. Thus, (i) only two of six monoclonal antibodies to HHV-6 cross-reacted with HHV-7-infected cells, (ii) Western immunoblot analyses of viral proteins revealed different patterns for HHV-6- and HHV-7-infected cells, (iii) tests of sequential serum samples from children revealed seroconversion to HHV-6 without concomitant seroconversion to HHV-7, and (iv) in some instances HHV-7 infection occurred in the presence of high titers of HHV-6 antibodies, suggesting the lack of apparent protection of children seropositive for HHV-6 against subsequent infection with HHV-7. On the basis of the analyses of sera from children and adults it can be concluded that HHV-7 is a prevalent human herpesvirus which, like other human herpesviruses, infects during childhood. The age of infection appears to be somewhat later than the very early age documented for HHV-6.

An inverse relationship between binding of [(14)C]penicillin to cells of Neisseria gonorrhoeae and the minimal inhibitory concentration of penicillin was recently reported by us. Herein we report a similar relationship in binding by cytoplasmic membranes derived from 10 strains of gonococci. Membranes were extracted after Braun homogenization and differential centrifugation of the resulting extracts. Membranes derived from penicillin-susceptible cells bound 140 to 200 nmol of [(14)C]penicillin per g of enzyme, whereas relatively nonsusceptible strains bound 18 to 59 nmol. Binding by cell walls was only a small fraction of the total binding and probably represents contamination of the walls by membrane. Pretreatment of cell membranes with either unlabeled penicillin or cephalothin prior to [(14)C]penicillin exposure markedly decreased (14)C binding. Slab gel electrophoresis of membranes revealed 13 protein bands, 8 of which were labeled.

Infants and young children with rotavirus (RV) or visualized adenovirus in their stools were tested for the simultaneous presence of a respiratory viral pathogen in their upper respiratory tract. Overall, at least 10.7% of 484 study subjects had such dual infections, including 8.3% of 385 RV-positive gastroenteritis patients and 24.3% of 37 RV-positive respiratory disease patients. Respiratory syncytial virus was present in 34.1% of 41 dual infections with RV and at least 40% of the 12 to 15 dual infections with visualized fecal adenovirus. Other pathogens found in the respiratory tract of patients with RV or visualized fecal adenovirus infections included influenza viruses, adenoviruses, parainfluenza viruses, rhinoviruses, and a cytomegalovirus.

An approximate 10% suspension in water of the first available stool sample from 411 infants and young children with acute gastroenteritis was examined by electron microscopy (EM) after 2 min of negative staining. This procedure enabled the detection of 88% of the 199 rotavirus infections, all of the 22 adenovirus infections, and 47% of the 15 approximately 27-nm virus infections ultimately detected by a combination of techniques, including immune electron microscopy (IEM) and rotavirus enzyme-linked immunosorbent assay (ELISA). Of the 204 infections detected by direct EM of stools, 76% were detected within 2 min of viewing, and 94% were detected within 6 min of viewing. Type 1 and type 2 rotavirus particles were visualized with approximately equal efficiency, although type 2 rotavirus infections were more common. Rectal swab preparations were clearly inferior to stool preparations for the detection of virus infection by direct EM. IEM examination was required for efficient visualization of viruses in rectal swab specimens. ELISA was the most sensitive method for the detection of rotaviruses; with this method, all infections in which rotavirus particles were visualized by EM or IEM were detected. However, 73% of the 1,834 specimens which were presumptively positive for rotavirus by conventional indirect ELISA proved to be falsely positive on the basis of EM, IEM, blocking ELISA, confirmatory ELISA, or a combination of these methods. False-positive rotavirus ELISA reactions apparently were eliminated when fecal specimens were tested in a modified confirmatory ELISA with a lower dilution of rotavirus-negative (pre-immunization) than rotavirus-positive (post-immunization) capture antibody from the same animal.

The potential exposure to ribavirin aerosol in the environment was assessed in nurses caring for infants and children with severe lower respiratory tract infections due to respiratory syncytial virus. Ribavirin aerosol was administered via a ventilator, oxygen tent, or oxygen hood. Participants worked directly with infants receiving ribavirin for 20.0 to 35.0 h over a 3-day period. No toxic or adverse effects of ribavirin aerosol were observed in any of the 19 nurses studied, and ribavirin was not detected in erythrocytes, plasma, or urine collected after the potential exposure period.

The serum antibody response of 50 infants and children infected with respiratory syncytial virus (RSV) was determined by a glycoprotein-specific enzyme-linked immunosorbent assay, and the effects of age and preexisting antibody titer at the time of RSV infection on response to the G and F glycoproteins of RSV were examined. The immune response to the G and F glycoproteins was assessed with anti-human immunoglobulin A to permit measurement of the response of young infants in the presence of maternally derived immunoglobulin G. The findings suggested that age primarily affects the response to the F glycoprotein and that preexisting antibody titer affects the response to the G glycoprotein.

The serum antibody response of infants and children immunized with Formalin-inactivated respiratory syncytial virus (RSV) vaccine 20 years ago was determined by using an enzyme-linked immunosorbent assay specific for the RSV fusion (F) and large (G) glycoproteins and a neutralization assay. Twenty-one young infants (2 to 6 months of age) developed a high titer of antibodies to the F glycoprotein but had a poor response to the G glycoprotein. Fifteen older individuals (7 to 40 months of age) developed titers of F and G antibodies comparable to those in children who were infected with RSV. However, both immunized infants and children developed a lower level of neutralizing antibodies than did individuals of comparable age with natural RSV infections. Thus, the treatment of RSV with Formalin appears to have altered the epitopes of the F or G glycoproteins or both that stimulate neutralizing antibodies, with the result that the immune response consisted largely of "nonfunctional" (i.e., nonneutralizing) antibodies. Subsequent natural infection of the vaccinees with wild-type RSV resulted in enhanced pulmonary disease. Despite this potentiation of illness, the infected vaccinees developed relatively poor G, F, and neutralizing antibody responses. Any or all of three factors may have contributed to the enhancement of disease in the RSV-infected vaccinees. First, nonfunctional antibodies induced by the inactivated RSV vaccine may have participated in a pulmonary Arthus reaction during RSV infection. Second, the poor antibody response of infants to the G glycoprotein present in the Formalin-inactivated vaccine may have been inadequate to provide effective resistance to subsequent wild-type virus infection. Third, the relatively reduced neutralizing antibody response of the infant vaccinees to wild-type RSV infection may have contributed to their enhanced disease by delaying the clearance of virus from their lungs.

During 5.5 years of a study in Washington, D.C., hospitalizations of children for rotavirus gastroenteritis tended to be more common after a month of cold or dry weather than after a corresponding calendar month of warm or wet weather. Overall, there were 84% more (178 versus 97) inpatients with rotavirus gastroenteritis after a set of relatively colder individual months taken as a group than after an equal number of warmer corresponding calendar months taken as a group. Comparable differences were not seen with nonrotavirus gastroenteritis patients. There also were 45% more rotavirus hospitalizations after the set of months with the least depth of precipitation compared with the set of corresponding calendar months with the greatest depth of precipitation. Rotavirus infection in young infants, the children least likely to be directly exposed to outdoor conditions, showed some of the most marked weather-associated effects. These findings suggest that weather-related low indoor relative humidity and indoor crowding may be key factors in the epidemiology of rotavirus disease.

Monoclonal antibody specific for subgroup F enteric adenoviruses (EAds) was prepared by fusing P3-NS1/Ag4-1 mouse myeloma cells with lymphocytes from BALB/c mice immunized with G1105, an adenovirus type 41 (Ad41) strain. Monoclone 3F11/2H9, which specifically recognized Ad41, was successfully used as detector antibody in an enzyme-linked immunosorbent assay (ELISA). Additionally, previously prepared monoclones 5D8/2C2 and 2H6/1E11, recognizing Ad40 plus Ad41 and Ad40 alone, respectively, were used to study stool and/or tissue culture specimens from 106 patients with adenovirus-positive gastroenteritis. By ELISA, 91 had EAds (22 were Ad40 and 69 were Ad41) and 15 had non-EAds. ELISA results were in concordance with restriction endonuclease results for 38 of 39 specimens, with dot blot data for 19 of 20 specimens, and with neutralization test results for 74 of 78 specimens. ELISA was at least 10-fold more sensitive than direct electron microscopy was for the detection of EAds in stool specimens.

Infusions of 50 mg of sulbactam per kg per day and 400 mg of ampicillin per kg per day in divided doses to infants and children with bacterial meningitis produced levels in cerebrospinal fluid approximately one-third those in serum. Concentrations in cerebrospinal fluid of 5.5 micrograms of sulbactam per ml and 16.0 micrograms of ampicillin per ml declined within a few days of therapy to 1.9 microgram of sulbactam per ml and 5.2 micrograms of ampicillin per ml.

The quantity of adenoviruses in a diarrhea stool provided a strong presumptive indication of the presence or absence of an adenovirus from subgenus F or G (proposed species 40 or 41). These adenoviruses were found in the stools of 91% of 56 acutely ill diarrhea patients with one or more than one adenovirus particle per min of direct electron microscopic viewing, as compared with 40% of 20 acutely ill diarrhea patients with less than one detected adenovirus particle per min of viewing.

During the period January 1974 through July 1982, fecal samples from 1,537 pediatric inpatients with gastroenteritis were tested for enteric viruses by electron microscopic and rotavirus enzyme-linked immunosorbent assay techniques. Rotaviruses were detected in 34.5% of these patients, enteric adenoviruses were detected in 4.7%, approximately 27-nm viruses were detected in 1.6%, and at least one of these agents was found in 40.1% of the study subjects. Three infections were by an apparently new agent which morphologically is a rotavirus, but which failed to react in the rotavirus enzyme-linked immunosorbent assay. During the first 8 calendar years of study, rotaviruses were detected in 39.0% of 577 patients in the even-numbered years and 30.3% of 702 patients in the odd-numbered years. Adenoviruses were found in all calendar months. Rotaviruses were found in inpatients in November through July, whereas approximately 27-nm viruses were found in October through June. The percentage of patients who had a demonstrated viral infection rose steadily from 7.4% in September to 72.0% in January and then steadily declined to 2.9% in August. Viral infection was especially common in study subjects who were 7 through 24 months of age; 61% of such children had one or more enteric viruses. Rotavirus-infected patients tended to be younger during the months of greatest rotavirus activity than at the beginning and end of the rotavirus season, presumably because of a greater exposure to virus at the height of the rotavirus outbreak.

A latex agglutination (LA) test (Slidex Rota-Kit; bioMérieux, Marcy-l'Etoile, France) was a rapid, easily used method for detecting rotavirus (RV) in pediatric fecal specimens. With 45 RV-positive and 50 RV-negative diarrhea specimens, the sensitivity of the LA test was 82%, and the specificity was 100%. Six other specimens produced indeterminate results. The frequency of positive LA tests appeared to be proportional to the concentration of virions in the stool.