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Extract: Two live “attenuated” respiratory syncytial virus (RSV) vaccines were administered intranasally and by aerosol in placebo-controlled trials among asthmatic children hospitalized at National Jewish Hospital and Research Center (NJH). The first vaccine, a 26° -adapted RSV vaccine, was given to 28 children, and a placebo control was given to 25. Twenty-one of 28 vaccinees (75%) had “takes,” as judged by virus shedding and/or rises in serum antibody and/or rises in nasal secretion neutralizing activity. No excess in wheezing was attributable to the vaccine administration, although there was a high background level of acute respiratory symptoms in both vaccinees and control subjects. In an outbreak of natural RSV infection which occurred some months after the vaccine was given, there was some evidence that those who received the vaccine less than 4 months before exposure to wild virus were protected against reinfection. Protection was not evident when this interval was greater than 4 months. The second vaccine, a temperature-sensitive mutant strain (ts-1), was administered to 22 children, and placebo to 21. Thirteen children (59%) had “takes.” In vaccinees under 6 years of age, 7 of 7 had “takes.” Again, no excess wheezing was seen in vaccinees as compared with control subjects, although there was some evidence that upper respiratory symptoms were more frequent in younger vaccinees. Four of 10 vaccinees shed virus with temperature-sensitive characteristics somewhat different from those of the vaccine strain. Vaccine virus was demonstrated to spread to uninoculated or placebo control children. Natural RSV challenge did not occur during the period of study. Speculation: One of two live “attenuated” RSV vaccines may have produced a brief period of protection against natural infection. This finding offers hope that such live vaccines might prevent disease in selected children over a critical time period, such as infants for the 1st year of life, or allergic or asthmatic children during periods of epidemic prevalence. Asthmatic children did not appear to develop symptoms of wheezing after attenuated RSV infection. This finding suggests that the mechanism of wheezing in asthmatic children with RSV infection may be dependent on, among other factors, the virulence of the virus strain (perhaps its capacity to replicate in and, possibly, invade the lower respiratory tract), rather than on an allergic response to antigens introduced into, and limited to, the upper airway. In view of the spread of the ts-1 vaccine and its apparent loss of temperature sensitivity in some vaccinees, the vaccine may have had the potential for reversion to virulence and hence initiation of epidemic disease. These characteristics are undesirable in live respiratory virus vaccines and should, if possible, be avoided in the development of future such vaccines.

Persistent colonization of the respiratory tract with μs. aerug. is a major problem in children with cystic fibrosis (CF). Because gentamicin penetration of CF sputum is inadequate after parenteral administration, we undertook an investigation of the safety and efficacy of gentamicin aerosol. Nine CF children (5F, 4M) ages 6-15 years with moderately severe disease were studied. Following baseline pulmonary and microbial studies, each child received 40 mg of gentamicin sulfate by nebulization three times daily for one week. Gentamicin disposition and pulmonary function were studied initially and at the end of the treatment program. No adverse effects from the treatment were observed. Peak sputum concentrations of gentamicin varied from 3.6 to 18.5 mcg/ml after one dose to 6.4 to 33 mcg/ml after one week of therapy. Peak blood concentrations ranged from 0 to 0.35 mcg/ml initially and were somewhat higher at the end of the treatment program. Urinary concentrations were insignificant. The mean clearance of gentamicin from the sputum was 51 ml/min/1.73 m2 (6 pts). Microbial studies in five patients demonstrated a striking decrease in pseudomonas colony counts. No strains developed resistance to gentamicin. Pulmonary function tests improved in 5 patients, showed no change in 3, and diminished in 1, perhaps in association with a clinical URI. All the children showed marked clinical improvement. These results provide a rationale for, and strongly warrant, a clinical trial of aerosolized gentamicin in CF patients.

To determine if children with acute lymohoblastic leukemia (ALL) can mount a primary response to immunization with a new antigen and a secondary response to a known antigen, 39 children with ALL and 51 sibling controls received 2 doses of bivalent split-product influenza vaccine, A Victoria/75, A New Jersey/76 (A/Vic, A/NJ). Before immunization 90% of patients and controls had hemagglutination inhibiting antibody (HAI) to A/Vic of ≥ 1:8; none showed HAI antibodies to A/NJ. Four weeks after the first dose 74% of patients and controls showed at least a 4-fold rise in HAI titer to A/Vic. Only 48% of patients on chemotherapy responded to the first A/NJ immunization compared to 68% of controls and 89% of patients off therapy. Following the second dose, 86% of patients on therapy demonstrated at least a 4-fold rise in titers to both viruses with geometric mean titers of 1:68 to A/Vic and 1:43 to A/NJ. Patients who were off therapy developed higher HAI titers than controls. The results demonstrate that patients receiving chemotherapy can produce anti-influenza antibody in response to immunization with either an old antigen or a new antigen. Responses to the new antigen in patients on chemotherapy are more sluggish than those of controls but adequate antibody levels are achieved with booster immunization.

Experiences With A Multiple Resistant Klebsiella pneumonias In An Infant Intensive Care Unit