Children with influenza A infection: treatment with rimantadine.

Treatment with rimantadine of influenza in children and the potential development of resistance in clinical isolates associated with therapy have not been previously studied. We compared rimantadine to acetaminophen therapy in a controlled, double-blind study of 91 children with influenza-like illness. Of 69 children with proven influenza A/H3N2 infection, 37 received rimantadine and 32 received acetaminophen for five days. Children receiving rimantadine showed significantly greater reduction in fever and improvement in daily scores for symptoms and severity of illness during the first three days. Viral shedding also diminished significantly during the first two days but subsequently increased such that by days 6 and 7 the proportion of children shedding virus, as well as the quantity of virus shed, was significantly greater in the rimantadine group. During the seven-day study, of the 22 children in the rimantadine group with serial isolates tested, ten (45.5%) had resistant isolates compared with two (12.5%) of those with serial isolates in the acetaminophen group (P less than .03). Thus, of the total 37 children in the rimantadine group, 27% were found to have resistant isolated compared with 6% in the total group receiving acetaminophen (P less than .04). Furthermore, the mean inhibitory concentration of rimantadine increased with time in the rimantadine group (r = .4, P = .002) but not in the acetaminophen group. Rimantadine therapy, thus, appears to be significantly more effective than acetaminophen in ameliorating the clinical signs and symptoms of influenza in children. Treatment with rimantadine was also associated with increased viral shedding after the medication was discontinued and with the development of resistance in the clinical isolates, the significance of which is unknown.

Long-term prospective study in children after respiratory syncytial virus infection.

We have prospectively evaluated for the past 8 years 29 children who were hospitalized during infancy with acute lower respiratory tract illness caused by respiratory syncytial virus (RSV). No differences in the prevalence of a family history of atopy or breast-feeding in these infants compared with controls were noted. However, a history of parental smoking was significantly associated with hospital admission for RSV lower respiratory tract disease. Evidence of atopy, as defined by serum IgE levels and radioallergosorbent testing, have developed in only three (10%) of 29 children. Six children (21%) continue to have recurrent lower respiratory tract disease. Fifty-five percent of these children had abnormally low oxyhemoglobin levels (SaO2) measured by ear oximetry for the first 3 to 4 years after the acute illness. Twenty-one percent have persistently low SaO2 levels during the eighth year of follow-up. Spirometric values indicate evidence of peripheral airway obstruction. These studies suggest that an association between RSV lower respiratory tract infections and chronic abnormalities of pulmonary function may be detected sequentially through the first 8 years of life. These abnormalities are not limited to those children developing an atopic state during that same time period.

Ribavirin treatment of respiratory syncytial viral infection in infants with underlying cardiopulmonary disease.

Aerosolized ribavirin was evaluated in the treatment of respiratory syncytial virus lower respiratory tract disease in 53 infants, 36 of whom had underlying diseases. Of the total infants, 26 were studied in a double-blind, placebo-controlled manner; 14 received ribavirin and 12 received placebo, a water aerosol, for an average of five days. When the infants with bronchopulmonary dysplasia and congenital heart disease treated with ribavirin were compared with those receiving placebo, the treated infants showed a significantly faster rate of improvement in their illness severity score. The degree of improvement in the total group of infants receiving ribavirin compared with those receiving placebo was similarly greater, and at the end of therapy significantly greater improvement was also demonstrated in their arterial blood gas values and in the amount of virus shed from their nasal washes. No toxic or adverse effects of the aerosol therapy were observed in any of the 53 infants studied, and resistance to ribavirin did not develop in any of the respiratory syncytial virus strains isolated, despite prolonged treatment in some of the more ill infants.

Risk of secondary bacterial infection in infants hospitalized with respiratory syncytial viral infection.

Because infants hospitalized with respiratory syncytial virus (RSV) infection frequently receive antibiotics, our study was undertaken to determine what the actual risk of secondary bacterial infections in patients with RSV infection is and what effect antibiotic treatment might have on the course of illness. In a 9-year prospective study of 1706 children hospitalized with acute respiratory illnesses, 565 children had documented RSV infections. A subsequent bacterial infection rarely developed in those with RSV lower respiratory tract disease. The rate of subsequent bacterial infection was 1.2% in the total group of children infected with RSV, and 0.6% in the 352 children who received no antibiotics. A significantly greater proportion (4.5%) of subsequent bacterial infections occurred in infants who received parenteral antibiotics (p = 0.01), and especially in a subgroup who received parenteral antibiotics for 5 or more days (11%, p less than 0.001). We conclude that the risk of secondary bacterial infection appears to be low for most infants with RSV infection. In a few infants given parenteral broad-spectrum antibiotics the risk may be greater, but whether this is related to the antibiotic therapy or to other risk factors is not clear.

Aerosolized ribavirin treatment of infants with respiratory syncytial viral infection. A randomized double-blind study.

We evaluated a new antiviral agent, ribavirin, in the treatment of infants hospitalized with lower-respiratory-tract disease from respiratory syncytial virus. Ribavirin or placebo was administered to 33 infants in a double-blind manner by continuous aerosol for three to six days. Seventeen infants were treated with placebo, and 16 with ribavirin. By the end of treatment, infants receiving ribavirin had significantly greater improvement in their overall score for severity of illness, in lower-respiratory-tract signs, and in arterial oxygen saturation. Viral shedding was also diminished in the treated groups as compared with the placebo group. No side effects or toxicity were associated with the aerosol therapy. Isolates of respiratory syncytial virus obtained from the infants over the course of therapy showed no change in sensitivity to ribavirin.

The use of eye-nose goggles to control nosocomial respiratory syncytial virus infection.

We evaluated an eye-nose goggle to determine its usefulness in reducing nosocomial RSV infection in patients and staff members on our infant ward. During a community outbreak of RSV in 1984, infection was assessed by biweekly routine viral cultures on all ward personnel and patients and also by seroconversion in personnel. For three weeks staff members wore the goggles; two (5%) adults and one (6%) child acquired nosocomial infection. During the subsequent three-week study period, goggles were not used and 34% of personnel and 43% of susceptible infants became infected. The use of the disposable eye-nose goggles was associated with a significant decrease in nosocomial RSV infections (P less than .003 for staff and P less than .05 for contact infants).

Respiratory syncytial viral infection in children with compromised immune function.

For 10 winters, 608 children five years old or younger who were hospitalized with respiratory syncytial virus (RSV) infection were prospectively studied to evaluate the relation between their immune status and the severity of their infection. Forty-seven had been immunocompromised by chemotherapy, steroid therapy, or a primary immunodeficiency disorder. Among the immunocompromised children, those receiving chemotherapy for cancer and those with immunodeficiency disease had more severe RSV disease, with pneumonia occurring at all ages, and a higher mortality rate. Children receiving long-term steroid therapy did not appear to have more severe clinical manifestations than normal children. Viral shedding, however, was significantly greater and more prolonged in the children receiving steroid therapy, and particularly in those receiving chemotherapy or with an immunodeficiency disease. Giant-cell pneumonia was documented in one child with leukemia. Over half the immunocompromised children acquired the RSV infection nosocomially. These findings indicate that children receiving chemotherapy for cancer and those with immunodeficiency disease are at risk for complicated or fatal infections from RSV and should be considered for antiviral and other therapies as they become available. Efforts should also be made to protect compromised children if hospitalization cannot be avoided.

Influenza in children with cancer.

We prospectively followed a group of unimmunized, immunosuppressed children with cancer to determine their relative risk of influenza and the severity of infection compared with those of siblings or matched community controls. The incidence of influenza infection was higher in children with cancer (23/73, 32%) than in control subjects (10/70, 14%, p = 0.02). A preseason hemagglutination inhibition titer greater than or equal to 1:32, generally used as a marker of successful immunization in vaccine trials, was protective for all children in the control groups, but did not prevent influenza infection in 24% of the patients with cancer. Infection rates of patients and community controls with titers greater than or equal to 1:32 differed significantly (p = 0.006). No significant differences were noted in duration of reported symptoms between groups, and clinical complications occurred too infrequently to analyze. However, 2 (11%) of 18 of the cancer patients with positive culture results were hospitalized during the illness and one patient developed a nosocomial infection. None of the control children was hospitalized. These findings suggest the need for further study of the immunologic response of immunosuppressed children to influenza infection and a clinical efficacy trial of the influenza vaccine in these patients.