Ribavirin in respiratory syncytial virus infection

At a recent workshop on infection the indications for ribavirin were discussed. Ribavirin has recently been licensed for hospital use in the United Kingdom having previously been available only on a named patient basis. Nebulised ribavirin is being vigorously promoted by the United Kingdom marketing company, Brittania Pharmaceuticals, for selected use in respiratory syncytial virus infections largely based on the 1986 guidelines of the American Academy of Pediatrics (AAP).l The AAP suggest that nebulised ribavirin should be considered for the following patients with proved infection by respiratory syncytial virus. (1) Patients at high risk: infants with congenital heart disease, bronchopulmonary dysplasia and other chronic lung conditions, certain premature infants, children with immune deficiency (especially severe combined immune deficiency), recent transplant recipients, and those on chemotherapy for malignancy; (2) Severely ill infants: those with PaO2 concentrations of <8*66 kPa or rising PaCO2 concentrations; (3) Infants with mild disease which may progress: infants under 6 weeks of age and those with an underlying condition such as multiple congenital anomalies, neurological or metabolic diseases. Although one of us has previously reached similar conclusions to the AAP2 we are concerned that the climate of opinion, certainly in the United States, is tending to imply that the case for ribavirin is proved and clinical trials are no longer ethical. There is evidence that infants with congenital heart disease3 and children with compromised immunity4 have an increased mortality from respiratory syncytial virus infection. The severity of the infection in preterm infants and the degree to which the lower respiratory tract is affected seems to increase with postnatal age.97 In one study four of 23 neonates who contracted respiratory syncytial virus died, two of them suddenly and unexpectedly, although the role of the virus was unclear. The mortality of full term infants without underlying disease who are hospitalised with respiratory syncytial virus infection is less than 1%.' Controlled trials of the use of ribavirin in such infants show modest improvement in clinical parameters and oxygenation, "1 which although statistically significant is of doubtful clinical significance. Nasal shedding of respiratory syncytial virus was reduced in only one of the four studies and may anyway not reflect bronchiolar titres of the virus.8 The total number of treated infants in the four controlled trials is 62. No children in treatment or control groups died and there was no reduction in hospital stay in the only study which recorded this.11 MacDonald et al reported a mortality of 37% in infants with:congenital heart disease and infection with respiratory syncytial virus,3 but Hall et al, in a prospective trial, reported that none of seven infants with congenital heart disease or bronchopulmonary dysplasia, or both, who received placebo and none of six who received ribavirin died.12 It is possible that earlier recognition and improved conventional, supportive treatment of respiratory syncytial virus infection in infants with cardiopulmonary disease may be more important than any antiviral treatment. There are anecdotal reports of nebulised ribavirin clearing persistent respiratory syncytial virus and parainfluenza virus infections in immune deficient children who could subsequently receive bone marrow transplants.13 14 Such children are few in number and a controlled trial would be impractical. Most would agree that infection by respiratory syncytial virus in a child with severe immune deficiency is an indication for ribavirin treatment, but there is no evidence that children on chemotherapy for malignancy are helped by ribavirin.