A daring treatment and a successful outcome: The need for targeted therapies for pediatric respiratory viruses

The report by Stankova et al. in this issue tells the fascinating and inspiring story of a child with SCID who underwent two sequential human stem cell transplantations (HSCT), a myeloablative pre-conditioning regimen, and many posttransplant complications, all while she was actively infected with human parainfluenza virus type 3 (HPIV3). The child never developed severe respiratory disease, and three yr later had no evidence of damage to the respiratory tract. The child’s physicians had elected to initiate aerosolized ribavirin two wk before HSCT, and continued this medication for 10 months in an effort to prevent the HPIV3 infection from progressing in severity; the report cautiously suggests that this therapy may have contributed to the gratifying outcome. This brave physicians report begs the question: Why are we relying on untested, unproven, partially active agents for a virus that is so important in children? The valiant attempt to treat parainfluenza viral respiratory tract disease with ribavirin points to our more general dilemma for pediatric respiratory viral diseases; we are often guessing, trying therapies based upon thin evidence for their use for a different pathogen, or on inadequate in vitro data. Even for RSV, ribavirin is a nucleoside analog that has good activity against RSV in vitro but has produced conflicting clinical data and uncertainty with regard to its utility in most cases. As far as ribavirin use in cases of HPIV3 infection, most reports have focused on early diagnosis and treatment. The authors of this piece seem to have been the first to treat active HPIV3 infection, in anticipation of transplant. Published reports do not suggest a strong link between ribavirin use in cases of HPIV infection and improved outcome. In one large series, ribavirin was used to treat nine of 27 HPIVinfected stem cell transplant patients, without effect on mortality rate (18). In a small pilot study designed to address preemptive therapy in HSCT patients, Chakrabar et al. treated five patients with HPIV3 infection – one asymptomatic and four symptomatic with URTI – with oral ribavirin. Three of these individuals, including the patient who had been asymptomatic at the initiation of therapy, had no virologic response. One of those three died; the other two (including the person with no symptoms of respiratory disease) were placed on IV ribavirin and resolved. The role of ribavirin in preventing progression of URTI is uncertain, at best. In the patient treated by Stankova et al., the question of the significance of risk factors makes interpretation even more difficult. Known risks for increased mortality from HPIV3 after transplantation include graft vs. host disease, steroid use, and the presence of copathogens (2, 11, 17); the child had none of these. However, infection with HPIV3 within the first 100 days after transplant has also been associated with increased mortality (2), and this patient was certainly infected throughout the high-impact period. This combination of high and low risk factors makes it even more difficult to evaluate the role of ribavirin in the positive outcome. The child in this case was treated for upper respiratory tract infection (URTI), in an effort to prevent progression to lower respiratory tract disease (LRTI). LRTI is a well-known consequence of URTI infection with HPIV3; in one study of 228 patients who underwent bone marrow transplantation and acquired HPIV3 infection, 198 individuals presented with symptoms of URTI, and 24% of these progressed to LRTI (11). Although the authors of that study Pediatr Transplantation 2007: 11: 121–123. Copyright 2007 Blackwell Munksgaard