Intravenous Ribavirin Treatment for Severe Adenovirus Disease in Immunocompromised Children

Adenovirus is an important cause of morbidity and mortality in the immunocompromised host. The incidence of severe adenovirus disease in pediatrics is increasing in association with growing numbers of immunocompromised children, where case fatality rates as high as 50% to 80% have been reported. There are no approved antiviral agents with proven efficacy for the treatment of severe adenovirus disease, nor are there any prospective randomized, controlled trials of potentially useful anti-adenovirus therapies. Apparent clinical success in the treatment of severe adenovirus disease is limited to a few case reports and small series. Experience is greatest with intravenous ribavirin and cidofovir. Ribavirin, a guanosine analogue, has broad antiviral activity against both RNA and DNA viruses, including documented activity against adenovirus in vitro. Ribavirin is licensed in aerosol form for the treatment of respiratory syncytial virus infection, and orally in combination with interferon to treat hepatitis C. Intravenous ribavirin is the treatment of choice for infection with hemorrhagic fever viruses. The most common adverse effect of intravenous ribavirin is reversible mild anemia. The use of cidofovir in severe adenovirus infection has been limited by adverse effects, the most significant of which is nephrotoxicity. We report our experience with intravenous ribavirin therapy for severe adenovirus disease in a series of immunocompromised children and review the literature. We retrospectively reviewed the medical records of 5 children treated with intravenous ribavirin for documented severe adenovirus disease. Two patients developed adenovirus hemorrhagic cystitis after cardiac and bone marrow transplants, respectively. The bone marrow transplant patient also received intravenous cidofovir for progressive disseminated disease. An additional 3 children developed adenovirus pneumonia; 2 were neonates, 1 of whom had partial DiGeorge syndrome. The remaining infant had recently undergone a cardiac transplant. Intravenous ribavirin was administered on a compassionate-use protocol. Complete clinical recovery followed later by viral clearance was observed in 2 children: the cardiac transplant recipient with adenovirus hemorrhagic cystitis and the immunocompetent neonate with adenovirus pneumonia. The remaining 3 children died of adenovirus disease. Intravenous ribavirin therapy was well tolerated. Use of cidofovir in 1 child was associated with progressive renal failur