Risk of severe respiratory syncytial virus disease, identification of high risk infants and recommendations for prophylaxis with palivizumab.

Abstract

To The Editors: In the United States ∼110 000 infants are hospitalized annually in the first 12 months of life for treatment of bronchiolitis. Data from the CDC suggest that the number of yearly hospital admissions because of bronchiolitis has increased more than 2-fold since 1980. 1 Respiratory syncytial virus (RSV) infection accounts for ∼70% of these hospitalizations, making RSV bronchiolitis the single most common reason for hospitalization among infants in the first year of life. 2 The rate of hospitalization attributable to severe RSV infection is highest among premature infants who may or may not have chronic lung disease of prematurity, infants with hemodynamically significant congenital heart disease and certain other groups of infants including infants with congenital anomalies of their airways. 3 The annual rates of hospitalization among infants in these high risk groups varies between 10 and 20% depending on the study cited and the particular group under consideration. 4 Despite a rate of hospitalization among high risk infants that is ∼5 times higher than the rate of hospitalization in non-high risk infants, most infants hospitalized because of an RSV infection do not have an underlying risk factor that categorizes them in a high risk group. About 70% of infants with an RSV-associated hospitalization are term infants with no underlying anatomic abnormality. A safe and effective RSV vaccine has been an elusive goal. 5 In contrast remarkable success has been achieved in demonstrating the efficacy, ease of administration and safety of passive protection against RSV. In slightly more than 10 years, the field of passive immunoprophylaxis has evolved from clinical trials with standard intravenous immunoglobulin to the use of a RSV-hyperimmune intravenous globulin (Respigam) to an intramuscular, humanized, murine monoclonal antibody (palivizumab) directed against a conserved epitope on the fusion glycoprotein. 4 Phase I clinical trials will soon begin with a molecule (MEDI-524) with even greater in vitro RSV-neutralizing activity than palivizumab and which may offer even lower rates of RSV breakthrough disease than that provided with palivizumab prophylaxis. Use of passive immunoprophylaxis has been restricted to infants and children at highest risk of RSV-induced hospitalization because of the high cost of this intervention. The American Academy of Pediatrics published guidelines for selection of infants who should be considered for passive prophylaxis soon after palivizumab was licensed by the Food and Drug Administration in June 1998. 6 In December 2003 revised guidelines were issued by the AAP to delineate further which high risk infants are most likely to benefit from prophylaxis. 7 The revised guidelines represent a compromise between the opportunity to reduce the incidence of RSV hospitalization in infants and children at greatest risk and the cost of prophylaxis. A recent publication suggests that some discrepancies may exist in the guidelines. 8 Three hypothetical examples were proposed to demonstrate that infants with a younger gestational age might receive fewer months of palivizumab prophylaxis than infants with a greater gestational age. However, in these examples the need for at least two additional risk factors for infants born after 32 to 35 weeks gestation was not considered. When additional risk factors are taken into consideration, as recommended in the revised guidelines, it is unlikely that an infant at greater risk of RSV-induced hospitalization would receive fewer doses of palivizumab than an infant with lesser risk. Elhassan et al. 8 also suggest that evaluation of postconceptional age would enhance selection of infants most likely to benefit from prophylaxis. However, results of most studies on the risk of hospitalization as a function of gestational age demonstrate little difference in risk of RSV-induced hospitalization rate between infants with gestational age ≤28 weeks, infants 29 to 32 weeks gestational age and infants 33 to 35 weeks gestational age. 9–12 Thus the AAP decided that routinely classifying premature infants into 2-week categories based on gestational age would increase the complexity of assessment without offering sufficient improvement in identifying infants at increased risk of hospitalization. Modification of existing recommendations is a dynamic process, as is evident by changes in the revised AAP guidelines which represent the most appropriate approach for selection of high risk infants for palivizumab prophylaxis. 7 H. Cody Meissner, M.D. Margaret B. Rennels, M.D. Larry K. Pickering, M.D. Caroline B. Hall, M.D.