Abstract
Respiratory syncytial virus (RSV) causes seasonal respiratory infection, with hospitalization rates of up to 50% in high-risk infants. Palivizumab provides safe and effective, yet costly, immunoprophylaxis. The American Academy of Pediatrics (AAP) recommends palivizumab only for high-risk infants and only during the RSV season. Outside of Florida, the current guidelines do not recommend regional adjustments to the timing of the immunoprophylaxis regimen. Our hypothesis is that adjusting the RSV prophylaxis regimen in Connecticut based on spatial variation in the timing of RSV incidence can reduce the disease burden compared to the current AAP-recommended prophylaxis regimen. We obtained weekly RSV-associated hospital admissions by ZIP-code in Connecticut between July 1996 and June 2013. We estimated the fraction of all Connecticut RSV cases occurring during the period of protection offered by immunoprophylaxis (“preventable fraction”) under the AAP guidelines. We then used the same model to estimate protection conferred by immunoprophylaxis regimens with alternate start dates, but unchanged duration. The fraction of RSV hospitalizations preventable by the AAP guidelines varies by county because of variations in epidemic timing. Prophylaxis regimens adjusted for state- or county-level variation in the timing of RSV seasons are superior to the AAP-recommended regimen. The best alternative strategy yielded a preventable fraction of 95.1% (95% CI 94.7–95.4%), compared to 94.1% (95% CI 93.7–94.5%) for the AAP recommendation. In Connecticut, county-level recommendations would provide only a minimal additional benefit while adding complexity. Initiating RSV prophylaxis based on state-level data may improve protection compared with the AAP recommendations.
Highlights
Risk factors of serious illness and hospitalization due to Respiratory syncytial virus (RSV) infection include prematurity, chronic lung disease of prematurity, congenital heart disease, anatomic pulmonary abnormalities, neuromuscular disorders, trisomy 21, and immunocompromised status[6]
Motivated by the Academy of Pediatrics (AAP)’s recognition of the significance of spatial variation in formulating prophylaxis guidelines and the known spatial variability of RSV incidence in Connecticut, we aim to determine whether protection due to RSV prophylaxis would be enhanced by having localized guidelines for the initiation of prophylaxis by addressing the following questions:
Our analysis confirms the existence of county-level variation of RSV season timing in Connecticut observable at the county level
Summary
Risk factors of serious illness and hospitalization due to RSV infection include prematurity, chronic lung disease of prematurity, congenital heart disease, anatomic pulmonary abnormalities, neuromuscular disorders, trisomy 21, and immunocompromised status[6]. The hospitalization rate due to RSV among high-risk infants is anywhere from two to ten times higher than among infants with no comorbidities[4]. Palivizumab has been found to be effective in reducing hospitalizations due to RSV; in double-blinded trials in high-risk infants, it reduced the hospitalization rate by 45–55% compared to p lacebo[9,10]. Owing to the high cost, the 2014 revision of the AAP RSV prophylaxis guidelines recommends palivizumab only for high-risk infants and only during the RSV s eason[6,11,12]. The AAP acknowledges the potential significance of spatial and temporal variation in RSV incidence, but—outside of Florida, whose RSV season leads most of the rest of the nation by approximately 2 months—does not recommend local variance from nationwide prophylaxis guidelines[6]. Motivated by the AAP’s recognition of the significance of spatial variation in formulating prophylaxis guidelines and the known spatial variability of RSV incidence in Connecticut, we aim to determine whether protection due to RSV prophylaxis would be enhanced by having localized guidelines for the initiation of prophylaxis by addressing the following questions:
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