Reduced-Dose Schedule of Prophylaxis Based on Local Data Provides Near-Optimal Protection Against Respiratory Syncytial Virus

Abstract

Background: Respiratory syncytial virus (RSV) is a major cause of respiratory infections among young children and can lead to severe disease among some infants. Infants at high risk for severe RSV infection receive monthly injections of a prophylactic monoclonal antibody during the RSV season based on national guidelines. We considered whether a reduced-dose schedule tailored to the local RSV season in the continental United States would provide adequate protection.

Methods: Hospitalization data for 1942 counties across 38 states from 1997 to 2009 were obtained from the State Inpatient Databases (Agency for Healthcare Research and Quality). We assessed the timing of RSV epidemics at the county and state levels using a 2-stage hierarchical Bayesian change point model. We used a simple summation approach to estimate the fraction of RSV cases that occur during the window of protection provided by initiating RSV prophylaxis during different weeks of the year.

Results: The timing of RSV epidemic onset varied significantly at the local level. Nevertheless, the national recommendations for initiation of prophylaxis provided near-optimal coverage of the RSV season in most of the continental United States. Reducing from 5 to 4 monthly doses (with a later initiation) provides near-optimal coverage (<5% decrease in coverage) in most settings. Earlier optimal dates for initiating 4 doses of prophylaxis were associated with being farther south and east, higher population density, and having a higher percentage of the population that was black or Hispanic.

Conclusions: A 4-dose schedule of prophylactic injections timed with local RSV epidemics could provide protection comparable to 5 doses and could be considered as a way to improve the cost-effectiveness of prophylaxis.

Keywords: RSV; palivizumab; prophylaxis; respiratory syncytial virus; spatial variation.

Figure 1.

A, Average weekly incidence of respiratory syncytial virus (RSV) hospitalizations in each state. The black bar represents the 24-week period when a child would be protected by prophylaxis, based on the national guidelines of 5 doses beginning 1 November. B, Year-to-year variations in the estimated week of epidemic onset at the state level. The states are ordered by latitude, with the southernmost states at the bottom. C, Variations in the estimated week of epidemic onset between counties and years in each state, with each bubble representing an estimate from each county and year. The estimates are obtained using a 2-stage model, where onset is estimated separately for each state/county and year, then entered into a hierarchical model that borrows information between years and geographic areas to obtain stabilized (shrinkage) estimates. The size of the bubbles in (A) and (B) is proportional to the inverse posterior variance of the estimate. Darker shading indicates that multiple bubbles are overlapping.

Figure 2.

Percentage of cases that occur during the 24-week or 20-week window of protection provided by respiratory syncytial virus (RSV) prophylaxis if the dosing series is started in each week between the beginning of July (week 0) and the end of December. The maximum on each curve indicates the average optimum week for initiating prophylaxis in that state or county. The curves are calculated separately by year and state/county and then averaged across all available years. A and B, Protection provided by 5 doses at the state (A) and county (B) level. C and D, Protection provided by either a 5-dose series (blue) or a 4-dose series (red) at the state level (C) or county level (D). The vertical dotted lines are placed at 1 November, when the national recommendations suggest starting prophylaxis for most states. The horizontal dashed line represents 90% coverage. Only counties with an average of at least 25 cases are shown in (B) and (D). Counties in Florida are excluded from (B) and (D).

Figure 3.

A, Optimal week for initiating respiratory syncytial virus (RSV) prophylaxis among counties for which data were available. B, Predicted optimal week for initiating RSV prophylaxis in each county in the continental United States, based on county-level characteristics. Darker colors indicate later weeks. The color scale indicates the number of weeks since the beginning of July.