RSV Mortality in Healthy Infants Lower Than Prior Estimates

Diana Phillips

December 08, 2014

Infants with life-threatening or complex, chronic conditions are the most vulnerable to RSV-associated death, according to a new study.

Most of the deaths associated with RSV occur in infants with life-threatening or complex chronic conditions in addition to the virus, Carrie L. Byington, MD, from the Department of Pediatrics at the University of Utah in Salt Lake City, and colleagues report in an article published online December 8 in Pediatrics, noting that the annual mortality rate for the condition appears to be far lower than previous estimates.

Although RSV is one of the most common childhood infections, and a leading cause of pediatric hospitalizations, public health agencies do not require deaths resulting from RSV to be reported. Thus, the authors explain, "the relative contribution of RSV infection to childhood mortality is unclear."

Because current mortality estimates for RSV hospitalizations are based on decades-old studies, the researchers designed the current investigation to describe contemporary RSV mortality rates and to identify conditions associated with RSV mortality in hospitalized infants and children younger than 2 years, who are most vulnerable to the virus.

The investigators used two national pediatric databases, the Agency for Healthcare Research and Quality and Healthcare Cost Utilization Project Kids' Inpatient Database (KID) and the Pediatric Health Information System (PHIS) database, to identify RSV-associated hospital admissions and deaths according to diagnosis and procedure codes.

The KID data sets identified a total of 607,937 RSV-associated admissions and 550 deaths in the 2000, 2003, 2006, and 2009 data sets, for a rate of 9.0 deaths per 10,000 admissions. The PHIS data set identified 264,721 RSV-associated admissions and 671 deaths from 2000 to 2011, for a mortality rate of 25.4 deaths per 10,000 admissions, the authors report.

The RSV mortality rate ranged from a high of 10.4/10,000 in 2000 to a low of 8.1/10,000 in 2006 in the KID data sets and from a high of 34.4/10,000 in 2003 to a low of 16.9/10,000 in 2011 in the PHIS data set, the authors note. The PHIS mortality rates were lower in the later 5 years of the study compared with in the first 5 years.

The majority of deaths in both data sets (85% in KID and 77% in PHIS) occurred in infants aged 12 months or younger, the authors write.

In addition, the majority of RSV-associated deaths occurred in infants and children with chronic, complex conditions (CCC), increasing with age in both data sets. "In the KID and PHIS data sets, respectively, 68% and 76% of infants aged ≤12 months who died had CCC compared with 85% and 84% of those aged 13 to 24 months," the authors write, noting that cardiovascular conditions were the most frequent CCC identified and that nearly 40% of children who dad had two or more CCC identified.

Mortality during RSV-associated hospitalizations among children with a primary diagnosis of RSV occurred in 3 to 4 of every 10,000 admissions, according to the authors. "The KID data set estimated 121 deaths nationally in infants and children with RSV-associated admissions, 84 deaths during RSV season, and 42 deaths with a primary diagnosis of RSV in 2009. The PHIS data set had a mean of 56 deaths per year, with 39 during RSV season and 21 with a primary diagnosis of RSV," they report. "The annual deaths documented in these contemporary data sources are 5 to 100 times lower than 20th century estimates."

The number of deaths with a primary diagnosis of RSV is comparable to the annual death rate associated with influenza for children younger than 2 years, the authors state.

In both data sets, patients who died had prolonged hospital stays averaging 40 days, and the majority had International Classification of Diseases, Ninth Revision, Clinical Modification, codes for potentially life-threatening conditions, such as sepsis or surgical complications, in addition to RSV infection, according to the analysis.

"The duration of hospitalization may indicate that RSV infection was present during the hospitalization but may have been remote from the actual death," the authors hypothesize. "Our finding that the majority of children who died had other potentially life-threatening conditions [including bacterial sepsis and surgical complications during their RSV-associated hospitalizations] supports this possibility."

The finding that most RSV-associated deaths occur in infants with CCC points to the vulnerability of this population, along with the elderly, to the virus. "These populations should be prioritized if a safe and effective vaccine is developed," the authors stress. Further, they conclude, "[o]ur findings may help to inform policy makers as they model the costs associated with RSV prevention and treatment strategies, including palivizumab and investigational therapeutics and vaccines under development."

Dr Byington has intellectual property in and receives royalties from BioFire Diagnostics, Inc. The other authors have disclosed no relevant financial relationships.

Pediatrics. Published online December 8, 2014.

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