Hospitalization for respiratory syncytial virus infection in young children: development of a clinical prediction rule.

BACKGROUND: Because passive immunization against respiratory syncytial virus (RSV) is costly, its use should be restricted to well-defined groups of high risk children. We aimed to develop a clinical prediction rule that estimates the individual monthly risk of hospitalization for RSV infection in young children. METHODS: A retrospective cohort study was conducted in the southwestern part of The Netherlands. We included children born between January 1, 1996 and December 31, 1998. Children hospitalized for proven RSV infection were compared with children not hospitalized for RSV infection. The monthly risk was estimated with a logistic regression model including 5 clinical predictors (gender, gestational age, birth weight, presence of bronchopulmonary dysplasia and age) and the mean seasonal monthly pattern of RSV infections. We compared the predictive performance of the prediction rule with the guidelines of the American Academy of Pediatrics (AAP). FINDINGS: Information was collected on 2469 hospitalized children and 140,661 children who were 1,181,790 months at risk. All predictors were statistically significant, with age and the seasonal monthly RSV pattern having the strongest effects. The clinical prediction rule that included these predictors could better discriminate between high and low risk children than the AAP guidelines and would potentially reduce the number of immunizations by 20%. INTERPRETATION: The prediction rule reliably estimates individual monthly risks of hospitalization for RSV infection in the population studied. It provides an improved index for passive immunization but further validation in other populations is required.

Anticipated costs of hospitalization for respiratory syncytial virus infection in young children at risk.

BACKGROUND: Reliable estimates of hospitalization costs for severe respiratory syncytial virus (RSV) infection are necessary to perform economic analyses of preventive strategies of severe RSV disease. We aimed to develop a model that predicts anticipated mean RSV hospitalization costs of groups of young children at risk for hospitalization, but not yet hospitalized, based on readily available child characteristics. METHODS: We determined real direct medical costs of RSV hospitalization from a societal perspective, using a bottom-up strategy, in 3458 infants and young children hospitalized for severe RSV disease during the RSV seasons 1996-1997 to 1999-2000 in the Southwest of the Netherlands. We used a linear regression model to predict anticipated mean RSV hospitalization costs of groups of children at risk, based on 4 child characteristics [age, gestational age, birth weight and bronchopulmonary dysplasia (BPD)], expressed in EC Euros as of the year 2000. FINDINGS: The mean RSV hospitalization costs of all patients were 3110 Euros. RSV hospitalization costs were higher for patients with lower gestational age (5555 Euros; gestational age,

Passive immunisation against respiratory syncytial virus: a cost-effectiveness analysis.

AIM: The cost-effectiveness of passive immunisation against respiratory syncytial virus (RSV) in the Netherlands was studied by assessing incremental costs to prevent one hospitalisation in high-risk children using a novel individualised monthly approach. METHODS: Cost-effectiveness analysis was performed by combining estimates of individual hospitalisation costs and monthly hospitalisation risks, with immunisation costs, parental costs and efficacy of passive immunisation for a reference case with the highest hospitalisation risks and costs of hospitalisation during the RSV season (male, gestational age < or =28 weeks, birth weight < or =2500 g, having bronchopulmonary dysplasia (BPD), aged 0 months at the beginning of the season (October)). Various sensitivity analyses and a cost-neutrality analysis were performed. RESULTS: Cost-effectiveness of passive immunisation varied widely by child characteristics and seasonal month. For the reference case it was most cost effective in December at euro13,190 per hospitalisation averted. Cost-effectiveness was most sensitive to changes in hospitalisation risk. For the reference case, cost neutrality was reached in December, if acquisition costs of passive immunisation decreased from euro 930 to euro 375, monthly hospitalisation risk increased from 7.6% to 17%, or hospitalisation costs increased from euro 10 250 to euro 23 250 per hospitalisation. Even if passive immunisation prevented all hospitalisations, costs per hospitalisation averted in December would still exceed euro 2645. CONCLUSIONS: Although cost-effectiveness of passive immunisation varied strongly by child characteristics and seasonal month, incremental costs per hospitalisation averted were always high. A restrictive immunisation policy only immunising children with BPD in high-risk months is therefore recommended. The costs of passive immunisation would have to be considerably reduced to achieve cost-effectiveness.

Influence of promoter variants of interleukin-10, interleukin-9, and tumor necrosis factor-alpha genes on respiratory syncytial virus bronchiolitis.

Previously, we reported genetic associations between severe respiratory syncytial virus (RSV) bronchiolitis in infants and polymorphisms in the interleukin (IL)-4 and IL-4 receptor alpha (IL-4Ralpha) genes, providing evidence for involvement of T helper type 2 cytokines in the pathogenesis of RSV bronchiolitis. We expanded our studies to polymorphisms in genes encoding IL-9, IL-10, and tumor necrosis factor (TNF)-alpha, using both a transmission/disequilibrium test and a case-control approach. Children homozygous for the IL-10 -592C or -592A allele had a higher risk of hospitalization for RSV bronchiolitis than did heterozygous carriers (odds ratio [OR], 1.73 vs. 2.55; 95% confidence interval [CI], 1.13-2.66 vs. 1.21-5.39). In children hospitalized at < or =6 months of age, a significant association between RSV bronchiolitis and the IL-10 -592C allele was found (OR, 1.61; 95% CI, 1.10-2.35). No significant associations of TNF-alpha and IL-9 polymorphisms with RSV bronchiolitis were observed. We also explored the interactions between different polymorphisms and found an interaction between the IL-4Ralpha Q551R and IL-10 C-592A polymorphisms.

Association of severe respiratory syncytial virus bronchiolitis with interleukin-4 and interleukin-4 receptor alpha polymorphisms.

The association of variants of genes encoding interleukin (IL)-4 and the IL-4 receptor alpha chain (IL-4Ralpha) with respiratory syncytial virus (RSV) bronchiolitis was examined in hospitalized infants. Polymorphisms in IL-4 (C-590T) and IL-4Ralpha (I50V and Q551R) were genotyped by restriction fragment-length polymorphism analysis. Control subjects included parents of the hospitalized children (for the transmission/disequilibrium test), and a random population sample (for the case-control study). Results were also analyzed in a combination of these 2 tests, using Fisher's method. The IL-4 590T allele was found more frequently among children hospitalized with RSV than expected in the case-control (odds ratio [OR], 1.43; P=.04) and combination (OR, 1.41; P=.02) tests. Among children who were >6 months old when they were hospitalized, compared with the control group or with the <6 months old who were hospitalized for RSV infection, higher frequencies of both the IL-4 590T allele and the IL-4Ralpha R551 allele were found. These results indicate that gain-of-function variants of T helper type 2 cytokine genes may play a role in increasing the severity of RSV disease, which appears more pronounced after the first half-year of life.