RESUMEN
OBJECTIVE: To examine whether genetic variations within the surfactant protein A2 (SP-A2) gene are associated with respiratory syncytial virus (RSV) disease severity in infected children. STUDY DESIGN: Naturally infected children aged < or =24 months were prospectively enrolled in 3 RSV seasons. SP-A2 genotyping was performed. Independent clinical predictors of disease severity were analyzed. The association of SP-A2 genetic diversity and disease severity was tested by using multivariate logistic regression models and 4 levels of disease gradation as outcome measures. RESULTS: Homozygosity of the 1A(0) allele was protective against hospitalization (odds ratio [OR] = 0.15, P = .0010). This remained significant in African American patients (OR = 0.24, P = .042) and Caucasian patients (OR = 0.05, P = .021) after adjustment for other co-variates. Hospitalized children with the 1A(2) allele demonstrated significant protection from severe disease with univariate analyses, but only a trend for protection with multivariate analyses. Patients homozygous or heterozygous for an asparagine at amino acid position 9 were twice or more likely to need intensive care unit admission (OR = 2.15, P = .022), require intubation (OR = 3.04, P = .005), and have a hospitalization lasting > or =4 days (OR = 1.89, P = .02) compared with children homozygous for a threonine at this position. CONCLUSIONS: SP-A2 polymorphisms are associated with the severity of RSV infection in infants.
Asunto(s)
Hospitalización , Polimorfismo de Nucleótido Simple , Proteína A Asociada a Surfactante Pulmonar/genética , Infecciones por Virus Sincitial Respiratorio/genética , Infecciones del Sistema Respiratorio/genética , Preescolar , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Lactante , Unidades de Cuidado Intensivo Pediátrico , Tiempo de Internación , Masculino , Respiración Artificial , Infecciones por Virus Sincitial Respiratorio/terapia , Infecciones del Sistema Respiratorio/terapia , Análisis de Secuencia de Proteína , Índice de Severidad de la EnfermedadRESUMEN
Previously healthy children hospitalized with respiratory syncytial virus (RSV) received motavizumab (3, 15, or 30 mg/kg intravenously), an RSV-specific monoclonal antibody, or placebo. Safety, tolerability, motavizumab concentrations, and immunogenicity were assessed. Cultivatable RSV in the upper respiratory tract was significantly reduced with motavizumab compared with placebo day 1 post-treatment. No adverse events were considered motavizumab-related by site investigators.
Asunto(s)
Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales/farmacología , Antivirales/efectos adversos , Antivirales/farmacología , Infecciones por Virus Sincitial Respiratorio/tratamiento farmacológico , Infecciones por Virus Sincitial Respiratorio/prevención & control , Virus Sincitial Respiratorio Humano/efectos de los fármacos , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales Humanizados , Anticuerpos Neutralizantes/administración & dosificación , Anticuerpos Neutralizantes/efectos adversos , Anticuerpos Neutralizantes/farmacología , Antivirales/administración & dosificación , Femenino , Humanos , Lactante , Masculino , Placebos/administración & dosificación , Virus Sincitial Respiratorio Humano/inmunología , Sistema Respiratorio/virologíaRESUMEN
It has not been determined whether respiratory syncytial virus (RSV) fusion protein monoclonal antibody (MAb) (palivizumab) reduces infection or simply ameliorates disease. In a prospective observational study, 27 hospitalized premature infants with RSV who were not receiving MAb were compared with 10 such patients who were receiving MAb. Mean (SEM) RSV loads in the MAb and non-MAb groups were 3.36 (0.59) versus 4.89 (0.27) logPFU/ml (P=.01). Prophylactic palivizumab reduces nasal RSV in premature hospitalized infants.