ABSTRACT
BACKGROUND: Respiratory syncytial virus (RSV) is a significant cause of infant morbidity and mortality worldwide. Most children experience at least one 1 RSV infection by the age of two 2 years, but not all develop severe disease. However, the understanding of genetic risk factors for severe RSV is incomplete. Consequently, we conducted a genome-wide association study of RSV severity. METHODS: Disease severity was assessed by the ReSVinet scale, in a cohort of 251 infants aged 1 week to 1 year. Genotyping data were collected from multiple European study sites as part of the RESCEU Consortium. Linear regression models were used to assess the impact of genotype on RSV severity and gene expression as measured by microarray. RESULTS: While no SNPs reached the genome-wide statistical significance threshold (P < 5 × 10-8), we identified 816 candidate SNPs with a P-value of <1 × 10-4. Functional annotation of candidate SNPs highlighted genes relevant to neutrophil trafficking and cytoskeletal functions, including LSP1 and RAB27A. Moreover, SNPs within the RAB27A locus significantly altered gene expression (false discovery rate, FDR P < .05). CONCLUSIONS: These findings may provide insights into genetic mechanisms driving severe RSV infection, offering biologically relevant information for future investigations.
Subject(s)
Respiratory Syncytial Virus Infections , Respiratory Syncytial Virus, Human , Infant , Child , Humans , Genome-Wide Association Study , Respiratory Syncytial Virus, Human/genetics , Genotype , Microarray AnalysisSubject(s)
Anti-Bacterial Agents/therapeutic use , Drug Prescriptions/statistics & numerical data , Drug Utilization/statistics & numerical data , Emergency Service, Hospital , Adolescent , Anti-Bacterial Agents/adverse effects , Child , Child Welfare , Child, Preschool , Cohort Studies , Female , Humans , Infant , Male , Pediatrics/standards , Pediatrics/trends , Retrospective Studies , Risk Assessment , United KingdomABSTRACT
BACKGROUND: In August 2012, new national guidance (National Institute of Health and Care Excellence (NICE) CG149) for management of early onset sepsis (EOS) was introduced in the UK. The guidance outlined a consistent approach for septic screens in newborn infants based on risk factors, and suggested biochemical and clinical parameters to guide management. In particular, it advised a second C-reactive protein level (CRP) 18-24 h into treatment to help determine length of antibiotic course, need for lumbar puncture (LP), and suggested review of blood culture at 36 h. OBJECTIVE: We evaluated impact of this guidance in our neonatal unit. METHODS: We compared two time periods, before and following the guidance. We evaluated length of stay, second CRP 18-24 h into treatment, percentage of babies having LP and duration of antibiotics. RESULTS: Before NICE guidance, 38.1% of screened babies stayed <72 h. This reduced to 18.4% following guidance. Before guidance, 20.9% babies stayed >5 days, which increased to 27.7% following NICE recommendations. Repeat CRP measurements increased from 45% to 97%. In 58% of these babies, repeat CRPs influenced management and hospital stay. An increase in LPs performed from 14% to 23% was noted. There were no positive blood cultures or LP results. CONCLUSIONS: We envisaged shorter hospital stays with new NICE standards, particularly, with the aim of 36 h blood culture reporting. However, repeat CRP led to further investigations, increased LPs and longer durations of treatment and stay. This, in turn, impacted on workload and cost, and influenced parental experience in the first few days of life.