Project description:Viral infections are among the most common causes for fever without an apparent source (FWS) in young children; however, many febrile children are treated with antibiotics despite the absence of bacterial infection. Adenovirus, human herpesvirus 6 (HHV-6) and enterovirus are detected in children with FWS more often than other viral species. Virus and bacteria interact with pattern recognition receptors in circulating blood leukocytes and trigger specific host transcriptional programs that mediate immune response, and unique transcriptional signatures may be ascertained to discriminate between viral and bacterial causes for children with FWS. Microarray analyses were conducted on peripheral blood samples obtained from 51 pediatric patients with confirmed adenovirus, human herpesvirus 6 (HHV-6), enterovirus or bacterial infection. Whole blood transcriptional profiles could clearly distinguish febrile children from healthy controls, and febrile children with viral infections from afebrile children carrying the same virus. Molecular pathways regulating host immune response were the most affected in febrile children with infection. Pattern recognition programs were prominently activated in all febrile children with infection, while differential activation of transcriptional programs was observed among viral species. Interferon signaling pathway was uniquely activated in children with febrile viral infection, while a different set of pathways was uniquely activated in children with bacterial infection. Transcriptional signatures were identified and classified febrile children with viral or bacterial infection with 87% overall accuracy, an improvement from the current clinical practice of deducing from white blood cell (WBC) count status. Similar degree of accuracy was observed when we validated the signature probes on data sets from an independent study with different microarray platforms. The current study confirms the clinical utility of blood transcriptional analysis, suggests the composition of transcriptional signatures which can be used to ascertain the infectious etiology of febrile young children without an apparent source, thus limit the overuse of antibiotics on febrile children presenting with this common clinical complaint. Total RNA samples extracted from whole blood of young children were processed for hybridization onto Illumina Human-HT12 version 4 beadchips, and differential expression of the transcripts was analyzed between sick children with either viral or bacterial infection and healthy children.
Project description:Viral infections are among the most common causes for fever without an apparent source (FWS) in young children; however, many febrile children are treated with antibiotics despite the absence of bacterial infection. Adenovirus, human herpesvirus 6 (HHV-6) and enterovirus are detected in children with FWS more often than other viral species. Virus and bacteria interact with pattern recognition receptors in circulating blood leukocytes and trigger specific host transcriptional programs that mediate immune response, and unique transcriptional signatures may be ascertained to discriminate between viral and bacterial causes for children with FWS. Microarray analyses were conducted on peripheral blood samples obtained from 51 pediatric patients with confirmed adenovirus, human herpesvirus 6 (HHV-6), enterovirus or bacterial infection. Whole blood transcriptional profiles could clearly distinguish febrile children from healthy controls, and febrile children with viral infections from afebrile children carrying the same virus. Molecular pathways regulating host immune response were the most affected in febrile children with infection. Pattern recognition programs were prominently activated in all febrile children with infection, while differential activation of transcriptional programs was observed among viral species. Interferon signaling pathway was uniquely activated in children with febrile viral infection, while a different set of pathways was uniquely activated in children with bacterial infection. Transcriptional signatures were identified and classified febrile children with viral or bacterial infection with 87% overall accuracy, an improvement from the current clinical practice of deducing from white blood cell (WBC) count status. Similar degree of accuracy was observed when we validated the signature probes on data sets from an independent study with different microarray platforms. The current study confirms the clinical utility of blood transcriptional analysis, suggests the composition of transcriptional signatures which can be used to ascertain the infectious etiology of febrile young children without an apparent source, thus limit the overuse of antibiotics on febrile children presenting with this common clinical complaint.
Project description:By studying differently expressed immune genes with gene expression profiling in immune competent children researchers have been able to distinguish between children with asymptomatic viral infection and those with symptomatic viral infection as well as patients with bacterial infection. In this study we asked if gene expression profiling is feasible as a diagnostic tool in febrile neutropenia. We included children under treatment for a malignancy presenting with febrile neutropenia. Clinical data regarding the infectious episode was prospectively collected and children grouped based on microbiological agent detected into virus, bacteria, co-infection and unknown aetiology. Fourty three episodes had sufficient RNA for RNA-sequencing, 15 with respiratory tract virus, 22 with unknown etiology, 4 with co-infection and 2 with bacteria. No pathogen specific host-innate immune expression profile was seen in the group with virus, bacteria nor unknown aetiology probably due to the low white blood cell account (WBC). In the co-infection group with higher WBC but lower absolute neutrophil count (ANC) compared to the other groups, a downregulated innate response were detected. We conclude that gene expression profiling in children presenting with neutropenic fever is not a feasible diagnostic tool for febrile neutropenia in children with cancer due the low WBC.:
Project description:RNA sequencing data from children with febrile illness and multisystem inflammatory syndrome in children (MIS-C). Samples used were Whole Blood. Febrile illness controls include children with bacterial and viral infections and healthy controls. This dataset contains samples from patients recruited into the DIAMONDS study.
Project description:To identify a diagnostic blood transcriptomic signature that distinguishes multisystem inflammatory syndrome in children (MIS-C) from Kawasaki Disease (KD), bacterial infections and viral infections.
Children presenting with MIS-C to participating hospitals in the United Kingdom and the European Union between April 2020-April 2021 were prospectively recruited. Whole blood RNA Sequencing was performed, contrasting the transcriptomes of children with MIS-C to those from children with KD, definite bacterial and viral infections. Data deposited here comprises samples from patients recruited into the DIAMONDS study.
Project description:Febrile patients PCR positive for H1N1 swine flu, seasonal H1N1 and seasonal H3N2 in nasal swabs and controls consisting of febrile patients with rhinovirus infection or febrile patients of non-viral etiology (nasal swabs PCR negative for common respiratory viruses and blood PCR negative for dengue and parvovirus B19) were assessed consecutively for global transcriptional changes in whole blood
Project description:Febrile patients PCR positive for H1N1 swine flu, seasonal H1N1 and seasonal H3N2 in nasal swabs and controls consisting of febrile patients with rhinovirus infection or febrile patients of non-viral etiology (nasal swabs PCR negative for common respiratory viruses and blood PCR negative for dengue and parvovirus B19) were assessed consecutively for global transcriptional changes in whole blood Peripheral whole blood collected in PAX-gene tubes and extracted for total RNA