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: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:BACKGROUND:The objective of this study was to evaluate the ability of endothelial biomarkers to early predict clinical deterioration of patients admitted to the emergency department (ED) with a suspected sepsis. This was a prospective, multicentre, international study conducted in EDs. Adult patients with suspected acute bacterial infection and sepsis were enrolled but only those with confirmed infection were analysed. The kinetics of biomarkers and organ dysfunction were collected at T0, T6 and T24 hours after ED admission to assess prognostic performances of sVEGFR2, suPAR and procalcitonin (PCT). The primary outcome was the deterioration within 72 h and was defined as a composite of relevant outcomes such as death, intensive care unit admission and/or SOFA score increase validated by an independent adjudication committee. RESULTS:After adjudication of 602 patients, 462 were analysed including 124 who deteriorated (27%). On admission, those who deteriorated were significantly older (73 [60-82] vs 63 [45-78] y-o, p < 0.001) and presented significantly higher SOFA scores (2.15 ± 1.61 vs 1.56 ± 1.40, p = 0.003). At T0, sVEGFR2 (5794 [5026-6788] vs 6681 [5516-8059], p < 0.0001), suPAR (6.04 [4.42-8.85] vs 4.68 [3.50-6.43], p < 0.0001) and PCT (7.8 ± 25.0 vs 5.4 ± 17.9 ng/mL, p = 0.001) were associated with clinical deterioration. In multivariate analysis, low sVEGFR2 expression and high suPAR and PCT levels were significantly associated with early deterioration, independently of confounding parameters (sVEGFR2, OR = 1.53 [1.07-2.23], p < 0.001; suPAR, OR = 1.57 [1.21-2.07], p = 0.003; PCT, OR = 1.10 [1.04-1.17], p = 0.0019). Combination of sVEGFR2 and suPAR had the best prognostic performance (AUC = 0.7 [0.65-0.75]) compared to clinical or biological variables. CONCLUSIONS:sVEGFR2, either alone or combined with suPAR, seems of interest to predict deterioration of patients with suspected bacterial acute infection upon ED admission and could help front-line physicians in the triage process.

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Blood biomarkers in early bacterial infection and sepsis diagnostics in feverish young children.

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Blood biomarkers in early bacterial infection and sepsis diagnostics in feverish young children.

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