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简介：AbstractImportance:The current lack of reliable rapid tests for distinguishing between bacterial and viral infections has contributed to antibiotic misuse.Objective:This study aimed to develop a novel biomarker assay that integrates FAM89A and IFI44L measurements to assist in differentiating between bacterial and viral infections.Methods:This prospective study recruited children with febrile illness from two hospitals between July 1, 2018, and June 30, 2019. A panel of three experienced pediatricians performed reference standard diagnoses of all patients (i.e., bacterial or viral infection) using available clinical and laboratory data, including a 28-day follow-up assessment. Assay operators were blinded to the reference standard diagnoses. The expression levels of FAM89A and IFI44L were determined by quantitative real-time polymerase chain reaction assessment.Results:Of 133 potentially eligible patients with suspected bacterial or viral infection, 35 were excluded after the application of exclusion criteria. The resulting cohort included 98 patients: 59 with viral diagnoses and 39 with bacterial diagnoses. The areas under the curve (AUCs) of diagnoses using FAM89A and IFI44L were 0.694 [95% confidence interval (CI): 0.583-0.804] and 0.751 (95% CI: 0.651-0.851), respectively. The disease risk score (DRS) [log2(FAM89A expression) - log2(IFI44L expression)] signature achieved an improved area under the receiver operating characteristic curve (AUC, 0.825; 95% CI: 0.735-0.915), compared with the AUC generated from individual host RNA. A combination of the DRS and the C-reactive protein (CRP) level achieved an AUC of 0.896 (95% CI: 0.825-0.966). Optimal cutoffs for the DRS and CRP level were -3.18 and 19.80 mg/L, respectively.Interpretation:The DRS was significantly more accurate than the CRP level in distinguishing between bacterial and viral infections; the combination of these two parameters exhibited greater sensitivity and specificity. This study provides information that could be useful for the clinical application of FAM89A and IFI44L in terms of distinguishing between viral and bacterial infections.

简介：AbstractFever and rash illnesses (FRIs) are a series of common diseases with fever and rashes as clinical manifestations, most of which are caused by viral infection. The rashes of FRIs are generally nonspecific; therefore it is difficult to identify FRI-associated viruses solely based on clinical symptoms. To achieve rapid and accurate identification of FRI pathogens, a multiplex one-step real-time reverse transcription-polymerase chain reaction (RT-PCR) assay was developed and evaluated in this study. Primers and probes were selected for the detection of measles virus (MeV), rubella virus (RV), human enterovirus (EV), varicella-zoster virus (VZV), dengue virus (DENV), human parvovirus B19 (B19), Epstein-Barr virus (EBV), and human herpes virus 6 (HHV-6), which cover the most common pathogenic viruses of FRIs. Detection of the eight FRI-associated viruses, which was divided into two groups/tubes, was simultaneously performed under universal optimized reaction conditions in multiplex one-step real-time RT-PCR assay. The multiplex realtime RT-PCR showed high sensitivity and specificity in detecting the eight FRI-associated viruses. The limits of detection (LODs) for the eight viruses were in the range of 47–177 copies/reaction, and no cross reactions for the eight FRI-associated viruses were found in the multiplex assay. In addition, the results of the multiplex real-time RT-PCR assay were consistent with the results of a monoplex real-time RT-PCR assay and sequencing for clinical specimens obtained from FRI patients. With its advantages of high efficiency and rapid and accurate diagnosis, multiplex real-time RT-PCR was very feasible for the early diagnosis of FRI pathogenic viruses and would be of great help for the proper treatment, monitoring, and initiation of preventive measures for FRI cases.