Abstract
The diagnosis of bacterial infections in hospital settings is currently performed using bacterial culture from sterile site, but they are lengthy and limited. Transcriptomic biomarkers are becoming promising tools for diagnosis with potential applicability in clinical settings. We evaluated a RT-qPCR assay for a 2-transcript host expression signature (FAM89A and IFI44L genes) inferred from microarray data that allow to differentiate between viral and bacterial infection in febrile children. This assay was able to discriminate viral from bacterial infections (P-value = 1.04 × 10−4; AUC = 92.2%; sensitivity = 90.9%; specificity = 85.7%) and showed very high reproducibility regardless of the reference gene(s) used to normalize the data. Unexpectedly, the monogenic IFI44L expression signature yielded better results than those obtained from the 2-transcript test (P-value = 3.59 × 10−5; AUC = 94.1%; sensitivity = 90.9%; specificity = 92.8%). We validated this IFI44L signature in previously published microarray and whole-transcriptome data from patients affected by different types of viral and bacterial infections, confirming that this gene alone differentiates between both groups, thus saving time, effort, and costs. Herein, we demonstrate that host expression microarray data can be successfully translated into a fast, highly accurate and relatively inexpensive in vitro assay that could be implemented in the clinical routine.
Highlights
A common practice in hospitals is to systematically administer antibiotics to febrile patients until the results from culture tests are available as preventive method, with the outcome that many viral infections are inadequately treated with anti-microbial drugs[1,2]
Www.nature.com/scientificreports expression microarrays, Herberg et al.[16] found two genes with different expression levels depending on the nature of the causative pathogen: Interferon Induced Protein 44 Like (IFI44L) gene is up-regulated in viral febrile children and, in contrast, Family with Sequence Similarity 89 Member A (FAM89A) gene has elevated expression in febrile children with bacterial infection
We have shown that a RT-qPCR assay for a 2-transcript host expression signature (FAM89A and IFI44L genes) inferred from microarray data is able to efficiently separate viral from bacterial infections
Summary
A common practice in hospitals is to systematically administer antibiotics to febrile patients until the results from culture tests are available as preventive method, with the outcome that many viral infections are inadequately treated with anti-microbial drugs[1,2]. Www.nature.com/scientificreports expression microarrays, Herberg et al.[16] found two genes with different expression levels depending on the nature of the causative pathogen: Interferon Induced Protein 44 Like (IFI44L) gene is up-regulated in viral febrile children and, in contrast, Family with Sequence Similarity 89 Member A (FAM89A) gene has elevated expression in febrile children with bacterial infection. These biomarkers alone are capable of differentiating between bacterial and viral infections with high sensibility and specificity. A well optimized, cost- and time-effective qPCR-based protocol to discriminate between viral and bacterial infections could be implemented in the hospital molecular diagnostics laboratory routine
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