Diagnostic accuracy of VIDISCA-NGS in patients with suspected central nervous system infections

I.E Van Zeggeren,A.W.D Edridge,D Van De Beek,M Deijs,S.M Koekkoek,K.C Wolthers,L Van Der Hoek,M.C Brouwer

doi:10.1016/j.cmi.2020.06.012

Abstract

ObjectivesConfirming the diagnosis in viral central nervous system (CNS) infections can be difficult with the currently available diagnostic tools. Virus discovery cDNA-amplified fragment length polymorphism next-generation sequencing (VIDISCA-NGS) is a promising viral metagenomic technique that enables the detection of all viruses in a single assay. We performed a retrospective study on the diagnostic accuracy of VIDISCA-NGS in cerebrospinal fluid (CSF) of individuals with suspected CNS infections. MethodsConsecutive adult patients presenting to the Emergency Department or inpatients, who underwent a lumbar puncture for the suspicion of a CNS infection, were included if they were diagnosed with a viral CNS infection, or if a viral CNS infection was initially suspected but eventually a different diagnosis was made. A quantitative PCR panel of the most common causative viruses was performed on CSF of these patients as reference standard and compared with the results of VIDISCA-NGS, the index test. ResultsWe included 38 individuals with viral CNS infections and 35 presenting with suspected CNS infection for whom an alternative aetiology was finally established. Overall sensitivity and specificity were 52% (95% CI 31%–73%) and 100% (95% CI 91%–100%), respectively. One enterovirus, detected by VIDISCA-NGS, was only identified by quantitative PCR upon retesting. Additional viruses identified by VIDISCA-NGS consisted of GB virus C, human papillomavirus, human mastadenovirus C, Merkel cell polyoma virus and anelloviruses. ConclusionIn patients for whom routine diagnostics do not yield a causative pathogen, VIDISCA-NGS can be of additional value as it can detect a broader range of viruses, but it does not perform well enough to replace quantitativePCR.

Highlights

Viral central nervous system (CNS) infections have been asso ciated with substantial morbidity and mortality depending on the causative pathogen [1]
In the current study we examined the diagnostic accuracy of VIDISCA NGS on a cohort of patients with suspected CNS infections [2]
Of the 363 episodes included in the cohort (Figs. 1), 45 were clinically diagnosed as viral CNS infection

Summary

Introduction

Viral central nervous system (CNS) infections have been asso ciated with substantial morbidity and mortality depending on the causative pathogen [1]. Confirming the diagnosis can be difficult in individuals suspected of a CNS infection because the differential diagnosis is broad. A substantial proportion of individuals who are initially suspected of a CNS infection turn out to have a different diagnosis, including inflammatory diseases, epilepsy or stroke [2]. In individuals with a clinical diagnosis of a viral CNS infection, no causative virus can be identified in 35%e42% [1e3]. As part of routine diagnostics for CNS infections, a selection of viruses is tested using quantitative PCR (qPCR), currently the reference standard for the majority of the most common viruses causing CNS infection [4]. Alternative diagnostic assays, which allow detection of a broader range of viruses, are desirable, but currently not routinely available [4]

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Conclusion