Viral Molecular Testing of Cerebrospinal Fluid in Adults with Suspected Central Nervous System Infection in an Italian University Hospital Laboratory: A Retrospective Study on 1462 Consecutive Patients

Abstract

Background: Generally, about half of the patients with central nervous system infections cases remain unexplained. Therefore, we aimed to describe which viruses were detected in unselected patients with a suspected central nervous system infection and the first diagnostic workflow in a university hospital laboratory. Methods: A comprehensive virus testing in cerebrospinal fluid with an in-house real-time PCR method was employed. Determining how many and which viruses to test was at the full discretion of the treating physician. Results: 1462 patients were evaluated from 2011 to 2017 and 9 898 viral PCRs were made: 176 subjects (12%) had a positive result. There was great heterogeneity in the frequency of patients tested for each virus, ranging from 97.9% (1431 out of 1462) for herpes simplex virus (HSV) to 1.9% (28 out of 1462) for Parvovirus B19, positive in 1 patient. Enterovirus (EV) was the leading virus detected: the frequency was higher with respect to HSV (5.2% vs 2.4%, p=0.0004), varicella-zoster virus (VZV)(5.2% vs 2.9%, p=0.0052), human herpesvirus-6 (5.2% vs 1.7%, p=0.0014) and human herpesvirus-7 (HHV-7)(5.2% vs 2.5%, p=0.0406). Both VZV (83.5%) and HSV (97.9%) were tested significantly more than EV (68.7%, p<0.0001) and HHV-7 (24.1%, p<0.0001): the latter had a positivity comparable to HSV and it was detected in younger patients (median age 29 years), as for EV (median age 35 years). There was no difference found in the age of positive subjects with respect to negative ones for the other viruses tested. Conclusion: EV was the fifth virus frequently included in the diagnostic workflow but the most frequently detected, mostly in subjects aged less 40, as HHV-7 was. Testing these two viruses in all younger patients could reduce the number of unknown etiology.