Human herpesvirus infections of the central nervous system: Laboratory diagnosis based on DNA detection by nested PCR in plasma and cerebrospinal fluid samples

Abstract

Infections of the central nervous systems (CNS) present a diagnostic problem for which an accurate laboratory diagnosis is essential. Invasive practices, such as cerebral biopsy, have been replaced by obtaining a polymerase chain reaction (PCR) diagnosis using cerebral spinal fluid (CSF) as a reference method. Tests on DNA extracted from plasma are noninvasive, thus avoiding all of the collateral effects and patient risks associated with CSF collection. This study aimed to determine whether plasma can replace CSF in nested PCR analysis for the detection of CNS human herpesvirus (HHV) diseases by analysing the proportion of patients whose CSF nested PCR results were positive for CNS HHV who also had the same organism identified by plasma nested PCR. In this study, CSF DNA was used as the "gold standard," and nested PCR was performed on both types of samples. Fifty-two patients with symptoms of nervous system infection were submitted to CSF and blood collection. For the eight HHV, one positive DNA result-in plasma and/or CSF nested PCR-was considered an active HHV infection, whereas the occurrence of two or more HHVs in the same sample was considered a coinfection. HHV infections were positively detected in 27/52 (51.9%) of the CSF and in 32/52 (61.5%) of the plasma, difference not significant, thus nested PCR can be performed on plasma instead of CSF. In conclusion, this findings suggest that plasma as a useful material for the diagnosis of cases where there is any difficulty to perform a CSF puncture.

Human herpesvirus multiplex ddPCR detection in brain tissue from low- and high-grade astrocytoma cases and controls

“…Several in-vitro studies indicate that HHV-6 may activate EBV expression, which might promote EBV-associated diseases later in life [ 43 , 44 ]. A 2015 study reported two encephalitis cases with HHV-6 and EBV co-infection detected by PCR [ 45 ]. However, the coinfection of these two herpesviruses in our case cohort cannot be seen as causal agents of the astrocytoma.…”

Fatal encephalitis accompanied by ARDS in a child with HSV Infection

“…Rimerio et al reported the detection of infection with various herpesvirus strains in plasma and CSF using nested PCR. Notably, they found that the sensitivity of this method was low for HSV‐1 and EBV, and its positive predictive value (PPV) was low for HSV‐1 and HSV‐2 . Thus, low molecular detection sensitivity may be the main reason for the negative HSV DNA results from blood and CSF in our report.…”

Arbovirus, herpesvirus, and enterovirus associated with neurological syndromes in adult patients of a university hospital, 2017-2018

“…The variations may be due to different groupings (which may include socioeconomic differences), the absence of active virus replication, or even methodological failure. HHV latency and the high serological prevalence found with this viral family do not reflect the active viral infection; therefore, the detection of latent particles can also influence the higher prevalence in some studies 2 , 3 , 21 , 43 , 44 .…”