Next-Generation Sequencing of Cerebrospinal Fluid for the Diagnosis of Neurocysticercosis

Abstract

Background: Neurocysticercosis (NCC) is the most common helminthic infection of the central nervous system (CNS). The diagnosis of NCC is sometimes challenging due to its heterogenous clinical manifestations and the variable sensitivity and specificity of neuroimaging and serological tests.Methods: Next-generation sequencing (NGS) of cerebrospinal fluid (CSF) was used to detect pathogens in patients with clinically suspected CNS infections. A series of patients diagnosed with NCC is reviewed here.Results: Using NGS of CSF, four patients were diagnosed with NCC. The reads corresponding to Taenia solium ranged from 478 to 117,362, with genomic coverage of 0.0564–11.15%. Reads corresponding to T. solium were not found in non-template controls and far exceeded those of the background microorganisms in patients with NCC, facilitating the interpretation of the NGS results.Conclusions: This case series demonstrates that NGS of CSF is promising in the diagnosis of NCC in difficult to diagnose cases. Larger studies are needed in the future.

Metagenomic Next-generation Sequencing of Cerebrospinal Fluid for the Diagnosis of Central Nervous System Infections: A Multicentre Prospective Study

“…Importantly, mNGS can detect unsuspected pathogens that clinicians may fail to consider because of atypical clinical manifestations. Many cases of neurological infections have been unexpectedly diagnosed by mNGS of CSF 11,22,29,30 similar to the present study for the cases of L. monocytogenes , Brucella and T. solium 12–14 . In addition, as demonstrated in previous studies 10,20,21 and in the present study for the case of encephalitis caused by Suid herpesvirus 1 31 , mNGS of CSF has the ability to identify novel aetiologies of CNS infections.…”

Metagenomic Next-generation Sequencing of Cerebrospinal Fluid for the Diagnosis of Central Nervous System Infections: A Multicentre Cohort Study

“…Importantly, mNGS can detect unsuspected pathogens that clinicians may fail to consider because of atypical clinical manifestations. Many cases of neurological infections have been unexpectedly diagnosed by mNGS of CSF [11,22,29,30] similar to the present study for the cases of L. monocytogenes, Brucella and T. solium [12][13][14]. In addition, as demonstrated in previous studies [10,20,21] and in the present study for the case of encephalitis caused by Suid herpesvirus 1 [31], mNGS of CSF has the ability to identify novel aetiologies of CNS infections.…”

“…Compared with traditional individual target-specific tests, mNGS can identify pathogens without the input of clinical predictors or prior laboratory results. Several recent studies have demonstrated the capability of mNGS of CSF to identify known and unsuspected pathogens and to discover new microorganisms [10][11][12][13][14][15][16][17][18]. mNGS of CSF is being increasingly utilized in routine clinical settings for the rapid diagnosis of central nervous system infections.…”

“…mNGS of CSF is being increasingly utilized in routine clinical settings for the rapid diagnosis of central nervous system infections. However, most published studies are retrospective case reports or case series [11][12][13][14][15][16][17][19][20][21][22][23][24], and thus, large prospective studies are needed to demonstrate the clinical impact and cost-effectiveness of mNGS for the diagnosis of meningitis and encephalitis. We undertook a multicentre prospective study to comprehensively evaluate the performance of mNGS of CSF for the diagnosis of central nervous system (CNS) infections compared to conventional microbiological methodologies.…”

Clinicopathology conference: 41‐year‐old woman with chronic relapsing meningitis

“…This case thus highlights the utility of mNGS for the diagnosis of atypical presentations of common infections. 24,68,69 The case also vividly illustrates that either improvement or lack of clinical deterioration in the setting of immunosuppression does not rule out an underlying infectious etiology, even after years of treatment.…”