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

2019 ◽  
Author(s):  
Siyuan Fan ◽  
Xiaojuan Wang ◽  
Yafang Hu ◽  
Jingping Shi ◽  
Yueli Zou ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Next Generation Sequencing ◽  
Bacterial Infections ◽  
Bacterial Species ◽  
Next Generation ◽  
Central Nervous System Infections ◽  
Varicella Zoster ◽  
Generation Sequencing

Abstract Background: Infectious encephalitis and meningitis are often treated empirically without identification of the causative pathogen, even if comprehensive conventional diagnostic technologies are applied. Metagenomic next-generation sequencing (mNGS) is a high throughput technology that enables the detection of pathogens independent of prior clinical or laboratory information.Methods: The present study was a multicentre prospective evaluation of mNGS of cerebrospinal fluid (CSF) for the diagnosis of suspected central nervous system infections in China, where routine PCR was not widely used. Results: A total of 276 patients were enrolled in this study between Jan 1, 2017 and Jan 1, 2018. Identification of an aetiologic pathogen in CSF by mNGS was achieved in 101 patients (36.6%). mNGS detected 11 bacterial species, 7 viral species, 2 fungal species, and 2 parasitic species. The leading positive detections were Mycobacterium tuberculosis (14), Listeria monocytogenes (8), Brucella (7), varicella-zoster virus (17), herpes simplex virus 1 (12), Epstein-Barr virus (12), and Cryptococcus neoformans (7). False positives occurred in 12 (4.3%) patients with bacterial infections known to be widespread in hospital environments. False negatives occurred in 16 (5.8%) patients and included bacterial, viral and fungal aetiologies. Conclusions: This study shows that mNGS of CSF is a powerful diagnostic method to identify the pathogen for many central nervous system infections. The result of mNGS should be interpreted with clinical information sometimes.

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

2019 ◽  
Author(s):  
Siyuan Fan ◽  
Xiaojuan Wang ◽  
Yafang Hu ◽  
Jingping Shi ◽  
Yueli Zou ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Next Generation Sequencing ◽  
Bacterial Infections ◽  
Bacterial Species ◽  
Next Generation ◽  
Central Nervous System Infections ◽  
Varicella Zoster ◽  
Generation Sequencing

ABSTRACTBackgroundInfectious encephalitis and meningitis are often treated empirically without identification of the causative pathogen. Metagenomic next-generation sequencing (mNGS) is a high throughput technology that enables the detection of pathogens independent of prior clinical or laboratory information.MethodsThe present study was a multicentre prospective evaluation of mNGS of cerebrospinal fluid (CSF) for the diagnosis of suspected central nervous system infections.ResultsA total of 276 patients were enrolled in this study between Jan 1, 2017 and Jan 1, 2018. Identification of an etiologic pathogen in CSF by mNGS was achieved in 101 patients (36.6%). mNGS detected 11 bacterial species, 7 viral species, 2 fungal species, and 2 parasitic species. The five leading positive detections were varicella-zoster virus (17), Mycobacterium tuberculosis (14), herpes simplex virus 1 (12), Epstein-Barr virus (12), and Cryptococcus neoformans (7). False positives occurred in 12 (4.3%) patients with bacterial infections known to be widespread in hospital environments. False negatives occurred in 16 (5.8%) patients and included bacterial, viral and fungal aetiologies.ConclusionsmNGS of CSF is a powerful diagnostic method to identify the pathogen for many central nervous system infections.

scholarly journals Metagenomic Next-generation Sequencing of Cerebrospinal Fluid for the Diagnosis of Central Nervous System infections in HIV-infected patients

2019 ◽  
Author(s):  
Nai qing Zheng ◽  
Pengle Guo ◽  
Xiejie Chen ◽  
Haolan He ◽  
Yueping Li ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Next Generation Sequencing ◽  
Clinical Diagnosis ◽  
Central Nervous System Infection ◽  
Next Generation ◽  
Central Nervous System Infections ◽  
Cns Infections ◽  
Conventional Methods ◽  
Generation Sequencing

Abstract Background HIV-infected patients have extremely low immunity and various opportunistic infections. Early diagnosis and treatment of these pathogens is critical for patients with HIV infection, especially those with central nervous system (CNS) infections. Metagenomic next generation sequencing (mNGS) has the advantage of identifying a broad range of pathogens and was suggested as a promising tool in the clinical diagnosis for infectious diseases. The clinical application of mNGS in the diagnosis of CNS infections in patients infected with HIV remains inadequately characterized.Methods We retrospectively analyzed data from 22 patients with suspected central nervous system infections who underwent both mNGS and conventional methods including culture, PCR, X-pert/RIF and antigen testing to explored the utility of mNGS in clinical diagnostic microbiology of CNS infections in HIV-infected patients.Results A total of 22 patients participated in the study between June 2018 and May 2019. The consistency of positive percentage of mNGS compared to clinical diagnosis was significantly higher than that of conventional methods (86.36% vs. 45.21%). The proportion of co-infections in mNGS positive samples was significantly higher than that in traditional methods (40.91% vs. 14.39%). Sixteen Extra Pathogens in 14 cases identified by metagenomic NGS only, 6 pathogens affected clinical reasoning and 7 pathogens guided antimicrobial therapy.Conclusions MNGS is a powerful diagnostic method for identifying pathogens in central nervous system infections and provide actionable information in some cases. MNGS technology has positive significance for the diagnosis and clinical treatment of central nervous system infection in HIV-infected patients.

Cerebrospinal Fluid Analysis for Viruses by Metagenomic Next-Generation Sequencing in Pediatric Encephalitis: Not Yet Ready for Prime Time?

2020 ◽  
pp. 088307382097223
Author(s):  
Guliz Erdem ◽  
Irina Kaptsan ◽  
Himanshu Sharma ◽  
Arvind Kumar ◽  
Shawn C. Aylward ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Next Generation Sequencing ◽  
Intracranial Hypertension ◽  
Immunocompromised Patient ◽  
Unknown Etiology ◽  
Next Generation ◽  
Viral Pathogens ◽  
Generation Sequencing

Background: Metagenomic next-generation sequencing offers an unbiased approach to identifying viral pathogens in cerebrospinal fluid of patients with meningoencephalitis of unknown etiology. Methods: In an 11-month case series, we investigated the use of cerebrospinal fluid metagenomic next-generation sequencing to diagnose viral infections among pediatric hospitalized patients presenting with encephalitis or meningoencephalitis of unknown etiology. Cerebrospinal fluid from patients with known enterovirus meningitis were included as positive controls. Cerebrospinal fluid from patients with primary intracranial hypertension were included to serve as controls without known infections. Results: Cerebrospinal fluid metagenomic next-generation sequencing was performed for 37 patients. Among 27 patients with encephalitis or meningoencephalitis, 4 were later diagnosed with viral encephalitis, 6 had non–central nervous system infections with central nervous system manifestations, 6 had no positive diagnostic tests, and 11 were found to have a noninfectious diagnosis. Metagenomic next-generation sequencing identified West Nile virus (WNV) in the cerebrospinal fluid of 1 immunocompromised patient. Among the 4 patients with known enterovirus meningitis, metagenomic next-generation sequencing correctly identified enteroviruses and characterized the viral genotype. No viral sequences were detected in the cerebrospinal fluid of patients with primary intracranial hypertension. Metagenomic next-generation sequencing also identified sequences of nonpathogenic torque Teno virus in cerebrospinal fluid specimens from 13 patients. Conclusions: Our results showed viral detection by cerebrospinal fluid metagenomic next-generation sequencing only in 1 immunocompromised patient and did not offer a diagnostic advantage over conventional testing. Viral phylogenetic characterization by metagenomic next-generation sequencing could be used in epidemiologic investigations of some viral pathogens, such as enteroviruses. The finding of torque Teno viruses in cerebrospinal fluid by metagenomic next-generation sequencing is of unknown significance but may merit further exploration for a possible association with noninfectious central nervous system disorders.

scholarly journals Metagenomic Next-Generation Sequencing for Pathogen Detection and Transcriptomic Analysis in Pediatric Central Nervous System Infections

2021 ◽  
Author(s):  
Nanda Ramchandar ◽  
Nicole G Coufal ◽  
Anna S Warden ◽  
Benjamin Briggs ◽  
Toni Schwarz ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Next Generation Sequencing ◽  
Usual Care ◽  
Transcriptomic Analysis ◽  
Cns Infection ◽  
Metagenomic Sequencing ◽  
Next Generation ◽  
Cns Infections ◽  
Generation Sequencing

Abstract Background Pediatric central nervous system (CNS) infections are potentially life-threatening and may incur significant morbidity. Identifying a pathogen is important, both in terms of guiding therapeutic management, but also in characterizing prognosis. Usual care testing by culture and PCR is often unable to identify a pathogen. We examined the systematic application of metagenomic next-generation sequencing (mNGS) for detecting organisms and transcriptomic analysis of cerebrospinal fluid (CSF) in children with CNS infections. Methods We conducted a prospective multi-site study that aimed to enroll all children with a CSF pleocytosis and suspected CNS infection admitted to one of three tertiary pediatric hospitals during the study timeframe. After usual care testing had been performed, the remaining CSF was sent for mNGS and transcriptomic analysis. Results We screened 221 and enrolled 70 subjects over a 12-month recruitment period. A putative organism was isolated from CSF in 25 (35.7%) subjects by any diagnostic modality. mNGS of the CSF samples identified a pathogen in 20 (28.6%) subjects, which were also all identified by usual care testing. The median time to result was 38 hours. Conclusion Metagenomic sequencing of CSF has the potential to rapidly identify pathogens in children with CNS infections.

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