scholarly journals The Performance of Metagenomic Next-Generation Sequencing In Suspected Central Nervous System Infection

2021 ◽  
Author(s):  
Li Liu ◽  
Yamin Yu ◽  
Yi Shi ◽  
Xin Su
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Next Generation Sequencing ◽  
Predictive Value ◽  
Central Nervous System Infection ◽  
Positive Case ◽  
Next Generation ◽  
Negative Case ◽  
Conventional Methods ◽  
Generation Sequencing

Abstract Background: To explore the performance of metagenomic next-generation sequencing (mNGS) technology in patients of suspected central nervous system infection.Methods: From January 2018 to March 2021, 75 cases were enrolled in this retrospective analysis at Hunan Provincial People’s Hospital. The clinical data of patients with suspected central nervous system infection who underwent cerebrospinal fluid mNGS were analyzed. The performances of mNGS were compared with the conventional methods.Result: The sensitivity of mNGS, culture and smear in the diagnosis of 75 patients were 55%, 4.4%, 6.7%; theirs’specificity were 54.3%, 100%, 100%; theirs’ positive predictive value (PPV ) were 57.9%, 100%, 100%; theirs’negative predictive value (NPV) were 51.4%, 41.4%, 41.7%, respectively. There was 41(54.6%) cases whose mNGS results were consistent with the final diagnosis. 22(29.3%) mNGS results were considered as both mNGS positive/Case consistent; 19( 25.3%) mNGS results were considered as both mNGS negative/Case consistent; 18(24%) mNGS results were considered as both mNGS positive/Case inconsistent; 16(21.3%) mNGS results were considered as both mNGS negative/Case inconsistent. mNGS identified 35 irrelavant pathogens in this study.Conclusion: mNGS showed a high sensitivity compared to conventional methods. There are still several challenges in clinical application. It is necessary to establish unified and effective standards for interpreting mNGS results.

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.

scholarly journals Case Report: Metagenomic Next-Generation Sequencing Confirmed a Case of Central Nervous System Infection With Brucella melitensis in Non-endemic Areas

2021 ◽  
Vol 8 ◽  
Author(s):  
Jun Cao ◽  
Qingqing Cai ◽  
Wentao Su ◽  
Zi Ge ◽  
Hui Zhao ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Next Generation Sequencing ◽  
Brucella Melitensis ◽  
Quantitative Polymerase Chain Reaction ◽  
Central Nervous System Infection ◽  
Cns Infection ◽  
Next Generation ◽  
Endemic Areas ◽  
Generation Sequencing

Brucellosis is a highly contagious zoonotic disease caused by bacteria that belong to the genus Brucella. It is a major endemic disease in northern China. We reported a rare case of central nervous system (CNS) infection caused by Brucella melitensis in a patient living in non-endemic areas. The medical history of the patient included chronic headache and trunk numbness. Based on the presented clinical symptoms and medical examinations, a clinical diagnosis of binocular uveo-encephalitis was made in the local hospital. The patient's symptoms were unrelieved after being treated with empiric therapy. Soon after, the patient was admitted to our hospital because of the obnubilation and coma in the trip. We ran a few examinations and sent the cerebrospinal fluid (CSF) for metagenomic next-generation sequencing (mNGS) immediately. The Magnetic resonance imaging (MRI) examination was unremarkable, and bilateral mastoid inflammation was attached. Metagenomic next-generation sequencing suggested a CNS infection caused by Brucella melitensis. Then, the results of the serum agglutination test and quantitative polymerase chain reaction assay also confirmed that. After being treated with doxycycline, rifampin, and cefatriaxone, consciousness of the patient was restored and headache diminished. Two months later, a lumbar puncture was used to check the pressure of the CSF, and the total course of treatment was more than 6 months. This case highlighted the potential value of mNGS in early clinal diagnosis. We believe that mNGS may be a complementary method for rapid identification of infection of CNS caused by the pathogen.

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.

scholarly journals 342. Clinical Utility of a Next Generation Sequencing Test for Pathogen Detection in Pediatric Central Nervous System Infections

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S241-S241
Author(s):  
Nanda Ramchandar ◽  
Jennifer Foley ◽  
Claudia Enriquez ◽  
Stephanie Osborne ◽  
Antonio Arrieta ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Next Generation Sequencing ◽  
Standard Care ◽  
Cns Infection ◽  
Next Generation ◽  
Diagnostic Modality ◽  
Cns Infections ◽  
Pcr Multiplex ◽  
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. However, standard care testing by culture, serology, and PCR is often unable to identify a pathogen. We examined use of next generation sequencing (NGS) of cerebrospinal fluid (CSF) in detecting an organism in children with CNS infections. Methods We prospectively enrolled children with CSF pleocytosis and suspected CNS infection admitted to 3 tertiary pediatric hospitals. After standard care testing had been performed, the remaining CSF was submitted for analysis by NGS. Results We enrolled 70 subjects over a 12-month recruitment period. A putative organism was isolated from CSF in 24 (34.3%) subjects by any diagnostic modality. NGS of the CSF samples identified a pathogen in 20 (28.6%) subjects. False positive results by NGS were identified in 2 patients. There were no cases in which NGS alone identified a pathogen. In 4 cases, a putative organism was recovered by standard care testing of the CSF, but not by CSF NGS. CSF culture recovered a putative organism in 12 cases (12.1%). A CSF PCR multiplex panel was utilized for 51 subjects. An organism was detected in 15 of these (29.4%). Using a reference composite of standard care testing, we determined the sensitivity and specificity of CSF NGS to be 83.3% (95% CI, 62.6–95.3%) and 91.3% (95% CI, 79.2–97.6%) respectively. Conclusion Sequencing of CSF has the potential to rapidly and comprehensively identify infection with a single test. Further studies are needed to determine the optimal use of NGS for diagnosis of CNS infections. Disclosures All Authors: No reported disclosures

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.

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