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Buddle S, Torres O, Morfopoulou S, Breuer J, Brown JR. The use of metagenomics to enhance diagnosis of encephalitis. Expert Rev Mol Diagn 2025:1-18. [PMID: 40329854 DOI: 10.1080/14737159.2025.2500655] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2024] [Accepted: 04/07/2025] [Indexed: 05/08/2025]
Abstract
INTRODUCTION Encephalitis has a broad etiology, including infectious and auto-immune causes. In infectious encephalitis, the breadth of causative organisms results in incomplete testing and low diagnostic yields.Metagenomics sequences all DNA and RNA allowing untargeted detection of all organisms in a single specimen; this is of particular use in diagnosis of encephalitis with a broad etiology. AREAS COVERED We review the literature and discuss metagenomics workflows, host depletion and pathogen enrichment methods, bioinformatics analysis and potential analysis of the host transcriptome to aid diagnosis. We discuss the clinical use of metagenomics for diagnosis of neurological infection including time to result, cost, quality assurance, patient cohorts in whom metagenomics adds the most value, recommended specimen types, limitations and review published cases in which metagenomics has been used to diagnose encephalitis. EXPERT OPINION There is good evidence for the utility of metagenomics to diagnose infection in encephalitis. Due to infections with rare, unexpected or novel pathogens, metagenomics adds most value to diagnosis in immunocompromised patients and the greatest diagnostic yield is in brain biopsies. Technical advances are needed to reduce the complexity, cost and time to result which will enable wider adoption in clinical laboratories and use as a first-line test.
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Affiliation(s)
- Sarah Buddle
- Infection, Immunity and Inflammation Department, Great Ormond Street Institute of Child Health, University College London, London, UK
| | - Oscar Torres
- Infection, Immunity and Inflammation Department, Great Ormond Street Institute of Child Health, University College London, London, UK
| | - Sofia Morfopoulou
- Infection, Immunity and Inflammation Department, Great Ormond Street Institute of Child Health, University College London, London, UK
| | - Judith Breuer
- Infection, Immunity and Inflammation Department, Great Ormond Street Institute of Child Health, University College London, London, UK
- Department of Microbiology, Virology and Infection Prevention & Control, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK
| | - Julianne R Brown
- Department of Microbiology, Virology and Infection Prevention & Control, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK
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He J, Chen Y, Jiang Z, Li F, Zhu M, Xu Z, Wang M, Tang M, Wu Y, Li Y. Diagnostic value of metagenomic next-generation sequencing in detecting Pneumocystis jirovecii pneumonia in HIV-infected patients. Front Med (Lausanne) 2025; 12:1567484. [PMID: 40206488 PMCID: PMC11978654 DOI: 10.3389/fmed.2025.1567484] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2025] [Accepted: 03/11/2025] [Indexed: 04/11/2025] Open
Abstract
Introduction Accurate diagnosis of Pneumocystis jirovecii pneumonia (PJP) in HIV patients remains challenging. This study compares metagenomic next-generation sequencing (mNGS) with PCR, GMS staining, and serum β-D-glucan (BG) assays for PJP detection and co-infection identification. Methods BALF samples from 34 HIV-positive PJP patients and 50 non-PJP controls were analyzed. Diagnostic performance metrics (sensitivity, specificity, NPV, AUC) and co-pathogen profiles were evaluated for mNGS versus conventional methods. Results mNGS and PCR both achieved 100% sensitivity. mNGS showed higher specificity (91.3% vs. 88%) and AUC (0.898 vs. 0.940 for PCR). Co-infections were detected in 67.6% of PJP cases by mNGS, including cytomegalovirus (41.2%), Epstein-Barr virus (29.4%), and non-tuberculous mycobacteria (14.7%). GMS and BG assays exhibited lower sensitivity (64.7% and 76.5%, respectively). Discussion mNGS offers superior specificity, accuracy, and co-infection detection compared to traditional methods. Its high NPV (100%) supports clinical utility in ruling out PJP. While resource-intensive, mNGS is a promising first-line diagnostic tool for HIV-associated PJP, particularly in polymicrobial infection settings.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | - Yang Li
- Hangzhou Xixi Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, China
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Lin F. Tuberculous meningitis diagnosis and treatment: classic approaches and high-throughput pathways. Front Immunol 2025; 15:1543009. [PMID: 39867878 PMCID: PMC11757110 DOI: 10.3389/fimmu.2024.1543009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2024] [Accepted: 12/24/2024] [Indexed: 01/28/2025] Open
Abstract
Tuberculous meningitis (TBM), a severe form of non-purulent meningitis caused by Mycobacterium tuberculosis (Mtb), is the most critical extrapulmonary tuberculosis (TB) manifestation, with a 30-40% mortality rate despite available treatment. The absence of distinctive clinical symptoms and effective diagnostic tools complicates early detection. Recent advancements in nucleic acid detection, genomics, metabolomics, and proteomics have led to novel diagnostic approaches, improving sensitivity and specificity. This review focuses on nucleic acid-based methods, including Xpert Ultra, metagenomic next-generation sequencing (mNGS), and single-cell sequencing of whole brain Tissue, alongside the diagnostic potential of metabolomic and proteomic biomarkers. By evaluating the technical features, diagnostic accuracy, and clinical applicability, this review aims to inform the optimization of TBM diagnostic strategies and explores the integration and clinical translation of multi-omics technologies.
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Affiliation(s)
- Fangbo Lin
- Rehabilitation Medicine Department, The Affiliated Changsha Hospital of Xiangya School
of Medicine, Central South University (The First Hospital of Changsha, Changsha, China
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4
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Huang SS, Qiu JY, Li SP, Ma YQ, He J, Han LN, Jiao LL, Xu C, Mao YM, Zhang YM. Microbial signatures predictive of short-term prognosis in severe pneumonia. Front Cell Infect Microbiol 2024; 14:1397717. [PMID: 39157177 PMCID: PMC11327560 DOI: 10.3389/fcimb.2024.1397717] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2024] [Accepted: 07/15/2024] [Indexed: 08/20/2024] Open
Abstract
Objective This retrospective cohort study aimed to investigate the composition and diversity of lung microbiota in patients with severe pneumonia and explore its association with short-term prognosis. Methods A total of 301 patients diagnosed with severe pneumonia underwent bronchoalveolar lavage fluid metagenomic next-generation sequencing (mNGS) testing from February 2022 to January 2024. After applying exclusion criteria, 236 patients were included in the study. Baseline demographic and clinical characteristics were compared between survival and non-survival groups. Microbial composition and diversity were analyzed using alpha and beta diversity metrics. Additionally, LEfSe analysis and machine learning methods were employed to identify key pathogenic microorganism associated with short-term mortality. Microbial interaction modes were assessed through network co-occurrence analysis. Results The overall 28-day mortality rate was 37.7% in severe pneumonia. Non-survival patients had a higher prevalence of hypertension and exhibited higher APACHE II and SOFA scores, higher procalcitonin (PCT), and shorter hospitalization duration. Microbial α and β diversity analysis showed no significant differences between the two groups. However, distinct species diversity patterns were observed, with the non-survival group showing a higher abundance of Acinetobacter baumannii, Klebsiella pneumoniae, and Enterococcus faecium, while the survival group had a higher prevalence of Corynebacterium striatum and Enterobacter. LEfSe analysis identified 29 distinct terms, with 10 potential markers in the non-survival group, including Pseudomonas sp. and Enterococcus durans. Machine learning models selected 16 key pathogenic bacteria, such as Klebsiella pneumoniae, significantly contributing to predicting short-term mortality. Network co-occurrence analysis revealed greater complexity in the non-survival group compared to the survival group, with differences in central genera. Conclusion Our study highlights the potential significance of lung microbiota composition in predicting short-term prognosis in severe pneumonia patients. Differences in microbial diversity and composition, along with distinct microbial interaction modes, may contribute to variations in short-term outcomes. Further research is warranted to elucidate the clinical implications and underlying mechanisms of these findings.
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Affiliation(s)
- Shen-Shen Huang
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, China
| | - Jia-Yong Qiu
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, China
- Department of Respiratory and Critical Care Medicine, The Second Hospital of Hebei Medical University, Shijiazhuang, China
| | - Shuang-Ping Li
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, China
| | - Ya-Qing Ma
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, China
| | - Jun He
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, China
| | - Li-Na Han
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, China
| | - Long-Long Jiao
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, China
| | - Chong Xu
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, China
| | - Yi-Min Mao
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, China
| | - Yong-Mei Zhang
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, China
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Zou S, Chen Z, Tan Y, Tan M, Guo W, Wu S, Liu J, Song S, Peng Y, Wang M, Liang K. Microbiomes detected by cerebrospinal fluid metagenomic next-generation sequencing among patients with and without HIV with suspected central nervous system infection. HIV Med 2024; 25:794-804. [PMID: 38515324 DOI: 10.1111/hiv.13634] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2023] [Accepted: 03/02/2024] [Indexed: 03/23/2024]
Abstract
BACKGROUND Opportunistic infections in the central nervous system (CNS) can be a serious threat to people living with HIV. Early aetiological diagnosis and targeted treatment are crucial but difficult. Metagenomic next-generation sequencing (mNGS) has significant advantages over traditional detection methods. However, differences in the cerebrospinal fluid (CSF) microbiome profiles of patients living with and without HIV with suspected CNS infections using mNGS and conventional testing methods have not yet been adequately evaluated. METHODS We conducted a retrospective cohort study in the first hospital of Changsha between January 2019 and June 2022 to investigate the microbiomes detected using mNGS of the CSF of patients living with and without HIV with suspected CNS infections. The pathogens causing CNS infections were concurrently identified using both mNGS and traditional detection methods. The spectrum of pathogens identified was compared between the two groups. RESULTS Overall, 173 patients (140 with and 33 without HIV) with suspected CNS infection were enrolled in our study. In total, 106 (75.7%) patients with and 16 (48.5%) patients without HIV tested positive with mNGS (p = 0.002). Among the enrolled patients, 71 (50.7%) with HIV and five (15.2%) without HIV tested positive for two or more pathogens (p < 0.001). Patients with HIV had significantly higher proportions of fungus (20.7% vs. 3.0%, p = 0.016) and DNA virus (59.3% vs. 21.2%, p < 0.001) than those without HIV. Epstein-Barr virus (33.6%) was the most commonly identified potential pathogen in the CSF of patients living with HIV using mNGS, followed by cytomegalovirus (20.7%) and torque teno virus (13.8%). The top three causative pathogens identified in patients without HIV were Streptococcus (18.2%), Epstein-Barr virus (12.1%), and Mycobacterium tuberculosis (9.1%). In total, 113 patients living with HIV were diagnosed as having CNS infections. The rate of pathogen detection in people living with HIV with a CNS infection was significantly higher with mNGS than with conventional methods (93.8% vs. 15.0%, p < 0.001). CONCLUSION CSF microbiome profiles differ between patients living with and without HIV with suspected CNS infection. mNGS is a powerful tool for the diagnosis of CNS infection among people living with HIV, especially in those with mixed infections.
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Affiliation(s)
- Shi Zou
- Department of Infectious Diseases, Zhongnan Hospital of Wuhan University, Wuhan, China
- Wuhan Research Center for Infectious Diseases and Cancer, Chinese Academy of Medical Sciences, Wuhan, China
| | - Zhong Chen
- The Institute of HIV/AIDS, The First Hospital of Changsha, Changsha, China
| | - Yuting Tan
- Department of Infectious Diseases, Zhongnan Hospital of Wuhan University, Wuhan, China
- Wuhan Research Center for Infectious Diseases and Cancer, Chinese Academy of Medical Sciences, Wuhan, China
| | - Miao Tan
- Department of Infectious Diseases, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Wei Guo
- Department of Pathology, Zhongnan Hospital of Wuhan University, Wuhan, China
- Department of Pathology, School of Basic Medical Sciences, Wuhan University, Wuhan, China
| | - Songjie Wu
- Wuhan Research Center for Infectious Diseases and Cancer, Chinese Academy of Medical Sciences, Wuhan, China
- Department of Nosocomial Infection Management, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Jie Liu
- Department of Infectious Diseases, Zhongnan Hospital of Wuhan University, Wuhan, China
- Wuhan Research Center for Infectious Diseases and Cancer, Chinese Academy of Medical Sciences, Wuhan, China
| | - Shihui Song
- Department of Infectious Diseases, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Yongquan Peng
- Graduate Collaborative Training Base of the First Hospital of Changsha, Hengyang Medical School, Uni-versity of South China, Hengyang, China
| | - Min Wang
- The Institute of HIV/AIDS, The First Hospital of Changsha, Changsha, China
| | - Ke Liang
- Department of Infectious Diseases, Zhongnan Hospital of Wuhan University, Wuhan, China
- Wuhan Research Center for Infectious Diseases and Cancer, Chinese Academy of Medical Sciences, Wuhan, China
- Department of Nosocomial Infection Management, Zhongnan Hospital of Wuhan University, Wuhan, China
- Hubei Engineering Center for Infectious Disease Prevention, Control and Treatment, Wuhan, China
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Sun J, Han X, Yan H, Zhang X, Jiang T, Zhang T, Wu H, Kaminskiy G, Ma Y, Karamov E, Su B. Advances in technology for the laboratory diagnosis of individuals with HIV/AIDS coinfected with Mycobacterium tuberculosis. BIOSAFETY AND HEALTH 2024; 6:133-142. [PMID: 40078723 PMCID: PMC11895006 DOI: 10.1016/j.bsheal.2024.04.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2023] [Revised: 04/22/2024] [Accepted: 04/25/2024] [Indexed: 03/14/2025] Open
Abstract
The high morbidity and mortality rate of individuals with human immunodeficiency virus (HIV) / acquired immunodeficiency syndrome (AIDS) coinfected with Mycobacterium tuberculosis (MTB) is a tough challenge for current global tuberculosis prevention and control efforts. HIV/MTB coinfection is more complex than a single infection, and the interaction between the two diseases aggravates the deterioration caused by the disease, resulting in increased hospitalizations and deaths. Rapid screening and early diagnosis facilitate the timely initiation of anti-tuberculosis treatment in HIV/MTB coinfected individuals, thereby reducing transmission and the incidence of adverse prognoses. To date, pathogenic detection has remained the gold standard for diagnosing tuberculosis, but its sensitivity and specificity are greatly affected by the body's immune status, which limits its application in the diagnosis of HIV/MTB coinfection. Recently, immunology and molecular detection technology has developed rapidly. New detection technologies, such as interferon-γ release assays, interferon-gamma inducible protein 10, and GeneXpert MTB/RIF assay have overcome the limitations of traditional detection methods, significantly improved the sensitivity and specificity of tuberculosis diagnosis, and brought new hope to the detection of HIV/MTB coinfection. In this article, the principle, scope of application, and latest research progress of relevant detection methods are reviewed to provide a reference for the early diagnosis of HIV/MTB coinfection.
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Affiliation(s)
- Jin Sun
- Beijing Key Laboratory for HIV/AIDS Research, Clinical and Research Center for Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing 100069, China
| | - Xiaoxu Han
- Beijing Key Laboratory for HIV/AIDS Research, Clinical and Research Center for Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing 100069, China
| | - Hongxia Yan
- Beijing Key Laboratory for HIV/AIDS Research, Clinical and Research Center for Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing 100069, China
| | - Xin Zhang
- Beijing Key Laboratory for HIV/AIDS Research, Clinical and Research Center for Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing 100069, China
| | - Taiyi Jiang
- Beijing Key Laboratory for HIV/AIDS Research, Clinical and Research Center for Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing 100069, China
| | - Tong Zhang
- Beijing Key Laboratory for HIV/AIDS Research, Clinical and Research Center for Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing 100069, China
| | - Hao Wu
- Beijing Key Laboratory for HIV/AIDS Research, Clinical and Research Center for Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing 100069, China
| | - Grigory Kaminskiy
- State Health Organization Tula Regional Center for Control and Prevention of AIDS and Infectious Diseases, Tula 300002, Russia
| | - Yingmin Ma
- Department of Respiratory and Critical Care Medicine, Beijing Youan Hospital, Capital Medical University, Beijing 100069, China
| | - Eduard Karamov
- Gamaleya National Research Centre for Epidemiology and Microbiology of the Ministry of Health of the Russian Federation, Moscow 123098, Russia
| | - Bin Su
- Beijing Key Laboratory for HIV/AIDS Research, Clinical and Research Center for Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing 100069, China
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Yang X, Zhou S, Chang Z, Xi X, Li J, Miao M, Chen Y, Chen W, Zhang H, Ding R, Hu Z. Nanopore targeted sequencing-based diagnosis of central nervous system infections in HIV-infected patients. Ann Clin Microbiol Antimicrob 2024; 23:22. [PMID: 38424544 PMCID: PMC10905896 DOI: 10.1186/s12941-024-00682-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2023] [Accepted: 02/19/2024] [Indexed: 03/02/2024] Open
Abstract
BACKGROUND Early and accurate etiological diagnosis is very important for improving the prognosis of central nervous system (CNS) infections in human immunodeficiency virus (HIV)-infected patients. The goal is not easily achieved by conventional microbiological tests. We developed a nanopore targeted sequencing (NTS) platform and evaluated the diagnostic performance for CNS infections in HIV-infected patients, with special focus on cryptococcal meningitis (CM). We compared the CM diagnostic performance of NTS with conventional methods and cryptococcal polymerase chain reaction (PCR). METHODS This study included 57 hospitalized HIV-infected patients with suspected CNS infections from September 2018 to March 2022. The diagnosis established during hospitalization includes 27 cases of CM, 13 CNS tuberculosis, 5 toxoplasma encephalitis, 2 cytomegalovirus (CMV) encephalitis and 1 Varicella-zoster virus (VZV) encephalitis. The 2 cases of CMV encephalitis also have co-existing CM. Target-specific PCR amplification was used to enrich pathogen sequences before nanopore sequencing. NTS was performed on stored cerebrospinal fluid (CSF) samples and the results were compared with the diagnosis during hospitalization. RESULTS 53 (93.0%) of the patients were male. The median CD4 cell count was 25.0 (IQR: 14.0-63.0) cells/uL. The sensitivities of CSF culture, India ink staining, cryptococcal PCR and NTS for CM were 70.4% (95%CI: 51.5 - 84.1%), 76.0% (95%CI: 56.6 - 88.5%), 77.8% (59.2 - 89.4%) and 85.2% (95%CI: 67.5 - 94.1%), respectively. All those methods had 100% specificity for CM. Our NTS platform could identify Cryptococcus at species level. Moreover, NTS was also able to identify all the 5 cases of toxoplasma encephalitis, 2 cases of CMV encephalitis and 1 VZV encephalitis. However, only 1 of 13 CNS tuberculosis cases was diagnosed by NTS, and so did Xpert MTB/RIF assay. CONCLUSIONS NTS has a good diagnostic performance for CM in HIV-infected patients and may have the ability of simultaneously detecting other pathogens, including mixed infections. With continuing improving of the NTS platform, it may be a promising alterative microbiological test for assisting with the diagnosis of CNS infections.
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Affiliation(s)
- Xihong Yang
- Department of Infectious Disease, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, China
| | - Shuilian Zhou
- State Key Laboratory of Neurology and Oncology Drug Development, Jiangsu Simcere Pharmaceutical Co.,Ltd, Jiangsu Simcere Diagnostics Co.,Ltd., Nanjing, China
- Nanjing Simcere Medical Laboratory Science Co., Ltd., Nanjing, China
| | - Ziwei Chang
- Department of Infectious Disease, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, China
| | - Xiaotong Xi
- State Key Laboratory of Neurology and Oncology Drug Development, Jiangsu Simcere Pharmaceutical Co.,Ltd, Jiangsu Simcere Diagnostics Co.,Ltd., Nanjing, China
- Nanjing Simcere Medical Laboratory Science Co., Ltd., Nanjing, China
| | - Jiahui Li
- Department of Infectious Disease, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, China
| | - Mengjiao Miao
- Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Yaling Chen
- Department of Infectious Disease, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, China
| | - Wei Chen
- Clinical Research Center, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, China
| | - Hongying Zhang
- Nanjing Center for Disease Control and Prevention, Nanjing Medical University, Nanjing, China.
| | - Ran Ding
- State Key Laboratory of Neurology and Oncology Drug Development, Jiangsu Simcere Pharmaceutical Co.,Ltd, Jiangsu Simcere Diagnostics Co.,Ltd., Nanjing, China.
- Nanjing Simcere Medical Laboratory Science Co., Ltd., Nanjing, China.
| | - Zhiliang Hu
- Department of Infectious Disease, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, China.
- Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China.
- Inovention Center for Infectious Disease of Jiangsu Province, Nanjing, China.
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Zhang M, Chen L, Zhao H, Qiao T, Jiang L, Wang C, Zhong X, Li X, Xu Y. Metagenomic next-generation sequencing for diagnosis of infectious encephalitis and meningitis: a retrospective study of 90 patients. Neurol Res 2024; 46:187-194. [PMID: 37931016 DOI: 10.1080/01616412.2023.2265243] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2022] [Accepted: 09/24/2023] [Indexed: 11/08/2023]
Abstract
BACKGROUND Infections of the central nervous system (CNS) are potentially life-threatening and can cause serious morbidity. We evaluated the clinical value of metagenomic next-generation sequencing (mNGS) in the diagnosis of infectious encephalitis and meningitis and explored the factors affecting the results of mNGS. METHODS Patients with suspected cases of encephalitis or meningitis who presented in Northern Jiangsu People's Hospital from 1 March 2018 to 30 September 2022 were collected. Demographic, historical, and clinical information were obtained, and cerebrospinal fluid (CSF) samples were treated with mNGS. The pathogen was identified using National Center for Biotechnology Information (NCBI) GenBank sequence data. RESULTS Ninety-six patients were screened and finally 90 subjects enrolled. Of the 90 enrolled cases, 67 (74.4%) were diagnosed with central nervous system infections, which included 48 cases (71.6%) of viral infection, 11 (12.2%) of bacterial infection, 5 (7.5%) of mycobacterium tuberculosis, 2 (3.0%) of fungal infection, and 1 (1.5%) of rickettsia infection. From these cases, mNGS identified 40 (44.4%) true-positive cases, 3 (3.3%) false-positive case, 22 (24.4%) true-negative cases, and 25 (27.8%) false-negative cases. The sensitivity and specificity of mNGS were 61.5% and 88%, respectively. mNGS of CSF could show a higher positive rate in patients with marked CSF abnormalities, including elevated protein concentrations and monocyte counts. CONCLUSION mNGS of CSF is an effective method for detecting infectious encephalitis and meningitis, and the results should be analyzed combined with conventional microbiological testing results.
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Affiliation(s)
- Mengling Zhang
- Department of Neurology, Northern Jiangsu People's Hospital, Clinical Medical College of Yangzhou University, Yangzhou, China
| | - Lanlan Chen
- Department of Neurology, Northern Jiangsu People's Hospital, Clinical Medical College of Yangzhou University, Yangzhou, China
| | - Haina Zhao
- Department of Neurology, Northern Jiangsu People's Hospital, Clinical Medical College of Yangzhou University, Yangzhou, China
| | - Tingting Qiao
- Department of Neurology, Northern Jiangsu People's Hospital, Clinical Medical College of Yangzhou University, Yangzhou, China
| | - Li Jiang
- Department of Gerontology Northern Jiangsu People's Hospital, Clinical Medical School of Yangzhou University, Yangzhou, China
| | - Chenxin Wang
- Department of Neurology, Northern Jiangsu People's Hospital, The Yangzhou School of Clinical Medicine of Dalian Medical University, Yangzhou, China
| | - Xingxing Zhong
- Department of Neurology, Northern Jiangsu People's Hospital, Clinical Medical College of Yangzhou University, Yangzhou, China
| | - Xiaobo Li
- Department of Neurology, Northern Jiangsu People's Hospital, Clinical Medical College of Yangzhou University, Yangzhou, China
| | - Yao Xu
- Department of Neurology, Northern Jiangsu People's Hospital, Clinical Medical College of Yangzhou University, Yangzhou, China
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9
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Tian Y, Gao R, Wang Y, Zhou Y, Xu S, Duan Y, Lv W, Wang S, Hou M, Chen Y, Li F, Gao W, Zhang L, Zhou JX. Economic impact of metagenomic next-generation sequencing versus traditional bacterial culture for postoperative central nervous system infections using a decision analysis mode: study protocol for a randomized controlled trial. mSystems 2023; 8:e0058123. [PMID: 37937972 PMCID: PMC10734456 DOI: 10.1128/msystems.00581-23] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2023] [Accepted: 09/26/2023] [Indexed: 11/09/2023] Open
Abstract
IMPORTANCE Diagnosing and treating postoperative central nervous system infections (PCNSIs) remains challenging due to the low detection rate and time-consuming nature of traditional methods for identifying microorganisms in cerebrospinal fluid. Metagenomic next-generation sequencing (mNGS) technology provides a rapid and comprehensive understanding of microbial composition in PCNSIs by swiftly sequencing and analyzing the microbial genome. The current study aimed to assess the economic impact of using mNGS versus traditional bacterial culture-directed PCNSIs diagnosis and therapy in post-neurosurgical patients from Beijing Tiantan Hospital. mNGS is a relatively expensive test item, and whether it has the corresponding health-economic significance in the clinical application of diagnosing intracranial infection has not been studied clearly. Therefore, the investigators hope to explore the clinical application value of mNGS detection in PCNSIs after neurosurgery.
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Affiliation(s)
- Ying Tian
- Department of Critical Care Medicine, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Ran Gao
- Department of Critical Care Medicine, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Yumei Wang
- Department of Critical Care Medicine, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Yimin Zhou
- Department of Critical Care Medicine, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Shanshan Xu
- Department of Critical Care Medicine, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Yuqing Duan
- Department of Critical Care Medicine, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Wenyi Lv
- Department of Critical Care Medicine, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Shuya Wang
- Department of Critical Care Medicine, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Mengxue Hou
- Department of Critical Care Medicine, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Yuqing Chen
- Department of Critical Care Medicine, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Fangqiang Li
- Department of Clinical Diagnosis, Laboratory of Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Wei Gao
- Department of Microbiology and Immunology, Peter Doherty Institute, University of Melbourne, Melbourne, Victoria, Australia
| | - Linlin Zhang
- Department of Critical Care Medicine, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
- Beijing Engineering Research Center of Digital Healthcare for Neurological Diseases, Beijing, China
| | - Jian-Xin Zhou
- Department of Critical Care Medicine, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
- Beijing Engineering Research Center of Digital Healthcare for Neurological Diseases, Beijing, China
- Beijing Shijitan Hospital, Capital Medical University, Beijing, China
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Liang X, Wang Q, Liu J, Ma J, Zhang Y, Wang M, Yu Y, Wang L. Coinfection of SARS-CoV-2 and influenza A (H3N2) detected in bronchoalveolar lavage fluid of a patient with long COVID using metagenomic next-generation sequencing: a case report. Front Cell Infect Microbiol 2023; 13:1224794. [PMID: 37724290 PMCID: PMC10505437 DOI: 10.3389/fcimb.2023.1224794] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2023] [Accepted: 08/16/2023] [Indexed: 09/20/2023] Open
Abstract
The growing number of long COVID cases has drawn clinical attention to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has been spreading worldwide since winter 2019. Its symptoms are not limited to fatigue and shortness of breath but also affect daily life. We report the use of metagenomic next-generation sequencing (mNGS) to detect coinfection with SARS-CoV-2 and influenza A virus in a patient with long COVID. The patient was admitted with fever, expectoration, fatigue, and shortness of breath. The PCR test was negative due to possible clearance of SARS-Cov-2 in the upper respiratory tract of patients with long COVID. Other routine microbiological tests were also negative, making the clinical diagnosis difficult. Bronchoalveolar lavage fluid (BALF) samples were tested using mNGS. The patient was diagnosed and treated promptly, recovered quickly, and continued taking azvudine after discharge; his condition was stable. This study illustrates that mNGS may be valuable for the timely diagnosis of patients with long COVID and their mixed infections.
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Affiliation(s)
- Xuefei Liang
- Department of Respiratory and Critical Care Medicine, Sinopharm North Hospital, Baotou, China
| | - Qiushi Wang
- Infection Business Unit, Tianjin Novogene Med LAB Co., Ltd., Tianjin, China
- Infection Business Unit, Novogene Co., Ltd., Beijing, China
| | - Jia Liu
- Infection Business Unit, Tianjin Novogene Med LAB Co., Ltd., Tianjin, China
- Infection Business Unit, Novogene Co., Ltd., Beijing, China
| | - Jing Ma
- Department of Respiratory and Critical Care Medicine, Sinopharm North Hospital, Baotou, China
| | - Yajuan Zhang
- Department of Respiratory and Critical Care Medicine, Sinopharm North Hospital, Baotou, China
| | - Meng Wang
- Infection Business Unit, Tianjin Novogene Med LAB Co., Ltd., Tianjin, China
- Infection Business Unit, Novogene Co., Ltd., Beijing, China
| | - Yang Yu
- Infection Business Unit, Tianjin Novogene Med LAB Co., Ltd., Tianjin, China
- Infection Business Unit, Novogene Co., Ltd., Beijing, China
| | - Linlin Wang
- Department of Respiratory and Critical Care Medicine, Sinopharm North Hospital, Baotou, China
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11
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He S, Wei J, Feng J, Liu D, Wang N, Chen L, Xiong Y. The application of metagenomic next-generation sequencing in pathogen diagnosis: a bibliometric analysis based on Web of Science. Front Cell Infect Microbiol 2023; 13:1112229. [PMID: 37600953 PMCID: PMC10434771 DOI: 10.3389/fcimb.2023.1112229] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Accepted: 07/18/2023] [Indexed: 08/22/2023] Open
Abstract
Background Infectious disease is a large burden on public health globally. Metagenomic next-generation sequencing (mNGS) has become popular as a new tool for pathogen diagnosis with numerous advantages compared to conventional methods. Recently, research on mNGS increases yearly. However, no bibliometric analysis has systematically presented the full spectrum of this research field. Therefore, we reviewed all the publications associated with this topic and performed this study to analyze the comprehensive status and future hotspots of mNGS for infectious disease diagnosis. Methods The literature was searched in the Web of Science Core Collection and screened without year or language restrictions, and the characteristics of the studies were also identified. The outcomes included publication years, study types, journals, countries, authorship, institutions, frontiers, and hotspots with trends. Statistical analysis and visualization were conducted using VOSviewer (version 1.6.16) and CiteSpace (version 6.1. R3). Results In total, 325 studies were included in the analysis after screening. Studies were published between 2009 and 2022 with a significantly increasing number from 1 to 118. Most of the studies were original articles and case reports. Frontiers in Cellular and Infection Microbiology and Clinical Infectious Disease were the most commonly cited and co-cited journals. Institutions and researchers from China contributed the most to this field, followed by those from the USA. The hotspots and frontiers of these studies are pneumonia, tuberculosis, and central nervous system infections. Conclusion This study determined that mNGS is a hot topic in the diagnosis of infectious diseases with development trends and provides insights into researchers, institutions, hotspots and frontiers in mNGS, which can offer references to related researchers and future research.
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Affiliation(s)
- Sike He
- West China School of Medicine, Sichuan University, Chengdu, China
| | - Jingwen Wei
- West China School of Medicine, Sichuan University, Chengdu, China
| | - Jiaming Feng
- West China School of Medicine, Sichuan University, Chengdu, China
| | - Dan Liu
- Department of Periodical Press, West China Hospital, Sichuan University, Chengdu, China
| | - Neng Wang
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China
| | - Liyu Chen
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China
| | - Ying Xiong
- Department of Periodical Press, West China Hospital, Sichuan University, Chengdu, China
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12
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Batool M, Galloway-Peña J. Clinical metagenomics-challenges and future prospects. Front Microbiol 2023; 14:1186424. [PMID: 37448579 PMCID: PMC10337830 DOI: 10.3389/fmicb.2023.1186424] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2023] [Accepted: 06/12/2023] [Indexed: 07/15/2023] Open
Abstract
Infections lacking precise diagnosis are often caused by a rare or uncharacterized pathogen, a combination of pathogens, or a known pathogen carrying undocumented or newly acquired genes. Despite medical advances in infectious disease diagnostics, many patients still experience mortality or long-term consequences due to undiagnosed or misdiagnosed infections. Thus, there is a need for an exhaustive and universal diagnostic strategy to reduce the fraction of undocumented infections. Compared to conventional diagnostics, metagenomic next-generation sequencing (mNGS) is a promising, culture-independent sequencing technology that is sensitive to detecting rare, novel, and unexpected pathogens with no preconception. Despite the fact that several studies and case reports have identified the effectiveness of mNGS in improving clinical diagnosis, there are obvious shortcomings in terms of sensitivity, specificity, costs, standardization of bioinformatic pipelines, and interpretation of findings that limit the integration of mNGS into clinical practice. Therefore, physicians must understand the potential benefits and drawbacks of mNGS when applying it to clinical practice. In this review, we will examine the current accomplishments, efficacy, and restrictions of mNGS in relation to conventional diagnostic methods. Furthermore, we will suggest potential approaches to enhance mNGS to its maximum capacity as a clinical diagnostic tool for identifying severe infections.
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Affiliation(s)
| | - Jessica Galloway-Peña
- Department of Veterinary Pathobiology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, United States
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13
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Deng L, Li Q, Hu W, Chen X, Chen T, Song S, Mo P, Zou S, Zhang Y, Gao S, Chen L, Zhuang K, Yang R, Xiong Y. Metagenomic next-generation sequencing versus traditional laboratory methods for the diagnosis of central nervous system opportunistic infections in HIV-infected Chinese adults. Sci Rep 2023; 13:4921. [PMID: 36966258 PMCID: PMC10039683 DOI: 10.1038/s41598-023-31974-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2023] [Accepted: 03/20/2023] [Indexed: 03/27/2023] Open
Abstract
To evaluate clinical value of metagenomic next-generation sequencing (mNGS) in people living with HIV/AIDS (PLWHA) who had CNS disorders. Cerebrospinal fluid (CSF) samples from 48 PLWHA presenting with CNS disorders were sequenced using mNGS and compared with clinical conventional diagnostic methods. In total, 36/48 ss(75%) patients were diagnosed with pathogen(s) infection by mNGS, and the positive detection proportion by mNGS was higher than that by clinical conventional diagnostic methods (75% vs 52.1%, X2 = 5.441, P = 0.020). Thirteen out of 48 patients (27.1%) were detected with 3-7 pathogens by mNGS. Moreover, 77 pathogen strains were detected, of which 94.8% (73/77) by mNGS and 37.0% (30/77) by clinical conventional methods (X2 = 54.206, P < 0.001). The sensitivity and specificity of pathogens detection by mNGS were 63.9% (23/36) and 66.7% (8/12), respectively, which were superior to that by clinical conventional methods (23/36 vs 9/25, X2 = 4.601, P = 0.032; 8/12 vs 5/23, X2 = 5.029, P = 0.009). The application of mNGS was superior for its ability to detect a variety of unknown pathogens and multiple pathogens infection, and relatively higher sensitivity and specificity in diagnosis of CNS disorders in PLWHA.
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Affiliation(s)
- Liping Deng
- Department of Infectious Diseases, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China
| | - Qian Li
- Department of Infectious Diseases, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China
| | - Wenjia Hu
- Department of Infectious Diseases, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China
| | - Xiaoping Chen
- Department of Infectious Diseases, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China
| | - Tielong Chen
- Department of Infectious Diseases, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China
| | - Shihui Song
- Department of Infectious Diseases, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China
| | - Pingzheng Mo
- Department of Infectious Diseases, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China
| | - Shi Zou
- Department of Infectious Diseases, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China
| | - Yongxi Zhang
- Department of Infectious Diseases, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China
| | - Shicheng Gao
- Department of Infectious Diseases, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China
| | - Liangjun Chen
- Department of Laboratory Medicine, Zhongnan Hospital, Wuhan University, Wuhan, Hubei, China
| | - Ke Zhuang
- ABSL-III Laboratory at the Center for Animal Experiment, State Key Laboratory of Virology, Wuhan University, Wuhan, Hubei, China
| | - Rongrong Yang
- Department of Infectious Diseases, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China.
| | - Yong Xiong
- Department of Infectious Diseases, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China.
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14
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Liu Y, Zhu W, Jiao M, Guo W, Luo Y. Clinical application value of metagenomic next-generation sequencing in the diagnosis of central nervous system infections. Front Bioeng Biotechnol 2023; 11:885877. [PMID: 37113662 PMCID: PMC10126497 DOI: 10.3389/fbioe.2023.885877] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Accepted: 02/14/2023] [Indexed: 04/29/2023] Open
Abstract
Objectives: The purpose of this study is to evaluate the clinical application value of metagenomic next-generation sequencing (mNGS) in central nervous system (CNS) infections. Methods: Both mNGS and routine examination of cerebrospinal fluid (CSF) samples from patients with CNS infections retrospectively analyzed the efficacy of mNGS in this cohort and were ultimately compared with a clinical diagnosis. Results: A total of 94 cases consistent with CNS infections were included in the analysis. The positive rate for mNGS is 60.6% (57/94), which is significantly higher than 20.2% (19/94; p < 0.01) detected using conventional methods. mNGS detected 21 pathogenic strains that could not be detected by routine testing. Routine tests were positive for two pathogens but negative for mNGS. The sensitivity and specificity of mNGS in the diagnosis of central nervous system infections were 89.5% and 44%, respectively, when compared with traditional tests. At discharge, 20 (21.3%) patients were cured, 55 (58.5%) patients showed improvements, five (5.3%) patients did not recover, and two (2.1%) patients died. Conclusion: mNGS has unique advantages in the diagnosis of central nervous system infections. mNGS tests can be performed when patients are clinically suspected of having a central nervous system infection but no pathogenic evidence.
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Affiliation(s)
- Ying Liu
- Gene Hospital of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Weiwei Zhu
- Gene Hospital of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Mengfan Jiao
- Gene Hospital of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Wenhu Guo
- Agene Medical Laboratory, Fuzhou, China
- School of Medical Technology and Engineering, Fujian Medical University, Zhengzhou, China
| | - Yonggang Luo
- Department of Intensive Care Unit, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- *Correspondence: Yonggang Luo,
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15
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Zhu Y, Zhao W, Yang X, Zhang Y, Lin X, Weng X, Wang Y, Cheng C, Chi Y, Wei H, Peng Z, Hu Z. Metagenomic next-generation sequencing for identification of central nervous system pathogens in HIV-infected patients. Front Microbiol 2022; 13:1055996. [PMID: 36458193 PMCID: PMC9705764 DOI: 10.3389/fmicb.2022.1055996] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2022] [Accepted: 10/31/2022] [Indexed: 11/17/2023] Open
Abstract
Although considerable interest in metagenomic next-generation sequencing (mNGS) has been attracted in recent years, limited data are available regarding the performance of mNGS in HIV-associated central nervous system (CNS) infection. Here, we conducted a retrospectively analyzing of the cerebrospinal fluid (CSF) mNGS reports and other clinical data from 80 HIV-infected patients admitted to the Second Hospital of Nanjing, China from March, 2018 to March, 2022. In our study, CSF mNGS reported negative result, mono-infection, and mixed infection in 8.8, 36.2, and 55% of the patients, respectively. Epstein-Barr virus (EBV), positive in 52.5% of samples, was the most commonly reported pathogen, followed by cytomegalovirus (CMV), John Cunningham virus (JCV), torque teno virus (TTV), cryptococcus neoformans (CN), toxoplasma Gondii (TE), and mycobacterium tuberculosis (MTB). 76.2% of the EBV identification and 54.2% of the CMV identification were not considered clinically important, and relative less sequence reads were reported in the clinical unimportant identifications. The clinical importance of the presence of TTV in CSF was not clear. Detection of JCV, CN, or TE was 100% suggestive of specific CNS infection, however, 60% of the MTB reports were considered contamination. Moreover, of the 44 (55%) mixed infections reported by mNGS, only 4 (5%) were considered clinical important, and mNGS failed to identify one mixed infection. Additionally, except for MTB, CSF mNGS tended to have high sensitivity to identify the above-mentioned pathogens (almost with 100% sensitivity). Even all the diagnostic strategies were evaluated, the cause of neurological symptoms remained undetermined in 6 (7.5%) patients. Overall, our results suggest that mNGS is a very sensitive tool for detecting common opportunistic CNS pathogen in HIV-infected patients, although its performance in CNS tuberculosis is unsatisfactory. EBV and CMV are commonly detected by CSF mNGS, however, the threshold of a clinical important detection remains to be defined.
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Affiliation(s)
- Yunqi Zhu
- Department of Infectious Disease, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, China
| | - Wenxuan Zhao
- Department of Infectious Disease, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, China
| | - Xihong Yang
- Department of Infectious Disease, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, China
| | - Yuanyuan Zhang
- Department of Infectious Disease, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, China
| | - Xiaoling Lin
- Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Xing Weng
- BGI Infection Pharmaceutical Technology, BGI-Shenzhen, Shenzhen, China
- Clinical Laboratory of BGI Health, BGI-Shenzhen, Shenzhen, China
| | - Yali Wang
- Clinical Laboratory of BGI Health, BGI-Shenzhen, Shenzhen, China
- Clinical Infectious Disease Center of Nanjing, Nanjing, China
| | - Cong Cheng
- Department of Infectious Disease, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, China
- Clinical Infectious Disease Center of Nanjing, Nanjing, China
| | - Yun Chi
- Department of Infectious Disease, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, China
- Clinical Infectious Disease Center of Nanjing, Nanjing, China
| | - Hongxia Wei
- Department of Infectious Disease, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, China
- Clinical Infectious Disease Center of Nanjing, Nanjing, China
| | - Zhihang Peng
- School of Public Health, Nanjing Medical University, Nanjing, China
| | - Zhiliang Hu
- Department of Infectious Disease, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, China
- Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China
- Clinical Infectious Disease Center of Nanjing, Nanjing, China
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16
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Chen YY, Guo Y, Xue XH, Pang F. Application of metagenomic next-generation sequencing in the diagnosis of infectious diseases of the central nervous system after empirical treatment. World J Clin Cases 2022; 10:7760-7771. [PMID: 36158512 PMCID: PMC9372857 DOI: 10.12998/wjcc.v10.i22.7760] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2022] [Revised: 04/27/2022] [Accepted: 06/17/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The diagnostic value of metagenomic next-generation sequencing (mNGS) in central nervous system (CNS) infectious diseases after empirical treatment has not been reported.
AIM To investigate the diagnostic value of mNGS of cerebrospinal fluid (CSF) in the empirically treated CNS infectious diseases.
METHODS A total of 262 CSF samples from patients with suspected CNS infections were collected between August 2020 and December 2021. Both mNGS and conventional methods were used for testing. The conventional methods included microbial culture, smear, polymerase chain reaction, etc.
RESULTS Among 262 suspected cases, 183 cases (69.84%) were diagnosed as CNS infection, including 86 cases of virus infection (47.00%), 70 cases of bacterial infection (38.25%) and 27 cases of fungal infection (14.76%). The sensitivity and specificity of mNGS were 65.6% (95%CI: 58.2%-72.3%) and 89.6% (95%CI: 79.1%-95.3%), respectively. The PPV of mNGS was 94.5% (95%CI: 88.6%-97.6%), and the NPV was 48.8% (95%CI: 39.7%–57.9%). The pathogen detective sensitivity and accuracy of mNGS were higher than those of conventional methods (Sensitivity: 65.6% vs 37.2%; P < 0.001; Accuracy: 72.0% vs 50%, P < 0.001). The results showed that compared with conventional methods, mNGS technology was a more sensitive method for the diagnosis of CNS infection after empirical treatment.
CONCLUSION mNGS can be a better method applied in the diagnosis of CNS infection after empirical treatment.
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Affiliation(s)
- Ying-Ying Chen
- Department of Neurology, Liaocheng People's Hospital, Liaocheng 252000, Shandong Province, China
| | - Yan Guo
- Department of Neurology, Liaocheng People's Hospital, Liaocheng 252000, Shandong Province, China
| | - Xin-Hong Xue
- Department of Neurology, Liaocheng People's Hospital, Liaocheng 252000, Shandong Province, China
| | - Feng Pang
- Central Laboratory, Liaocheng People's Hospital, Liaocheng 252000, Shandong Province, China
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Xu J, Huang Q, Yu J, Liu S, Yang Z, Wang F, Shi Y, Li E, Li Z, Xiao Y. Metagenomic Next-Generation Sequencing for the Diagnosis of Suspected Opportunistic Infections in People Living with HIV. Infect Drug Resist 2022; 15:1767-1775. [PMID: 35431561 PMCID: PMC9012299 DOI: 10.2147/idr.s350047] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2022] [Accepted: 03/25/2022] [Indexed: 11/23/2022] Open
Abstract
Objective The diagnosis of suspected opportunistic infections in HIV patients is challenging due to the wide range of potential causes. This study used mNGS to analyse specimens of suspected opportunistic infections in HIV patients from a single centre to explore this method’s applicability as a diagnostic tool compared to that of CMTs. Methods We retrospectively investigated 46 suspected opportunistic infections in people living with HIV(PLWH) Hospitalized at Hangzhou Xixi hospital from January 2020 to August 2021. In total, we collected 49 samples (3 patients provided 2 samples) and sent them out for mNGS. Results mNGS had a better detection rate for fungi and nontuberculous mycobacteria than that of CMTs. Specifically, the diagnostic detection rate of fungi (11 vs 19, P<0.05) and nontuberculous mycobacteria (1 vs 6, p<0.05) was significantly higher; there was no difference in detection rate for other pathogens (bacteria, Mycobacterium tuberculosis, or viruses). The sensitivity of mNGS was 90.91%, 50%, 0%, 100%, and 100% for detecting fungi, bacteria, Mycobacterium tuberculosis, nontuberculous mycobacteria, and viruses, respectively; the corresponding specificities were 74.29%, 97.73%, 86.36%, 86.67%, and 91.11%. Conclusion mNGS technology provides an alternative and promising method of identifying suspected opportunistic infections in PLWH. Thus, the best diagnosis strategy may be using a combination of mNGS and CMTs.
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Affiliation(s)
- Jingying Xu
- Department of Infectious Diseases, Affiliated Hangzhou Xixi Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310023, People’s Republic of China
| | - Qian Huang
- Department of Infectious Diseases, Affiliated Hangzhou Xixi Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310023, People’s Republic of China
| | - Jianhua Yu
- Department of Infectious Diseases, Affiliated Hangzhou Xixi Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310023, People’s Republic of China
| | - Shourong Liu
- Department of Infectious Diseases, Affiliated Hangzhou Xixi Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310023, People’s Republic of China
| | - Zongxing Yang
- Department of Infectious Diseases, Affiliated Hangzhou Xixi Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310023, People’s Republic of China
| | - Fei Wang
- Department of Infectious Diseases, Affiliated Hangzhou Xixi Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310023, People’s Republic of China
| | - Yue Shi
- Department of Infectious Diseases, Affiliated Hangzhou Xixi Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310023, People’s Republic of China
| | - Er Li
- Department of Infectious Diseases, Affiliated Hangzhou Xixi Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310023, People’s Republic of China
| | - Zhaoyi Li
- Department of Infectious Diseases, Affiliated Hangzhou Xixi Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310023, People’s Republic of China
| | - Yunlei Xiao
- Department of Infectious Diseases, Affiliated Hangzhou Xixi Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310023, People’s Republic of China
- Correspondence: Yunlei Xiao; Jingying Xu, Department of Infectious Diseases, Affiliated Hangzhou Xixi Hospital, Zhejiang University School of Medicine, No. 2, Hengbu Street, Liu Xia Town, Xihu District, Hangzhou, Zhejiang, 310023, People’s Republic of China, Tel +8615258639960; +8613588037550, Email ;
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18
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Xie Y, Ruan B, Lang G, Zhu B. Case Report: Streptococcus Suis Meningitis Diagnosed in a HIV-Infected Patient With Cryptococcal Meningitis Using Next-Generation Sequencing. Front Med (Lausanne) 2021; 8:736064. [PMID: 34778300 PMCID: PMC8581154 DOI: 10.3389/fmed.2021.736064] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2021] [Accepted: 10/06/2021] [Indexed: 12/25/2022] Open
Abstract
Background: Streptococcus suis has been recognized as a zoonotic pathogen that may cause infections in humans. Although rarely described, it is not surprising that both cryptococcal and streptococcus suis meningitis infections can co-exist in a HIV-infected patient with a low CD4 count. However, a fast and accurate diagnose of meningitis of multipathogenic infections is challenging. In this report, we describe such a case of a HIV-infected patient with meningitis of multipathogenic infections. Case Presentation: The patient was a 34-year-old Chinese male who was diagnosed with cryptococcal meningitis and HIV at the same time about 1 year ago. During the same time period, he had received (with good compliance) fluconazole and tenofovir-lamivudine- dolutegravir based antiretroviral therapy (ART). However, symptom of progressively worsening occipital headache appeared after he was exposed to a truck which was used for transporting pigs. Initial workup indicated an increase of the cerebrospinal fluid (CSF) opening pressure (OP) and an increase in the number of lymphocytes and proteins in CSF. A magnetic resonance imaging (MRI) scan revealed that partial cerebellar surface enhancement. The cryptococcus capsular antigen test of CSF was positive. The results of the India Ink microscopy for cryptococcus, nucleic acid of CMV and EBV and mycobacterium tuberculosis (MTB) tests of CSF were negative. The results of the bacteria and fungi smear and culture of CSF were also negative. Eventually, streptococcus suis was detected using next-generation sequencing (NGS) in CSF. The diagnosis of Streptococcus suis meningitis was made based on the patient's contact history with carrier pigs and the clinical findings addressed above. The treatment of 2 weeks of intravenous ceftriaxone and 1 week of oral moxifloxacin resulted in improvement of the condition of CSF. The anti-fungal treatment using fluconazole continued until the CFS OP went down to a normal level and the cryptococcus capsular antigen test of CSF was negative 6 months later. Conclusion: This case highlights that NGS might be beneficial to HIV-infected patients who have meningitis with negative CSF culture results. Multiple etiologies for such condition in the immunocompromised patients must be taken into consideration and early stage NGS is recommended.
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Affiliation(s)
- Yirui Xie
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The Department of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Bing Ruan
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The Department of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Guanjing Lang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The Department of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Biao Zhu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The Department of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
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