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Metagenomic next-generation sequencing for identification of central nervous system pathogens in HIV-infected patients

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 cerebrospin...

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Autores principales: Zhu, Yunqi, Zhao, Wenxuan, Yang, Xihong, Zhang, Yuanyuan, Lin, Xiaoling, Weng, Xing, Wang, Yali, Cheng, Cong, Chi, Yun, Wei, Hongxia, Peng, Zhihang, Hu, Zhiliang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9705764/
https://www.ncbi.nlm.nih.gov/pubmed/36458193
http://dx.doi.org/10.3389/fmicb.2022.1055996
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author Zhu, Yunqi
Zhao, Wenxuan
Yang, Xihong
Zhang, Yuanyuan
Lin, Xiaoling
Weng, Xing
Wang, Yali
Cheng, Cong
Chi, Yun
Wei, Hongxia
Peng, Zhihang
Hu, Zhiliang
author_facet Zhu, Yunqi
Zhao, Wenxuan
Yang, Xihong
Zhang, Yuanyuan
Lin, Xiaoling
Weng, Xing
Wang, Yali
Cheng, Cong
Chi, Yun
Wei, Hongxia
Peng, Zhihang
Hu, Zhiliang
author_sort Zhu, Yunqi
collection PubMed
description 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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spelling pubmed-97057642022-11-30 Metagenomic next-generation sequencing for identification of central nervous system pathogens in HIV-infected patients Zhu, Yunqi Zhao, Wenxuan Yang, Xihong Zhang, Yuanyuan Lin, Xiaoling Weng, Xing Wang, Yali Cheng, Cong Chi, Yun Wei, Hongxia Peng, Zhihang Hu, Zhiliang Front Microbiol Microbiology 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. Frontiers Media S.A. 2022-11-15 /pmc/articles/PMC9705764/ /pubmed/36458193 http://dx.doi.org/10.3389/fmicb.2022.1055996 Text en Copyright © 2022 Zhu, Zhao, Yang, Zhang, Lin, Weng, Wang, Cheng, Chi, Wei, Peng and Hu. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Zhu, Yunqi
Zhao, Wenxuan
Yang, Xihong
Zhang, Yuanyuan
Lin, Xiaoling
Weng, Xing
Wang, Yali
Cheng, Cong
Chi, Yun
Wei, Hongxia
Peng, Zhihang
Hu, Zhiliang
Metagenomic next-generation sequencing for identification of central nervous system pathogens in HIV-infected patients
title Metagenomic next-generation sequencing for identification of central nervous system pathogens in HIV-infected patients
title_full Metagenomic next-generation sequencing for identification of central nervous system pathogens in HIV-infected patients
title_fullStr Metagenomic next-generation sequencing for identification of central nervous system pathogens in HIV-infected patients
title_full_unstemmed Metagenomic next-generation sequencing for identification of central nervous system pathogens in HIV-infected patients
title_short Metagenomic next-generation sequencing for identification of central nervous system pathogens in HIV-infected patients
title_sort metagenomic next-generation sequencing for identification of central nervous system pathogens in hiv-infected patients
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9705764/
https://www.ncbi.nlm.nih.gov/pubmed/36458193
http://dx.doi.org/10.3389/fmicb.2022.1055996
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