Metagenomic Next-Generation Sequencing for Diagnosis of Infectious Encephalitis and Meningitis: A Large, Prospective Case Series of 213 Patients
Purpose: We assessed the performance of metagenomic next-generation sequencing (mNGS) in the diagnosis of infectious encephalitis and meningitis.Methods: This was a prospective multicenter study. Cerebrospinal fluid samples from patients with viral encephalitis and/or meningitis, tuberculous meningi...
| Main Authors: | , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2020-03-01
|
| Series: | Frontiers in Cellular and Infection Microbiology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fcimb.2020.00088/full |
| _version_ | 1811331099559723008 |
|---|---|
| author | Xiao-Wei Xing Jia-Tang Zhang Jia-Tang Zhang Yu-Bao Ma Mian-Wang He Guo-En Yao Wei Wang Xiao-Kun Qi Xiao-Yan Chen Lei Wu Xiao-Lin Wang Yong-Hua Huang Juan Du Hong-Fen Wang Rong-Fei Wang Fei Yang Sheng-Yuan Yu Sheng-Yuan Yu |
| author_facet | Xiao-Wei Xing Jia-Tang Zhang Jia-Tang Zhang Yu-Bao Ma Mian-Wang He Guo-En Yao Wei Wang Xiao-Kun Qi Xiao-Yan Chen Lei Wu Xiao-Lin Wang Yong-Hua Huang Juan Du Hong-Fen Wang Rong-Fei Wang Fei Yang Sheng-Yuan Yu Sheng-Yuan Yu |
| author_sort | Xiao-Wei Xing |
| collection | DOAJ |
| description | Purpose: We assessed the performance of metagenomic next-generation sequencing (mNGS) in the diagnosis of infectious encephalitis and meningitis.Methods: This was a prospective multicenter study. Cerebrospinal fluid samples from patients with viral encephalitis and/or meningitis, tuberculous meningitis, bacterial meningitis, fungal meningitis, and non-central nervous system (CNS) infections were subjected to mNGS.Results: In total, 213 patients with infectious and non-infectious CNS diseases were finally enrolled from November 2016 to May 2019; the mNGS-positive detection rate of definite CNS infections was 57.0%. At a species-specific read number (SSRN) ≥2, mNGS performance in the diagnosis of definite viral encephalitis and/or meningitis was optimal (area under the curve [AUC] = 0.659, 95% confidence interval [CI] = 0.566–0.751); the positivity rate was 42.6%. At a genus-specific read number ≥1, mNGS performance in the diagnosis of tuberculous meningitis (definite or probable) was optimal (AUC=0.619, 95% CI=0.516–0.721); the positivity rate was 27.3%. At SSRNs ≥5 or 10, the diagnostic performance was optimal for definite bacterial meningitis (AUC=0.846, 95% CI = 0.711–0.981); the sensitivity was 73.3%. The sensitivities of mNGS (at SSRN ≥2) in the diagnosis of cryptococcal meningitis and cerebral aspergillosis were 76.92 and 80%, respectively.Conclusion: mNGS of cerebrospinal fluid effectively identifies pathogens causing infectious CNS diseases. mNGS should be used in conjunction with conventional microbiological testing.Trial Registration: Chinese Clinical Trial Registry, ChiCTR1800020442. |
| first_indexed | 2024-04-13T16:13:46Z |
| format | Article |
| id | doaj.art-7dfbd81ee6fe42d090715bf274369163 |
| institution | Directory Open Access Journal |
| issn | 2235-2988 |
| language | English |
| last_indexed | 2024-04-13T16:13:46Z |
| publishDate | 2020-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj.art-7dfbd81ee6fe42d090715bf2743691632022-12-22T02:40:08ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882020-03-011010.3389/fcimb.2020.00088515268Metagenomic Next-Generation Sequencing for Diagnosis of Infectious Encephalitis and Meningitis: A Large, Prospective Case Series of 213 PatientsXiao-Wei Xing0Jia-Tang Zhang1Jia-Tang Zhang2Yu-Bao Ma3Mian-Wang He4Guo-En Yao5Wei Wang6Xiao-Kun Qi7Xiao-Yan Chen8Lei Wu9Xiao-Lin Wang10Yong-Hua Huang11Juan Du12Hong-Fen Wang13Rong-Fei Wang14Fei Yang15Sheng-Yuan Yu16Sheng-Yuan Yu17Department of Neurology, Hainan Hospital of PLA General Hospital, Sanya, ChinaDepartment of Neurology, First Medical Center of PLA General Hospital, Beijing, ChinaMedical School of Chinese PLA, Beijing, ChinaDepartment of Neurology, First Medical Center of PLA General Hospital, Beijing, ChinaDepartment of Neurology, First Medical Center of PLA General Hospital, Beijing, ChinaDepartment of Neurology, Fourth Medical Center of PLA General Hospital, Beijing, ChinaDepartment of Neurology, Eighth Medical Center of PLA General Hospital, Beijing, ChinaDepartment of Neurology, Sixth Medical Center of PLA General Hospital, Beijing, ChinaDepartment of Neurology, First Medical Center of PLA General Hospital, Beijing, ChinaDepartment of Neurology, First Medical Center of PLA General Hospital, Beijing, ChinaDepartment of Neurology, First Medical Center of PLA General Hospital, Beijing, ChinaDepartment of Neurology, Seventh Medical Center of PLA General Hospital, Beijing, ChinaDepartment of Neurology, PLA Strategic Support Force Characteristic Medical Center, Beijing, ChinaDepartment of Neurology, First Medical Center of PLA General Hospital, Beijing, ChinaDepartment of Neurology, First Medical Center of PLA General Hospital, Beijing, ChinaDepartment of Neurology, First Medical Center of PLA General Hospital, Beijing, ChinaDepartment of Neurology, First Medical Center of PLA General Hospital, Beijing, ChinaMedical School of Chinese PLA, Beijing, ChinaPurpose: We assessed the performance of metagenomic next-generation sequencing (mNGS) in the diagnosis of infectious encephalitis and meningitis.Methods: This was a prospective multicenter study. Cerebrospinal fluid samples from patients with viral encephalitis and/or meningitis, tuberculous meningitis, bacterial meningitis, fungal meningitis, and non-central nervous system (CNS) infections were subjected to mNGS.Results: In total, 213 patients with infectious and non-infectious CNS diseases were finally enrolled from November 2016 to May 2019; the mNGS-positive detection rate of definite CNS infections was 57.0%. At a species-specific read number (SSRN) ≥2, mNGS performance in the diagnosis of definite viral encephalitis and/or meningitis was optimal (area under the curve [AUC] = 0.659, 95% confidence interval [CI] = 0.566–0.751); the positivity rate was 42.6%. At a genus-specific read number ≥1, mNGS performance in the diagnosis of tuberculous meningitis (definite or probable) was optimal (AUC=0.619, 95% CI=0.516–0.721); the positivity rate was 27.3%. At SSRNs ≥5 or 10, the diagnostic performance was optimal for definite bacterial meningitis (AUC=0.846, 95% CI = 0.711–0.981); the sensitivity was 73.3%. The sensitivities of mNGS (at SSRN ≥2) in the diagnosis of cryptococcal meningitis and cerebral aspergillosis were 76.92 and 80%, respectively.Conclusion: mNGS of cerebrospinal fluid effectively identifies pathogens causing infectious CNS diseases. mNGS should be used in conjunction with conventional microbiological testing.Trial Registration: Chinese Clinical Trial Registry, ChiCTR1800020442.https://www.frontiersin.org/article/10.3389/fcimb.2020.00088/fullencephalitismeningitispathogensmetagenomic next-generation sequencingdiagnosis |
| spellingShingle | Xiao-Wei Xing Jia-Tang Zhang Jia-Tang Zhang Yu-Bao Ma Mian-Wang He Guo-En Yao Wei Wang Xiao-Kun Qi Xiao-Yan Chen Lei Wu Xiao-Lin Wang Yong-Hua Huang Juan Du Hong-Fen Wang Rong-Fei Wang Fei Yang Sheng-Yuan Yu Sheng-Yuan Yu Metagenomic Next-Generation Sequencing for Diagnosis of Infectious Encephalitis and Meningitis: A Large, Prospective Case Series of 213 Patients Frontiers in Cellular and Infection Microbiology encephalitis meningitis pathogens metagenomic next-generation sequencing diagnosis |
| title | Metagenomic Next-Generation Sequencing for Diagnosis of Infectious Encephalitis and Meningitis: A Large, Prospective Case Series of 213 Patients |
| title_full | Metagenomic Next-Generation Sequencing for Diagnosis of Infectious Encephalitis and Meningitis: A Large, Prospective Case Series of 213 Patients |
| title_fullStr | Metagenomic Next-Generation Sequencing for Diagnosis of Infectious Encephalitis and Meningitis: A Large, Prospective Case Series of 213 Patients |
| title_full_unstemmed | Metagenomic Next-Generation Sequencing for Diagnosis of Infectious Encephalitis and Meningitis: A Large, Prospective Case Series of 213 Patients |
| title_short | Metagenomic Next-Generation Sequencing for Diagnosis of Infectious Encephalitis and Meningitis: A Large, Prospective Case Series of 213 Patients |
| title_sort | metagenomic next generation sequencing for diagnosis of infectious encephalitis and meningitis a large prospective case series of 213 patients |
| topic | encephalitis meningitis pathogens metagenomic next-generation sequencing diagnosis |
| url | https://www.frontiersin.org/article/10.3389/fcimb.2020.00088/full |
| work_keys_str_mv | AT xiaoweixing metagenomicnextgenerationsequencingfordiagnosisofinfectiousencephalitisandmeningitisalargeprospectivecaseseriesof213patients AT jiatangzhang metagenomicnextgenerationsequencingfordiagnosisofinfectiousencephalitisandmeningitisalargeprospectivecaseseriesof213patients AT jiatangzhang metagenomicnextgenerationsequencingfordiagnosisofinfectiousencephalitisandmeningitisalargeprospectivecaseseriesof213patients AT yubaoma metagenomicnextgenerationsequencingfordiagnosisofinfectiousencephalitisandmeningitisalargeprospectivecaseseriesof213patients AT mianwanghe metagenomicnextgenerationsequencingfordiagnosisofinfectiousencephalitisandmeningitisalargeprospectivecaseseriesof213patients AT guoenyao metagenomicnextgenerationsequencingfordiagnosisofinfectiousencephalitisandmeningitisalargeprospectivecaseseriesof213patients AT weiwang metagenomicnextgenerationsequencingfordiagnosisofinfectiousencephalitisandmeningitisalargeprospectivecaseseriesof213patients AT xiaokunqi metagenomicnextgenerationsequencingfordiagnosisofinfectiousencephalitisandmeningitisalargeprospectivecaseseriesof213patients AT xiaoyanchen metagenomicnextgenerationsequencingfordiagnosisofinfectiousencephalitisandmeningitisalargeprospectivecaseseriesof213patients AT leiwu metagenomicnextgenerationsequencingfordiagnosisofinfectiousencephalitisandmeningitisalargeprospectivecaseseriesof213patients AT xiaolinwang metagenomicnextgenerationsequencingfordiagnosisofinfectiousencephalitisandmeningitisalargeprospectivecaseseriesof213patients AT yonghuahuang metagenomicnextgenerationsequencingfordiagnosisofinfectiousencephalitisandmeningitisalargeprospectivecaseseriesof213patients AT juandu metagenomicnextgenerationsequencingfordiagnosisofinfectiousencephalitisandmeningitisalargeprospectivecaseseriesof213patients AT hongfenwang metagenomicnextgenerationsequencingfordiagnosisofinfectiousencephalitisandmeningitisalargeprospectivecaseseriesof213patients AT rongfeiwang metagenomicnextgenerationsequencingfordiagnosisofinfectiousencephalitisandmeningitisalargeprospectivecaseseriesof213patients AT feiyang metagenomicnextgenerationsequencingfordiagnosisofinfectiousencephalitisandmeningitisalargeprospectivecaseseriesof213patients AT shengyuanyu metagenomicnextgenerationsequencingfordiagnosisofinfectiousencephalitisandmeningitisalargeprospectivecaseseriesof213patients AT shengyuanyu metagenomicnextgenerationsequencingfordiagnosisofinfectiousencephalitisandmeningitisalargeprospectivecaseseriesof213patients |