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  1. Article: Application of VirCapSeq-VERT and BacCapSeq In the Diagnosis of Presumed and Definitive Neuroinfectious Diseases.

    Boruah, Abhilasha P / Kroopnick, Adam / Thakkar, Riddhi / Wapniarski, Annie E / Kim, Carla / Dugue, Rachelle / Harrigan, Eileen / Lipkin, W Ian / Mishra, Nischay / Thakur, Kiran T

    Research square

    2023  

    Abstract: Background: Unbiased high-throughput sequencing (HTS) has enabled new insights into the diversity of agents implicated in central nervous system (CNS) infections. The addition of positive selection capture methods to HTS has enhanced the sensitivity ... ...

    Abstract Background: Unbiased high-throughput sequencing (HTS) has enabled new insights into the diversity of agents implicated in central nervous system (CNS) infections. The addition of positive selection capture methods to HTS has enhanced the sensitivity while reducing sequencing costs and complexity of bioinformatic analysis. Here we report the use of virus capture based sequencing for vertebrate viruses (VirCapSeq-VERT) and bacterial capture sequencing (BacCapSeq) in investigating CNS infections.
    Design/methods: Thirty-four samples were categorized: (1) Patients with definitive CNS infection by routine testing; (2) Patients meeting clinically Brighton Criteria (BC) for meningoencephalitis (3) Patients with presumptive infectious etiology highest on the differential. RNA extracts from cerebrospinal fluid (CSF) were used for VirCapSeq-VERT and DNA extracts were used for BacCapSeq analysis.
    Results: Among 8 samples from known CNS infections in group 1, VirCapSeq and BacCapSeq confirmed 3 expected diagnoses (42.8%), were negative in 2 (25%), yielded an alternative result in 1 (11.1%), and did not detect 2 expected negative pathogens. The confirmed cases identified HHV-6, HSV-2, and VZV while the negative samples included JCV and HSV-2. In groups 2 and 3,11/26 samples (42%) were positive for at least one pathogen, however 27% of the total samples (7/26) were positive for commensal organisms. No microbial nucleic acids were detected in negative control samples.
    Conclusions: HTS showed limited promise for pathogen identification in presumed CNS infectious diseases in our small sample. Before conducting larger-scale prospective studies to assess clinical value of this novel technique, clinicians should understand benefits and limitations of using this modality.
    Language English
    Publishing date 2023-07-11
    Publishing country United States
    Document type Preprint
    DOI 10.21203/rs.3.rs-2675665/v1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Application of VirCapSeq-VERT and BacCapSeq in the diagnosis of presumed and definitive neuroinfectious diseases.

    Boruah, Abhilasha P / Kroopnick, Adam / Thakkar, Riddhi / Wapniarski, Anne E / Kim, Carla / Dugue, Rachelle / Harrigan, Eileen / Lipkin, W Ian / Mishra, Nischay / Thakur, Kiran T

    Journal of neurovirology

    2023  Volume 29, Issue 6, Page(s) 678–691

    Abstract: Unbiased high-throughput sequencing (HTS) has enabled new insights into the diversity of agents implicated in central nervous system (CNS) infections. The addition of positive selection capture methods to HTS has enhanced the sensitivity while reducing ... ...

    Abstract Unbiased high-throughput sequencing (HTS) has enabled new insights into the diversity of agents implicated in central nervous system (CNS) infections. The addition of positive selection capture methods to HTS has enhanced the sensitivity while reducing sequencing costs and the complexity of bioinformatic analysis. Here we report the use of virus capture-based sequencing for vertebrate viruses (VirCapSeq-VERT) and bacterial capture sequencing (BacCapSeq) in investigating CNS infections. Thirty-four samples were categorized: (1) patients with definitive CNS infection by routine testing; (2) patients meeting clinically the Brighton criteria (BC) for meningoencephalitis; (3) patients with presumptive infectious etiology highest on the differential. RNA extracts from cerebrospinal fluid (CSF) were used for VirCapSeq-VERT, and DNA extracts were used for BacCapSeq analysis. Among 8 samples from known CNS infections in group 1, VirCapSeq and BacCapSeq confirmed 3 expected diagnoses (42.8%), were negative in 2 (25%), yielded an alternative result in 1 (11.1%), and did not detect 2 expected negative pathogens. The confirmed cases identified HHV-6, HSV-2, and VZV while the negative samples included JCV and HSV-2. In groups 2 and 3, 11/26 samples (42%) were positive for at least one pathogen; however, 27% of the total samples (7/26) were positive for commensal organisms. No microbial nucleic acids were detected in negative control samples. HTS showed limited promise for pathogen identification in presumed CNS infectious diseases in our small sample. Before conducting larger-scale prospective studies to assess the clinical value of this novel technique, clinicians should understand the benefits and limitations of using this modality.
    MeSH term(s) Humans ; Prospective Studies ; Viruses ; High-Throughput Nucleotide Sequencing/methods ; Meningoencephalitis ; Herpesvirus 2, Human/genetics
    Language English
    Publishing date 2023-10-18
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 1283265-0
    ISSN 1538-2443 ; 1355-0284
    ISSN (online) 1538-2443
    ISSN 1355-0284
    DOI 10.1007/s13365-023-01172-w
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Clinical use of steroids in viral central nervous system (CNS) infections: three challenging cases.

    Kroopnick, Adam / Jia, Dan Tong / Rimmer, Kathryn / Namale, Vivian S / Kim, Carla / Ofoezie, Ugoada / Thakur, Kiran T

    Journal of neurovirology

    2021  Volume 27, Issue 5, Page(s) 727–734

    Abstract: The role of adjunctive corticosteroids in reducing morbidity and mortality of viral CNS infections remains poorly defined. Clinicians are often left in a quagmire regarding steroid use in complex and rapidly evolving viral CNS infections. Limited studies ...

    Abstract The role of adjunctive corticosteroids in reducing morbidity and mortality of viral CNS infections remains poorly defined. Clinicians are often left in a quagmire regarding steroid use in complex and rapidly evolving viral CNS infections. Limited studies have explored the underlying mechanisms behind the potential benefit of steroids. Here, we describe steroid use in three cases of viral CNS disease: varicella zoster virus (VZV), Powassan virus, and influenza A-associated acute necrotizing encephalopathy.
    MeSH term(s) Adrenal Cortex Hormones/therapeutic use ; Central Nervous System ; Central Nervous System Viral Diseases/drug therapy ; Herpes Zoster ; Herpesvirus 3, Human/physiology ; Humans ; Steroids/therapeutic use
    Chemical Substances Adrenal Cortex Hormones ; Steroids
    Language English
    Publishing date 2021-10-01
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 1283265-0
    ISSN 1538-2443 ; 1355-0284
    ISSN (online) 1538-2443
    ISSN 1355-0284
    DOI 10.1007/s13365-021-01008-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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