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Application of Pathogen Discovery/Metagenomic Sequencing in CNS HIV

  • Central Nervous System and Cognition (SS Spudich, Section Editor)
  • Published:
Current HIV/AIDS Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Neurological conditions associated with HIV/AIDS including central nervous system (CNS), opportunistic infections (OI), chronic conditions including HIV-associated neurocognitive disorder, and cerebrospinal fluid (CSF) viral escape remain major contributors to morbidity and mortality worldwide. CNS infections in HIV-infected patients are often challenging to diagnose by traditional microbiological testing, impacting treatment and outcome.

Recent Findings

Recent advances in diagnostic techniques, including metagenomic next-generation sequencing (mNGS), are changing the landscape of microbiological testing, mainly in resource-rich settings. Pathogen discovery techniques offer a hypothesis-free approach to diagnostic testing, yielding comprehensive analysis of microbial genetic material. Given the extent of genetic material produced, deep sequencing tools not only hold promise in the diagnosis of CNS infections but also in defining key pathogenic steps which have previously been unanswered.

Summary

Significant challenges remain to implementing pathogen discovery techniques in routine clinical practice including cost, expertise and infrastructure needed including laboratory and bioinformatics support, and sample contamination risk. The use in resource-limited regions where the burden of CNS complications due to HIV/AIDS is highest remains poorly defined. Though, major opportunities utilizing pathogen discovery techniques exist to enhance surveillance and diagnosis and improve our understanding of mechanisms of neuroinvasion in CNS conditions associated with HIV.

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Authors and Affiliations

  1. Columbia University Irving Medical Center, New York, NY, USA

    Kiran T. Thakur

  2. New York Presbyterian Hospital, New York, NY, USA

    Kiran T. Thakur

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Appendix. Select References on Methodology and Application of Pathogen Discovery Techniques

Appendix. Select References on Methodology and Application of Pathogen Discovery Techniques

Gu W, Miller S, Chiu CY. Clinical metagenomic next-generation sequencing for pathogen detection. Annu Rev Pathol. 2019;14:319–338. doi:https://doi.org/10.1146/annurev-pathmechdis-012418-012751

Schlaberg S, Chiu CY, Miller S, Procop GW, Weinstock G. Validation of Metagenomic Next-Generation Sequencing Tests for Universal Pathogen Detection. Arch Pathol Lab Med. 2017; 141(6):776–786. https://doi.org/10.5858/arpa.2016-0539-RA

Yohe S, Thyagarajan B. Review of Clinical Next-Generation Sequencing. Arch Pathol Lab Med. 2017;141(11):1544–1557. doi:https://doi.org/10.5858/arpa.2016-0501-RA

Besser J, Carleton HA, Gerner-Smidt P, Lindsey RL, Trees E. Next-generation sequencing technologies and their application to the study and control of bacterial infections. Clin Microbiol Infect. 2018;24 (4):335–341. doi:https://doi.org/10.1016/j.cmi.2017.10.013

Slatko BE, Gardner AF, Ausubel FM. Overview of Next-Generation Sequencing Technologies. Curr Protoc Mol Biol. 2018;122(1):e59. doi:https://doi.org/10.1002/cpmb.59

Ilyas M. Next-Generation Sequencing in Diagnostic Pathology. Pathobiology. 2017;84(6):292–305. doi:https://doi.org/10.1159/000480089

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Thakur, K.T. Application of Pathogen Discovery/Metagenomic Sequencing in CNS HIV. Curr HIV/AIDS Rep 17, 507–513 (2020). https://doi.org/10.1007/s11904-020-00514-1

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