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J Infect. 2019 Nov;79(5):407-418. doi: 10.1016/j.jinf.2019.08.005. Epub 2019 Aug 9.

Mass spectrometry-based proteomic techniques to identify cerebrospinal fluid biomarkers for diagnosing suspected central nervous system infections. A systematic review.

Author information

1
Institute of Glycobiology, Department of Biochemistry, South Parks Road, Oxford OX1 3RQ, United Kingdom; Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit (LOMWRU), Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao Democratic People's Republic. Electronic address: t.bharucha@doctors.org.uk.
2
Institute of Glycobiology, Department of Biochemistry, South Parks Road, Oxford OX1 3RQ, United Kingdom.
3
Unité des Virus Émergents (UVE: Aix-Marseille Univ - IRD 190 - Inserm 1207 - IHU Méditerranée Infection), Marseille, France.
4
Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit (LOMWRU), Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao Democratic People's Republic; Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, Churchill Hospital, Oxford, United Kingdom.
5
Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, Churchill Hospital, Oxford, United Kingdom; Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, 3/F, 60th Anniversary Chalermprakiat Building, 420/6 Rajvithi Road, Bangkok 10400, Thailand.
6
Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit (LOMWRU), Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao Democratic People's Republic; Unité des Virus Émergents (UVE: Aix-Marseille Univ - IRD 190 - Inserm 1207 - IHU Méditerranée Infection), Marseille, France; Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, Churchill Hospital, Oxford, United Kingdom.

Abstract

OBJECTIVES:

Central nervous system (CNS) infections account for considerable death and disability every year. An urgent research priority is scaling up diagnostic capacity, and introduction of point-of-care tests. We set out to assess current evidence for the application of mass spectrometry (MS) peptide sequencing in identification of diagnostic biomarkers for CNS infections.

METHODS:

We performed a systematic review (PROSPEROCRD42018104257) using PRISMA guidelines on use of MS to identify cerebrospinal fluid (CSF) biomarkers for diagnosing CNS infections. We searched PubMed, Embase, Web of Science, and Cochrane for articles published from 1 January 2000 to 1 February 2019, and contacted experts. Inclusion criteria involved primary research except case reports, on the diagnosis of infectious diseases except HIV, applying MS to human CSF samples, and English language.

RESULTS:

4,620 papers were identified, of which 11 were included, largely confined to pre-clinical biomarker discovery, and eight (73%) published in the last five years. 6 studies performed further work termed verification or validation. In 2 of these studies, it was possible to extract data on sensitivity and specificity of the biomarkers detected by ELISA, ranging from 89-94% and 58-92% respectively.

CONCLUSIONS:

The findings demonstrate feasibility and potential of the methods in a variety of infectious diseases, but emphasise the need for strong interdisciplinary collaborations to ensure appropriate study design and biomarker validation.

KEYWORDS:

Biomarkers; Diagnosis; Mass spectrometry; Neurological infections; Proteomics

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