You are here

Article Text

Article menu
XML
Infectious diseases
Protocol
Host blood transcriptomic biomarkers of tuberculosis disease in people living with HIV: a systematic review protocol
  1. Simon C Mendelsohn1,
  2. Humphrey Mulenga1,
  3. Stanley Kimbung Mbandi1,
  4. Fatoumatta Darboe1,
  5. Mary Shelton2,
  6. Thomas J Scriba1,
  7. Mark Hatherill1
  1. 1South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, Division of Immunology, Department of Pathology, University of Cape Town Faculty of Health Sciences, Cape Town, Western Cape, South Africa
  2. 2Bongani Mayosi Health Sciences Library, University of Cape Town, Cape Town, Western Cape, South Africa
  1. Correspondence to Professor Mark Hatherill; mark.hatherill{at}uct.ac.za

Abstract

Introduction Current tuberculosis triage and predictive tools offer poor accuracy and are ineffective for detecting asymptomatic disease in people living with HIV (PLHIV). Host tuberculosis transcriptomic biomarkers hold promise for diagnosing prevalent and predicting progression to incident tuberculosis and guiding further investigation, preventive therapy and follow-up. We aim to conduct a systematic review of performance of transcriptomic signatures of tuberculosis in PLHIV.

Methods and analysis We will search MEDLINE (PubMed), WOS Core Collection, Biological Abstracts, and SciELO Citation Index (Web of Science), Africa-Wide Information and General Science Abstracts (EBSCOhost), Scopus, and Cochrane Central Register of Controlled Trials databases for articles published in English between 1990 and 2020. Case–control, cross-sectional, cohort and randomised controlled studies evaluating performance of diagnostic and prognostic host-response transcriptomic signatures in PLHIV of all ages and settings will be included. Eligible studies will include PLHIV in signature test or validation cohorts, and use microbiological, clinical, or composite reference standards for pulmonary or extrapulmonary tuberculosis diagnosis. Study quality will be evaluated using the ‘Quality Assessment of Diagnostic Accuracy Studies-2’ tool and cumulative review evidence assessed using the ‘Grading of Recommendations Assessment, Development and Evaluation’ approach. Study selection, quality appraisal and data extraction will be performed independently by two reviewers. Study, cohort and signature characteristics of included studies will be tabulated, and a narrative synthesis of findings presented. Primary outcomes of interest, biomarker sensitivity and specificity with estimate precision, will be summarised in forest plots. Expected heterogeneity in signature characteristics, study settings, and study designs precludes meta-analysis and pooling of results. Review reporting will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses of Diagnostic Test Accuracy Studies guidelines.

Ethics and dissemination Formal ethics approval is not required as primary human participant data will not be collected. Results will be disseminated through peer-reviewed publication and conference presentation.

PROSPERO registration number CRD42021224155.

  • tuberculosis
  • HIV & AIDS
  • molecular diagnostics
http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

https://doi.org/10.1136/bmjopen-2021-048623

Statistics from Altmetric.com

    Request Permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

    View Full Text

    Supplementary materials

    • Supplementary Data

      This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.

    Footnotes

    • TJS and MH contributed equally.

    • Contributors SCM and MH conceived the idea and planned the study protocol. SCM, MS and MH undertook a scoping search and designed the search strategy. SCM wrote the protocol under supervision from MH and TS. SCM, HM, SKM, FD, MS, TS, and MH have contributed to, reviewed, and approved the final protocol, and will participate in the interpretation of the results.

    • Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. SCM is a recipient of PhD funding from the Fogarty International Center of the National Institutes of Health (NIH) under Award Number D43 TW010559, the Harry Crossley Clinical Research Fellowship, the South African Medical Research Council (SAMRC) through its Division of Research Capacity Development under the SAMRC Clinician Researcher Programme, and the South African Medical Association (SAMA).

    • Disclaimer The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH, Harry Crossley Foundation, SAMRC, or SAMA.

    • Competing interests TS is a coinventor of two patents of host-blood transcriptomic signatures of tuberculosis risk.

    • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

    • Provenance and peer review Not commissioned; externally peer reviewed.