Latest Research: Systematic review of diagnostic and prognostic host blood transcriptomic signatures of tuberculosis disease in people living with HIV

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SATVI's Professors Mark Hatherill, Tom Scriba, Drs. Simon Mendelsohn & Humphrey Mulenga have authored: "Systematic review of diagnostic & prognostic host blood transcriptomic signatures of  TB disease in people living with HIV" appearing in Gate Open Research. 

Antigen Availability Shapes T Cell Differentiation and Function during Tuberculosis

Abstract

Background HIV-associated tuberculosis (TB) has high mortality; however, current triage and prognostic tools offer poor sensitivity and specificity, respectively. We conducted a systematic review of diagnostic and prognostic host-blood transcriptomic signatures of TB in people living with HIV (PLHIV). Methods We systematically searched online databases for studies published in English between 1990-2020. Eligible studies included PLHIV of any age in test or validation cohorts, and used microbiological or composite reference standards for TB diagnosis. Inclusion was not restricted by setting or participant age. Study selection, quality appraisal using the QUADAS-2 tool, and data extraction were conducted independently by two reviewers. Thereafter, narrative synthesis of included studies, and comparison of signatures performance, was performed. Results We screened 1,580 records and included 12 studies evaluating 31 host-blood transcriptomic signatures in 10 test or validation cohorts of PLHIV that differentiated individuals with TB from those with HIV alone, latent Mycobacterium tuberculosis infection, or other diseases (OD). Two (2/10; 20%) cohorts were prospective (29 TB cases; 51 OD) and 8 (80%) case-control (353 TB cases; 606 controls) design. All cohorts (10/10) were recruited in Sub-Saharan Africa and 9/10 (90%) had a high risk of bias. Ten signatures (10/31; 32%) met minimum WHO Target Product Profile (TPP) criteria for TB triage tests. Only one study (1/12; 8%) evaluated prognostic performance of a transcriptomic signature for progression to TB in PLHIV, which did not meet the minimum WHO prognostic TPP. Conclusions Generalisability of reported findings is limited by few studies enrolling PLHIV, limited geographical diversity, and predominantly case-control design, which also introduces spectrum bias. New prospective cohort studies are needed that include PLHIV and are conducted in diverse settings. Further research exploring the effect of HIV clinical, virological, and immunological factors on diagnostic performance is necessary for development and implementation of TB transcriptomic signatures in PLHIV.

Keywords: HIV; Host; blood; diagnostic; gene; prognostic; signatures; tuberculosis.

Citation: Mendelsohn SC, Verhage S, Mulenga H, Scriba TJ, Hatherill M. Systematic review of diagnostic and prognostic host blood transcriptomic signatures of tuberculosis disease in people living with HIV. Gates Open Research 7:27. Read Publication. 

 

Funding: Bill & Melinda Gates Foundation [OPP1151915]. 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, and the South African Medical Research Council (SAMRC) through its Division of Research Capacity Development under the SAMRC Clinician Researcher Programme. The content is solely the responsibility of the authors and does not necessarily represent the official views of the BMGF, NIH, the Harry Crossley Foundation, or the SAMRC.