Systematic review of diagnostic and prognostic host blood transcriptomic signatures of tuberculosis disease in people living with HIV [version 2; peer review: 2 approved]
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...
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| Format: | Article |
| Language: | English |
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F1000 Research Ltd
2023-05-01
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| Series: | Gates Open Research |
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| Online Access: | https://gatesopenresearch.org/articles/7-27/v2 |
| _version_ | 1797832771644686336 |
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| author | Simon C Mendelsohn Humphrey Mulenga Savannah Verhage Thomas J Scriba Mark Hatherill |
| author_facet | Simon C Mendelsohn Humphrey Mulenga Savannah Verhage Thomas J Scriba Mark Hatherill |
| author_sort | Simon C Mendelsohn |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-09T14:14:11Z |
| format | Article |
| id | doaj.art-7530a3cf362c4c4fbb6c53266f2911b0 |
| institution | Directory Open Access Journal |
| issn | 2572-4754 |
| language | English |
| last_indexed | 2024-04-09T14:14:11Z |
| publishDate | 2023-05-01 |
| publisher | F1000 Research Ltd |
| record_format | Article |
| series | Gates Open Research |
| spelling | doaj.art-7530a3cf362c4c4fbb6c53266f2911b02023-05-06T00:00:00ZengF1000 Research LtdGates Open Research2572-47542023-05-01716010Systematic review of diagnostic and prognostic host blood transcriptomic signatures of tuberculosis disease in people living with HIV [version 2; peer review: 2 approved]Simon C Mendelsohn0Humphrey Mulenga1Savannah Verhage2Thomas J Scriba3Mark Hatherill4https://orcid.org/0000-0003-3491-1809South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, Western Cape, 7935, South AfricaSouth African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, Western Cape, 7935, South AfricaSouth African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, Western Cape, 7935, South AfricaSouth African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, Western Cape, 7935, South AfricaSouth African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, Western Cape, 7935, South AfricaBackground 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.https://gatesopenresearch.org/articles/7-27/v2Host blood diagnostic prognostic gene signatureseng |
| spellingShingle | Simon C Mendelsohn Humphrey Mulenga Savannah Verhage Thomas J Scriba Mark Hatherill Systematic review of diagnostic and prognostic host blood transcriptomic signatures of tuberculosis disease in people living with HIV [version 2; peer review: 2 approved] Gates Open Research Host blood diagnostic prognostic gene signatures eng |
| title | Systematic review of diagnostic and prognostic host blood transcriptomic signatures of tuberculosis disease in people living with HIV [version 2; peer review: 2 approved] |
| title_full | Systematic review of diagnostic and prognostic host blood transcriptomic signatures of tuberculosis disease in people living with HIV [version 2; peer review: 2 approved] |
| title_fullStr | Systematic review of diagnostic and prognostic host blood transcriptomic signatures of tuberculosis disease in people living with HIV [version 2; peer review: 2 approved] |
| title_full_unstemmed | Systematic review of diagnostic and prognostic host blood transcriptomic signatures of tuberculosis disease in people living with HIV [version 2; peer review: 2 approved] |
| title_short | Systematic review of diagnostic and prognostic host blood transcriptomic signatures of tuberculosis disease in people living with HIV [version 2; peer review: 2 approved] |
| title_sort | systematic review of diagnostic and prognostic host blood transcriptomic signatures of tuberculosis disease in people living with hiv version 2 peer review 2 approved |
| topic | Host blood diagnostic prognostic gene signatures eng |
| url | https://gatesopenresearch.org/articles/7-27/v2 |
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