Lancet Global Health: A blood test to find those at high risk of tuberculosis in people living with HIV.

14 Apr 2021
Blood test TB
14 Apr 2021

The Lancet Global Health journal reports the findings of a study of a host blood test that can find those at high risk of tuberculosis in people living with HIV. The blood mRNA biomarker differentiated between people living with HIV who had active tuberculosis from those without TB, and predicted which individuals would develop TB within 15 months.

Performance of host blood transcriptomic signatures for diagnosing and predicting progression to tuberculosis disease in HIV-negative adults and adolescents: a systematic review protocol

14 April 2021: Researchers from the South African Tuberculosis Vaccine Initiative at the University of Cape Town, the Aurum Institute, the Centre for the AIDS Programme of Research in South Africa, Stellenbosch University, the London School of Hygiene and Tropical Medicine and the Fred Hutchinson Cancer Research Center have published the results from a study of a blood-based RNA biomarker which tested diagnostic and prognostic performance for tuberculosis (TB) in people living with HIV in The Lancet Global Health journal.


Almost a quarter of the world’s population is estimated to be infected with the bacterium (M. tuberculosis) responsible for TB disease. Importantly, only 5-10% of people with the infection are at risk of progression to TB disease and would benefit from antibiotic treatment. Existing tests for M. tuberculosis infection (the tuberculin skin test [TST] or interferon gamma release assay [IGRA]) would result in considerable over-treatment with preventive therapy. Traditional TB symptom screening would miss the majority of undiagnosed TB in people living with HIV in community settings, as the majority of early TB is asymptomatic. The repercussions of a missed TB diagnosis in people living with HIV are potentially catastrophic: severe illness, hospitalisation, long-term lung damage, and death. A delayed diagnosis could also potentially allow onward transmission of TB to family members and close contacts.

These results bring us one step closer to a TB blood test for use at point of care to guide curative and preventive TB therapy for people living with HIV”

Prof. Mark Hatherill. 

This publication advances the development of a point-of care blood test with which health practitioners could accurately identify people at risk of TB disease, who would then require confirmatory diagnostic testing and treatment, or others who are likely to progress from M. tuberculosis infection to active TB disease and make it possible to apply available TB preventive antibiotic regimens selectively to those who are most likely to benefit in communities.

These promising results are similar to those seen in a trial of the RISK11 biomarker in HIV-uninfected persons. They highlight the importance of finding people with undiagnosed, subclinical TB.

Prof. Tom Scriba, SATVI


The research team set out to test the diagnostic and prognostic performance of a blood-based RNA biomarker of TB risk (RISK11) in people living with HIV. The study was conducted between 2017 and 2019 across five distinct geographic communities across South Africa.

Results: A total of 861 adults living with HIV from communities in Worcester, Ravensmead, Durban, Klerksdorp, and Rustenberg were screened for participation. All participants were intensively tested for TB at baseline, if symptomatic during the 15-months of follow up, and again at the end of the study. More than 70% of detected TB cases did not have any symptom compatible with TB disease and would not have been detected by current TB screening strategies, which require symptoms as the entry point to investigation. The RISK11 blood test differentiated between individuals with current TB disease or those who would progress to incident TB within 15 months after testing, and individuals who remained healthy, with excellent performance. The risk of current TB was 13-times higher in those with a positive RISK11 test versus a negative RISK11 test, and the risk of developing TB within 15 months of testing was 16-times higher in those with a positive RISK11 test versus a negative RISK11 test. The recorded performance of RISK11 as a screening test for active disease in people living with HIV with TB symptoms exceeds the World Health Organisation requirements for a triage test. Diagnostic performance in asymptomatic participants also approached these requirements. The RISK11 signature was able to predict TB disease progression within 15 months of testing in this trial population with prognostic performance approaching, but not meeting, the World Health Organisation requirements for a TB prognostic test.

Current South African guidelines advocate 12 months of universal isoniazid preventive therapy for people living with HIV who have not yet received TB preventive therapy, irrespective of M. tuberculosis infection status. This study suggests that an RNA biomarker of TB risk, such as RISK11, might be more specific in determining need for targeted preventive therapy for people living with HIV. Two-thirds of the 38 million people living with HIV worldwide are on antiretroviral therapy and, with the advent of well tolerated and effective short-course TB preventive regimens, annual or semi-annual community-based testing of people living with HIV might be useful to monitor risk of progression to TB and target those likely to benefit from repeat courses of preventive therapy.


CitationMendelsohn SC, Fiore-Gartland A, Penn-Nicholson A, Mulenga H, Mbandi SK, Borate B, Hadley K, Hikuam C, Musvosvi M, Bilek N, Erasmus M, Jaxa L, Raphela R, Nombida O, Kaskar M, Sumner T, White RG, Innes C, Brumskine W, Hiemstra A, Malherbe ST, Hassan-Moosa R, Tameris M, Walzl G, Naidoo K, Churchyard G, Scriba TJ, Hatherill M; CORTIS-HR Study Team. V2021. alidation of a host blood transcriptomic biomarker for pulmonary tuberculosis in people living with HIV: a prospective diagnostic and prognostic accuracy study. Lancet Global Health, 9(6):e841-e853. Click here. 


Funding: This study was funded by the Bill & Melinda Gates Foundation and the South African Medical Research Council.

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