A blood biomarker of tuberculosis discriminated between people at high risk for tuberculosis and those who remained healthy, but an effective preventive therapy for people at risk remains elusive. The findings of a study have been reported of a host blood signature of TB that differentiated between people who had or would develop active TB and those who remained healthy, and investigated in parallel the effect of giving TB preventive therapy based on a positive signature result.
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 Centre have published the results from a study into a blood-based RNA biomarker which tested diagnostic and prognostic performance for TB and the efficacy of TB preventive therapy for biomarker-positive individuals.
Treatment of all people who have a latent infection with the TB bacterium is not a feasible prospect because the majority of our population is infected and due to the logistical and financial challenges. Importantly, only 5-10% of people with latent infection are at risk of progression to TB disease and would benefit from antibiotic treatment.
The strategy proposed advances the development of a point-of care test blood test with which health practitioners could accurately identify people who have TB disease, or who are likely to progress from latent infection to active TB disease, and make it possible to apply available TB preventive and treatment regimens selectively, and with greater accuracy to those who are most likely to benefit, to impact on transmission in communities.
The study was conducted between 2016 and 2019 across five distinct geographic communities across South Africa. The research team set out to test the performance of a transcriptomic signature of tuberculosis (RISK11), as well as the efficacy of signature-guided preventive therapy using a parallel, three-arm hybrid study design.
A total 20,207 adult volunteers from communities in Worcester, Ravensmead, Durban, Klerksdorp and Rustenberg were screened for participation. More than 80% of detected TB cases did not have any symptom compatible with TB disease and would not have been detected by current TB screening strategies that require symptoms as the entry point to investigation. The RISK11 blood test discriminated between individuals with current TB disease or those who would progress to incident TB within 6 months after testing, and individuals who remained healthy, with excellent performance.
Disappointingly, the provision of a 3-month regimen of once-weekly, high-dose isoniazid and rifapentine (3HP), which is effective in treating latent TB infection, did not reduce the rate of TB disease in RISK11-positive participants over 15 months of follow-up.
Performance of RISK11 as a screening test for active disease in people with TB symptoms exceeded the WHO requirements for a triage test. But diagnostic performance in asymptomatic participants did not meet these requirements, highlighting how challenging diagnosis of asymptomatic TB can be.
The RISK11 signature was able to predict risk for TB disease progression in this trial population with TB incidence exceeding one case per 100 person-years, but optimal prognostic performance was limited to a period of 6-month after testing.
This study was funded by the Bill and Melinda Gates Foundation and the South African Medical Research Council.
The Lancet Infectious Diseases study not yet available online