Abstract
Current diagnostic tests for Mycobacterium tuberculosis (MTB) infection have low prognostic specificity for identifying individuals who will develop tuberculosis (TB) disease, making mass preventive therapy strategies targeting all MTB-infected individuals impractical in high-burden TB countries. Here we discuss general considerations for a risk-targeted test-and-treat strategy based on a highly specific transcriptomic biomarker that can identify individuals who are most likely to progress to active TB disease as well as individuals with TB disease who have not yet presented for medical care. Such risk-targeted strategies may offer a rapid, ethical and cost-effective path towards decreasing the burden of TB disease and interrupting transmission and would also be critical to achieving TB elimination in countries nearing elimination. We also discuss design considerations for a Correlate of Risk Targeted Intervention Study (CORTIS), which could provide proof-of-concept for the strategy. One such study in South Africa is currently enrolling 1500 high-risk and 1700 low-risk individuals, as defined by biomarker status, and is randomizing high-risk participants to TB preventive therapy or standard of care treatment. All participants are monitored for progression to active TB with primary objectives to assess efficacy of the treatment and performance of the biomarker.
Highlights
1.7 billion individuals worldwide are infected with Mycobacterium tuberculosis (MTB) [1]
The basic underpinning of the ethical considerations for any clinical trial is that the potential benefits outweigh the potential risks for each participant and a hybrid design in which correlate of risk (COR)+ individuals predicted to be at higher risk of TB disease are not allocated treatment is potentially contentious
A higher COR threshold does not allow for post hoc analyses of a hypothetical lower threshold, since participants with a COR below the actual threshold would not have been randomized to the COR+ groups
Summary
1.7 billion individuals worldwide are infected with Mycobacterium tuberculosis (MTB) [1]. A successful mass campaign to halt TB transmission using a risktargeted test-and-treat strategy would require an effective and safe short-course, sterilizing preventive therapy, such as the 12-dose onceweekly rifapentine 900 mg plus isoniazid 900 mg (3HP) regimen [18,19] This regimen has been shown to be as effective as 9 months of isoniazid alone at preventing TB disease in latently infected individuals [19]; more data are needed to determine its efficacy in a biomarker-selected high-risk subgroup and in hyper-endemic settings with a high force of infection. Applied at the community level, such risk-targeted strategies are anticipated to accelerate reduction in TB incidence and mortality and to reduce the pool of MTB-infected individuals independently of ongoing improvements in TB vaccines, diagnostics, and therapeutics
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
