Considerations for Biomarker-targeted Intervention Strategies for Tuberculosis Disease Prevention

Overview

Journal Tuberculosis (Edinb)

Specialties Infectious Diseases
Pulmonary Medicine

Date 2018 Mar 22

PMID 29559122

Citations 22

Authors

Andrew Fiore-Gartland

Lindsay N Carpp

Kogieleum Naidoo

Ethan Thompson

Daniel E Zak

Steve Self

Gavin Churchyard

Gerhard Walzl

Adam Penn-Nicholson

Thomas J Scriba

Mark Hatherill

Affiliations

Soon will be listed here.

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.

Citing Articles

Transcriptomic Signatures of Progression to Tuberculosis Disease Among Close Contacts in Brazil.

Mendelsohn S, Andrade B, Mbandi S, Andrade A, Muwanga V, Figueiredo M J Infect Dis. 2024; 230(6):e1355-e1365.

PMID: 38709708 PMC: 11646616. DOI: 10.1093/infdis/jiae237.

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

Mendelsohn S, Verhage S, Mulenga H, Scriba T, Hatherill M Gates Open Res. 2023; 7:27.

PMID: 37123047 PMC: 10133453. DOI: 10.12688/gatesopenres.14327.2.

Functions of exosomal non-coding RNAs to the infection with .

Wang J, Li Y, Wang N, Wu J, Ye X, Jiang Y Front Immunol. 2023; 14:1127214.

PMID: 37033928 PMC: 10073540. DOI: 10.3389/fimmu.2023.1127214.

Biomarkers Correlated with Tuberculosis Preventive Treatment Response: A Systematic Review and Meta-Analysis.

Zhang H, Sun Z, Liu Y, Wei R, Che N Microorganisms. 2023; 11(3).

PMID: 36985316 PMC: 10057454. DOI: 10.3390/microorganisms11030743.

Predictive genomic tools in disease stratification and targeted prevention: a recent update in personalized therapy advancements.

Jain N, Nagaich U, Pandey M, Chellappan D, Dua K EPMA J. 2022; 13(4):561-580.

PMID: 36505888 PMC: 9727029. DOI: 10.1007/s13167-022-00304-2.

References

Kik S, Denkinger C, Casenghi M, Vadnais C, Pai M . Tuberculosis diagnostics: which target product profiles should be prioritised?. Eur Respir J. 2014; 44(2):537-40. DOI: 10.1183/09031936.00027714. View

Churchyard G, Fielding K, Grant A . A trial of mass isoniazid preventive therapy for tuberculosis control. N Engl J Med. 2014; 370(17):1662-3. DOI: 10.1056/NEJMc1402073. View

Penn-Nicholson A, Scriba T, Hatherill M, White R, Sumner T . A novel blood test for tuberculosis prevention and treatment. S Afr Med J. 2017; 107(1):4-5. DOI: 10.7196/SAMJ.2016.v107.i1.12230. View

Malherbe S, Shenai S, Ronacher K, Loxton A, Dolganov G, Kriel M . Persisting positron emission tomography lesion activity and Mycobacterium tuberculosis mRNA after tuberculosis cure. Nat Med. 2016; 22(10):1094-1100. PMC: 5053881. DOI: 10.1038/nm.4177. View

Kunnath-Velayudhan S, Gennaro M . Immunodiagnosis of tuberculosis: a dynamic view of biomarker discovery. Clin Microbiol Rev. 2011; 24(4):792-805. PMC: 3194832. DOI: 10.1128/CMR.00014-11. View

Mahomed H, Ehrlich R, Hawkridge T, Hatherill M, Geiter L, Kafaar F . TB incidence in an adolescent cohort in South Africa. PLoS One. 2013; 8(3):e59652. PMC: 3606161. DOI: 10.1371/journal.pone.0059652. View

Akolo C, Adetifa I, Shepperd S, Volmink J . Treatment of latent tuberculosis infection in HIV infected persons. Cochrane Database Syst Rev. 2010; (1):CD000171. PMC: 7043303. DOI: 10.1002/14651858.CD000171.pub3. View

McIvor A, Koornhof H, Kana B . Relapse, re-infection and mixed infections in tuberculosis disease. Pathog Dis. 2017; 75(3). DOI: 10.1093/femspd/ftx020. View

Smieja M, Marchetti C, Cook D, Smaill F . Isoniazid for preventing tuberculosis in non-HIV infected persons. Cochrane Database Syst Rev. 2000; (2):CD001363. PMC: 6532737. DOI: 10.1002/14651858.CD001363. View

10.

Sacher A, Gandhi L . Biomarkers for the Clinical Use of PD-1/PD-L1 Inhibitors in Non-Small-Cell Lung Cancer: A Review. JAMA Oncol. 2016; 2(9):1217-22. DOI: 10.1001/jamaoncol.2016.0639. View

11.

Janes H, Brown M, Pepe M . Designing a study to evaluate the benefit of a biomarker for selecting patient treatment. Stat Med. 2015; 34(27):3503-15. PMC: 4626364. DOI: 10.1002/sim.6564. View

12.

Bern C . Chagas' Disease. N Engl J Med. 2015; 373(19):1882. DOI: 10.1056/NEJMc1510996. View

13.

Dye C, Glaziou P, Floyd K, Raviglione M . Prospects for tuberculosis elimination. Annu Rev Public Health. 2012; 34:271-86. DOI: 10.1146/annurev-publhealth-031912-114431. View

14.

Bloom C, Graham C, Berry M, Wilkinson K, Oni T, Rozakeas F . Detectable changes in the blood transcriptome are present after two weeks of antituberculosis therapy. PLoS One. 2012; 7(10):e46191. PMC: 3462772. DOI: 10.1371/journal.pone.0046191. View

15.

Mandrekar S, Sargent D . Clinical trial designs for predictive biomarker validation: one size does not fit all. J Biopharm Stat. 2009; 19(3):530-42. PMC: 2931323. DOI: 10.1080/10543400902802458. View

16.

Witney A, Bateson A, Jindani A, Phillips P, Coleman D, Stoker N . Use of whole-genome sequencing to distinguish relapse from reinfection in a completed tuberculosis clinical trial. BMC Med. 2017; 15(1):71. PMC: 5371199. DOI: 10.1186/s12916-017-0834-4. View

17.

Paez J, Janne P, Lee J, Tracy S, Greulich H, Gabriel S . EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science. 2004; 304(5676):1497-500. DOI: 10.1126/science.1099314. View

18.

Stylianou E, Aukrust P, Bendtzen K, Muller F, Froland S . Interferons and interferon (IFN)-inducible protein 10 during highly active anti-retroviral therapy (HAART)-possible immunosuppressive role of IFN-alpha in HIV infection. Clin Exp Immunol. 2000; 119(3):479-85. PMC: 1905596. DOI: 10.1046/j.1365-2249.2000.01144.x. View

19.

Marx F, Dunbar R, Enarson D, Williams B, Warren R, van der Spuy G . The temporal dynamics of relapse and reinfection tuberculosis after successful treatment: a retrospective cohort study. Clin Infect Dis. 2014; 58(12):1676-83. DOI: 10.1093/cid/ciu186. View

20.

Cliff J, Kaufmann S, McShane H, van Helden P, OGarra A . The human immune response to tuberculosis and its treatment: a view from the blood. Immunol Rev. 2015; 264(1):88-102. PMC: 4368415. DOI: 10.1111/imr.12269. View