Current status and future of tuberculosis precision medicine_West China Medical Journal

Authors：

GU Jin ¹ ,  TANG Shenjie ²

1. Clinical and Research Center of Tuberculosis, Shanghai Key Lab of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, P. R. China;
2. Multidisciplinary Diagnosis and Treatment Center, Beijing Chest Hospital, Capital Medical University; Beijing Tuberculosis and Thoracic Tumor Research Institute; Beijing 101149, P. R. China;

Corresponding author：

TANG Shenjie, Email: tangsj1106@vip.sina.com

Keywords：

Tuberculosis; Precision medicine; Drug-resistant tuberculosis; Host-directed therapy; Nano-targeted therapy

DOI：

10.7507/1002-0179.201807046

Video：

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The application of precision medicine in the field of tuberculosis is still in its infancy. The precision medicine of tuberculosis cannot be separated from the rapid and accurate diagnosis, the effective anti-tuberculosis drugs, and the comprehensive application of new cutting-edge technologies. In recent years, the precision medicine of tuberculosis has focused on drug-resistant tuberculosis, host-directed therapy and nano-targeted therapy, which has achieved certain results, providing an important mean for the treatment of tuberculosis, especially for the drug-resistant tuberculosis. In the future, the development of new drugs and the application of emerging technologies are the focus of precision medicine of tuberculosis. It is necessary to gradually carry out relevant clinical trial research and objectively evaluate its application value and prospects.

Citation： GU Jin, TANG Shenjie. Current status and future of tuberculosis precision medicine. West China Medical Journal, 2018, 33(8): 930-934. doi: 10.7507/1002-0179.201807046 Copy

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7.	Tiberi S, du Plessis N, Walzl G, et al. Tuberculosis: progress and advances in development of new drugs, treatment regimens, and host-directed therapies. Lancet Infect Dis, 2018, 18(7): e183-e198.
8.	World Health Organization. WHO treatment guidelines for drug-resistant tuberculosis, 2016 update. October 2016 revision. Geneva: World Health Organization, 2016. http://apps.who.int/iris/bitstream/handle/10665/250125/9789241549639-eng.pdf;sequence=1.
9.	World Health Organization. WHO treatment guidelines for isoniazid-resistant tuberculosis: supplement to the WHO treatment guidelines for drug-resistant tuberculosis. Geneva: World Health Organization, 2018. http://apps.who.int/iris/ bitstream/handle/10665/260494/9789241550079-eng.pdf?sequence=1.
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11.	Keane J, Gershon S, Wise RP, et al. Tuberculosis associated with infliximab, a tumor necrosis factor α-neutralizing agent. N Engl J Med, 2001, 345(15): 1098-1104.
12.	Koo MS, Manca C, Yang G, et al. Phosphodiesterase 4 inhibition reduces innate immunity and improves isoniazid clearance of Mycobacterium tuberculosis in the lungs of infected mice. PLoS One, 2011, 6(2): e17091.
13.	Tsenova L, O’brien P, Holloway J, et al. Etanercept exacerbates inflammation and pathology in a rabbit model of active pulmonary tuberculosis. J Interferon Cytokine Res, 2014, 34(9): 716-726.
14.	Oehlers SH, Cronan MR, Scott NR, et al. Interception of host angiogenic signalling limits mycobacterial growth. Nature, 2015, 517(7536): 612-615.
15.	Datta M, Via LE, Kamoun WS, et al. Anti-vascular endothelial growth factor treatment normalizes tuberculosis granuloma vasculature and improves small molecule delivery. Proc Natl Acad Sci USA, 2015, 112(6): 1827-1832.
16.	Mily A, Rekha RS, Kamal SM, et al. Significant effects of oral phenylbutyrate and vitamin D₃ adjunctive therapy in pulmonary tuberculosis: a randomized controlled trial. PLoS One, 2015, 10(9): e0138340.
17.	Coussens AK, Wilkinson RJ, Hanifa YA, et al. Vitamin D accelerates resolution of inflammatory responses during tuberculosis treatment. Proc Natl Acad Sci USA, 2012, 109(38): 15449-15454.
18.	Salahuddin N, Ali F, Hasan Z, et al. Vitamin D accelerates clinical recovery from tuberculosis: results of the SUCCINCT Study [Supplementary cholecalciferol in recovery from tuberculosis]. A randomized, placebo-controlled, clinical trial of vitamin D supplementation in patients with pulmonar. BMC Infect Dis, 2013, 13(1): 22.
19.	Schiebler M, Brown K, Hegyi K, et al. Functional drug screening reveals anticonvulsants as enhancers of mTOR-independent autophagic killing of Mycobacterium tuberculosis through inositol depletion. EMBO Mol Med, 2015, 7(2): 127-139.
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25.	Skrahin A, Ahmed RK, Ferrara G, et al. Autologous mesenchymal stromal cell infusion as adjunct treatment in patients with multidrug and extensively drug-resistant tuberculosis: an open-label phase 1 safety trial. Lancet Respir Med, 2014, 2(2): 108-122.
26.	Joshi L, Chelluri LK, Gaddam S. Mesenchymal stromal cell therapy in MDR/XDR tuberculosis: a concise review. Arch Immunol Ther Exp (Warsz), 2015, 63(6): 427-433.
27.	张立群, 唐神结. 纳米技术在结核病中的应用研究及其进展. 中华结核和呼吸杂志, 2016, 39(5): 393-395.
28.	Mukherjee B. Nanosize drug delivery system. Curr Pharm Biotechnol, 2013, 14(15): 1221.
29.	Coler RN, Bertholet S, Pine SO, et al. Therapeutic immunization against Mycobacterium tuberculosis is an effective adjunct to antibiotic treatment. J Infect Dis, 2013, 207(8): 1242-1252.
30.	Dhanasooraj D, Kumar RA, Mundayoor S. Vaccine delivery system for tuberculosis based on nano-sized hepatitis B virus core protein particles. Int J Nanomedicine, 2013, 8: 835-843.
31.	Feng G, Jiang Q, Xia M, et al. Enhanced immune response and protective effects of nano-chitosan-based DNA vaccine encoding T cell epitopes of Esat-6 and FL against Mycobacterium tuberculosis infection. PLoS One, 2013, 8(4): e61135.
32.	Gaspar DP, Faria V, Gonçalves LM, et al. Rifabutin-loaded solid lipid nanoparticles for inhaled antitubercular therapy: physicochemical and in vitro studies. Int J Pharm, 2016, 497(1/2): 199-209.
33.	Boeree MJ, Heinrich N, Aarnoutse R, et al. High-dose rifampicin, moxifloxacin, and SQ109 for treating tuberculosis: a multi-arm, multi-stage randomised controlled trial. Lancet Infect Dis, 2017, 17(1): 39-49.
34.	Lee RE, Hurdle JG, Liu J, et al. Spectinamides: a new class of semisynthetic antituberculosis agents that overcome native drug efflux. Nat Med, 2014, 20(2): 152-158.

1. Collins FS, Varmus H. A new initiative on precision medicine. N Engl J Med, 2015, 372(9): 793-795.
2. World Health Organization. Global tuberculosis report 2017. Geneva: World Health Organization, 2017: 23. http://www.who.int/tb/publications/global_report/gtbr2017_main_text.pdf.
3. Dorman SE, Schumacher SG, Alland D, et al. Xpert MTB/RIF ultra for detection of Mycobacterium tuberculosis and rifampicin resistance: a prospective multicentre diagnostic accuracy study. Lancet Infect Dis, 2018, 18(1): 76-84.
4. Walzl G, Mcnerney R, du Plessis N, et al. Tuberculosis: advances and challenges in development of new diagnostics and biomarkers. Lancet Infect Dis, 2018, 18(7): e199-e210.
5. World Health Organization. Companion handbook to the WHO guidelines for the programmatic management of drug-resistant tuberculosis. Geneva: World Health Organization, 2014: 11. http://apps.who.int/iris/bitstream/handle/10665/130918/9789241548809_eng.pdf?sequence=1.
6. World Health Organization. The use of molecular line probe assays for the detection of resistance to second-line anti-tuberculosis drugs. Policy guidance. Geneva: World Health Organization, 2016. http://www.who.int/tb/WHOPolicyStatementSLLPA.pdf.
7. Tiberi S, du Plessis N, Walzl G, et al. Tuberculosis: progress and advances in development of new drugs, treatment regimens, and host-directed therapies. Lancet Infect Dis, 2018, 18(7): e183-e198.
8. World Health Organization. WHO treatment guidelines for drug-resistant tuberculosis, 2016 update. October 2016 revision. Geneva: World Health Organization, 2016. http://apps.who.int/iris/bitstream/handle/10665/250125/9789241549639-eng.pdf;sequence=1.
9. World Health Organization. WHO treatment guidelines for isoniazid-resistant tuberculosis: supplement to the WHO treatment guidelines for drug-resistant tuberculosis. Geneva: World Health Organization, 2018. http://apps.who.int/iris/ bitstream/handle/10665/260494/9789241550079-eng.pdf?sequence=1.
10. 唐神结, 李亮, 高文, 等. 中国结核病年鉴2017. 北京: 人民卫生出版社, 2018.
11. Keane J, Gershon S, Wise RP, et al. Tuberculosis associated with infliximab, a tumor necrosis factor α-neutralizing agent. N Engl J Med, 2001, 345(15): 1098-1104.
12. Koo MS, Manca C, Yang G, et al. Phosphodiesterase 4 inhibition reduces innate immunity and improves isoniazid clearance of Mycobacterium tuberculosis in the lungs of infected mice. PLoS One, 2011, 6(2): e17091.
13. Tsenova L, O’brien P, Holloway J, et al. Etanercept exacerbates inflammation and pathology in a rabbit model of active pulmonary tuberculosis. J Interferon Cytokine Res, 2014, 34(9): 716-726.
14. Oehlers SH, Cronan MR, Scott NR, et al. Interception of host angiogenic signalling limits mycobacterial growth. Nature, 2015, 517(7536): 612-615.
15. Datta M, Via LE, Kamoun WS, et al. Anti-vascular endothelial growth factor treatment normalizes tuberculosis granuloma vasculature and improves small molecule delivery. Proc Natl Acad Sci USA, 2015, 112(6): 1827-1832.
16. Mily A, Rekha RS, Kamal SM, et al. Significant effects of oral phenylbutyrate and vitamin D₃ adjunctive therapy in pulmonary tuberculosis: a randomized controlled trial. PLoS One, 2015, 10(9): e0138340.
17. Coussens AK, Wilkinson RJ, Hanifa YA, et al. Vitamin D accelerates resolution of inflammatory responses during tuberculosis treatment. Proc Natl Acad Sci USA, 2012, 109(38): 15449-15454.
18. Salahuddin N, Ali F, Hasan Z, et al. Vitamin D accelerates clinical recovery from tuberculosis: results of the SUCCINCT Study [Supplementary cholecalciferol in recovery from tuberculosis]. A randomized, placebo-controlled, clinical trial of vitamin D supplementation in patients with pulmonar. BMC Infect Dis, 2013, 13(1): 22.
19. Schiebler M, Brown K, Hegyi K, et al. Functional drug screening reveals anticonvulsants as enhancers of mTOR-independent autophagic killing of Mycobacterium tuberculosis through inositol depletion. EMBO Mol Med, 2015, 7(2): 127-139.
20. Blum CA, Nigro N, Briel M, et al. Adjunct prednisone therapy for patients with community-acquired pneumonia: a multicentre, double-blind, randomised, placebo-controlled trial. Lancet, 2015, 385(9977): 1511-1518.
21. Remmelts HF, Meijvis SA, Biesma DH, et al. Dexamethasone downregulates the systemic cytokine response in patients with community-acquired pneumonia. Clin Vaccine Immunol, 2012, 19(9): 1532-1538.
22. Mortensen EM, Restrepo MI, Anzueto A, et al. The effect of prior statin use on 30-day mortality for patients hospitalized with community-acquired pneumonia. Respir Res, 2005, 6(1): 82.
23. Thomsen RW, Hundborg HH, Johnsen SP, et al. Statin use and mortality within 180 days after bacteremia: a population-based cohort study. Crit Care Med, 2006, 34(4): 1080-1086.
24. Shen H, Min R, Tan Q, et al. The beneficial effects of adjunctive recombinant human interleukin-2 for multidrug resistant tuberculosis. Arch Med Sci, 2015, 11(3): 584-590.
25. Skrahin A, Ahmed RK, Ferrara G, et al. Autologous mesenchymal stromal cell infusion as adjunct treatment in patients with multidrug and extensively drug-resistant tuberculosis: an open-label phase 1 safety trial. Lancet Respir Med, 2014, 2(2): 108-122.
26. Joshi L, Chelluri LK, Gaddam S. Mesenchymal stromal cell therapy in MDR/XDR tuberculosis: a concise review. Arch Immunol Ther Exp (Warsz), 2015, 63(6): 427-433.
27. 张立群, 唐神结. 纳米技术在结核病中的应用研究及其进展. 中华结核和呼吸杂志, 2016, 39(5): 393-395.
28. Mukherjee B. Nanosize drug delivery system. Curr Pharm Biotechnol, 2013, 14(15): 1221.
29. Coler RN, Bertholet S, Pine SO, et al. Therapeutic immunization against Mycobacterium tuberculosis is an effective adjunct to antibiotic treatment. J Infect Dis, 2013, 207(8): 1242-1252.
30. Dhanasooraj D, Kumar RA, Mundayoor S. Vaccine delivery system for tuberculosis based on nano-sized hepatitis B virus core protein particles. Int J Nanomedicine, 2013, 8: 835-843.
31. Feng G, Jiang Q, Xia M, et al. Enhanced immune response and protective effects of nano-chitosan-based DNA vaccine encoding T cell epitopes of Esat-6 and FL against Mycobacterium tuberculosis infection. PLoS One, 2013, 8(4): e61135.
32. Gaspar DP, Faria V, Gonçalves LM, et al. Rifabutin-loaded solid lipid nanoparticles for inhaled antitubercular therapy: physicochemical and in vitro studies. Int J Pharm, 2016, 497(1/2): 199-209.
33. Boeree MJ, Heinrich N, Aarnoutse R, et al. High-dose rifampicin, moxifloxacin, and SQ109 for treating tuberculosis: a multi-arm, multi-stage randomised controlled trial. Lancet Infect Dis, 2017, 17(1): 39-49.
34. Lee RE, Hurdle JG, Liu J, et al. Spectinamides: a new class of semisynthetic antituberculosis agents that overcome native drug efflux. Nat Med, 2014, 20(2): 152-158.

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