Персонализированный подход как основа будущей диагностики туберкулёза (обзор литературы)

Несмотря на внедрение программ, нацеленных на совершенствование системы эпидемиологического над-зора за туберкулёзом, глобальное распространение данного заболевания остаётся одной из актуальных проблем практического здравоохранения. Анализ данных, представленных в современной отечественной и  зарубежной  литературе,  позволяет  сделать  выводы  о  том,  что  лечение  туберкулёзной  инфекции должно иметь персонализированный подход. В первую очередь это обусловлено тем, что взаимодействие патогенных микобактерий с организмом человека представляет собой процесс противостояния микро-организма, «вооружённого» специфическими факторами вирулентности, факторам иммунной защиты макроорганизма. Кроме этого, особое значение в прогнозе исхода заболевания и эффективности лечения, играет определение принадлежности выделенного из клинического материала штамма Mycobacterium tuberculosis к известному эпидемически значимому генотипу, например, к генотипу Beijing. Следует также отметить, что эволюционная «эффективность» данного генотипа основана на большом разнообразии мутаций, активно способствующих как выживанию в организме хозяина и преодолению защитных ме-ханизмов его иммунной системы, так и формированию новых «стратегий выживания», основанных на агрессивном течении болезни, высокой вирулентности и низкой эффективности применения специфических противотуберкулёзных препаратов. Рост числа новых случаев инфицирования населения данным геноти-пом в ранее благополучных по туберкулёзной инфекции странах требует к себе пристального внимания. В  схемы  диагностики  данного  заболевания  необходимо  включать  не  только  обнаружение  патогена  и определение профиля чувствительности инфекционного агента к противотуберкулёзным препаратам, но и исследование особенностей полиморфизма генов иммунной системы человека. Такой подход позволит понять возможное развитие заболевания и вовремя подобрать индивидуальную схему лечения.

1. Houben RMGJ, Dodd PJ. The global burden of latent tuberculosis infection: A re-estimation using mathematical modelling. PLoS Med. 2016; 13(10): e1002152. doi: 10.1371/journal.pmed.1002152

2. Васильева И.А., Белиловский Е.М., Борисов С.Е., Стерликов С.А. Заболеваемость, смертность и распространенность как показатели бремени туберкулёза в регионах ВОЗ, странах мира и в Российской Федерации. Часть 1. Заболеваемость и распространенность туберкулёза. Туберкулёз и болезни лёгких. 2017; 95(6): 9-21. doi: 10.21292/2075-1230-2017-95-6-9-21

3. Хромова П.А., Огарков О.Б., Жданова С.Н., Синьков В.В., Моисеева Е.Я., Цыренова Т.А., и др. Выявление высокотрансмиссивных генотипов возбудителя в клиническом материале для прогноза неблагоприятного течения туберкулёза. Клиническая лабораторная диагностика.2017; 10(62): 622-627. doi: 10.18821/0869-2084-2017-62-10-622-627

4. Жданова С.Н., Огарков О.Б., Винокурова М.К., Алексеева Г.И., Кравченко А.Ф., Савилов Е.Д. Моделирование эпидемического распространения генотипа Beijing Mycobacterium tuberculosisв Республике Саха (Якутия). Туберкулёз и болезни лёгких.2017; 7(95): 40-47. doi: 10.21292/2075-1230-2017-95-7-40-47

5. Савилов Е.Д., Синьков В.В., Огарков О.Б. Эпидемиология туберкулёза на Евро-Азиатском континенте: оценка глобального движения штаммов генотипа «Пекин».Иркутск: РИО ГБОУ ДПО ИГМАПО; 2013.

6. Schulte PA, Perera FP. Molecular Epidemiology: Principles and Practices. Orlando, FL: Academic Press; 1993.

7. van Soolingen D, Qian L, de Haas PE, Douglas JT, Traore H, Portaels F, et al. Predominance of a single genotype of Mycobacterium tuberculosis in countries of East Asia. J Clin Microbiol.1995; 33(12): 3234-3238.

8. Bifani PJ, Mathema B, Kurepina NE, Kreiswirth BN. Global dissemination of the Mycobacterium tuberculosis W-Beijing family strains. Trends Microbiol2002; 10(1): 45-52.

9. Sinkov VV, Savilov ED, Ogarkov OB. Reconstruction of the epidemic history of the Beijing genotype of Mycobacterium tuberculosis in Russia and former Soviet countries using spoligotyping. Mol Genet Microbiol Virol. 2011; 26(3): 120-125. doi: 10.3103/S0891416811030050

10. Огарков О.Б., Савилов Е.Д., Синьков В.В. К истории заноса и распространения «Пекинского» генотипа Mycobacterium tuberculosis на территории России и постсоветском пространстве. Туберкулёз и болезни лёгких. 2011; 5(88): 84-85.

11. Fedrizzi T, Meehan CJ, Grottola A, Giacobazzi E, Fregni Serpini G, Tagliazucchi S, et al. Genomic characterization of nontuberculous mycobacteria. Sci Rep. 2017; 7: 45258. doi: 10.1038/srep45258

12. Rogall T, Wolters J, Flohr T, Böttger E.C. Towards a phylogeny and definition of species at the molecular level within the genus Mycobacterium. Int J Syst Bacteriol.1990; 40(4): 323-330. doi: 10.1099/00207713-40-4-323

13. Brites D, Gagneux S. Old and new selective pressures on Mycobacterium tuberculosis. Infect Genet Evol.2012; 12(4): 678-685. doi: 10.1016/j.meegid.2011.08.010

14. Jang J, Becq J, Gicquel B, Deschavanne P, Neyrolles O. Horizontally acquired genomic islands in the tubercle bacilli. Trends Microbiol. 2008; 16(7): 303-308. doi: 10.1016/j.tim.2008.04.005

15. VanderVen BC, Huang L, Rohde KH, Russell DG. The minimal unit of infection: Mycobacterium tuberculosis in the macrophage. In: Jacobs Jr W, McShane H, Mizrahi V, Orme I (ed.). Tuberculosis and the Tubercle Bacillus. Second Edition. ASM Press, Washington, DC; 2017: 635-652. doi: 10.1128/microbiolspec.TBTB2-0025-2016

16. Dheda K, Barry CE, Maartens G. Tuberculosis. Lancet (London, England). 2016; 387(10024): 1211-1226. doi: 10.1016/S0140-6736(15)00151-8

17. Brites D, Gagneux S. Co-evolution of Mycobacterium tuberculosis and Homo sapiens. Immunol Rev. 2015; 264(1): 6-24. doi: 10.1111/imr.12264

18. Comas I, Coscolla M, Luo T, Borrell S, Holt KE, Kato-Maeda M, et al. Out-of-Africa migration and Neolithic coexpansion of Mycobacterium tuberculosis with modern humans. Nat Genet. 2013; 45(10): 1176-1182. doi: 10.1038/ng.2744

19. Gagneux S. Host-pathogen coevolution in human tuberculosis. Philos Trans R Soc Lond B Biol Sci. 2012; 367(1590): 850-859. doi: 10.1098/rstb.2011.0316

20. Reed MB, Pichler VK, McIntosh F, Mattia A, Fallow A, Masala S, et al. Major Mycobacterium tuberculosis lineages associate with patient country of origin. J Clin Microbiol. 2009; 47(4): 1119-1128. doi: 10.1128/JCM.02142-08

21. Woolhouse MEJ, Webster JP, Domingo E, Charlesworth B, Levin BR. Biological and biomedical implications of the co-evolution of pathogens and their hosts. Nat Genet. 2002; 32(4): 569-577.

22. Meena LS, Rajni. Survival mechanisms of pathogenic Mycobacterium tuberculosis H37Rv. FEBS J. 2010; 277(11): 2416-2427. doi: 10.1111/j.1742-4658.2010.07666.x

23. Stamm CE, Collins AC, Shiloh MU. Sensing of Mycobacterium tuberculosis and consequences to both host and bacillus. Immunol Rev. 2015; 264(1): 204-219. doi: 10.1111/imr.12263

24. O’Garra A, Redford PS, McNab FW, Bloom CI, Wilkinson RJ, Berry MPR. The immune response in tuberculosis. Annu Rev Immunol. 2013; 31: 475-527. doi: 10.1146/annurev-immunol-032712-095939

25. Azad AK, Sadee W, Schlesinger LS. Innate immune gene polymorphisms in tuberculosis. Infect Immun. 2012; 80(10): 3343-3359. doi: 10.1128/IAI.00443-12

26. Kleinnijenhuis J, Oosting M, Joosten LA, Netea MG, Van Crevel R. Innate immune recognition of Mycobacterium tuberculosis. Clin Dev Immunol. 2011; 2011: 405310. doi: 10.1155/2011/405310

27. Tailleux L, Schwartz O, Herrmann JL, Pivert E, Jackson M, Amara A, et al. DC-SIGN is the major Mycobacterium tuberculosis receptor on human dendritic cells. J Exp Med. 2003; 197(1): 121-127.

28. Yi L, Zhang K, Mo Y, Zhen G, Zhao J. The association between CD209 gene polymorphisms and pulmonary tuberculosis susceptibility: a meta-analysis. Int J Clin Exp Pathol. 2015; 8(10): 12437-12445.

29. Chang K, Deng S, Lu W, Wang F, Jia S, Li F, et al. Association between CD209 -336A/G and -871A/G polymorphisms and susceptibility of tuberculosis: a meta-analysis. PloS One. 2012; 7(7): e41519. doi: 10.1371/journal.pone.0041519

30. Ogarkov O, Mokrousov I, Sinkov V, Zhdanova S, Antipina S, Savilov E. ‘Lethal’ combination of Mycobacterium tuberculosis Beijing genotype and human CD209 -336G allele in Russian male population. Infect Genet Evol. 2012; 12(4): 732-736. doi: 10.1016/j.meegid.2011.10.005

31. Ghiran I, Barbashov SF, Klickstein LB, Tas SW, Jensenius JC, Nicholson-Weller A. Complement receptor 1/CD35 is a receptor for mannan-binding lectin. J Exp Med.2000; 192(12): 1797-808.

32. Bonar A, Chmiela M, Rudnicka W, Rózalska B. Mannose-binding lectin enhances the attachment and phagocytosis of mycobacteria in vitro. Arch Immunol Ther Exp (Warsz). 2005; 53(5): 437-441.

33. Ahmadi F, Ghadiri A, NashibI R, Roozbeh F, Alizadeh-Navaei R. Serum mannan-binding lectin in patients with pulmonary tuberculosis: Its lack of a relationship to the disease and response to treatment. Med J Islam Repub Iran. 2017; 31: 66. doi: 10.14196/mjiri.31.66

34. Liu C, He T, Rong Y, Du F, Ma D, Wei Y, et al. Association of mannose-binding lectin polymorphisms with tuberculosis susceptibility among Chinese. Sci Rep. 2016; 6: 36488. doi: 10.1038/srep36488

35. Chen M, Liang Y, Li W, Wang M, Hu L, Abuaku B.K, et al. Impact of MBL and MASP-2 gene polymorphism and its interaction on susceptibility to tuberculosis. BMC Infect Dis. 2015; 15: 151. doi: 10.1186/s12879-015-0879-y

36. Amiri A, Sabooteh T, Shahsavar F, Anbari K, Pouremadi F. Mannose-binding Lectin gene polymorphisms in susceptibility to pulmonary tuberculosis among the Lur population of Lorestan Province of Iran. Genom Data. 2017; 12: 146-150. doi: 10.1016/j.gdata.2017.05.005

37. Guo YL, Liu Y, Ban WJ, Sun Q, Shi GL. Association of mannose-binding lectin gene polymorphisms with the development of pulmonary tuberculosis in China. BMC Infect Dis. 2017; 17(1): 210. doi: 10.1186/s12879-017-2310-3

38. Chalmers JD, Matsushita M, Kilpatrick DC, Hill AT. No strong relationship between components of the lectin pathway of complement and susceptibility to pulmonary tuberculosis. Inflammation. 2015; 38(4): 1731-1737. doi: 10.1007/s10753-015-0150-0

39. Thye T, Niemann S, Walter K, Homolka S, Intemann CD, Chinbuah MA, et al. Variant G57E of mannose binding lectin associated with protection against tuberculosis caused by Mycobacterium africanum but not by M. tuberculosis. PloS One. 2011; 6(6): e20908. doi: 10.1371/journal.pone.0020908

40. Caws M, Thwaites G, Dunstan S, Hawn TR, Lan NT, Thuong NT, et al. The influence of host and bacterial genotype on the development of disseminated disease with Mycobacterium tuberculosis. PLoS Pathog. 2008; 4(3): e1000034. doi: 10.1371/journal.ppat.1000034

41. van Crevel R, Parwati I, Sahiratmadja E, Marzuki S, Ottenhoff TH, Netea MG, et al. Infection with Mycobacterium tuberculosis Beijing genotype strains is associated with polymorphisms in SLC11A1/NRAMP1 in Indonesian patients with tuberculosis. J Infect Dis. 2009; 200(11): 1671-1674. doi: 10.1086/648477

42. Takahashi K, Hasegawa Y, Abe T, Yamamoto T, Nakashima K, Imaizumi K, et al. SLC11A1 (formerly NRAMP1)polymorphisms associated with multidrug-resistant tuberculosis. Tuberculosis (Edinb). 2008; 88(1): 52-57. doi: 10.1016/j.tube.2007.08.008

43. Dunlap MD, Howard N, Das S, Scott N, Ahmed M, Prince O, et al. A novel role for C-C motif chemokine receptor 2 during infection with hypervirulent Mycobacterium tuberculosis. Mucosal Immunol. 2018; 11(6): 1727-1742. doi: 10.1038/s41385-018-0071-y

44. Treerat P, Prince O, Cruz-Lagunas A, Muñoz-Torrico M, Salazar-Lezama MA, Selman M, et al. Novel role for IL-22 in protection during chronic Mycobacterium tuberculosis HN878 infection. Mucosal Immunol. 2017; 10(4): 1069-1081. doi: 10.1038/mi.2017.15

45. Behrends J, Renauld JC, Ehlers S, Hölscher C. IL-22 is mainly produced by IFNγ-secreting cells but is dispensable for host protection against Mycobacterium tuberculosis infection. PloS One. 2013; 8(2): e57379. doi: 10.1371/journal.pone.0057379

46. Thuong NT, Tram TT, Dinh TD, Thai PV, Heemskerk D, Bang ND, et al. MARCO variants are associated with phagocytosis, pulmonary tuberculosis susceptibility and Beijing lineage. Genes Immun. 2016; 17(7): 419-425. doi: 10.1038/gene.2016.43

47. Gröschel MI, Sayes F, Simeone R, Majlessi L, Brosch R. ESX secretion systems: mycobacterial evolution to counter host immunity. Nat Rev Microbiol. 2016; 14(11): 677-691. doi: 10.1038/nrmicro.2016.131

48. Ates LS, van der Woude AD, Bestebroer J, van Stempvoort G, Musters RJ, Garcia-Vallejo JJ, et al. The ESX-5 system of pathogenic mycobacteria is involved in capsule integrity and virulence through its substrate PPE10. PLoS Pathog. 2016; 12(6): e1005696. doi: 10.1371/journal.ppat.1005696

49. Forrellad MA, Klepp LI, Gioffré A, Sabio García J, Morbidoni HR, de la Paz Santangelo M, et al. Virulence factors of the Mycobacterium tuberculosis complex. Virulence. 2013; 4(1): 3-66. doi: 10.4161/viru.22329

50. Choi SY, Kwon KW, Kim H, Choi HH, Shin SJ. Vaccine potential of ESAT-6 protein fused with consensus CD4+ T-cell epitopes of PE/PPE proteins against highly pathogenic Mycobacterium tuberculosis strain HN878. Biochem Biophys Res Commun. 2018; 503(4): 2195-2201. doi: 10.1016/j.bbrc.2018.06.017

51. Ates LS, Dippenaar A, Ummels R, Piersma SR, van der Woude AD, van der Kuij K, et al. Mutations in ppe38 block PE_PGRS secretion and increase virulence of Mycobacterium tuberculosis. Nat Microbiol. 2018; 3(2): 181-188. doi: 10.1038/s41564-017-0090-6

52. Mokrousov I, Narvskaya O, Vyazovaya A, Millet J, Otten T, Vishnevsky B, et al. Mycobacterium tuberculosis Beijing genotype in Russia: in search of informative variable-number tandem-repeat loci. J Clin Microbiol. 2008; 46(11): 3576-3584. doi: 10.1128/JCM.00414-08

53. Drobniewski F, Balabanova Y, Nikolayevsky V, Ruddy M, Kuznetzov S, Zakharova S, et al. Drug-resistant tuberculosis, clinical virulence, and the dominance of the Beijing strain family in Russia. JAMA. 2005; 293(22): 2726-2731. doi: 10.1001/jama.293.22.2726

54. Merker M, Blin C, Mona S, Duforet-Frebourg N, Lecher S, Willery E, et al. Evolutionary history and global spread of the Mycobacterium tuberculosis Beijing lineage. Nat Genet. 2015; 47(3): 242-249. doi: 10.1038/ng.3195

55. Mokrousov I, Ly HM, Otten T, Lan NN, Vyshnevskyi B, Hoffner S, et al. Origin and primary dispersal of the Mycobacterium tuberculosis Beijing genotype: clues from human phylogeography. Genome Res. 2005; 15(10): 1357-1364. doi: 10.1101/gr.384060

56. Синьков В.В., Савилов Е.Д., Огарков О.Б. Эпидемиология туберкулёза в России: эпидемиологические и исторические доказательства в пользу сценария распространения «Пекинского» генотипа M. tuberculosis в XX веке. Эпидемиология и вакцинопрофилактика. 2010; 6(55): 23-28.

57. Савилов Е.Д., Синьков В.В., Огарков О.Б. Пекинский генотип М. Tuberculosis. Эпидемиология и инфекционные болезни. 2010; 4: 50-53.

58. Mokrousov I. Genetic geography of Mycobacterium tuberculosis Beijing genotype: a multifacet mirror of human history? Infect Genet Evol. 2008; 8(6): 777-785. doi: 10.1016/j.meegid.2008.07.003

59. Mokrousov I, Narvskaya O, Limeschenko E, Vyazovaya A, Otten T, Vyshnevskiy B. Analysis of the allelic diversity of the mycobacterial interspersed repetitive units in Mycobacterium tuberculosis strains of the Beijing family: practical implications and evolutionary considerations. J Clin Microbiol. 2004; 42(6): 2438-2444. doi: 10.1128/JCM.42.6.2438-2444.2004

60. Mokrousov I, Narvskaya O, Vyazovaya A, Otten T, Jiao WW, Gomes LL, et al. Russian “successful” clone B0/W148 of Mycobacterium tuberculosis Beijing genotype: a multiplex PCR assay for rapid detection and global screening. J Clin Microbiol. 2012; 50(11): 3757-3759. doi: 10.1128/JCM.02001-12

61. Bespyatykh J, Smolyakov A, Guliaev A, Shitikov E, Arapidi G, Butenko I, et al. Proteogenomic analysis of Mycobacterium tuberculosis Beijing B0/W148 cluster strains. J Proteomics. 2019; 192: 18-26. doi: 10.1016/j.jprot.2018.07.002

62. Narvskaya O, Otten T, Limeschenko E, Sapozhnikova N, Graschenkova O, Steklova L, et al. Nosocomial outbreak of multidrug-resistant tuberculosis caused by a strain of Mycobacterium tuberculosis W-Beijing family in St. Petersburg, Russia. Eur J Clin Microbiol Infect Dis. 2002; 21(8): 596-602. doi: 10.1007/s10096-002-0775-4

63. Borrell S, Gagneux S. Infectiousness, reproductive fitness and evolution of drug-resistant Mycobacterium tuberculosis. Int J Tuberc Lung Dis. 2009; 13(12): 1456-1466.

64. Billington OJ, McHugh TD, Gillespie SH. Physiological cost of rifampin resistance induced in vitro in Mycobacterium tuberculosis. Antimicrob Agents Chemother.1999; 43(8): 1866-1869.

65. Pym AS, Saint-Joanis B, Cole ST. Effect of katG mutations on the virulence of Mycobacterium tuberculosis and the implication for transmission in humans. Infect Immun. 2002; 70(9): 4955-4960.

66. Lasunskaia E, Ribeiro SC, Manicheva O, Gomes LL, Suffys PN, Mokrousov I, et al. Emerging multidrug resistant Mycobacterium tuberculosis strains of the Beijing genotype circulating in Russia express a pattern of biological properties associated with enhanced virulence. Microbes Infect. 2010; 12(6): 467-475. doi: 10.1016/j.micinf.2010.02.008

67. Ritter C, Lucke K, Sirgel FA, Warren RW, van Helden PD, Böttger EC, et al. Evaluation of the AID TB resistance line probe assay for rapid detection of genetic alterations associated with drug resistance in Mycobacterium tuberculosis strains. J Clin Microbiol. 2014; 52(3): 940-946. doi: 10.1128/JCM.02597-13

68. Nathavitharana RR, Hillemann D, Schumacher SG, Schlueter B, Ismail N, Omar SV, et al. Multicenter noninferiority evaluation of hain genotype MTBDRplus version 2 and Nipro NTM+MDRTB line probe assays for detection of rifampin and isoniazid resistance. J Clin Microbiol. 2016; 54(6): 1624-1630. doi: 10.1128/JCM.00251-16

69. Helb D, Jones M, Story E, Boehme C, Wallace E, Ho K, et al. Rapid detection of Mycobacterium tuberculosis and rifampin resistance by use of on-demand, near-patient technology. J Clin Microbiol. 2010; 48(1): 229-237. doi: 10.1128/JCM.01463-09

70. García-Basteiro A.L, DiNardo A, Saavedra B, Silva D.R, Palmero D, Gegia M, et al. Point of care diagnostics for tuberculosis. Pulmonology. 2018; 24(2): 73-85. doi: 10.1016/j.rppnen.2017.12.002

71. Notomi T, Mori Y, Tomita N, Kanda H. Loop-mediated isothermal amplification (LAMP): principle, features, and future prospects. J Microbiol. 2015; 53(1): 1-5. doi: 10.1007/s12275-015-4656-9

72. Kostera J, Leckie G, Tang N, Lampinen J, Szostak M, Abravaya K, et al. Analytical and clinical performance characteristics of the Abbott RealTime MTB RIF/INH Resistance, an assay for the detection of rifampicin and isoniazid resistant Mycobacterium tuberculosis in pulmonary specimens. Tuberculosis (Edinb).2016; 101: 137-143. doi: 10.1016/j.tube.2016.09.006

73. Scott L, David A, Noble L, Nduna M, Silva PD, Black A, et al. Performance of the Abbott Real Time MTB and MTB RIF/INH Assays in a Setting of High Tuberculosis and HIV co-infection in South Africa. J Clin Microbiol. 2017; 55(8): 2491-2501. doi: 10.1128/JCM.00289-17

74. Horita N, Yamamoto M, Sato T, Tsukahara T, Nagakura H, Tashiro K, et al. Sensitivity and specificity of Cobas TaqMan MTB real-time polymerase chain reaction for culture-proven Mycobacterium tuberculosis: meta-analysis of 26999 specimens from 17 Studies. Sci Rep. 2015; 5: 18113, doi: 10.1038/srep18113

75. Coll F, McNerney R, Preston MD, Guerra-Assunção JA, Warry A, Hill-Cawthorne G, et al. Rapid determination of anti-tuberculosis drug resistance from whole-genome sequences. Genome Med. 2015; 7(1): 51. doi: 10.1186/s13073-015-0164-0

76. Miotto P, Tessema B, Tagliani E, Chindelevitch L, Starks A.M, Emerson C, et al. A standardised method for interpreting the association between mutations and phenotypic drug resistance in Mycobacterium tuberculosis. Eur Respir J. 2017; 50(6): 1701354. doi: 10.1183/13993003.01354-2017

77. McNerney R, Zignol M, Clark TG. Use of whole genome sequencing in surveillance of drug resistant tuberculosis. Expert Rev Anti Infect Ther. 2018; 16(5): 433-442. doi: 10.1080/14787210.2018.1472577

78. Satta G, Atzeni A, McHugh TD. Mycobacterium tuberculosis and whole genome sequencing: a practical guide and online tools available for the clinical microbiologist. Clin Microbiol Infect. 2017; 23(2): 69-72. doi: 10.1016/j.cmi.2016.09.005

79. Walker TM, Merker M, Kohl TA, Crook DW, Niemann S, Peto TE. Whole genome sequencing for M/XDR tuberculosis surveillance and for resistance testing. Clin Microbiol Infect. 2017; 23(3): 161-166. doi: 10.1016/j.cmi.2016.10.014

80. Pankhurst LJ, Del Ojo Elias C, Votintseva AA, Walker TM, Cole K, Davies J, et al. Rapid, comprehensive, and affordable mycobacterial diagnosis with whole-genome sequencing: a prospective study. Lancet Respir Med. 2016; (1): 49-58. doi: 10.1016/S2213-2600(15)00466-X

81. Phelan J, O’Sullivan DM, Machado D, Ramos J, Whale AS, O’Grady J, et al. The variability and reproducibility of whole genome sequencing technology for detecting resistance to anti-tuberculous drugs. Genome Med. 2016; 8(1): 132. doi: 10.1186/s13073-016-0385-x

82. Papaventsis D, Casali N, Kontsevaya I, Drobniewski F, Cirillo D.M, Nikolayevskyy V. Whole genome sequencing of Mycobacterium tuberculosis for detection of drug resistance: a systematic review. Clin Microbiol Infect. 2017; 23(2): 61-68. doi: 10.1016/j.cmi.2016.09.008