Frontiers of Medicine

, Volume 12, Issue 1, pp 76–83 | Cite as

Recent transmission of Mycobacterium tuberculosis in China: the implication of molecular epidemiology for tuberculosis control

  • Chongguang Yang
  • Qian Gao


Tuberculosis (TB) has remained an ongoing concern in China. The national scale-up of the Directly Observed Treatment, Short Course (DOTS) program has accelerated the fight against TB in China. Nevertheless, many challenges still remain, including the spread of drug-resistant strains, high disease burden in rural areas, and enormous rural-to-urban migrations. Whether incident active TB represents recent transmission or endogenous reactivation has helped to prioritize the strategies for TB control. Evidence from molecular epidemiology studies has delineated the recent transmission of Mycobacterium tuberculosis (M. tuberculosis) strains in many settings. However, the transmission patterns of TB in most areas of China are still not clear. Studies carried out to date could not capture the real burden of recent transmission of the disease in China because of the retrospective study design, incomplete sampling, and use of low-resolution genotyping methods. We reviewed the implementations of molecular epidemiology of TB in China, the estimated disease burden due to recent transmission of M. tuberculosis strains, the primary transmission of drug-resistant TB, and the evaluation of a feasible genotyping method of M. tuberculosis strains in circulation.


tuberculosis recent transmission molecular epidemiology China 


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We would like to thank Dr. Ravi Prakash and Ms. Qi Jiang for critically reading and modifying this manuscript. We want to acknowledge the International Postdoctoral Fellowship Program of China Postdoctoral Science Foundation (No. 20150058 to C.Y.).

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  1. 1.
    Wang L, Zhang H, Ruan Y, Chin DP, Xia Y, Cheng S, Chen M, Zhao Y, Jiang S, Du X, He G, Li J, Wang S, Chen W, Xu C, Huang F, Liu X, Wang Y. Tuberculosis prevalence in China, 1990–2010; a longitudinal analysis of national survey data. Lancet 2014; 383 (9934): 2057–2064CrossRefPubMedGoogle Scholar
  2. 2.
    WHO. Global tuberculosis report 2015. Geneva: World Health Organization, 2015. Scholar
  3. 3.
    Zhao Y, Xu S, Wang L, Chin DP, Wang S, Jiang G, Xia H, Zhou Y, Li Q, Ou X, Pang Y, Song Y, Zhao B, Zhang H, He G, Guo J,Wang Y. National survey of drug-resistant tuberculosis in China. N Engl J Med 2012; 366(23): 2161–2170CrossRefPubMedGoogle Scholar
  4. 4.
    Tang S, Ping H. New features and controlling strategies of tuberculosis in the new century in China. Chin J Pract Intern Med (Zhongguo Shi Yong Nei Ke Za Zhi) 2011; 6:403–5 (in Chinese)Google Scholar
  5. 5.
    Lin HH, Wang L, Zhang H, Ruan Y, Chin DP, Dye C. Tuberculosis control in China: use of modelling to develop targets and policies. Bull World Health Organ 2015; 93(11): 790–798CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Small PM, Hopewell PC, Singh SP, Paz A, Parsonnet J, Ruston DC, Schecter GF, Daley CL, Schoolnik GK. The epidemiology of tuberculosis in San Francisco. A population-based study using conventional and molecular methods. N Engl J Med 1994; 330(24): 1703–1709CrossRefPubMedGoogle Scholar
  7. 7.
    Alland D, Kalkut GE, Moss AR, McAdam RA, Hahn JA, Bosworth W, Drucker E, Bloom BR. Transmission of tuberculosis in New York City. An analysis by DNA fingerprinting and conventional epidemiologic methods. N Engl J Med 1994; 330(24): 1710–1716PubMedGoogle Scholar
  8. 8.
    Clark CM, Driver CR, Munsiff SS, Driscoll JR, Kreiswirth BN, Zhao B, Ebrahimzadeh A, Salfinger M, Piatek AS, Abdelwahab J. Universal genotyping in tuberculosis control program, New York City, 2001–2003. Emerg Infect Dis 2006; 12(5): 719–724CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Glynn JR, Crampin AC, Yates MD, Traore H, Mwaungulu FD, Ngwira BM, Ndlovu R, Drobniewski F, Fine PE. The importance of recent infection with Mycobacterium tuberculosis in an area with high HIV prevalence: a long-term molecular epidemiological study in Northern Malawi. J Infect Dis 2005; 192(3): 480–487CrossRefPubMedGoogle Scholar
  10. 10.
    Jasmer RM, Hahn JA, Small PM, Daley CL, Behr MA, Moss AR, Creasman JM, Schecter GF, Paz EA, Hopewell PC. A molecular epidemiologic analysis of tuberculosis trends in San Francisco, 1991–1997. Ann Intern Med 1999; 130(12): 971–978CrossRefPubMedGoogle Scholar
  11. 11.
    Barnes PF, Cave MD. Molecular epidemiology of tuberculosis. N Engl J Med 2003; 349(12): 1149–1156CrossRefPubMedGoogle Scholar
  12. 12.
    Supply P, Allix C, Lesjean S, Cardoso-Oelemann M, Rüsch-Gerdes S, Willery E, Savine E, de Haas P, van Deutekom H, Roring S, Bifani P, Kurepina N, Kreiswirth B, Sola C, Rastogi N, Vatin V, Gutierrez MC, Fauville M, Niemann S, Skuce R, Kremer K, Locht C, van Soolingen D. Proposal for standardization of optimized mycobacterial interspersed repetitive unit-variable-number tandem repeat typing of Mycobacterium tuberculosis. J Clin Microbiol 2006; 44(12): 4498–4510CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Luo T, Yang C, Pang Y, Zhao Y, Mei J, Gao Q. Development of a hierarchical variable-number tandem repeat typing scheme for Mycobacterium tuberculosis in China. PLoS One 2014; 9(2): e89726CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Allix-Béguec C, Wahl C, Hanekom M, Nikolayevskyy V, Drobniewski F, Maeda S, Campos-Herrero I, Mokrousov I, Niemann S, Kontsevaya I, Rastogi N, Samper S, Sng LH, Warren RM, Supply P. Proposal of a consensus set of hypervariable mycobacterial interspersed repetitive-unit-variable-number tandemrepeat loci for subtyping of Mycobacterium tuberculosis Beijing isolates. J Clin Microbiol 2014; 52(1): 164–172CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Liu M, Luo T, Yang C, Liu Q, Gao Q. Evaluation of different sets of variable number of tandem repeats loci for genotyping Mycobacterium tuberculosis isolates in China. Chin J Tuberc Respir Dis (Zhonghua Jie He He Hu Xi Za Zhi) 2015; 38(10): 746–750 (in Chinese)Google Scholar
  16. 16.
    Lu B, Pourcel C, Liu JH, Dong HY, Zhang YY, Jiang Y, Liu ZG, Zhao XQ, Wan KL. Establishment of the standard operation program on multiple loci variable numbers tandem repeats analysis typing on Mycobacterium tuberculosis. Chin J Epidemiol (Zhonghua Liu Xing Bing Xue Za Zhi) 2008; 29(9): 919–924 (in Chinese)Google Scholar
  17. 17.
    Chen HX, Cai C, Liu JY, Zhang ZG, Yuan M, Jia JN, Sun ZG, Huang HR, Gao JM, Li WM. Discriminatory power of variable number on tandem repeats loci for genotyping Mycobacterium tuberculosis strains in China. Chin J Epidemiol (Zhonghua Liu Xing Bing Xue Za Zhi) 2017; 38(6): 794–799 (in Chinese)Google Scholar
  18. 18.
    Shi L, Dong H. BA Sang, Xi Luo, Suo L, Zhao X, Wan K. Evaluation and analysis on genetic diversity of clinical Mycobacterium tuberculos isisolates from Tibetan patients by variable-number tandem repeats of mycobacterial interspersed repetitive units. Chin J Zoonoses (Zhongguo Ren Shou Gong Huan Bing Xue Bao) 2014; 30: 4 (in Chinese)Google Scholar
  19. 19.
    Zhang L, Chen J, Shen X, Gui X, Mei J, Deriemer K, Gao Q. Highly polymorphic variable-number tandem repeats loci for differentiating Beijing genotype strains of Mycobacterium tuberculosis in Shanghai, China. FEMS Microbiol Lett 2008; 282(1): 22–31CrossRefPubMedGoogle Scholar
  20. 20.
    Gardy JL, Johnston JC, Ho Sui SJ, Cook VJ, Shah L, Brodkin E, Rempel S, Moore R, Zhao Y, Holt R, Varhol R, Birol I, Lem M, Sharma MK, Elwood K, Jones SJ, Brinkman FS, Brunham RC, Tang P. Whole-genome sequencing and social-network analysis of a tuberculosis outbreak. N Engl J Med 2011; 364(8): 730–739CrossRefPubMedGoogle Scholar
  21. 21.
    Walker TM, Ip CL, Harrell RH, Evans JT, Kapatai G, Dedicoat MJ, Eyre DW,Wilson DJ, Hawkey PM, Crook DW, Parkhill J, Harris D, Walker AS, Bowden R, Monk P, Smith EG, Peto TE. Wholegenome sequencing to delineate Mycobacterium tuberculosis outbreaks: a retrospective observational study. Lancet Infect Dis 2013; 13(2): 137–146CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Luo T, Yang C, Peng Y, Lu L, Sun G,Wu J, Jin X, Hong J, Li F, Mei J, DeRiemer K, Gao Q. Whole-genome sequencing to detect recent transmission of Mycobacterium tuberculosis in settings with a high burden of tuberculosis. Tuberculosis (Edinb) 2014; 94(4): 434–440CrossRefGoogle Scholar
  23. 23.
    Yang C, Luo T, Shen X, Wu J, Gan M, Xu P, Wu Z, Lin S, Tian J, Liu Q, Yuan Z, Mei J, DeRiemer K, Gao Q. Transmission of multidrug-resistant Mycobacterium tuberculosis in Shanghai, China: a retrospective observational study using whole-genome sequencing and epidemiological investigation. Lancet Infect Dis 2017; 17(3): 275–284CrossRefPubMedGoogle Scholar
  24. 24.
    Nikolayevskyy V, Kranzer K, Niemann S, Drobniewski F. Whole genome sequencing of Mycobacterium tuberculosis for detection of recent transmission and tracing outbreaks: a systematic review. Tuberculosis (Edinb) 2016; 98: 77–85CrossRefGoogle Scholar
  25. 25.
    Walker TM, Kohl TA, Omar SV, Hedge J, Del Ojo Elias C, Bradley P, Iqbal Z, Feuerriegel S, Niehaus KE, Wilson DJ, Clifton DA, Kapatai G, Ip CL, Bowden R, Drobniewski FA, Allix-Béguec C, Gaudin C, Parkhill J, Diel R, Supply P, Crook DW, Smith EG, Walker AS, Ismail N, Niemann S, Peto TE; Modernizing Medical Microbiology (MMM) Informatics Group. Whole-genome sequencing for prediction of Mycobacterium tuberculosis drug susceptibility and resistance: a retrospective cohort study. Lancet Infect Dis 2015; 15(10): 1193–1202CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Luo T, Comas I, Luo D, Lu B,Wu J,Wei L, Yang C, Liu Q, Gan M, Sun G, Shen X, Liu F, Gagneux S, Mei J, Lan R, Wan K, Gao Q. Southern East Asian origin and coexpansion of Mycobacterium tuberculosis Beijing family with Han Chinese. Proc Natl Acad Sci USA 2015; 112(26): 8136–8141CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Glynn JR, Vynnycky E, Fine PEM. Influence of sampling on estimates of clustering and recent transmission of Mycobacterium tuberculosis derived from DNA fingerprinting techniques. Am J Epidemiol 1999; 149(4): 366–371CrossRefPubMedGoogle Scholar
  28. 28.
    Yang C, Shen X, Peng Y, Lan R, Zhao Y, Long B, Luo T, Sun G, Li X, Qiao K, Gui X, Wu J, Xu J, Li F, Li D, Liu F, Shen M, Hong J, Mei J, DeRiemer K, Gao Q. Transmission of Mycobacterium tuberculosis in China: a population-based molecular epidemiologic study. Clin Infect Dis 2015; 61(2): 219–227CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Yang C, Luo T, Sun G, Qiao K, Sun G, DeRiemer K, Mei J, Gao Q. Mycobacterium tuberculosis Beijing strains favor transmission but not drug resistance in China. Clin Infect Dis 2012; 55(9): 1179–1187CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Hu Y, Jiang WL, Zhao Q, Wang WB, Xu B. The combined application of multiple genotyping methods in identifying genotypes of Mycobacterium tuberculosis strain circulating in rural China. Chin J Tuberc Respir Dis (Zhonghua Jie He He Hu Xi Za Zhi) 2009; 32(8): 576–580 (in Chinese)Google Scholar
  31. 31.
    Hu Y, Mathema B, Zhao Q, Chen L, Lu W, Wang W, Kreiswirth B, Xu B. Acquisition of second-line drug resistance and extensive drug resistance during recent transmission of Mycobacterium tuberculosis in rural China. Clin Microbiol Infect 2015; 21(12): 1093 e9–e18CrossRefPubMedGoogle Scholar
  32. 32.
    Wang W, Mathema B, Hu Y, Zhao Q, Jiang W, Xu B. Role of casual contacts in the recent transmission of tuberculosis in settings with high disease burden. Clin Microbiol Infect 2014; 20(11): 1140–1145CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Lu W, Lu B, Liu Q, Dong H, Shao Y, Jiang Y, Song H, Chen C, Li G, Xu W, Zhao X, Wan K, Zhu L. Genotypes of Mycobacterium tuberculosis isolates in rural China: using MIRU-VNTR and spoligotyping methods. Scand J Infect Dis 2014; 46(2): 98–106CrossRefPubMedGoogle Scholar
  34. 34.
    Tian LL, Si HY, Mu TJ, Fan WB,Wang J, Jiang WM, Li Q, Yang B, Zhang Y, Zhu BD. Molecular epidemiology of Mycobacterium tuberculosis in Gansu Province of China. Chin Med J (Engl) 2012; 125(19): 3458–3464Google Scholar
  35. 35.
    Li Y, Cao X, Li S, Wang H, Wei J, Liu P, Wang J, Zhang Z, Gao H, Li M, Wan K, Dai E. Characterization of Mycobacterium tuberculosis isolates from Hebei, China: genotypes and drug susceptibility phenotypes. BMC Infect Dis 2016; 16(1): 107CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Huang Y, Zhong J, Zhang Y, Chen S, Wang X. Outbreak of tuberculosis in a high school in Zhejiang, China. Chin J Epidemiol (Zhonghua Liu Xing Bing Xue Za Zhi) 2015; 36(2): 172–175 (in Chinese)Google Scholar
  37. 37.
    Ma MJ, Yang Y, Wang HB, Zhu YF, Fang LQ, An XP, Wan KL, Whalen CC, Yang XX, Lauzardo M, Zhang ZY, Cao JF, Tong YG, Dai EH, Cao WC. Transmissibility of tuberculosis among school contacts: an outbreak investigation in a boarding middle school, China. Infect Genet Evol 2015; 32: 148–155CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Chen W, Xia Y, Li X, Zhou L, Li C, Wan K, Cheng S. A tuberculosis outbreak among senior high school students in China in 2011. J Int Med Res 2012; 40(5): 1830–1839CrossRefPubMedGoogle Scholar
  39. 39.
    Nardell E, Churchyard G. What is thwarting tuberculosis prevention in high-burden settings? N Engl J Med 2011; 365(1): 79–81CrossRefPubMedGoogle Scholar
  40. 40.
    Shen X, Yang C, Wu J, Lin S, Gao X, Wu Z, Tian J, Gan M, Luo T, Wang L, Yu C, Mei J, Pan Q, DeRiemer K, Yuan Z, Gao Q. Recurrent tuberculosis in an urban area in China: relapse or exogenous reinfection? Tuberculosis (Edinb) 2017; 103: 97–104CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Shen G, Xue Z, Shen X, Sun B, Gui X, Shen M, Mei J, Gao Q. The study recurrent tuberculosis and exogenous reinfection, Shanghai, China. Emerg Infect Dis 2006; 12(11): 1776–1778CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Kan X, Wang K, Yang JA, Liu Z, Chen G, Zhang Y,Wang J, Liu X, Wang Q. Molecular epidemiology study on relapse after cure of smear positive cases. Anhui Med J (Anhui Yi Xue) 2011; 32(1): 89–91 (in Chinese)Google Scholar
  43. 43.
    Li X, Zhang Y, Shen X, Shen G, Gui X, Sun B, Mei J, Deriemer K, Small PM, Gao Q. Transmission of drug-resistant tuberculosis among treated patients in Shanghai, China. J Infect Dis 2007; 195 (6): 864–869CrossRefPubMedGoogle Scholar
  44. 44.
    Nsofor CA, Jiang Q,Wu J, Gan MY, Liu QY, Zuo TY, Zhu GF, Gao Q. Transmission is a noticeable cause of resistance among treated tuberculosis patients in Shanghai, China. Sci Rep 2017; 7(1): 7691CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Xue He G, van den Hof S, van der Werf MJ, Guo H, Hu YL, Fan JH, Zhang WM, Tostado CP, Borgdorff MW. Inappropriate tuberculosis treatment regimens in Chinese tuberculosis hospitals. Clin Infect Dis 2011; 52(7): e153–e156CrossRefPubMedGoogle Scholar
  46. 46.
    Liu Q, Via LE, Luo T, Liang L, Liu X,Wu S, Shen Q,Wei W, Ruan X, Yuan X, Zhang G, Barry CE 3rd, Gao Q. Within patient microevolution of Mycobacterium tuberculosis correlates with heterogeneous responses to treatment. Sci Rep 2015; 5(1): 17507CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Sun G, Luo T, Yang C, Dong X, Li J, Zhu Y, Zheng H, Tian W, Wang S, Barry CE 3rd, Mei J, Gao Q. Dynamic population changes in Mycobacterium tuberculosis during acquisition and fixation of drug resistance in patients. J Infect Dis 2012; 206(11): 1724–1733CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Gao Q, Li X. Transmission of MDR tuberculosis. Drug Discov Today Dis Mech 2010; 7(1): e61–e65CrossRefGoogle Scholar
  49. 49.
    Hu Y, Hoffner S, Jiang W, Wang W, Xu B. Extensive transmission of isoniazid resistant M. tuberculosis and its association with increased multidrug-resistant TB in two rural counties of eastern China: a molecular epidemiological study. BMC Infect Dis 2010; 10 (1): 43CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Mehra M, Cossrow N, Kambili C, Underwood R, Makkar R, Potluri R. Assessment of tuberculosis burden in China using a dynamic disease simulation model. Int J Tuberc Lung Dis 2013; 17(9): 1186–1194CrossRefPubMedGoogle Scholar
  51. 51.
    Liao P, Guo M, Tang F, Wang G, Siyuan LI, Yang Z, Cao B. Analysis of patients from active case finding in rural areas of Wusheng, Sichuan. Chin J Antituberculosis (Zhongguo Fang Lao Za Zhi) 2016; 38(7): 576–581 (in Chinese)Google Scholar
  52. 52.
    Azman AS, Golub JE, Dowdy DW. How much is tuberculosis screening worth? Estimating the value of active case finding for tuberculosis in South Africa, China, and India. BMC Med 2014; 12 (216): 1–9Google Scholar

Copyright information

© Higher Education Press and Springer-Verlag GmbH Germany 2018

Authors and Affiliations

  1. 1.Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, School of Basic Medical ScienceFudan UniversityShanghaiChina
  2. 2.Department of Epidemiology of Microbial Diseases, School of Public HealthYale UniversityNew HavenUSA

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