Skip directly to site content Skip directly to page options Skip directly to A-Z link Skip directly to A-Z link Skip directly to A-Z link
Volume 19, Number 3—March 2013
Research

Emergence and Spread of Extensively and Totally Drug-Resistant Tuberculosis, South Africa

Marisa Klopper, Robin Mark WarrenComments to Author , Cindy Hayes, Nicolaas Claudius Gey van Pittius, Elizabeth Maria Streicher, Borna Müller, Frederick Adriaan Sirgel, Mamisa Chabula-Nxiweni, Ebrahim Hoosain, Gerrit Coetzee, Paul David van Helden, Thomas Calldo Victor, and André Phillip Trollip
Author affiliations: Author affiliations: Stellenbosch University, Cape Town, South Africa (M. Klopper, R.M. Warren, N.C. Gey van Pittius, E.M. Streicher, B. Müller, F.A. Sirgel, P.D. van Helden, T.C. Victor, AP.. Trollip); National Health Laboratory Services, Port Elizabeth, South Africa (C. Hayes, G. Coetzee); Swiss Tropical and Public Health Institute, Basel, Switzerland (B. Müller); University of Basel, Basel (B. Müller); Nelson Mandela Metropolitan Municipality, Port Elizabeth (M. Chabula-Nxiweni); Human Sciences Research Council, Port Elizabeth (E. Hoosain)

Main Article

Table 1

Spoligotype classification of drug-sensitive and MDR TB isolates, Eastern Cape Province, South Africa, 2008–2009*

Spoligotype family†
ST no.
Culture-based DST, no. (%)
Molecular-based DST, no. (%)
Sensitive
MDRss
Pre-XDR
XDR

MDRss
Pre-XDR
XDR
Atypical Beijing 1 11 (3.6) 41 (27.0) 98 (92.5) 78 (92.9) 29 (22.5) 85 (87.6) 103 (95.4)
Typical Beijing 1 108 (35.0) 19 (12.5) 0 0 18 (14.0) 1 (1.0) 0
H 36; 47; 50; 62 7 (2.3) 2 (1.3) 1 (0.9) 0 2 (1.6) 1 (1.0) 0
LAM3 33; 130; 211 66 (21.4) 12 (7.9) 2 (1.9) 0 12 (9.3) 0 (0) 0
LAM4 60; 811 6 (1.9) 32 (21.1) 4 (3.8) 2 (1.9) 29 (22.5) 3 (3.1) 2 (1.9)
LAM (other) 4; 20; 42; 398 7 (2.3) 1 (0.7) 0 1 (1.2) 1 (0.8) 0 1 (0.9)
MANU2 1247 0 0 0 2 (2.4) 1 (0.8) 0 1 (0.9)
S 34; 71 8 (2.6) 8 (5.3) 0 1 (1.2) 8 (6.2) 0 1 (0.9)
T 44; 53; 73; 254; 926; 1240 51 (16.5) 18 (11.8) 0 0 13 (10.1) 5 (5.2) 0
U 443; 519; 790 1 (0.3) 2 (1.3) 0 0 2 (1.6) 0 0
X 18; 92; 119; 1751 6 (1.9) 3 (2.0) 0 0 3 (2.3) 0 0
CAS 21; 26; 1092 4 (1.3) 0 0 0 0 0 0
Orphan Not assigned 34 (11.0) 14 (9.2) 1 (0.9) 0 11 (8.5) 2 (2.1) 0
Total 309 152 106 84 129 97 108
Total MDR 342 334‡

*MDR TB, multidrug-resistant tuberculosis; ST, shared type (17); DST, drug susceptibility testing; MDRss, MDR sensu stricto; Pre-XDR, pre–extensively drug resistant; XDR, extensively drug resistant.
†For Beijing isolates a distinction was made between typical and atypical based on the presence or absence of an IS6110 insertion in the noise transfer region (18,19).
‡Molecular-based DST total differs from culture-based DST total, because some results were not available.

Main Article

References
  1. World Health Organization, WHO-IUTALD Global Project on Anti-Tuberculosis Drug Resistance Surveillance. Anti-tuberculosis drug resistance in the world (report no. 4) [cited 2008 Apr 30]. http://www.who.int/tb/publications/2008/drs_report4_26feb08.pdf
  2. Cox  HS, McDermid  C, Azevedo  V, Muller  O, Coetzee  D, Simpson  J, Epidemic levels of drug resistant tuberculosis (MDR and XDR-TB) in a high HIV prevalence setting in Khayelitsha, South Africa. PLoS ONE. 2010;5:e13901 and. DOIPubMedGoogle Scholar
  3. World Health Organization. Multidrug and extensively drug-resistant TB (M/XDR-TB) 2010. Global report on surveillance and response [cited 2010 Jun 26]. http://whqlibdoc.who.int/publications/2010/9789241599191_eng.pdf
  4. National Health Laboratory Services. National Institute for Communicable Diseases annual report 2009 [cited 2012 Jan 26]. http://www.nicd.ac.za/assets/files/Annual_report_2009.pdf
  5. Shean  KP, Willcox  PA, Siwendu  SN, Laserson  KF, Gross  L, Kammerer  S, Treatment outcome and follow-up of multidrug-resistant tuberculosis patients, West Coast/Winelands, South Africa, 1992–2002. Int J Tuberc Lung Dis. 2008;12:11829 .PubMedGoogle Scholar
  6. Dheda  K, Shean  K, Zumla  A, Badri  M, Streicher  EM, Page-Shipp  L, Early treatment outcomes and HIV status of patients with extensively drug-resistant tuberculosis in South Africa: a retrospective cohort study. Lancet. 2010;375:1798807 and. DOIPubMedGoogle Scholar
  7. Van Rie  A, Warren  R, Richardson  M, Gie  RP, Enarson  DA, Beyers  N, Classification of drug-resistant tuberculosis in an epidemic area. Lancet. 2000;356:225 and. DOIPubMedGoogle Scholar
  8. Johnson  R, Warren  RM, van der Spuy  GD, Gey Van Pittius  NC, Theron  D, Streicher  EM, Drug-resistant tuberculosis epidemic in the Western Cape driven by a virulent Beijing genotype strain. Int J Tuberc Lung Dis. 2010;14:11921 .PubMedGoogle Scholar
  9. Johnson  R, Warren  R, Strauss  OJ, Jordaan  AM, Falmer  AA, Beyers  N, An outbreak of drug-resistant tuberculosis caused by a Beijing strain in the Western Cape, South Africa. Int J Tuberc Lung Dis. 2006;10:14124 .PubMedGoogle Scholar
  10. Strauss  OJ, Warren  RM, Jordaan  A, Streicher  EM, Hanekom  M, Falmer  AA, Spread of a low-fitness drug-resistant Mycobacterium tuberculosis strain in a setting of high human immunodeficiency virus prevalence. J Clin Microbiol. 2008;46:15146 and. DOIPubMedGoogle Scholar
  11. Gagneux  S, Long  CD, Small  PM, Van  T, Schoolnik  GK, Bohannan  BJ. The competitive cost of antibiotic resistance in Mycobacterium tuberculosis. Science. 2006;312:19446 and. DOIPubMedGoogle Scholar
  12. Kvasnovsky  CL, Cegielski  JP, Erasmus  R, Siwisa  NO, Thomas  K, der Walt  ML. Extensively drug-resistant TB in Eastern Cape, South Africa: high mortality in HIV-negative and HIV-positive patients. J Acquir Immune Defic Syndr. 2011;57:14652 and. DOIPubMedGoogle Scholar
  13. Gandhi  NR, Moll  A, Sturm  AW, Pawinski  R, Govender  T, Lalloo  U, Extensively drug resistant tuberculosis as a cause of death in patients co-infected with tuberculosis and HIV in a rural area of South Africa. Lancet. 2006;368:157580 and. DOIPubMedGoogle Scholar
  14. Van Rie  A, Enarson  D. XDR tuberculosis: an indicator of public-health negligence. Lancet. 2006;368:15546 and. DOIPubMedGoogle Scholar
  15. Sharma  M, Thibert  L, Chedore  P, Shandro  C, Jamieson  F, Tyrrell  G, Canadian multicenter laboratory study for standardized second-line antimicrobial susceptibility testing of Mycobacterium tuberculosis. J Clin Microbiol. 2011;49:41126 and. DOIPubMedGoogle Scholar
  16. Warren  RM, Victor  TC, Streicher  EM, Richardson  M, Beyers  N, van Pittius  NC, Patients with active tuberculosis often have different strains in the same sputum specimen. Am J Respi Crit Care Med. 2004;169:610–4.
  17. Kamerbeek  J, Schouls  L, Kolk  A, van Agterveld  M, van Soolingen  D, Kuijper  S, Simultaneous detection and strain differentiation of Mycobacterium tuberculosis for diagnosis and epidemiology. J Clin Microbiol. 1997;35:90714 .PubMedGoogle Scholar
  18. Streicher  EM, Victor  TC. van der SG, Sola C, Rastogi N, van Helden PD, et al. Spoligotype signatures in the Mycobacterium tuberculosis complex. J Clin Microbiol. 2007;45:237–40.
  19. Mokrousov  I, Narvskaya  O, Otten  T, Vyazovaya  A, Limeschenko  E, Steklova  L, Phylogenetic reconstruction within Mycobacterium tuberculosis Beijing genotype in northwestern Russia. Res Microbiol. 2002;153:62937 and. DOIPubMedGoogle Scholar
  20. Plikaytis  BB, Marden  JL, Crawford  JT, Woodley  CL, Butler  WR, Shinnick  TM. Multiplex PCR assay specific for the multidrug-resistant strain W of Mycobacterium tuberculosis. J Clin Microbiol. 1994;32:15426 .PubMedGoogle Scholar
  21. Warren  R, de Kock  M, Engelke  E, Myburgh  R, Gey van Pittius  NC, Victor  T, Safe Mycobacterium tuberculosis DNA extraction method that does not compromise integrity. J Clin Microbiol. 2006;44:2546 and. DOIPubMedGoogle Scholar
  22. Calver  AD, Falmer  AA, Murray  M, Strauss  OJ, Streicher  EM, Hanekom  M, Emergence of increased resistance and extensively drug-resistant tuberculosis despite treatment adherence, South Africa. Emerg Infect Dis. 2010;16:26471 and. DOIPubMedGoogle Scholar
  23. Sirgel  FA, Tait  M, Warren  RM, Streicher  EM, Bottger  EC, van Helden  PD, Mutations in the rrs A1401G gene and phenotypic resistance to amikacin and capreomycin in Mycobacterium tuberculosis. Microb Drug Resist. 2012;18:1937 . DOIPubMedGoogle Scholar
  24. Mlambo  CK, Warren  RM, Poswa  X, Victor  TC, Duse  AG, Marais  E. Genotypic diversity of extensively drug-resistant tuberculosis (XDR-TB) in South Africa. Int J Tuberc Lung Dis. 2008;12:99104 .PubMedGoogle Scholar
  25. Pillay  M, Sturm  AW. Evolution of the extensively drug-resistant F15/LAM4/KZN strain of Mycobacterium tuberculosis in KwaZulu-Natal, South Africa. Clin Infect Dis. 2007;45:140914 and. DOIPubMedGoogle Scholar
  26. Porteous  JB. The treatment of pulmonary tuberculosis. S Afr Med J. 1959;33:2657 .PubMedGoogle Scholar
  27. Ioerger  TR, Koo  S, No  EG, Chen  X, Larsen  MH, Jacobs  WR Jr, Genome analysis of multi- and extensively-drug-resistant tuberculosis from KwaZulu-Natal, South Africa. PLoS ONE. 2009;4:e7778 and. DOIPubMedGoogle Scholar
  28. Streicher  EM, Muller  B, Chihota  V, Mlambo  C, Tait  M, Pillay  M, Emergence and treatment of multidrug resistant (MDR) and extensively drug-resistant (XDR) tuberculosis in South Africa. Infect Genet Evol. 2012;12:68694 and. DOIPubMedGoogle Scholar
  29. Hillemann  D, Rusch-Gerdes  S, Richter  E. Feasibility of the GenoType MTBDRsl assay for fluoroquinolone, amikacin-capreomycin, and ethambutol resistance testing of Mycobacterium tuberculosis strains and clinical specimens. J Clin Microbiol. 2009;47:176772 and. DOIPubMedGoogle Scholar
  30. Velayati  AA, Masjedi  MR, Farnia  P, Tabarsi  P, Ghanavi  J, Ziazarifi  AH, Emergence of new forms of totally drug-resistant tuberculosis bacilli: super extensively drug-resistant tuberculosis or totally drug-resistant strains in Iran. Chest. 2009;136:4205 and. DOIPubMedGoogle Scholar
  31. World Health Organization Stop TB Department. Drug-resistant tuberculosis: frequently asked questions, January 26, 2012 [cited 2012 Feb 8]. http://www.who.int/tb/challenges/mdr/TDRFAQs160112final.pdf
  32. Chihota  VN, Muller  B, Mlambo  CK, Pillay  M, Tait  M, Streicher  EM, The population structure of multi- and extensively drug-resistant tuberculosis in South Africa. J Clin Microbiol. 2012;50:9951002 and. DOIPubMedGoogle Scholar
  33. Sandgren  A, Strong  M, Muthukrishnan  P, Weiner  BK, Church  GM, Murray  MB. Tuberculosis drug resistance mutation database. 2009. PLoS Med. 2009;6:e2 and. DOIPubMedGoogle Scholar
  34. Müller  B, Streicher  EM, Hoek  KG, Tait  M, Trollip  A, Bosman  ME, inhA promoter mutations: a gateway to extensively drug-resistant tuberculosis in South Africa? Int J Tuberc Lung Dis. 2011;15:34451 .PubMedGoogle Scholar
  35. Barnard  M, Albert  H, Coetzee  G, O’Brien  R, Bosman  ME. Rapid molecular screening for multidrug-resistant tuberculosis in a high-volume public health laboratory in South Africa. 2008. Am J Respi Crit Care Med. 2008;177:787–92.

Main Article

Page created: February 12, 2013
Page updated: February 12, 2013
Page reviewed: February 12, 2013
The conclusions, findings, and opinions expressed by authors contributing to this journal do not necessarily reflect the official position of the U.S. Department of Health and Human Services, the Public Health Service, the Centers for Disease Control and Prevention, or the authors' affiliated institutions. Use of trade names is for identification only and does not imply endorsement by any of the groups named above.
file_external