Multidrug-Resistant Tuberculosis: A Global Challenge

  • Ignatius W. Fong
Part of the Emerging Infectious Diseases of the 21st Century book series (EIDC)


It is estimated that more than one-third of the world’s population harbor tuberculosis (predominantly latent infection), and the number of new cases continue to grow with almost 10,000,000 in 2010 [1]. Already 36 million people have been treated since the World Health Organization’s (WHO) strategy for tuberculosis (TB) control in 1995. There is an inequitable global distribution of the disease with 22 high-burden countries accounting for 80 % of active TB cases in the world, and more than one-third in India and China [2]. Many of these countries have social, economic problems with overcrowding, high rates of poverty and unemployment, and inadequate social and healthcare infrastructures. Although Western developed Nations have to a large degree held tuberculosis in check for the past 50 years, due to effective public health systems, there is a real danger of increase due to the emergence of multidrug-resistant TB (MDR-TB) and the ever expanding immigration from high-burden countries.


Beijing Strain Beijing Genotype Beijing Family Sputum Culture Conversion Integrate Therapy Group 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Dye C, William BG (2010) The population dynamics and control of tuberculosis. Science 328:856–861PubMedGoogle Scholar
  2. 2.
    Russell DG, Clifton EB 3rd, Flynn J (2010) Tuberculosis: what we don’t know can, and does, hurt us. Science 328:852–855PubMedGoogle Scholar
  3. 3.
    World Health Organization (2010) Global tuberculosis control: a short update to the 2009 report (WHO/HTM/TB/2011.16). WHO, GenevaGoogle Scholar
  4. 4.
    Ahmad S, Mokaddas E (2009) Recent advances in the diagnosis and treatment of multidrug–resistant tuberculosis. Respir Med 103:1777–1790PubMedGoogle Scholar
  5. 5.
    McEvoy CR, van Helden PD, Warren RM, Gey van Pittius NC (2009) Evidence for a rapid rate of molecular evolution at the hypervariable and immunogenic Mycobacterium tuberculosis PPE38 gene region. BMC Evol Biol 9:237–258PubMedGoogle Scholar
  6. 6.
    Hazbon MH, Brimacombe M, Bobadilla del Valle M et al (2006) Population genetics study of isoniazid resistant mutations and evolution of multidrug–resistant Mycobacterium tuberculosis. Antimicrob Agents Chemother 50:2640–2649PubMedGoogle Scholar
  7. 7.
    Prammananan T, Cheunoy W, Taechamahapun D et al (2008) Distribution of rpoB mutations among multidrug–resistant Mycobacterium (MDR–TB) strains from Thailand and development of a rapid method for mutation detection. Clin Mirobiol Infect 14:446–453Google Scholar
  8. 8.
    Wright A, Zignol M, Van Deun A et al (2009) Epidemiology of antituberculosis drug resistance 2002–07: an updated analysis of the global project on anti-tuberculosis drug resistance surveillance. Lancet 373:1861–1873PubMedGoogle Scholar
  9. 9.
    Chiang CY, Centis R, Migliori GB (2010) Drug–resistant tuberculosis: past, present and future. Respirology 15:413–432PubMedGoogle Scholar
  10. 10.
    Grobush MP (2010) Drug–resistant and extensively drug–resistant tuberculosis in Southern Africa. Curr Opin Pulm Med 16:180–185Google Scholar
  11. 11.
    Amor YB, Nemser B, Singh A, Sankin A, Schluger N (2008) Under reported threat of multidrug–resistant tuberculosis in Africa. Emerg Infect Dis 14:1345–1351PubMedGoogle Scholar
  12. 12.
    Yang XY, Li YP, Mei YW et al (2010) Time and spatial distribution of multidrug–resistant tuberculosis among Chinese people 1981–2006: systematic review. Int J Infect Dis 14:e828–e837PubMedGoogle Scholar
  13. 13.
    Shen X, DeReimer K, Yuan ZA et al (2009) Drug–resistant tuberculosis in Shanghai, China, 2000–2006: prevalence, trends and risk factors. Int J Tuberc Lung Dis 13:253–259PubMedGoogle Scholar
  14. 14.
    Wang D, Yang C, Kuang T et al (2010) Prevalence of multidrug and extensively drug–resistant tuberculosis in Beijing, China: a hospital based retrospective study. Jpn J Infect Dis 63:368–371PubMedGoogle Scholar
  15. 15.
    Migliori GB, Centis R, Lange C, Richardson MD, Sotgiu G (2010) Emerging epidemic of drug–resistant tuberculosis in Europe, Russia, China, South America and Asia: current status and global perspectives. Curr Opin Pulm Med 16:171–179PubMedGoogle Scholar
  16. 16.
    WHO Global tuberculosis control. WHO report (2011). World Health Organization, Geneva. WHO, TB.
  17. 17.
    Centers for Disease Control and Prevention (CDC) (2006) Noticed to readers; revised definition of extensively drug–resistant tuberculosis. MMWR Morb Mortal Wkly Rep 55:1176Google Scholar
  18. 18.
    Gandhi NR, Nunn P, Dheda K et al (2010) Tuberculosis 2. Multidrug–resistant and extensively drug–resistant tuberculosis: a threat to global control of tuberculosis. Lancet 35: 1830–1843Google Scholar
  19. 19.
    Sotgiu G, Ferrara G, Matteelli A et al (2009) Epidemiology and clinical management of X DR–TB: systematic review by TBNET. Eur Respir J 33:871–881PubMedGoogle Scholar
  20. 20.
    WHO Global map on X DR–TB (2011). Scholar
  21. 21.
    Medical Research Council (1948) Streptomycin treatment of pulmonary tuberculosis: a Medical Research Council investigation. Br Med J 2(4582):769–782Google Scholar
  22. 22.
    Mitchison DA (1985) The action of antituberculosis drugs in short course chemotherapy. Tubercule 66:219–225Google Scholar
  23. 23.
    Mitchison DA (2005) The diagnosis and therapy of tuberculosis during the past 100 years. Am J Respir Crit Care Med 171:699–706PubMedGoogle Scholar
  24. 24.
    Mitchison DA (1998) How drug resistance emerges as a result of poor compliance during short course chemotherapy of tuberculosis. Int J Tuberc Lung Dis 2:10–15PubMedGoogle Scholar
  25. 25.
    Palaci M, Dietze R, Haddad DJ et al (2007) Cavitatory disease and quantitative sputum bacillary load in cases of pulmonary tuberculosis. J Clin Microbiol 45:4064–4066PubMedGoogle Scholar
  26. 26.
    Drobniewski F, Balanova Y, Ruddy M (2002) Rifampin–and multi–drug–resistant tuberculosis in Russian civilians and prison inmates: dominance of the Beijing strain family. Emerg Infect Dis 8:1320–1326PubMedGoogle Scholar
  27. 27.
    Kimerling ME, Phillips P, Patterson P, Hall M, Robinson CA, Dunlap NE (1998) Low serum antimycobacterial drug levels in non- HIV infected tuberculosis patients. Chest 113: 1178–1183PubMedGoogle Scholar
  28. 28.
    Suarez-Garcia I, Rodriquez-Blanko A, Vidal-Perrez JL, Garcia-Viejo MA, Joraz-Hernandez MJ, Lopez O, Noguerado Ascensio A (2009) Risk factors for multidrug–resistant tuberculosis in a tuberculosis unit in Madrid, Spain. Eur J Clin Microbiol Infect Dis 28:325–330PubMedGoogle Scholar
  29. 29.
    Cohen T, Dye C, Colijin C et al (2009) Mathematical models of the epidemiology and control of drug–resistant TB. Expert Rev Respir Med 3:67–79PubMedGoogle Scholar
  30. 30.
    Borrell S, Gagneux S (2009) Infectiousness, reproductive fitness and evolution of drug–resistant Mycobacterium tuberculosis. Int J Tuberc Lung Dis 13:1456–1466PubMedGoogle Scholar
  31. 31.
    Blower SM, Chou T (2004) Modeling the emergence of the “hot zones”: tuberculosis and amplification dynamics of drug resistance. Nat Med 10:1111–1116PubMedGoogle Scholar
  32. 32.
    Niemann S, Diel R, Khechinashvilli G, Gegia M, MDivani N, Tang YW (2010) Mycobacterium tuberculosis Beijing lineage favors the spread of multidrug–resistant tuberculosis. J Clin Microbiol 48:3544–3550PubMedGoogle Scholar
  33. 33.
    Loeger TR, Feng Y, Chen X et al (2010) The non-clonality of drug resistance in Beijing–genotype isolates of Mycobacterium tuberculosis from the Western Cape of South Africa. BMC Genomics 11:670Google Scholar
  34. 34.
    Parwati I, van Crevel R, van Soolingen D (2010) Possible underlying mechanisms for successful emergence of the Mycobacterium tuberculosis Beijing genotype strains. Lancet Infect Dis 10:103–111PubMedGoogle Scholar
  35. 35.
    Kremer K, van-der-Werf MJ, Au BK et al (2009) Vaccine–induced immunity circumvented by typical Mycobacterium tuberculosis Beijing strains. Emerg Infect Dis 15:335–339PubMedGoogle Scholar
  36. 36.
    Brudey K, Driscoll JR, Rigouts L et al (2006) Mycobacterium tuberculosis complex genetic adversity: mining the fourth international spoligotyping database (SpoLDB4) for classification, population genetics and epidemiology. BMC Microbiol 6:23PubMedGoogle Scholar
  37. 37.
    Devaux I, Kremer K, Heersma H, Van Soolingen D (2009) Clusters of multidrug–resistant Mycobacterium tuberculosis cases, Europe. Emerg Infect Dis 15:1052–1060PubMedGoogle Scholar
  38. 38.
    Lari N, Rindi L, Bonanni D, Tortoli E, Garzelli C (2006) Mutations in mutT genes of Mycobacterium tuberculosis isolates of Beijing genotype. J Med Microbiol 55:599–603PubMedGoogle Scholar
  39. 39.
    Park YK, Shin S, Ryu S et al (2005) Comparison of drug resistance genotypes between Beijing and non-Beijing family strains of Mycobacterium tuberculosis in Korea. J Microbiol Methods 63:165–172PubMedGoogle Scholar
  40. 40.
    Mokrousov I, Otten T, Vyshnevskiy B, Narvskaya O (2002) Detection of embB301 mutations in ethambutol–susceptible clinical isolates of Mycobacterium tuberculosis from Northwestern Russia: implications for genotype resistance testing. J Clin Microbiol 40:3810–3813PubMedGoogle Scholar
  41. 41.
    Dye C (2009) Doomsday postponed? Preventing and reversing epidemics of drug–resistant tuberculosis. Nat Rev Microbiol 7:81–87PubMedGoogle Scholar
  42. 42.
    Colijn C, Cohen T, Garnesh A, Murray M (2011) Spontaneous emergence of drug–resistance in tuberculosis before and during therapy. PLoS One 6:e18327PubMedGoogle Scholar
  43. 43.
    Jassal M, Bishai WR (2009) Extensively drug–resistant tuberculosis. Lancet Infect Dis 9:19–30PubMedGoogle Scholar
  44. 44.
    Bifani PJ, Mathema B, Liu Z et al (1999) Identification of W variant outbreak of Mycobacterium tuberculosis via population based molecular epidemiology. JAMA 282:2321–2327PubMedGoogle Scholar
  45. 45.
    Gandhi NR, Moll A, Sturm AW (2006) Extensively drug–resistant tuberculosis as a cause of death in patients co-infected with tuberculosis and H IV in a rural area of South Africa. Lancet 368:1575–1580PubMedGoogle Scholar
  46. 46.
    Pillay W, Sturm AW (2007) Evolution of the extensively drug–resistant FIS/LAM 4/KZN strain of Mycobacterium tuberculosis in Kwa-Zulu–Natal, South Africa. Clin Infect Dis 45:1409–1414PubMedGoogle Scholar
  47. 47.
    Mlambo CK, Warren RM, Poswa X, Victor TC, Duse AG, Marias E (2008) Genotypic diversity of extensively drug–resistant tuberculosis (XDR–TB) in South Africa. Int J Tuberc Lung Dis 12:99–104PubMedGoogle Scholar
  48. 48.
    van der Spuy GD, Kremer K, Ndabambi SI et al (2009) Changing Mycobacterium tuberculosis population highlights clade–specific pathogenic characteristics. Tuberculosis 89: 120–125PubMedGoogle Scholar
  49. 49.
    Orenstein EW, Basu S, Shah WS et al (2009) Treatment outcomes among patients with multidrug–resistant tuberculosis: systematic review and meta-analysis. Lancet Infect Dis 9:153–161PubMedGoogle Scholar
  50. 50.
    Loveday M, Thomson L, Chopra M, Ndela Z (2008) A health systems assessment of the Kwa-Zulu–Natal tuberculosis programme in the context of increasing drug resistance. Int J Tuberc Lung Dis 12:1042–1047PubMedGoogle Scholar
  51. 51.
    Albanna AS, Menzies D (2011) Drug–resistant tuberculosis: what are the treatment options? Drugs 171:815–825Google Scholar
  52. 52.
    Caminero JA, Sotgiu G, Zumla A, Migliori GB (2010) Best drug treatment for multidrug–resistant and extensive drug–resistant tuberculosis. Lancet Infect Dis 10:621–629PubMedGoogle Scholar
  53. 53.
    Van Deun A, Many AK, Salim MA, Das PK, Sarker MR, Daru P, Reider HL (2010) Short, highly effective, and inexpensive standardized treatment of multidrug–resistant tuberculosis. Am J Resp Crit Care Med 182:684–692PubMedGoogle Scholar
  54. 54.
    Bloss E, Kuksa L, Holtz TH, Riekstina V, Skripconoku V, Kammerer S, Leimane V (2010) Adverse events related to multidrug–resistant tuberculosis treatment, Latvia, 2000–2004. Int J Tuberc Lung Dis 14:275–281PubMedGoogle Scholar
  55. 55.
    Franke MF, Appleton SC, Bayona J et al (2008) Risk factors and mortality associated with default from multidrug–resistant tuberculosis. Clin Infect Dis 4–6:1844–1851Google Scholar
  56. 56.
    Ziganshina LE, Squire SB (2008) Fluoroquinolones for treating tuberculosis. Update of Cochrane Database Syst Rev 2005. Cochrane Database Syst Rev CD004795Google Scholar
  57. 57.
    Agrawal D, Udwaha ZF, Rodriquez C, Mehta A (2009) Increasing incidence of fluoroquinolone–resistant Mycobacterium tuberculosis in Mumbai, India. Int J Tuberc Lung Dis 13:79–83PubMedGoogle Scholar
  58. 58.
    Devassia RA, Blackham A, Gebretsadik T et al (2009) Fluoroquinolone resistance in Mycobacterium tuberculosis: the effect and duration and timing of fluoroquinolone exposure. Am J Resp Crit Care Med 180:365–370Google Scholar
  59. 59.
    Chen TC, Lu PL, Lin CY, Lin WR, Chen YH (2011) Fluoroquinolones are associated with delayed treatment and resistance in tuberculosis: systematic review and meta-analysis. Int J Infect Dis 15:e211–e216PubMedGoogle Scholar
  60. 60.
    von Gottberg A, Klugman KP, Cohen C et al (2008) Emergence of levofloxacin – non-susceptible Streptococcus pneumoniae and treatment for multidrug–resistant tuberculosis in children in South Africa: a cohort observational surveillance study. Lancet 371:1108–1113Google Scholar
  61. 61.
    Katiyar SK, Bihari S, Prakash S, Mamtani M, Kulkarni H (2008) A randomized controlled trial of high-dose isoniazid adjuvant therapy for multidrug–resistant tuberculosis. Int J Tuberc Lung Dis 12:139–145PubMedGoogle Scholar
  62. 62.
    Nathanson E, Lambregts-van Weesenbeek C, Rich ML et al (2006) Multidrug–resistant tuberculosis management in resource–limited settings. Emerg Infect Dis 12:1389–1397PubMedGoogle Scholar
  63. 63.
    Resch SC, Salomon JA, Murray M, Weinstein MC (2006) Cost effectiveness of treating multi–resistant tuberculosis. PLoS Med 3:e241PubMedGoogle Scholar
  64. 64.
    Siqiueira HR, Freitas FA, Oliveira DN, Barreto AM, Dalcolmu MP, Albano RM (2009) Clinical evolution of a group of patients with multidrug–resistant TB treated at a referral center in the city of Rio de Janeiro, Brazil. Tisilogia 35:54–62Google Scholar
  65. 65.
    Matthys F, Rigout S, Sizaire V et al (2009) Outcomes of chemotherapy with WHO category II regimen in a population with high prevalence of drug-resistant tuberculosis. PLoS One 4:e7954PubMedGoogle Scholar
  66. 66.
    Kliiman K, Altraja A (2009) Predictors of poor treatment outcome in multi–and extensively drug–resistant pulmonary TB. Eur Respir J 33:1085–1094PubMedGoogle Scholar
  67. 67.
    Rao NA, Irfan M, Mahfooz Z (2009) Treatment outcome of multidrug–resistant tuberculosis in a tertiary care hospital in Karachi. J Pak Med Assoc 59:694–698PubMedGoogle Scholar
  68. 68.
    Malla P, Kanitz EE, Akhtar M et al (2009) Ambulatory -based standardized therapy for multi–drug resistant tuberculosis: experience from Nepal, 2005–2006. PLoS One 4:e8313PubMedGoogle Scholar
  69. 69.
    Heller T, Lessells RJ, Wallrauch CG et al (2010) Community–based treatment for multidrug–resistant tuberculosis in rural Kwa Zulu-Natal, South Africa. Int J Tuberc Lung Dis 14: 420–426PubMedGoogle Scholar
  70. 70.
    Centers for Disease Control and Prevention (CDC) (2009) Plan to combat extensively drug–resistant tuberculosis: recommendation of the Federal Tuberculosis Task Force. Morbid Mortal Wkly Rep 58(RR–3):1–43Google Scholar
  71. 71.
    Kliiman K, Altraja A (2009) Predictors of extensively drug–resistant pulmonary tuberculosis. Ann Intern Med 150:766–775PubMedGoogle Scholar
  72. 72.
    Shin SS, Keshavjee S, Gelmanova IY et al (2010) Development of extensive drug–resistant tuberculosis during multidrug–resistant tuberculosis treatment. Am J Respir Crit Care Med 182:426–432PubMedGoogle Scholar
  73. 73.
    Gupta AK, Kotach VM, Chauhan DS, Sharma R, Singh M, Venkatesan K, Sharma VD (2010) Microarray analysis of efflux pump genes in multidrug–resistant Mycobacterium tuberculosis during stressed induced by common anti-tuberculosis drugs. Microb Drug Resist 16:21–28PubMedGoogle Scholar
  74. 74.
    Via LE, Cho SN, Hwang S et al (2010) Polymorphisms associated with resistance to aminoglycosides and capreomycin in Mycobacterium tuberculosis from South Korean patients with drug-resistant tuberculosis. J Clin Microbiol 48:402–411PubMedGoogle Scholar
  75. 75.
    Sugarwara I, Zhang J, Li C (2009) Cross-resistance of Mycobacterium tuberculosis isolates among streptomycin, kanamycin and amikacin. Indian J Exp Biol 47:520–522Google Scholar
  76. 76.
    Calver AD, Falmer AA, Murray M et al (2010) Emergence of increased resistance and extensively drug–resistant tuberculosis despite treatment adherence, South Africa. Emerg Infect Dis 16:264–271PubMedGoogle Scholar
  77. 77.
    Yelayati AA, Masjedi MR, Farnia P, Tabarsi P, Ghanavi J, Ziafarifi AH, Hoffner SC (2009) Emergence of new forms of totally drug–resistant tuberculosis bacilli: super extensively drug-resistant tuberculosis or totally drug–resistant strains in Iran. Chest 132:420–425Google Scholar
  78. 78.
    Abubakar I, Moore J, Drobniewski F et al (2009) Extensively drug–resistant tuberculosis in the UK: 1995–2007. Thorax 64:512–515PubMedGoogle Scholar
  79. 79.
    O’Donnell MR, Padayatchi N, Master I, Osburn G, Horsburg CR (2009) Improved early results for patients with extensively drug–resistant tuberculosis and HIV in South Africa. Int J Tuberc Lung Dis 13:855–861PubMedGoogle Scholar
  80. 80.
    Jeon DS, Kim DH, Kang HS et al (2009) Survival and predictors in non-HIV infected patients with extensively drug–resistant tuberculosis. Int J Tuberc Lung Dis 13:594–600PubMedGoogle Scholar
  81. 81.
    Jacobson KR, Tierney DB, Jeon CY, Mitnick CD, Murray MB (2010) Treatment outcomes among patients with extensively drug–resistant tuberculosis: systematic review and meta-analysis. Clin Infect Dis 51:6–14PubMedGoogle Scholar
  82. 82.
    Devasia RA, Blackman A, May C et al (2009) Fluoroquinolone resistance in Mycobacterium tuberculosis: an assessment of MGIT 960, MODS, and nitrate reductase assay and fluoroquinolone cross–resistance. J Antimicrob Chemother 63:1173–1178PubMedGoogle Scholar
  83. 83.
    Ginesberg AS, Grosset JH, Bishai WR (2003) Fluoroquinolones, tuberculosis and resistance. Lancet Infect Dis 3:432–442Google Scholar
  84. 84.
    Shandil RK, Jayaram R, Kaur P et al (2007) Moxifloxacin, ofloxacin, sparfloxacin, and ciprofloxacin against Mycobacterium tuberculosis: evaluation of in vitro and pharmacodynamic indices that best predict in vivo efficacy. Antimicrob Agents Chemother 51: 576–582PubMedGoogle Scholar
  85. 85.
    Poissy J, Aubry A, Fernandez C et al (2010) Should moxifloxacin be used for the treatment of extensively drug–resistant tuberculosis? An answer from a murine model. Antimicrob Agents Chemother 54:4765–4771PubMedGoogle Scholar
  86. 86.
    Mitnick CD, Shin SS, Seung KJ et al (2008) Comprehensive treatment of extensively drug–resistant tuberculosis. N Engl J Med 359:563–574PubMedGoogle Scholar
  87. 87.
    Kang MW, Kim HK, Choi YS, Kim K, Shim YM, Koh WJ, Kim J (2010) Surgical treatment for multidrug–resistant and extensively-drug resistant tuberculosis. Ann Thorac Surg 89:1597–1602PubMedGoogle Scholar
  88. 88.
    Somocurcio JG, Sotomayer A, Shin S, Portilla S, Valcarcel M, Guerra D, Furin J (2007) Surgery for patients with drug–resistant tuberculosis: Report of 121 cases receiving community–-based treatment in Lima, Peru. Thorax 62:416–421PubMedGoogle Scholar
  89. 89.
    Shiraishi Y, Katsuragi N, Kita H, Toisha M, Onda T (2008) Experience with pulmonary resection for extensively drug–resistant tuberculosis. Interact Cardiovasc Thorac Surg 7:1075–1078PubMedGoogle Scholar
  90. 90.
    WHO (2008) Guidelines for the programmatic management of drug–resistant tuberculosis an emergency update (WHO/Htm/TB/2008. 402). World Health Organization, GenevaGoogle Scholar
  91. 91.
    Lawn SD, Zumla AI (2011) Tuberculosis. Lancet 378:57–72PubMedGoogle Scholar
  92. 92.
    Blanc FX, Sok T, Laureilland D et al (2011) Earlier versus later start of antiretroviral therapy in HIV–infected adults with tuberculosis. N Engl J Med 365:1471–1481PubMedGoogle Scholar
  93. 93.
    Abdool Karim SS, Naidoo K, Grobler H et al (2010) Timing of initiation of antiretroviral therapy. N Engl J Med 362:697–706PubMedGoogle Scholar
  94. 94.
    Havlier D, Kendall MA, Ive P et al (2011) Timing of antiretroviral therapy for HIV–1 infection and tuberculosis. N Engl J Med 365:1482–1489Google Scholar
  95. 95.
    Abdool Karim SS, Naidoo K, Grobler A et al (2011) Integration of antiretroviral therapy with tuberculosis treatment. N Engl J Med 365:1492–1501PubMedGoogle Scholar
  96. 96.
    Torok ME, Farrar JJ (2011) When to start antiretroviral therapy in HIV–associated tuberculosis. N Engl J Med 365:1538–1540PubMedGoogle Scholar
  97. 97.
    Torok ME, Yen NT, Chau TT et al (2011) Timing of initiation of antiretroviral therapy the human immunodeficiency virus (HIV)–associated tuberculous meningitis. Clin Infect Dis 52:1374–1383PubMedGoogle Scholar
  98. 98.
    Coyne KM, Pozniak AL, Lamorde M, Boffito M (2009) Pharmacology of second–line antituberculous drugs and potential for interactions with antiretroviral agents. AIDS 23:437–446PubMedGoogle Scholar
  99. 99.
    WHO (2010) The global plan to stop TB, 2011–2015 (WHO/HTM/STB/2010.2.).World Health Organization, GenevaGoogle Scholar
  100. 100.
    Ralph AP, Anstey NM, Kelly PM (2009) Tuberculosis into the 2010’s: is the glass half full? Clin Infect Dis 49:574–583PubMedGoogle Scholar
  101. 101.
    Dorman SE (2010) New diagnostic tests for tuberculosis: bench, bedside, and beyond. Clin Infect Dis 50(S3):S173–S177PubMedGoogle Scholar
  102. 102.
    Boehme CC, Nabeta P, Hillemann D et al (2010) Rapid molecular detection of tuberculosis and rifampin resistance. N Engl J Med 363:1005–1015PubMedGoogle Scholar
  103. 103.
    WHO Roadmap for rolling out Xpert MTB/RIF for rapid diagnosis of TB and MDR–TB. http://http// Accessed Dec 2010Google Scholar
  104. 104.
    Lawn SD, Wood R (2011) Tuberculosis in antiretroviral treatment services in resource limited settings: addressing the challenges of screening and diagnosis. J Infect Dis 204:S1159–S1167PubMedGoogle Scholar
  105. 105.
    Vadwai V, Boehme C, Nabeta P et al (2011) Xpert MTB/RIF: a new pillar in diagnosis of extrapulmonary tuberculosis? J Clin Microbiol 49:2540–2545PubMedGoogle Scholar
  106. 106.
    Peter J, Green C, Hoelscher M, Mwaba P, Zumla A, Dheda K (2010) Urine for the diagnosis of tuberculosis: current approaches, clinical applicability, and new developments. Curr Opin Pulm Med 16:262–270PubMedGoogle Scholar
  107. 107.
    Lawn SD, Edwards DJ, Kranzer K, Vogt M, Bekker LG, Wood R (2009) Urine lipoarabinomannan assay for tuberculosis screening for antiretroviral therapy, diagnostic yield and association with immune reconstitution disease. AIDS 23:1875–1880PubMedGoogle Scholar
  108. 108.
    Dheda K, Davids V, Lenders L et al (2010) Clinical utility of a commercial LAM–ELISA assay for TB diagnosis in HIV–infected patients using urine and sputum samples. PLoS One 5:e9848PubMedGoogle Scholar
  109. 109.
    Kaufman SH (2011) Fact and fiction in tuberculosis vaccine research: 10 years later. Lancet Infect Dis 11:633–640Google Scholar
  110. 110.
    Orme IM (2006) Pre-clinical testing of new vaccines for tuberculosis: a comprehensive review. Vaccine 24:2–19PubMedGoogle Scholar
  111. 111.
    Lin PL, Dietrich J, Tan E et al (2012) The multistage vaccine H56 boosts the effects of BCG to protect cynomolgus macaques against active tuberculosis and reactivation of latent Mycobacterium tuberculosis infection. J Clin Invest 122:303–314PubMedGoogle Scholar
  112. 112.
    Herrera V, Perry S, Parsonnet J, Banaei N (2011) Clinical applications and limitations of interferon-g release assays for the diagnosis of latent tuberculosis infection. Clin Infect Dis 52:1031–1037PubMedGoogle Scholar
  113. 113.
    Sterling TR, Villarino E, Borisov AS et al (2011) Three months of rifapentine and isoniazid for latent tuberculosis infection. N Engl J Med 365:2155–2166PubMedGoogle Scholar
  114. 114.
    Dawson R, Masuka P, Edwards DJ et al (2010) Chest radiograph reading and recording system: evaluation for tuberculosis screening and patients with advanced HIV. Int J Tuberc Lung Dis 14:52–58PubMedGoogle Scholar
  115. 115.
    World Health Organization (2010) Guidelines for intensified tuberculosis case–finding and isoniazid preventive therapy for people living with HIV in resource constrained settings. WHO, Geneva. Accessed Dec 2010
  116. 116.
    Lienhardt C, Vernon A, Raviglione MC (2010) New drugs and new regimens for the treatment of tuberculosis: review of the drug development pipeline and implications for national programmes. Curr Opin Pulm Med 16:186–193PubMedGoogle Scholar
  117. 117.
    Diacon AH, Pym A, Grobusch M et al (2009) The diarylquinoline TMC207 for multidrug–resistant tuberculosis. N Engl J Med 360:2397–2405PubMedGoogle Scholar
  118. 118.
    Ma Z, Lienhardt C, McIlleron H, Nunn AJ, Wang X (2010) Global tuberculosis drug development pipeline: the need and the reality. Lancet 375:2100–2109PubMedGoogle Scholar
  119. 119.
    Williams KN, Brickner SJ, Stover CK et al (2009) Addition of PNU–100480 to first–line drugs shortens the time needed to cure murine tuberculosis. Am J Respir Crit Care 180:371–376Google Scholar
  120. 120.
    van Soolingen D, Hernandez-Pando R, Orozco H et al (2010) The antipsychotic thioridazine shows promising therapeutic activity in a mouse model of multidrug–resistant tuberculosis. PLoS One 5:e12640PubMedGoogle Scholar
  121. 121.
    Abbate E, Vescovo M, Natiello M et al (2012) Successful alternative treatment of extensively drug–resistant tuberculosis in Argentina with a combination of linezolid, moxifloxacin and thioridazine. J Antimicrob Chemother 67:473–477PubMedGoogle Scholar
  122. 122.
    Liang Y, Wu X, Zhang J et al (2011) Treatment of multi-drug resistant tuberculosis in mice with DNA vaccines alone or in combination with chemotherapeutic drugs. Scand J Immunol 74:42–46PubMedGoogle Scholar
  123. 123.
    Kelland K (2011) Risky tuberculosis spreading at an alarming rate in Europe: World Health Organization. Reuters Ltd, 14 Sept 2011Google Scholar
  124. 124.
    Chakroborty A (2011) Drug–resistant tuberculosis: an insurmountable epidemic? Inflammopharmacology 19:131–137PubMedGoogle Scholar
  125. 125.
    Udwadia ZF, Amale RA, Ajbani KK, Rodriques C (2011) Totally drug–resistant tuberculosis in India. Clin Infect Dis. doi:10,1093/CID 1 cir 889Google Scholar
  126. 126.
    Lowenberg S (2012) India reports cases of totally drug–resistant tuberculosis (World report). Lancet 379:205Google Scholar
  127. 127.
    Shah NS, Richardson J, Moodley P et al (2011) Increasing drug resistance in extensively drug–resistant tuberculosis, South Africa. Emerg Infect Dis 17:510–513PubMedGoogle Scholar
  128. 128.
    Selyukh A (2011) World tuberculosis cases decline for first-time ever: WHO. Reuters HealthGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Department of MedicineUniversity of TorontoTorontoCanada
  2. 2.Division of Infectious DiseasesSt. Michael’s HospitalTorontoCanada

Personalised recommendations