Mosquera-Restrepo SF, Mesa-Villanueva MC, Rojas-López M

Idioma: Español
Referencias bibliográficas: 194
Paginas: 513-550
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RESUMEN

El diagnóstico de la tuberculosis ha estado basado en la detección directa de la micobacteria; sin embargo, se estima que este se puede lograr solamente en el 10% de los casos y requiere que se combine con métodos confirmatorios como el cultivo, el cual puede tomar varias semanas para que el crecimiento sea evidente. Los métodos basados en la amplificación de la secuencia ácidos nucleicos muestran sensibilidad y especificidad altas, pero no siempre son accesibles a todos los laboratorios debido a sus requerimientos de infraestructura y el costo de los insumos. Las limitaciones para el diagnóstico hacen que se busque continuamente metabolitos micobacterianos, mediante diferentes aproximaciones, que sean, ulteriormente, fáciles de rastrear en condiciones muy básicas de laboratorio. En esta revisión se incluyen algunas de las aproximaciones metodológicas basadas en la detección de derivados micobacterianos y su valor como herramienta para el rastreo de la micobacteria.

REFERENCIAS (EN ESTE ARTÍCULO)

1. World Health Organization. Global tuberculosis report 2017. Ginebra, Suiza: World Health Organization; 2017.

2. World Health Organization. Tuberculosis data: Tuberculosis country profiles: Financing for TB prevention, diagnosis and treatment: Colombia. 2017. Disponible: http:// www.who.int/tb/country/data. Consultado: dic 2017.

3. Brodie D, Schluger NW. The diagnosis of tuberculosis. Clin Chest Med 2005; 26: 247-271, vi.

4. Druszczynska M, Kowalewicz-Kulbat M, Fol M, Wlodarczyk M, Rudnicka W. Latent M. tuberculosis infection-- pathogenesis, diagnosis, treatment and prevention strategies. Pol J Microbiol 2012; 61: 3-10.

5. Wilkinson RJ, Zhu X, Wilkinson KA, Lalvani A, Ivanyi J, Pasvol G, et al. 38 000 MW antigen-specific major histocompatibility complex class I restricted interferon-gamma- secreting CD8+ T cells in healthy contacts of tuberculosis. Immunology 1998; 95: 585-590.

6. Borgstrom E, Andersen P, Atterfelt F, Julander I, Kallenius G, Maeurer M, et al. Immune responses to ESAT-6 and CFP-10 by FASCIA and multiplex technology for diagnosis of M. tuberculosis infection; IP-10 is a promising marker. PLoS One 2012; 7: e43438.

7. Koul A, Vranckx L, Dhar N, Gohlmann HW, Ozdemir E, Neefs JM, et al. Delayed bactericidal response of Mycobacterium tuberculosis to bedaquiline involves remodelling of bacterial metabolism. Nat Commun 2014; 5: 3369.

8. Vlachaki E, Psathakis K, Tsintiris K, Iliopoulos A. Delayed response to anti-tuberculosis treatment in a patient on infliximab. Respir Med 2005; 99: 648-652.

9. Escobar AL, Coimbra CE, Jr., Camacho LA, Santos RV. Tuberculin reactivity and tuberculosis epidemiology in the Pakaanova (Wari’) Indians of Rondonia, south-western Brazilian Amazon. Int J Tuberc Lung Dis 2004; 8: 45-51.

10. Sellam J, Hamdi H, Roy C, Baron G, Lemann M, Puechal X, et al. Comparison of in vitro-specific blood tests with tuberculin skin test for diagnosis of latent tuberculosis before anti-TNF therapy. Ann Rheum Dis 2007; 66: 1610- 1615.

11. Reider RB, Farber SM. Changing Patterns in Chest Disease: A Perspective of Two Decades. Dis Chest 1963; 44: 573-586.

12. Lalvani A, Hill AV. Cytotoxic T-lymphocytes against malaria and tuberculosis: from natural immunity to vaccine design. Clin Sci (Lond) 1998; 95: 531-538.

13. von Reyn CF, Williams DE, Horsburgh CR, Jr., Jaeger AS, Marsh BJ, Haslov K, et al. Dual skin testing with Mycobacterium avium sensitin and purified protein derivative to discriminate pulmonary disease due to M. avium complex from pulmonary disease due to Mycobacterium tuberculosis. J Infect Dis 1998; 177: 730-736.

14. Black GF, Weir RE, Floyd S, Bliss L, Warndorff DK, Crampin AC, et al. BCG-induced increase in interferon-gamma response to mycobacterial antigens and efficacy of BCG vaccination in Malawi and the UK: two randomised controlled studies. Lancet 2002; 359: 1393-1401.

15. Kwamanga DO, Swai OB, Agwanda R, Githui W. Effect of non-tuberculous Mycobacteria infection on tuberculin results among primary school children in Kenya. East Afr Med J 1995; 72: 222-227.

16. American Thoracic Society, Centers for Disease Control and Prevention. Diagnostic Standards and Classification of Tuberculosis in Adults and Children. Am J Respir Crit Care Med 2000; 161: 19.

17. Dinnes J, Deeks J, Kunst H, Gibson A, Cummins E, Waugh N, et al. A systematic review of rapid diagnostic tests for the detection of tuberculosis infection. Health Technol Assess 2007; 11: 1-196.

18. Mahairas GG, Sabo PJ, Hickey MJ, Singh DC, Stover CK. Molecular analysis of genetic differences between Mycobacterium bovis BCG and virulent M. bovis. J Bacteriol 1996; 178: 1274-1282.

19. Philipp WJ, Nair S, Guglielmi G, Lagranderie M, Gicquel B, Cole ST. Physical mapping of Mycobacterium bovis BCG pasteur reveals differences from the genome map of Mycobacterium tuberculosis H37Rv and from M. bovis. Microbiology 1996; 142 ( Pt 11): 3135-3145.

20. Hsu T, Hingley-Wilson SM, Chen B, Chen M, Dai AZ, Morin PM, et al. The primary mechanism of attenuation of bacillus Calmette-Guerin is a loss of secreted lytic function required for invasion of lung interstitial tissue. Proc Natl Acad Sci U S A 2003; 100: 12420-12425.

21. Ganguly N, Siddiqui I, Sharma P. Role of M. tuberculosis RD-1 region encoded secretory proteins in protective response and virulence. Tuberculosis (Edinb) 2008; 88: 510-517.

22. Tan T, Lee WL, Alexander DC, Grinstein S, Liu J. The ESAT- 6/CFP-10 secretion system of Mycobacterium marinum modulates phagosome maturation. Cell Microbiol 2006; 8: 1417-1429.

23. Qiao D, Yang BY, Li L, Ma JJ, Zhang XL, Lao SH, et al. ESAT-6- and CFP-10-specific Th1, Th22 and Th17 cells in tuberculous pleurisy may contribute to the local immune response against Mycobacterium tuberculosis infection. Scand J Immunol 2011; 73: 330-337.

24. Meher AK, Lella RK, Sharma C, Arora A. Analysis of complex formation and immune response of CFP-10 and ESAT-6 mutants. Vaccine 2007; 25: 6098-6106.

25. Arend SM, Engelhard AC, Groot G, de Boer K, Andersen P, Ottenhoff TH, et al. Tuberculin skin testing compared with T-cell responses to Mycobacterium tuberculosis- specific and nonspecific antigens for detection of latent infection in persons with recent tuberculosis contact. Clin Diagn Lab Immunol 2001; 8: 1089-1096.

26. Johnson PD, Stuart RL, Grayson ML, Olden D, Clancy A, Ravn P, et al. Tuberculin-purified protein derivative-, MPT-64-, and ESAT-6-stimulated gamma interferon responses in medical students before and after Mycobacterium bovis BCG vaccination and in patients with tuberculosis. Clin Diagn Lab Immunol 1999; 6: 934-937.

27. Brock I, Munk ME, Kok-Jensen A, Andersen P. Performance of whole blood IFN-gamma test for tuberculosis diagnosis based on PPD or the specific antigens ESAT-6 and CFP-10. Int J Tuberc Lung Dis 2001; 5: 462-467.

28. Barnes PF. Diagnosing latent tuberculosis infection - Turning glitter to gold. Am J Respir Crit Care Med 2004; 170: 5-6.

29. Battaglioli T, Rintiswati N, Martin A, Palupi KR, Bernaerts G, Dwihardiani B, et al. Comparative performance of Thin Layer Agar and Lowenstein-Jensen culture for diagnosis of tuberculosis. Clin Microbiol Infect 2013; 19: E502-508.

30. Pathan AA, Wilkinson KA, Klenerman P, McShane H, Davidson RN, Pasvol G, et al. Direct ex vivo analysis of antigen-specific IFN-gamma-secreting CD4 T cells in Mycobacterium tuberculosis-infected individuals: associations with clinical disease state and effect of treatment. J Immunol 2001; 167: 5217-5225.

31. Bishop PJ, Neumann G. The history of the Ziehl-Neelsen stain. Tubercle 1970; 51: 196-206.

32. Mathew P, Kuo YH, Vazirani B, Eng RH, Weinstein MP. Are three sputum acid-fast bacillus smears necessary for discontinuing tuberculosis isolation? J Clin Microbiol 2002; 40: 3482-3484.

33. Hensler NM, Spivey CG, Jr., Dees TM. The use of hypertonic aerosol in production of sputum for diagnosis of tuberculosis. Comparison with gastric specimens. Dis Chest 1961; 40: 639-642.

34. Davies PD, Pai M. The diagnosis and misdiagnosis of tuberculosis. Int J Tuberc Lung Dis 2008; 12: 1226-1234.

35. Dalovisio JR, Montenegro-James S, Kemmerly SA, Genre CF, Chambers R, Greer D, et al. Comparison of the amplified Mycobacterium tuberculosis (MTB) direct test, Amplicor MTB PCR, and IS6110-PCR for detection of MTB in respiratory specimens. Clin Infect Dis 1996; 23: 1099- 1106; discussion 1107-1098.

36. Bergmann JS, Yuoh G, Fish G, Woods GL. Clinical evaluation of the enhanced Gen-Probe Amplified Mycobacterium Tuberculosis Direct Test for rapid diagnosis of tuberculosis in prison inmates. J Clin Microbiol 1999; 37: 1419-1425.

37. Johansen IS, Thomsen VO, Johansen A, Andersen P, Lundgren B. Evaluation of a new commercial assay for diagnosis of pulmonary and nonpulmonary tuberculosis. Eur J Clin Microbiol Infect Dis 2002; 21: 455-460.

38. Mederos LM, Quinones Y, Ruiz A, Teja I, Valdivia JA. [A chromatographic analysis of the Mycobacterium tuberculosis strains isolated from an outbreak in HIV patients in Cuba]. Rev Cubana Med Trop 1998; 50: 120-123.

39. Steingart KR, Flores LL, Dendukuri N, Schiller I, Laal S, Ramsay A, et al. Commercial serological tests for the diagnosis of active pulmonary and extrapulmonary tuberculosis: an updated systematic review and meta-analysis. PLoS Med 2011; 8: e1001062.

40. Flores LL, Steingart KR, Dendukuri N, Schiller I, Minion J, Pai M, et al. Systematic review and meta-analysis of antigen detection tests for the diagnosis of tuberculosis. Clin Vaccine Immunol 2011; 18: 1616-1627.

41. Ling DI, Flores LL, Riley LW, Pai M. Commercial nucleic- acid amplification tests for diagnosis of pulmonary tuberculosis in respiratory specimens: meta-analysis and meta-regression. PLoS One 2008; 3: e1536.

42. Flores LL, Pai M, Colford JM, Jr., Riley LW. In-house nucleic acid amplification tests for the detection of Mycobacterium tuberculosis in sputum specimens: meta-analysis and meta-regression. BMC Microbiol 2005; 5: 55.

43. Morgan M, Kalantri S, Flores L, Pai M. A commercial line probe assay for the rapid detection of rifampicin resistance in Mycobacterium tuberculosis: a systematic review and meta-analysis. BMC Infect Dis 2005; 5: 62.

44. Abdelhaleem AA, Hershan AA, Agarwal PK. Diagnostic Accuracy of IS6110 Insertion Gene, Hsp65, and Xpert MTB/RIF for Rapid Diagnosis of Pulmonary Tuberculosis. JTR 2017; 5: 1-12.

45. Nelson LJ, Wells CD. Global epidemiology of childhood tuberculosis. Int J Tuberc Lung Dis 2004; 8: 636-647.

46. Nelson LJ, Schneider E, Wells CD, Moore M. Epidemiology of childhood tuberculosis in the United States, 1993- 2001: the need for continued vigilance. Pediatrics 2004; 114: 333-341.

47. Lopez Avalos GG, Prado Montes de Oca E. Classic and new diagnostic approaches to childhood tuberculosis. J Trop Med 2012; 2012: 818219.

48. World Health Organization. International standards for tuberculosis care. Wkly Epidemiol Rec 2006; 81: 43-47.

49. Hopewell PC, Fair EL, Uplekar M. Updating the International Standards for Tuberculosis Care. Entering the era of molecular diagnostics. Ann Am Thorac Soc 2014; 11: 277-285.

50. Lewinsohn DA, Gennaro ML, Scholvinck L, Lewinsohn DM. Tuberculosis immunology in children: diagnostic and therapeutic challenges and opportunities. Int J Tuberc Lung Dis 2004; 8: 658-674.

51. Newton SM, Brent AJ, Anderson S, Whittaker E, Kampmann B. Paediatric tuberculosis. Lancet Infect Dis 2008; 8: 498-510.

52. Marais BJ, Gie RP, Hesseling AC, Schaaf HS, Lombard C, Enarson DA, et al. A refined symptom-based approach to diagnose pulmonary tuberculosis in children. Pediatrics 2006; 118: e1350-1359.

53. Imaz MS, Comini MA, Zerbini E, Sequeira MD, Spoletti MJ, Etchart AA, et al. Evaluation of the diagnostic value of measuring IgG, IgM and IgA antibodies to the recombinant 16-kilodalton antigen of mycobacterium tuberculosis in childhood tuberculosis. Int J Tuberc Lung Dis 2001; 5: 1036-1043.

54. Nicol MP, Pienaar D, Wood K, Eley B, Wilkinson RJ, Henderson H, et al. Enzyme-linked immunospot assay responses to early secretory antigenic target 6, culture filtrate protein 10, and purified protein derivative among children with tuberculosis: implications for diagnosis and monitoring of therapy. Clin Infect Dis 2005; 40: 1301- 1308.

55. Hesseling AC, Gie RP. Scoring systems for the diagnosis of childhood tuberculosis: are we making progress? Int J Tuberc Lung Dis 2007; 11: 245.

56. Gomez-Pastrana D, Torronteras R, Caro P, Anguita ML, Lopez-Barrio AM, Andres A, et al. Comparison of amplicor, in-house polymerase chain reaction, and conventional culture for the diagnosis of tuberculosis in children. Clin Infect Dis 2001; 32: 17-22.

57. Khan EA, Starke JR. Diagnosis of tuberculosis in children: increased need for better methods. Emerg Infect Dis 1995; 1: 115-123.

58. World Health Organization. Guidance for national tuberculosis programmes on the management of tuberculosis in children (ed 2a). Ginebra, Suiza: WHO Press; 2014.

59. Zumla A, Schaaf HS. Tuberculosis. Preface. Clin Chest Med 2009; 30: xiii-xviii.

60. Perez-Velez CM, Marais BJ. Tuberculosis in children. N Engl J Med 2012; 367: 348-361.

61. Triasih R, Rutherford M, Lestari T, Utarini A, Robertson CF, Graham SM. Contact investigation of children exposed to tuberculosis in South East Asia: a systematic review. J Trop Med 2012; 2012: 301808.

62. Graham SM. Missed opportunities for prevention of tuberculosis in children. Ann Trop Paediatr 2011; 31: 297- 299.

63. Hill PC, Rutherford ME, Audas R, van Crevel R, Graham SM. Closing the policy-practice gap in the management of child contacts of tuberculosis cases in developing countries. PLoS Med 2011; 8: e1001105.

64. Hesseling AC, Graham SM, Cuevas LE. Rapid molecular detection of tuberculosis. N Engl J Med 2011; 364: 183- 184; author reply 184-185.

65. Graham SM. The use of diagnostic systems for tuberculosis in children. Indian J Pediatr 2011; 78: 334-339.

66. Van Rie A, Page-Shipp L, Scott L, Sanne I, Stevens W. Xpert((R)) MTB/RIF for point-of-care diagnosis of TB in high-HIV burden, resource-limited countries: hype or hope? Expert Rev Mol Diagn 2010; 10: 937-946.

67. Blakemore R, Story E, Helb D, Kop J, Banada P, Owens MR, et al. Evaluation of the analytical performance of the Xpert MTB/RIF assay. J Clin Microbiol 2010; 48: 2495- 2501.

68. 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: 229-237.

69. Steingart KR, Sohn H, Schiller I, Kloda LA, Boehme CC, Pai M, et al. Xpert(R) MTB/RIF assay for pulmonary tuberculosis and rifampicin resistance in adults. Cochrane Database Syst Rev 2013; 1: CD009593.

70. Horne DJ, Pinto LM, Arentz M, Lin SY, Desmond E, Flores LL, et al. Diagnostic accuracy and reproducibility of WHO-endorsed phenotypic drug susceptibility testing methods for first-line and second-line antituberculosis drugs. J Clin Microbiol 2013; 51: 393-401.

71. Davis JL, Cattamanchi A, Cuevas LE, Hopewell PC, Steingart KR. Diagnostic accuracy of same-day microscopy versus standard microscopy for pulmonary tuberculosis: a systematic review and meta-analysis. Lancet Infect Dis 2013; 13: 147-154.

72. Boehme CC, Nabeta P, Hillemann D, Nicol MP, Shenai S, Krapp F, et al. Rapid molecular detection of tuberculosis and rifampin resistance. N Engl J Med 2010; 363: 1005- 1015.

73. Shinnick TM, Good RC. Diagnostic mycobacteriology laboratory practices. Clin Infect Dis 1995; 21: 291-299.

74. Li LM, Bai LQ, Yang HL, Xiao CF, Tang RY, Chen YF, et al. Sputum induction to improve the diagnostic yield in patients with suspected pulmonary tuberculosis. Int J Tuberc Lung Dis 1999; 3: 1137-1139.

75. Parry CM, Kamoto O, Harries AD, Wirima JJ, Nyirenda CM, Nyangulu DS, et al. The use of sputum induction for establishing a diagnosis in patients with suspected pulmonary tuberculosis in Malawi. Tuber Lung Dis 1995; 76: 72-76.

76. Hartung TK, Maulu A, Nash J, Fredlund VG. Suspected pulmonary tuberculosis in rural South Africa--sputum induction as a simple diagnostic tool? S Afr Med J 2002; 92: 455-458.

77. Abadco DL, Steiner P. Gastric lavage is better than bronchoalveolar lavage for isolation of Mycobacterium tuberculosis in childhood pulmonary tuberculosis. Pediatr Infect Dis J 1992; 11: 735-738.

78. Pomputius WF, 3rd, Rost J, Dennehy PH, Carter EJ. Standardization of gastric aspirate technique improves yield in the diagnosis of tuberculosis in children. Pediatr Infect Dis J 1997; 16: 222-226.

79. Connett GJ. Bronchoalveolar lavage. Paediatr Respir Rev 2000; 1: 52-56.

80. Wainwright CE, Grimwood K, Carlin JB, Vidmar S, Cooper PJ, Francis PW, et al. Safety of bronchoalveolar lavage in young children with cystic fibrosis. Pediatr Pulmonol 2008; 43: 965-972.

81. de Gracia J, Curull V, Vidal R, Riba A, Orriols R, Martin N, et al. Diagnostic value of bronchoalveolar lavage in suspected pulmonary tuberculosis. Chest 1988; 93: 329- 332.

82. Grange JM, Stanford JL, Beck JS. Lymphocyte and lymphocyte subset numbers in blood and bronchoalveolar lavage and pleural fluid in various forms of human pulmonary tuberculosis. Thorax 1992; 47: 1085-1086.

83. Chan HS, Sun AJ, Hoheisel GB. Bronchoscopic aspiration and bronchoalveolar lavage in the diagnosis of sputum smear-negative pulmonary tuberculosis. Lung 1990; 168: 215-220.

84. Liam CK, Chen YC, Yap SF, Srinivas P, Poi PJ. Detection of Mycobacterium tuberculosis in bronchoalveolar lavage from patients with sputum smear-negative pulmonary tuberculosis using a polymerase chain reaction assay. Respirology 1998; 3: 125-129.

85. Chow F, Espiritu N, Gilman RH, Gutierrez R, Lopez S, Escombe AR, et al. La cuerda dulce--a tolerability and acceptability study of a novel approach to specimen collection for diagnosis of paediatric pulmonary tuberculosis. BMC Infect Dis 2006; 6: 67.

86. Beatty WL, Rhoades ER, Ullrich HJ, Chatterjee D, Heuser JE, Russell DG. Trafficking and release of mycobacterial lipids from infected macrophages. Traffic 2000; 1: 235- 247.

87. Beatty WL, Ullrich HJ, Russell DG. Mycobacterial surface moieties are released from infected macrophages by a constitutive exocytic event. Eur J Cell Biol 2001; 80: 31- 40.

88. Rhoades E, Hsu F, Torrelles JB, Turk J, Chatterjee D, Russell DG. Identification and macrophage-activating activity of glycolipids released from intracellular Mycobacterium bovis BCG. Mol Microbiol 2003; 48: 875-888.

89. Bhatnagar S, Schorey JS. Exosomes released from infected macrophages contain Mycobacterium avium glycopeptidolipids and are proinflammatory. J Biol Chem 2007; 282: 25779-25789.

90. Harth G, Horwitz MA, Tabatadze D, Zamecnik PC. Targeting the Mycobacterium tuberculosis 30/32-kDa mycolyl transferase complex as a therapeutic strategy against tuberculosis: Proof of principle by using antisense technology. Proc Natl Acad Sci U S A 2002; 99: 15614-15619.

91. Braunstein M, Espinosa BJ, Chan J, Belisle JT, Jacobs WR, Jr. SecA2 functions in the secretion of superoxide dismutase A and in the virulence of Mycobacterium tuberculosis. Mol Microbiol 2003; 48: 453-464.

92. de Jonge MI, Pehau-Arnaudet G, Fretz MM, Romain F, Bottai D, Brodin P, et al. ESAT-6 from Mycobacterium tuberculosis dissociates from its putative chaperone CFP- 10 under acidic conditions and exhibits membrane-lysing activity. J Bacteriol 2007; 189: 6028-6034.

93. Samuel LP, Song CH, Wei J, Roberts EA, Dahl JL, Barry CE, 3rd, et al. Expression, production and release of the Eis protein by Mycobacterium tuberculosis during infection of macrophages and its effect on cytokine secretion. Microbiology 2007; 153: 529-540.

94. Phillips M, Basa-Dalay V, Blais J, Bothamley G, Chaturvedi A, Modi KD, et al. Point-of-care breath test for biomarkers of active pulmonary tuberculosis. Tuberculosis (Edinb) 2012; 92: 314-320.

95. Phillips M, Basa-Dalay V, Bothamley G, Cataneo RN, Lam PK, Natividad MP, et al. Breath biomarkers of active pulmonary tuberculosis. Tuberculosis (Edinb) 2010; 90: 145-151.

96. Phillips M, Cataneo RN, Condos R, Ring Erickson GA, Greenberg J, La Bombardi V, et al. Volatile biomarkers of pulmonary tuberculosis in the breath. Tuberculosis (Edinb) 2007; 87: 44-52.

97. Syhre M, Manning L, Phuanukoonnon S, Harino P, Chambers ST. The scent of Mycobacterium tuberculosis- -part II breath. Tuberculosis (Edinb) 2009; 89: 263-266.

98. Bhatnagar S, Shinagawa K, Castellino FJ, Schorey JS. Exosomes released from macrophages infected with intracellular pathogens stimulate a proinflammatory response in vitro and in vivo. Blood 2007; 110: 3234-3244.

99. Geisel RE, Sakamoto K, Russell DG, Rhoades ER. In vivo activity of released cell wall lipids of Mycobacterium bovis bacillus Calmette-Guerin is due principally to trehalose mycolates. J Immunol 2005; 174: 5007-5015.

100. Guenin-Mace L, Simeone R, Demangel C. Lipids of pathogenic Mycobacteria: contributions to virulence and host immune suppression. Transbound Emerg Dis 2009; 56: 255-268.

101. Abdallah AM, Gey van Pittius NC, Champion PA, Cox J, Luirink J, Vandenbroucke-Grauls CM, et al. Type VII secretion-- mycobacteria show the way. Nat Rev Microbiol 2007; 5: 883-891.

102. Driessen NN, Ummels R, Maaskant JJ, Gurcha SS, Besra GS, Ainge GD, et al. Role of phosphatidylinositol mannosides in the interaction between mycobacteria and DCSIGN. Infect Immun 2009; 77: 4538-4547.

103. Mazurek J, Ignatowicz L, Kallenius G, Svenson SB, Pawlowski A, Hamasur B. Divergent effects of mycobacterial cell wall glycolipids on maturation and function of human monocyte-derived dendritic cells. PLoS One 2012; 7: e42515.

104. Vergne I, Fratti RA, Hill PJ, Chua J, Belisle J, Deretic V. Mycobacterium tuberculosis phagosome maturation arrest: mycobacterial phosphatidylinositol analog phosphatidylinositol mannoside stimulates early endosomal fusion. Mol Biol Cell 2004; 15: 751-760.

105. Guerardel Y, Maes E, Elass E, Leroy Y, Timmerman P, Besra GS, et al. Structural study of lipomannan and lipoarabinomannan from Mycobacterium chelonae. Presence of unusual components with alpha 1,3-mannopyranose side chains. J Biol Chem 2002; 277: 30635-30648.

106. Khoo KH, Dell A, Morris HR, Brennan PJ, Chatterjee D. Inositol phosphate capping of the nonreducing termini of lipoarabinomannan from rapidly growing strains of Mycobacterium. J Biol Chem 1995; 270: 12380-12389.

107. Brown MC, Taffet SM. Lipoarabinomannans derived from different strains of Mycobacterium tuberculosis differentially stimulate the activation of NF-kappa B and KBF1 in murine macrophages. Infect Immun 1995; 63: 1960-1968.

108. Mahon RN, Sande OJ, Rojas RE, Levine AD, Harding CV, Boom WH. Mycobacterium tuberculosis ManLAM inhibits T-cell-receptor signaling by interference with ZAP-70, Lck and LAT phosphorylation. Cell Immunol 2012; 275: 98-105.

109. Rojas M, Garcia LF, Nigou J, Puzo G, Olivier M. Mannosylated lipoarabinomannan antagonizes Mycobacterium tuberculosis-induced macrophage apoptosis by altering Ca+2-dependent cell signaling. J Infect Dis 2000; 182: 240-251.

110. Elbein AD, Pan YT, Pastuszak I, Carroll D. New insights on trehalose: a multifunctional molecule. Glycobiology 2003; 13: 17R-27R.

111. Reither K, Saathoff E, Jung J, Minja LT, Kroidl I, Saad E, et al. Low sensitivity of a urine LAM-ELISA in the diagnosis of pulmonary tuberculosis. BMC Infect Dis 2009; 9: 141.

112. Lopez-Sanchez LM, Jurado-Gamez B, Feu-Collado N, Valverde A, Canas A, Fernandez-Rueda JL, et al. Exhaled breath condensate biomarkers for the early diagnosis of lung cancer using proteomics. Am J Physiol Lung Cell Mol Physiol 2017; 313: L664-L676.

113. Mehta A, Cordero J, Dobersch S, Romero-Olmedo AJ, Savai R, Bodner J, et al. Non-invasive lung cancer diagnosis by detection of GATA6 and NKX2-1 isoforms in exhaled breath condensate. EMBO Mol Med 2016; 8: 1380- 1389.

114. Rozy A, Czerniawska J, Stepniewska A, Wozbinska B, Goljan A, Puscinska E, et al. Inflammatory markers in the exhaled breath condensate of patients with pulmonary sarcoidosis. J Physiol Pharmacol 2006; 57 Suppl 4: 335- 340.

115. Thomas PS, Lowe AJ, Samarasinghe P, Lodge CJ, Huang Y, Abramson MJ, et al. Exhaled breath condensate in pediatric asthma: promising new advance or pouring cold water on a lot of hot air? a systematic review. Pediatr Pulmonol 2013; 48: 419-442.

116. Lawn SD. Point-of-care detection of lipoarabinomannan (LAM) in urine for diagnosis of HIV-associated tuberculosis: a state of the art review. BMC Infect Dis 2012; 12: 103.

117. Hamasur B, Haile M, Pawlowski A, Schroder U, Kallenius G, Svenson SB. A mycobacterial lipoarabinomannan specific monoclonal antibody and its F(ab’) fragment prolong survival of mice infected with Mycobacterium tuberculosis. Clin Exp Immunol 2004; 138: 30-38.

118. Balcha TT, Winqvist N, Sturegard E, Skogmar S, Reepalu A, Jemal ZH, et al. Detection of lipoarabinomannan in urine for identification of active tuberculosis among HIV-positive adults in Ethiopian health centres. Trop Med Int Health 2014; 19: 734-742.

119. Boehme C, Molokova E, Minja F, Geis S, Loscher T, Maboko L, et al. Detection of mycobacterial lipoarabinomannan with an antigen-capture ELISA in unprocessed urine of Tanzanian patients with suspected tuberculosis. Trans R Soc Trop Med Hyg 2005; 99: 893-900.

120. Suwanpimolkul G, Kawkitinarong K, Manosuthi W, Sophonphan J, Gatechompol S, Ohata PJ, et al. Utility of urine lipoarabinomannan (LAM) in diagnosing tuberculosis and predicting mortality with and without HIV: prospective TB cohort from the Thailand Big City TB Research Network. Int J Infect Dis 2017; 59: 96-102.

121. Peter J, Green C, Hoelscher M, Mwaba P, Zumla A, Dheda K. Urine for the diagnosis of tuberculosis: current approaches, clinical applicability, and new developments. Curr Opin Pulm Med 2010; 16: 262-270.

122. Daley P, Michael JS, Hmar P, Latha A, Chordia P, Mathai D, et al. Blinded evaluation of commercial urinary lipoarabinomannan for active tuberculosis: a pilot study. Int J Tuberc Lung Dis 2009; 13: 989-995.

123. Mutetwa R, Boehme C, Dimairo M, Bandason T, Munyati SS, Mangwanya D, et al. Diagnostic accuracy of commercial urinary lipoarabinomannan detection in African tuberculosis suspects and patients. Int J Tuberc Lung Dis 2009; 13: 1253-1259.

124. Gupta-Wright A, Peters JA, Flach C, Lawn SD. Detection of lipoarabinomannan (LAM) in urine is an independent predictor of mortality risk in patients receiving treatment for HIV-associated tuberculosis in sub-Saharan Africa: a systematic review and meta-analysis. BMC Med 2016; 14: 53.

125. Peter JG, Theron G, Dheda K. Can point-of-care urine LAM strip testing for tuberculosis add value to clinical decision making in hospitalised HIV-infected persons? PLoS One 2013; 8: e54875.

126. Sabur NF, Esmail A, Brar MS, Dheda K. Diagnosing tuberculosis in hospitalized HIV-infected individuals who cannot produce sputum: is urine lipoarabinomannan testing the answer? BMC Infect Dis 2017; 17: 803.

127. Sahle SN, Asress DT, Tullu KD, Weldemariam AG, Tola HH, Awas YA, et al. Performance of point-of-care urine test in diagnosing tuberculosis suspects with and without HIV infection in selected peripheral health settings of Addis Ababa, Ethiopia. BMC Res Notes 2017; 10: 74.

128. Zijenah LS, Kadzirange G, Bandason T, Chipiti MM, Gwambiwa B, Makoga F, et al. Comparative performance characteristics of the urine lipoarabinomannan strip test and sputum smear microscopy in hospitalized HIVinfected patients with suspected tuberculosis in Harare, Zimbabwe. BMC Infect Dis 2016; 16: 20.

129. Drain PK, Gounder L, Sahid F, Moosa MY. Rapid Urine LAM Testing Improves Diagnosis of Expectorated Smear- Negative Pulmonary Tuberculosis in an HIV-endemic Region. Sci Rep 2016; 6: 19992.

130. Dheda K, Davids V, Lenders L, Roberts T, Meldau R, Ling D, et al. Clinical utility of a commercial LAM-ELISA assay for TB diagnosis in HIV-infected patients using urine and sputum samples. PLoS One 2010; 5: e9848.

131. Lawn SD, Kerkhoff AD, Burton R, Meintjes G. Underestimation of the incremental diagnostic yield of HIV-associated tuberculosis in studies of the Determine TB-LAM Ag urine assay. AIDS 2014; 28: 1846-1848.

132. Shah M, Variava E, Holmes CB, Coppin A, Golub JE, Mc- Callum J, et al. Diagnostic accuracy of a urine lipoarabinomannan test for tuberculosis in hospitalized patients in a High HIV prevalence setting. J Acquir Immune Defic Syndr 2009; 52: 145-151.

133. Sada E, Brennan PJ, Herrera T, Torres M. Evaluation of lipoarabinomannan for the serological diagnosis of tuberculosis. J Clin Microbiol 1990; 28: 2587-2590.

134. Sada E, Aguilar D, Torres M, Herrera T. Detection of lipoarabinomannan as a diagnostic test for tuberculosis. J Clin Microbiol 1992; 30: 2415-2418.

135. Pereira Arias-Bouda LM, Nguyen LN, Ho LM, Kuijper S, Jansen HM, Kolk AH. Development of antigen detection assay for diagnosis of tuberculosis using sputum samples. J Clin Microbiol 2000; 38: 2278-2283.

136. Dheda K, Van-Zyl Smit RN, Sechi LA, Badri M, Meldau R, Symons G, et al. Clinical diagnostic utility of IP-10 and LAM antigen levels for the diagnosis of tuberculous pleural effusions in a high burden setting. PLoS One 2009; 4: e4689.

137. Sardella IG, Singh M, Kumpfer S, Heringer RR, Saad MH, Sohler MP. Evaluation of Lionex TB kits and mycobacterial antigens for IgG and IgA detection in cerebrospinal fluid from tuberculosis meningitis patients. Mem Inst Oswaldo Cruz 2010; 105: 722-728.

138. Patel VB, Singh R, Connolly C, Coovadia Y, Peer AK, Parag P, et al. Cerebrospinal T-cell responses aid in the diagnosis of tuberculous meningitis in a human immunodeficiency virus- and tuberculosis-endemic population. Am J Respir Crit Care Med 2010; 182: 569-577.

139. Patel VB, Singh R, Connolly C, Kasprowicz V, Zumla A, Ndungu T, et al. Comparison of a clinical prediction rule and a LAM antigen-detection assay for the rapid diagnosis of TBM in a high HIV prevalence setting. PLoS One 2010; 5: e15664.

140. Demkow U, Filewska M, Bialas B, Szturmowicz M, Zielonka T, Wesolowski S, et al. [Antimycobacterial antibody level in pleural, pericardial and cerebrospinal fluid of patients with tuberculosis]. Pneumonol Alergol Pol 2004; 72: 105-110.

141. Fujita Y, Naka T, Doi T, Yano I. Direct molecular mass determination of trehalose monomycolate from 11 species of mycobacteria by MALDI-TOF mass spectrometry. Microbiology 2005; 151: 1443-1452.

142. Beccaria M, Mellors TR, Petion JS, Rees CA, Nasir M, Systrom HK, et al. Preliminary investigation of human exhaled breath for tuberculosis diagnosis by multidimensional gas chromatography - Time of flight mass spectrometry and machine learning. J Chromatogr B Analyt Technol Biomed Life Sci 2018; 1074-1075: 46-50.

143. French GL, Chan CY, Cheung SW, Oo KT. Diagnosis of pulmonary tuberculosis by detection of tuberculostearic acid in sputum by using gas chromatography-mass spectrometry with selected ion monitoring. J Infect Dis 1987; 156: 356-362.

144. James AT, Martin AJ. Gas-liquid partition chromatography: the separation and micro-estimation of ammonia and the methylamines. Biochem J 1952; 52: 238-242.

145. James AT, Martin AJ. Gas-liquid partition chromatography; the separation and micro-estimation of volatile fatty acids from formic acid to dodecanoic acid. Biochem J 1952; 50: 679-690.

146. Martin AJ, Synge RL. A new form of chromatogram employing two liquid phases: A theory of chromatography. 2. Application to the micro-determination of the higher monoamino-acids in proteins. Biochem J 1941; 35: 1358- 1368.

147. Jackson SK, Stark JM, Taylor S, Harwood JL. Changes in phospholipid fatty acid composition and triacylglycerol content in mouse tissues after infection with bacille Calmette-Guerin. Br J Exp Pathol 1989; 70: 435-441.

148. Ozbek A, Aktas O. Identification of three strains of Mycobacterium species isolated from clinical samples using fatty acid methyl ester profiling. J Int Med Res 2003; 31: 133-140.

149. Ohashi DK, Wade TJ, Mandle RJ. Characterization of ten species of mycobacteria by reaction-gas-liquid chromatography. J Clin Microbiol 1977; 6: 469-473.

150. Larsson L, Jantzen E, Johnsson J. Gas chromatographic fatty acid profiles for characterisation of mycobacteria: an interlaboratory methodological evaluation. Eur J Clin Microbiol 1985; 4: 483-487.

151. Cepelak I, Dodig S. Exhaled breath condensate: a new method for lung disease diagnosis. Clin Chem Lab Med 2007; 45: 945-952.

152. Teranishi R, Mon TR, Robinson AB, Cary P, Pauling L. Gas chromatography of volatiles from breath and urine. Anal Chem 1972; 44: 18-20.

153. Pauling L, Robinson AB, Teranishi R, Cary P. Quantitative analysis of urine vapor and breath by gas-liquid partition chromatography. Proc Natl Acad Sci U S A 1971; 68: 2374- 2376.

154. Kuban P, Foret F. Exhaled breath condensate: determination of non-volatile compounds and their potential for clinical diagnosis and monitoring. A review. Anal Chim Acta 2013; 805: 1-18.

155. Chambers ST, Scott-Thomas A, Epton M. Developments in novel breath tests for bacterial and fungal pulmonary infection. Curr Opin Pulm Med 2012; 18: 228-232.

156. Nizio KD, Perrault KA, Troobnikoff AN, Ueland M, Shoma S, Iredell JR, et al. In vitro volatile organic compound profiling using GCxGC-TOFMS to differentiate bacteria associated with lung infections: a proof-of-concept study. J Breath Res 2016; 10: 026008.

157. Reinhold P, Kirschvink N, Theegarten D, Berndt A. An experimentally induced Chlamydia suis infection in pigs results in severe lung function disorders and pulmonary inflammation. Vet Res 2008; 39: 35.

158. Yildirim Z, Bozkurt B, Ozol D, Armutcu F, Akgedik R, Karamanli H, et al. Increased Exhaled 8-Isoprostane and Interleukin- 6 in Patients with Helicobacter pylori Infection. Helicobacter 2016; 21: 389-394.

159. Syhre M, Chambers ST. The scent of Mycobacterium tuberculosis. Tuberculosis (Edinb) 2008; 88: 317-323.

160. Han D, Wang Z, Cheng J, Wang Q, Chen X, Wang H. Volatile organic compounds (VOCs) during non-haze and haze days in Shanghai: characterization and secondary organic aerosol (SOA) formation. Environ Sci Pollut Res Int 2017; 24: 18619-18629.

161. Hartikainen A, Yli-Pirila P, Tiitta P, Leskinen A, Kortelainen M, Orasche J, et al. Volatile organic compounds from logwood combustion: Emissions and transformation under dark and photochemical aging conditions in a smog chamber. Environ Sci Technol 2018.

162. Holopainen JK, Kivimaenpaa M, Nizkorodov SA. Plant-derived Secondary Organic Material in the Air and Ecosystems. Trends Plant Sci 2017; 22: 744-753.

163. Liu T, Liu Q, Li Z, Huo L, Chan M, Li X, et al. Emission of volatile organic compounds and production of secondary organic aerosol from stir-frying spices. Sci Total Environ 2017; 599-600: 1614-1621.

164. Mosquera-Restrepo SF, Caro AC, Garcia LF, Pelaez-Jaramillo CA, Rojas M. Fatty acid derivative, chemokine, and cytokine profiles in exhaled breath condensates can differentiate adult and children paucibacillary tuberculosis patients. J Breath Res 2017; 11: 016003.

165. Butler WR, Guthertz LS. Mycolic acid analysis by high-performance liquid chromatography for identification of Mycobacterium species. Clin Microbiol Rev 2001; 14: 704-726, table of contents.

166. Levy-Frebault V, Goh KS, David HL. Mycolic acid analysis for clinical identification of Mycobacterium avium and related mycobacteria. J Clin Microbiol 1986; 24: 835-839.

167. Viader-Salvado JM, Molina-Torres CA, Guerrero- Olazaran M. Detection and identification of mycobacteria by mycolic acid analysis of sputum specimens and young cultures. J Microbiol Methods 2007; 70: 479-483.

168. Guerrant GO, Lambert MA, Moss CW. Gas-chromatographic analysis of mycolic acid cleavage products in mycobacteria. J Clin Microbiol 1981; 13: 899-907.

169. Leite CQ, da Silva Rocha A, de Andrade Leite SR, Ferreira RM, Suffys PN, de Souza Fonseca L, et al. A comparison of mycolic acid analysis for nontuberculous mycobacteria identification by thin-layer chromatography and molecular methods. Microbiol Immunol 2005; 49: 571-578.

170. Tisdall PA, Anhalt JP. Rapid differentiation of Streptomyces from Nocardia by liquid chromatography. J Clin Microbiol 1979; 10: 503-505.

171. Kaal E, Kolk AH, Kuijper S, Janssen HG. A fast method for the identification of Mycobacterium tuberculosis in sputum and cultures based on thermally assisted hydrolysis and methylation followed by gas chromatography-mass spectrometry. J Chromatogr A 2009; 1216: 6319-6325.

172. Torrelles JB, Sieling PA, Zhang N, Keen MA, McNeil MR, Belisle JT, et al. Isolation of a distinct Mycobacterium tuberculosis mannose-capped lipoarabinomannan isoform responsible for recognition by CD1b-restricted T cells. Glycobiology 2012; 22: 1118-1127.

173. Larsson L, Mardh P, Odham G, Westerdahl G. Use of selected ion monitoring for detection of tuberculostearic and C32 mycocerosic acid in mycobacteria and in fiveday- old cultures of sputum specimens from patients with pulmonary tuberculosis. Acta Pathol Microbiol Scand B 1981; 89: 245-251.

174. Traunmuller F, Zeitlinger MA, Stoiser B, Lagler H, Abdel Salam HA, Presterl E, et al. Circulating tuberculostearic acid in tuberculosis patients. Scand J Infect Dis 2003; 35: 790-793.

175. Asselineau J, Lederer E. Structure of the mycolic acids of Mycobacteria. Nature 1950; 166: 782-783.

176. Liu J, Barry CE, 3rd, Besra GS, Nikaido H. Mycolic acid structure determines the fluidity of the mycobacterial cell wall. J Biol Chem 1996; 271: 29545-29551.

177. Dao DN, Sweeney K, Hsu T, Gurcha SS, Nascimento IP, Roshevsky D, et al. Mycolic acid modification by the mmaA4 gene of M. tuberculosis modulates IL-12 production. PLoS Pathog 2008; 4: e1000081.

178. Yuan Y, Zhu Y, Crane DD, Barry CE, 3rd. The effect of oxygenated mycolic acid composition on cell wall function and macrophage growth in Mycobacterium tuberculosis. Mol Microbiol 1998; 29: 1449-1458.

179. Minnikin DE, Minnikin SM, Parlett JH, Goodfellow M. Mycolic acid patterns of some rapidly-growing species of Mycobacterium. Zentralbl Bakteriol Mikrobiol Hyg A 1985; 259: 446-460.

180. Stodola FH, Deinema MH, Spencer JF. Extracellular lipids of yeasts. Bacteriol Rev 1967; 31: 194-213.

181. Etemadi AH. [Isolation of Isopentadecanoic and Isoheptadecanoic Acids from the Lipids of Corynebacterium Parvum]. Bull Soc Chim Biol (Paris) 1963; 45: 1423-1432.

182. Kaneda K, Naito S, Imaizumi S, Yano I, Mizuno S, Tomiyasu I, et al. Determination of molecular species com position of C80 or longer-chain alpha-mycolic acids in Mycobacterium spp. by gas chromatography-mass spectrometry and mass chromatography. J Clin Microbiol 1986; 24: 1060-1070.

183. Tisdall PA, Roberts GD, Anhalt JP. Identification of clinical isolates of mycobacteria with gas-liquid chromatography alone. J Clin Microbiol 1979; 10: 506-514.

184. Tisdall PA, DeYoung DR, Roberts GD, Anhalt JP. Identification of clinical isolates of mycobacteria with gas-liquid chromatography: a 10-month follow-up study. J Clin Microbiol 1982; 16: 400-402.

185. Aktas O, Ozbek A. Prevalence and in-vitro antimicrobial susceptibility patterns of Acinetobacter strains isolated from patients in intensive care units. J Int Med Res 2003; 31: 272-280.

186. Luquin M, Lopez F, Ausina V. Capillary gas chromatographic analysis of mycolic acid cleavage products, cellular fatty acids, and alcohols of Mycobacterium xenopi. J Clin Microbiol 1989; 27: 1403-1406.

187. Prout FS, Cason J, Ingersoll AW. The synthesis of tuberculostearic acid. J Am Chem Soc 1947; 69: 1233.

188. Anderson C. The chemistry of the lipids of the tubercle bacillus. J Biol Chem 1929; 85: 6.

189. Larsson L, Mardh PA, Odham G. Detection of tuberculostearic acid in mycobacteria and nocardiae by gas chromatography and mass spectrometry using selected ion monitoring. J Chromatogr 1979; 163: 221-224.

190. Odham G, Larsson L, Mardh PA. Demonstration of tuberculostearic acid in sputum from patients with pulmonary tuberculosis by selected ion monitoring. J Clin Invest 1979; 63: 813-819.

191. Pang JA, Chan HS, Chan CY, Cheung SW, French GL. A tuberculostearic acid assay in the diagnosis of sputum smear-negative pulmonary tuberculosis. A prospective study of bronchoscopic aspirate and lavage specimens. Ann Intern Med 1989; 111: 650-654.

192. Dang NA, Mourao M, Kuijper S, Walters E, Janssen HG, Kolk AH. Direct detection of Mycobacterium tuberculosis in sputum using combined solid phase extraction-gas chromatography-mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 2015; 986-987: 115-122.

193. Savic B, Sjobring U, Alugupalli S, Larsson L, Miorner H. Evaluation of polymerase chain reaction, tuberculostearic acid analysis, and direct microscopy for the detection of Mycobacterium tuberculosis in sputum. J Infect Dis 1992; 166: 1177-1180.

194. Mosquera-Restrepo SF, Caro AC, Pelaez-Jaramillo CA, Rojas M. Mononuclear phagocyte accumulates a stearic acid derivative during differentiation into macrophages. Effects of stearic acid on macrophage differentiation and Mycobacterium tuberculosis control. Cell Immunol 2016; 303: 24-33.