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Treatment of Latent Tuberculosis Infection

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  • Author: Connie A. Haley1
  • Editor: David Schlossberg2
  • VIEW AFFILIATIONS HIDE AFFILIATIONS
    Affiliations: 1: Division of Infectious Diseases and Southeast National Tuberculosis Center, University of Florida, Gainesville, FL 32611; 2: Philadelphia Health Department, Philadelphia, PA
  • Source: microbiolspec April 2017 vol. 5 no. 2 doi:10.1128/microbiolspec.TNMI7-0039-2016
  • Received 24 December 2016 Accepted 05 January 2017 Published 14 April 2017
  • Connie A. Haley, connie.haley@comcast.net
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  • Abstract:

    There are approximately 56 million people who harbor that may progress to active tuberculosis (TB) at some point in their lives. Modeling studies suggest that if only 8% of these individuals with latent TB infection (LTBI) were treated annually, overall global incidence would be 14-fold lower by 2050 compared to incidence in 2013, even in the absence of additional TB control measures. This highlights the importance of identifying and treating latently infected individuals, and that this intervention must be scaled up to achieve the goals of the Global End TB Strategy. The efficacy of LTBI treatment is well established, and the most commonly used regimen is 9 months of daily self-administered isoniazid. However, its use has been hindered by limited provider awareness of the benefits, concern about potential side effects such as hepatotoxicity, and low rates of treatment completion. There is increasing evidence that shorter rifamycin-based regimens are as effective, better tolerated, and more likely to be completed compared to isoniazid. Such regimens include four months of daily self-administered rifampin monotherapy, three months of once weekly directly observed isoniazid-rifapentine, and three months of daily self-administered isoniazid-rifampin. The success of LTBI treatment to prevent additional TB disease relies upon choosing an appropriate regimen individualized to the patient, monitoring for potential adverse clinical events, and utilizing strategies to promote adherence. Safer, more cost-effective, and more easily completed regimens are needed and should be combined with interventions to better identify, engage, and retain high-risk individuals across the cascade from diagnosis through treatment completion of LTBI.

  • Citation: Haley C. 2017. Treatment of Latent Tuberculosis Infection. Microbiol Spectrum 5(2):TNMI7-0039-2016. doi:10.1128/microbiolspec.TNMI7-0039-2016.

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References

1. World Health Organization. 2016. Global tuberculosis report 2016. World Health Organization, Geneva, Switzerland. http://www.who.int/tb/publications/global_report/en/. Accessed 20 December 2016.
2. Dye C, Glaziou P, Floyd K, Raviglione M. 2013. Prospects for tuberculosis elimination. Annu Rev Public Health 34:271–286. [PubMed]
3. World Health Organization. 2015. The End TB Strategy. Global Strategy and Targets for Tuberculosis Prevention, Care and Control after 2015. World Health Organization, Geneva, Switzerland. http://www.who.int/tb/post2015_strategy/en/. Accessed 20 December 2016.
4. Lönnroth K, Migliori GB, Abubakar I, D’Ambrosio L, de Vries G, Diel R, Douglas P, Falzon D, Gaudreau MA, Goletti D, González Ochoa ER, LoBue P, Matteelli A, Njoo H, Solovic I, Story A, Tayeb T, van der Werf MJ, Weil D, Zellweger JP, Abdel Aziz M, Al Lawati MR, Aliberti S, Arrazola de Oñate W, Barreira D, Bhatia V, Blasi F, Bloom A, Bruchfeld J, Castelli F, Centis R, Chemtob D, Cirillo DM, Colorado A, Dadu A, Dahle UR, De Paoli L, Dias HM, Duarte R, Fattorini L, Gaga M, Getahun H, Glaziou P, Goguadze L, Del Granado M, Haas W, Järvinen A, Kwon GY, Mosca D, Nahid P, Nishikiori N, Noguer I, O’Donnell J, Pace-Asciak A, Pompa MG, Popescu GG, Robalo Cordeiro C, Rønning K, Ruhwald M, Sculier JP, Simunović A, Smith-Palmer A, Sotgiu G, Sulis G, Torres-Duque CA, Umeki K, Uplekar M, van Weezenbeek C, Vasankari T, Vitillo RJ, Voniatis C, Wanlin M, Raviglione MC. 2015. Towards tuberculosis elimination: an action framework for low-incidence countries. Eur Respir J 45:928–952.
5. Getahun H, Matteelli A, Chaisson RE, Raviglione M. 2015. Latent Mycobacterium tuberculosis infection. N Engl J Med 372:2127–2135. [PubMed]
6. Getahun H, et al. 2015. Management of latent Mycobacterium tuberculosis infection: WHO guidelines for low tuberculosis burden countries. Eur Respir J 46:1563–1576. [PubMed]
7. Houben RM, Dodd PJ. 2016. The global burden of latent tuberculosis infection: a re-estimation using mathematical modelling. PLoS Med 13:e1002152 doi:10.1371/journal.pmed.1002152.
8. American Thoracic Society, Centers for Disease Control and Prevention. 2000. Targeted tuberculin testing and treatment of latent tuberculosis infection. Am J Respir Crit Care Med 161:S221–S247. [PubMed]
9. Institute of Medicine Committee on the Elimination of Tuberculosis in the United States. 2000. Ending Neglect: The Elimination of Tuberculosis in the United States. National Academies Press, Washington, DC.
10. Taylor Z, Nolan CM, Blumberg HM, American Thoracic Society, Centers for Disease Control and Prevention, Infectious Diseases Society of America. 2005. Controlling tuberculosis in the United States. Recommendations from the American Thoracic Society, CDC, and the Infectious Diseases Society of America. MMWR Recommend Rep 54(RR-12):1–81. [PubMed]
11. Zwerling A, Behr MA, Verma A, Brewer TF, Menzies D, Pai M. 2011. The BCG World Atlas: a database of global BCG vaccination policies and practices. PLoS Med 8(3):e1001012. [PubMed]
12. Abubakar I, Pimpin L, Ariti C, Beynon R, Mangtani P, Sterne JA, Fine PE, Smith PG, Lipman M, Elliman D, Watson JM, Drumright LN, Whiting PF, Vynnycky E, Rodrigues LC. 2013. Systematic review and meta-analysis of the current evidence on the duration of protection by bacillus Calmette-Guérin vaccination against tuberculosis. Health Technol Assess 17:1–372, v–vi. [PubMed]
13. Pai M, Behr MA, Dowdy D, Dheda K, Divangahi M, Boehme CC, Ginsberg A, Swaminathan S, Spigelman M, Getahun H, Menzies D, Raviglione M. 2016. Tuberculosis. Nat Rev Dis Primers 2:16076. [PubMed]
14. Lobato MN, Wang YC, Becerra JE, Simone PM, Castro KG. 2006. Improved program activities are associated with decreasing tuberculosis incidence in the United States. Public Health Rep 121:108–115. [PubMed]
15. Hill AN, Becerra J, Castro KG. 2012. Modelling tuberculosis trends in the USA. Epidemiol Infect 140:1862–1872. [PubMed]
16. Kahwati LC, Feltner C, Halpern M, Woodell CL, Boland E, Amick HR, Weber RP, Jonas DE. 2016. Primary care screening and treatment for latent tuberculosis infection in adults: evidence report and systematic review for the US Preventive Services Task Force. JAMA 316:970–983. [PubMed]
17. US Preventive Services Task Force. 6 September 2016. Screening for latent tuberculosis infection in adults: US Preventive Services Task Force recommendation statement. JAMA doi:10.1001/jama.2016.11046.
18. Barry CE, III, Boshoff HI, Dartois V, Dick T, Ehrt S, Flynn J, Schnappinger D, Wilkinson RJ, Young D. 2009. The spectrum of latent tuberculosis: rethinking the biology and intervention strategies. Nat Rev Microbiol 7:845–855. [PubMed]
19. Esmail H, Barry CE, III, Wilkinson RJ. 2012. Understanding latent tuberculosis: the key to improved diagnostic and novel treatment strategies. Drug Discov Today 17:514–521. [PubMed]
20. Lewinsohn DM, Leonard MK, LoBue PA, Cohn DL, Daley CL, Desmond E, Keane J, Lewinsohn DA, Loeffler AM, Mazurek GH, O’Brien RJ, Pai M, Richeldi L, Salfinger M, Shinnick TM, Sterling TR, Warshauer DM, Woods GL. 2016. Official American Thoracic Society/Infectious Diseases Society of America/Centers for Disease Control and Prevention clinical practice guidelines: diagnosis of tuberculosis in adults and children. Clin Infect Dis 64:111–115. [PubMed]
21. Comstock GW. 1999. How much isoniazid is needed for prevention of tuberculosis among immunocompetent adults? Int J Tuberc Lung Dis 3:847–850. [PubMed]
22. Ferebee SH. 1970. Controlled chemoprophylaxis trials in tuberculosis. A general review. Bibl Tuberc 26:28–106. [PubMed]
23. Sutherland I. 1976. Recent studies in the epidemiology of tuberculosis, based on the risk of being infected with tubercle bacilli. Adv Tuberc Res 19:1–63. [PubMed]
24. Bucher HC, Griffith LE, Guyatt GH, Sudre P, Naef M, Sendi P, Battegay M. 1999. Isoniazid prophylaxis for tuberculosis in HIV infection: a meta-analysis of randomized controlled trials. AIDS 13:501–507. [PubMed]
25. Cruz AT, Starke JR. 2010. Pediatric tuberculosis. Pediatr Rev 31:13–25; quiz, 25–26. [PubMed]
26. Markowitz N, Hansen NI, Hopewell PC, Glassroth J, Kvale PA, Mangura BT, Wilcosky TC, Wallace JM, Rosen MJ, Reichman LB, The Pulmonary Complications of HIV Infection Study Group. 1997. Incidence of tuberculosis in the United States among HIV-infected persons. Ann Intern Med 126:123–132. [PubMed]
27. Selwyn PA, Hartel D, Lewis VA, Schoenbaum EE, Vermund SH, Klein RS, Walker AT, Friedland GH. 1989. A prospective study of the risk of tuberculosis among intravenous drug users with human immunodeficiency virus infection. N Engl J Med 320:545–550. [PubMed]
28. Vernon A. 2013. Treatment of latent tuberculosis infection. Semin Respir Crit Care Med 34:67–86. [PubMed]
29. Cowie RL. 1994. The epidemiology of tuberculosis in gold miners with silicosis. Am J Respir Crit Care Med 150:1460–1462. [PubMed]
30. International Union Against Tuberculosis Committee on Prophylaxis. 1982. Efficacy of various durations of isoniazid preventive therapy for tuberculosis: five years of follow-up in the IUAT trial. Bull World Health Organ 60:555–564. [PubMed]
31. Sterling TR, Villarino ME, Borisov AS, Shang N, Gordin F, Bliven-Sizemore E, Hackman J, Hamilton CD, Menzies D, Kerrigan A, Weis SE, Weiner M, Wing D, Conde MB, Bozeman L, Horsburgh CR, Jr, Chaisson RE, TB Trials Consortium PREVENT TB Study Team. 2011. Three months of rifapentine and isoniazid for latent tuberculosis infection. N Engl J Med 365:2155–2166. [PubMed]
32. Sharma SK, Sharma A, Kadhiravan T, Tharyan P. 2013. Rifamycins (rifampicin, rifabutin and rifapentine) compared to isoniazid for preventing tuberculosis in HIV-negative people at risk of active TB. Cochrane Database Syst Rev 2013(7):CD007545. [PubMed]
33. Stagg HR, Zenner D, Harris RJ, Muñoz L, Lipman MC, Abubakar I. 2014. Treatment of latent tuberculosis infection: a network meta-analysis. Ann Intern Med 161:419–428. [PubMed]
34. Pediatric Tuberculosis Collaborative Group. 2004. Targeted tuberculin skin testing and treatment of latent tuberculosis infection in children and adolescents. Pediatrics 114(Suppl 4):1175–1201.
35. Centers for Disease Control and Prevention. 2013. Latent Tuberculosis Infection: A Guide for Primary Health Care Providers. Centers for Disease Control and Prevention, Atlanta, GA. http://www.cdc.gov/tb/publications/ltbi/. Accessed 19 December 2016.
36. Centre for Communicable Diseases and Infection Control, Public Health Agency of Canada. 2014. Canadian TB Standards, 7th ed. Centre for Communicable Diseases and Infection Control, Ottawa, Canada. http://www.respiratoryguidelines.ca/sites/all/files/Canadian_TB_Standards_7th_Edition_ENG.pdf.
37. National Institute for Health and Care Excellence. 2016. Tuberculosis: Prevention, Diagnosis, Management and Service Organisation. NICE guideline 33. National Institute for Health and Care Excellence, London, United Kingdom. https://www.nice.org.uk/guidance/ng33.
38. Mancuso JD, Diffenderfer JM, Ghassemieh BJ, Horne DJ, Kao TC. 2016. The prevalence of latent tuberculosis infection in the United States. Am J Respir Crit Care Med 194:501–509. [PubMed]
39. Salinas JL, Mindra G, Haddad MB, Pratt R, Price SF, Langer AJ. 2016. Leveling of tuberculosis incidence—United States, 2013–2015. MMWR Morb Mortal Wkly Rep 65:273–278. [PubMed]
40. Sterling TR, Bethel J, Goldberg S, Weinfurter P, Yun L, Horsburgh CR, Tuberculosis Epidemiologic Studies Consortium. 2006. The scope and impact of treatment of latent tuberculosis infection in the United States and Canada. Am J Respir Crit Care Med 173:927–931. [PubMed]
41. Jensen PA, Lambert LA, Iademarco MF, Ridzon R, CDC. 2005. Guidelines for preventing the transmission of Mycobacterium tuberculosis in health-care settings, 2005. MMWR Recommend Rep 54(RR-17):1–141. [PubMed]
42. Lönnroth K, Castro KG, Chakaya JM, Chauhan LS, Floyd K, Glaziou P, Raviglione MC. 2010. Tuberculosis control and elimination 2010–50: cure, care, and social development. Lancet 375:1814–1829. [PubMed]
43. Rehm J, Samokhvalov AV, Neuman MG, Room R, Parry C, Lönnroth K, Patra J, Poznyak V, Popova S. 2009. The association between alcohol use, alcohol use disorders and tuberculosis (TB). A systematic review. BMC Public Health 9:450. [PubMed]
44. Bates MN, Khalakdina A, Pai M, Chang L, Lessa F, Smith KR. 2007. Risk of tuberculosis from exposure to tobacco smoke: a systematic review and meta-analysis. Arch Intern Med 167:335–342. [PubMed]
45. Horsburgh CR, Jr. 2004. Priorities for the treatment of latent tuberculosis infection in the United States. N Engl J Med 350:2060–2067. [PubMed]
46. Linas BP, Wong AY, Freedberg KA, Horsburgh CR, Jr. 2011. Priorities for screening and treatment of latent tuberculosis infection in the United States. Am J Respir Crit Care Med 184:590–601. [PubMed]
47. Nahid P, Dorman SE, Alipanah N, Barry PM, Brozek JL, Cattamanchi A, Chaisson LH, Chaisson RE, Daley CL, Grzemska M, Higashi JM, Ho CS, Hopewell PC, Keshavjee SA, Lienhardt C, Menzies R, Merrifield C, Narita M, O’Brien R, Peloquin CA, Raftery A, Saukkonen J, Schaaf HS, Sotgiu G, Starke JR, Migliori GB, Vernon A. 2016. Official American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America clinical practice guidelines: treatment of drug-susceptible tuberculosis. Clin Infect Dis 63:e147–e195. [PubMed]
48. Comstock GW, Ferebee SH, Hammes LM. 1967. A controlled trial of community-wide isoniazid prophylaxis in Alaska. Am Rev Respir Dis 95:935–943. [PubMed]
49. Falk A, Fuchs GF. 1978. Prophylaxis with isoniazid in inactive tuberculosis. A Veterans Administration Cooperative Study XII. Chest 73:44–48. [PubMed]
50. Ferebee S, Mount FW, Anastasiades A. 1957. Prophylactic effects of isoniazid on primary tuberculosis in children; a preliminary report. Am Rev Tuberc 76:942–963. [PubMed]
51. Ferebee SH, Mount FW, Murray FJ, Livesay VT. 1963. A controlled trial of isoniazid prophylaxis in mental institutions. Am Rev Respir Dis 88:161–175. [PubMed]
52. Smieja MJ, Marchetti CA, Cook DJ, Smaill FM. 2000. Isoniazid for preventing tuberculosis in non-HIV infected persons. Cochrane Database Syst Rev 2000(2):CD001363. [PubMed]
53. Runyon EH. 1965. Preventive treatment in tuberculosis: a statement by the Committee on Therapy, American Thoracic Society. Am Rev Respir Dis 91:297–298. [PubMed]
54. Hirsch-Moverman Y, Daftary A, Franks J, Colson PW. 2008. Adherence to treatment for latent tuberculosis infection: systematic review of studies in the US and Canada. Int J Tuberc Lung Dis 12:1235–1254. [PubMed]
55. Horsburgh CR, Jr, Goldberg S, Bethel J, Chen S, Colson PW, Hirsch-Moverman Y, Hughes S, Shrestha-Kuwahara R, Sterling TR, Wall K, Weinfurter P, Tuberculosis Epidemiologic Studies Consortium. 2010. Latent TB infection treatment acceptance and completion in the United States and Canada. Chest 137:401–409. [PubMed]
56. Hirsch-Moverman Y, Shrestha-Kuwahara R, Bethel J, Blumberg HM, Venkatappa TK, Horsburgh CR, Colson PW, Tuberculosis Epidemiologic Studies Consortium. 2015. Latent tuberculous infection in the United States and Canada: who completes treatment and why? Int J Tuberc Lung Dis 19:31–38. [PubMed]
57. Centers for Disease Control and Prevention. 2010. Severe isoniazid-associated liver injuries among persons being treated for latent tuberculosis infection—United States, 2004–2008. MMWR Morb Mortal Wkly Rep 59:224–229. [PubMed]
58. Sterling TR, Scott NA, Miro JM, Calvet G, La Rosa A, Infante R, Chen MP, Benator DA, Gordin F, Benson CA, Chaisson RE, Villarino ME, Tuberculosis Trials Consortium, the AIDS Clinical Trials Group for the PREVENT TB Trial (TBTC Study 26ACTG 5259). 2011. Three months of once-weekly rifapentine and isoniazid for M. tuberculosis infection. N Engl J Med 365:2155–2166. [PubMed]
59. Centers for Disease Control and Prevention. 2011. Recommendations for use of an isoniazid-rifapentine regimen with direct observation to treat latent Mycobacterium tuberculosis infection. MMWR Morb Mortal Wkly Rep 60:1650–1653. [PubMed]
60. Ji B, Truffot-Pernot C, Lacroix C, Raviglione MC, O’Brien RJ, Olliaro P, Roscigno G, Grosset J. 1993. Effectiveness of rifampin, rifabutin, and rifapentine for preventive therapy of tuberculosis in mice. Am Rev Respir Dis 148:1541–1546. [PubMed]
61. Mitchison DA. 1985. The action of antituberculosis drugs in short-course chemotherapy. Tubercle 66:219–225.
62. Gordin F, Chaisson RE, Matts JP, Miller C, de Lourdes Garcia M, Hafner R, Valdespino JL, Coberly J, Schechter M, Klukowicz AJ, Barry MA, O’Brien RJ, Terry Beirn Community Programs for Clinical Research on AIDS, the Adult AIDS Clinical Trials Group, the Pan American Health Organization, and the Centers for Disease Control and Prevention Study Group. 2000. Rifampin and pyrazinamide vs isoniazid for prevention of tuberculosis in HIV-infected persons: an international randomized trial. JAMA 283:1445–1450. [PubMed]
63. Halsey NA, Coberly JS, Desormeaux J, Losikoff P, Atkinson J, Moulton LH, Contave M, Johnson M, Davis H, Geiter L, Johnson E, Huebner R, Boulos R, Chaisson RE. 1998. Randomised trial of isoniazid versus rifampicin and pyrazinamide for prevention of tuberculosis in HIV-1 infection. Lancet 351:786–792.
64. Hong Kong Chest Service, Tuberculosis Research Centre, and Madras/British Medical Research Council. 1992. A double-blind placebo-controlled clinical trial of three antituberculosis chemoprophylaxis regimens in patients with silicosis in Hong Kong. Hong Kong Chest Service/Tuberculosis Research Centre, Madras/British Medical Research Council. Am Rev Respir Dis 145:36–41. [PubMed]
65. Mwinga A, Hosp M, Godfrey-Faussett P, Quigley M, Mwaba P, Mugala BN, Nyirenda O, Luo N, Pobee J, Elliott AM, McAdam KP, Porter JD. 1998. Twice weekly tuberculosis preventive therapy in HIV infection in Zambia. AIDS 12:2447–2457. [PubMed]
66. Centers for Disease Control and Prevention, American Thoracic Society. 2003. Update: adverse event data and revised American Thoracic Society/CDC recommendations against the use of rifampin and pyrazinamide for treatment of latent tuberculosis infection—United States, 2003. MMWR Morb Mortal Wkly Rep 52:735–739. [PubMed]
67. Jasmer RM, Daley CL. 2003. Rifampin and pyrazinamide for treatment of latent tuberculosis infection: is it safe? Am J Respir Crit Care Med 167:809–810. [PubMed]
68. Jasmer RM, Saukkonen JJ, Blumberg HM, Daley CL, Bernardo J, Vittinghoff E, King MD, Kawamura LM, Hopewell PC, Short-Course Rifampin and Pyrazinamide for Tuberculosis Infection (SCRIPT) Study Investigators. 2002. Short-course rifampin and pyrazinamide compared with isoniazid for latent tuberculosis infection: a multicenter clinical trial. Ann Intern Med 137:640–647. [PubMed]
69. McElroy PD, Ijaz K, Lambert LA, Jereb JA, Iademarco MF, Castro KG, Navin TR. 2005. National survey to measure rates of liver injury, hospitalization, and death associated with rifampin and pyrazinamide for latent tuberculosis infection. Clin Infect Dis 41:1125–1133. [PubMed]
70. Priest DH, Vossel LF, Jr, Sherfy EA, Hoy DP, Haley CA. 2004. Use of intermittent rifampin and pyrazinamide therapy for latent tuberculosis infection in a targeted tuberculin testing program. Clin Infect Dis 39:1764–1771. [PubMed]
71. Stout JE, Engemann JJ, Cheng AC, Fortenberry ER, Hamilton CD. 2003. Safety of 2 months of rifampin and pyrazinamide for treatment of latent tuberculosis. Am J Respir Crit Care Med 167:824–827. [PubMed]
72. Schechter M, Zajdenverg R, Falco G, Barnes GL, Faulhaber JC, Coberly JS, Moore RD, Chaisson RE. 2006. Weekly rifapentine/isoniazid or daily rifampin/pyrazinamide for latent tuberculosis in household contacts. Am J Respir Crit Care Med 173:922–926. [PubMed]
73. Martinson NA, Barnes GL, Moulton LH, Msandiwa R, Hausler H, Ram M, McIntyre JA, Gray GE, Chaisson RE. 2011. New regimens to prevent tuberculosis in adults with HIV infection. N Engl J Med 365:11–20. [PubMed]
74. Sterling TR. 2008. New approaches to the treatment of latent tuberculosis. Semin Respir Crit Care Med 29:532–541. [PubMed]
75. Pape JW, Jean SS, Ho JL, Hafner A, Johnson WD, Jr. 1993. Effect of isoniazid prophylaxis on incidence of active tuberculosis and progression of HIV infection. Lancet 342:268–272. [PubMed]
76. Quigley MA, Mwinga A, Hosp M, Lisse I, Fuchs D, Godfrey-Faussett P, Godfrey-Faussett P, Porter JDH. 2001. Long-term effect of preventive therapy for tuberculosis in a cohort of HIV-infected Zambian adults. AIDS 15:215–222. [PubMed]
77. Whalen CC, Johnson JL, Okwera A, Hom DL, Huebner R, Mugyenyi P, Mugerwa RD, Ellner JJ, Nsubuga P, Vjecha M, Myanja H, Kityo C, Loughlin A, Milberg J, Pekovic V, Uganda-Case Western Reserve University Research Collaboration. 1997. A trial of three regimens to prevent tuberculosis in Ugandan adults infected with the human immunodeficiency virus. N Engl J Med 337:801–808. [PubMed]
78. Hawken MP, Meme HK, Elliott LC, Chakaya JM, Morris JS, Githui WA, Juma ES, Odhiambo JA, Thiong’o LN, Kimari JN, Ngugi EN, Bwayo JJ, Gilks CF, Plummer FA, Porter JD, Nunn PP, McAdam KP. 1997. Isoniazid preventive therapy for tuberculosis in HIV-1-infected adults: results of a randomized controlled trial. AIDS 11:875–882. [PubMed]
79. Woldehanna S, Volmink J. 2004. Treatment of latent tuberculosis infection in HIV infected persons. Cochrane Database Syst Rev 2004(1):CD000171. [PubMed]
80. Akolo C, Adetifa I, Shepperd S, Volmink J. 2010. Treatment of latent tuberculosis infection in HIV infected persons. Cochrane Database Syst Rev 2010(1):CD000171. [PubMed]
81. Golub JE, Saraceni V, Cavalcante SC, Pacheco AG, Moulton LH, King BS, Efron A, Moore RD, Chaisson RE, Durovni B. 2007. The impact of antiretroviral therapy and isoniazid preventive therapy on tuberculosis incidence in HIV-infected patients in Rio de Janeiro, Brazil. AIDS 21:1441–1448. [PubMed]
82. Golub JE, Pronyk P, Mohapi L, Thsabangu N, Moshabela M, Struthers H, Gray GE, McIntyre JA, Chaisson RE, Martinson NA. 2009. Isoniazid preventive therapy, HAART and tuberculosis risk in HIV-infected adults in South Africa: a prospective cohort. AIDS 23:631–636. [PubMed]
83. Samandari T, Agizew TB, Nyirenda S, Tedla Z, Sibanda T, Shang N, Mosimaneotsile B, Motsamai OI, Bozeman L, Davis MK, Talbot EA, Moeti TL, Moffat HJ, Kilmarx PH, Castro KG, Wells CD. 2011. 6-Month versus 36-month isoniazid preventive treatment for tuberculosis in adults with HIV infection in Botswana: a randomised, double-blind, placebo-controlled trial. Lancet 377:1588–1598.
84. Lawn SD, Wood R, De Cock KM, Kranzer K, Lewis JJ, Churchyard GJ. 2010. Antiretrovirals and isoniazid preventive therapy in the prevention of HIV-associated tuberculosis in settings with limited health-care resources. Lancet Infect Dis 10:489–498.
85. Panel on Opportunistic Infections in HIV-Infected Adults and Adolescents. Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. Department of Health and Human Services, Rockville, MD. http://aidsinfo.nih.gov/contentfiles/lvguidelines/adult_oi.pdf. Accessed 11 December 2016.
86. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services, Rockville, MD. https://aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-treatment-guidelines/0/. Accessed 4 April 2017.
87. Saukkonen JJ, Cohn DL, Jasmer RM, Schenker S, Jereb JA, Nolan CM, Peloquin CA, Gordin FM, Nunes D, Strader DB, Bernardo J, Venkataramanan R, Sterling TR, ATS (American Thoracic Society) Hepatotoxicity of Antituberculosis Therapy Subcommittee. 2006. An official ATS statement: hepatotoxicity of antituberculosis therapy. Am J Respir Crit Care Med 174:935–952. [PubMed]
88. Garibaldi RA, Drusin RE, Ferebee SH, Gregg MB. 1972. Isoniazid-associated hepatitis. Report of an outbreak. Am Rev Respir Dis 106:357–365. [PubMed]
89. Kopanoff DE, Snider, DE Jr, Caras GJ. 1978. Isoniazid-related hepatitis: a U.S. Public Health Service cooperative surveillance study. Am Rev Respir Dis 117:991–1001. [PubMed]
90. Mitchell JR, Zimmerman HJ, Ishak KG, Thorgeirsson UP, Timbrell JA, Snodgrass WR, Nelson SD. 1976. Isoniazid liver injury: clinical spectrum, pathology, and probable pathogenesis. Ann Intern Med 84:181–192. [PubMed]
91. Fountain FF, Tolley E, Chrisman CR, Self TH. 2005. Isoniazid hepatotoxicity associated with treatment of latent tuberculosis infection: a 7-year evaluation from a public health tuberculosis clinic. Chest 128:116–123. [PubMed]
92. LoBue PA, Moser KS. 2005. Isoniazid- and rifampin-resistant tuberculosis in San Diego County, California, United States, 1993–2002. Int J Tuberc Lung Dis 9:501–506. [PubMed]
93. Nolan CM, Goldberg SV, Buskin SE. 1999. Hepatotoxicity associated with isoniazid preventive therapy: a 7-year survey from a public health tuberculosis clinic. JAMA 281:1014–1018. [PubMed]
94. Rose DN, Schechter CB, Silver AL. 1986. The age threshold for isoniazid chemoprophylaxis. A decision analysis for low-risk tuberculin reactors. JAMA 256:2709–2713.
95. Sandgren A, Vonk Noordegraaf-Schouten M, van Kessel F, Stuurman A, Oordt-Speets A, van der Werf MJ. 2016. Initiation and completion rates for latent tuberculosis infection treatment: a systematic review. BMC Infect Dis 16:204. [PubMed]
96. Stuurman AL, Vonk Noordegraaf-Schouten M, van Kessel F, Oordt-Speets AM, Sandgren A, van der Werf MJ. 2016. Interventions for improving adherence to treatment for latent tuberculosis infection: a systematic review. BMC Infect Dis 16:257. [PubMed]
97. Lobato MN, Reves RR, Jasmer RM, Grabau JC, Bock NN, Shang N, 2RZ Study Group. 2005. Adverse events and treatment completion for latent tuberculosis in jail inmates and homeless persons. Chest 127:1296–1303.
98. Nolan CM. 1999. Community-wide implementation of targeted testing for and treatment of latent tuberculosis infection. Clin Infect Dis 29:880–887. [PubMed]
99. Reichman LB, Lardizabal A, Hayden CH. 2004. Considering the role of four months of rifampin in the treatment of latent tuberculosis infection. Am J Respir Crit Care Med 170:832–835. [PubMed]
100. Tulsky JP, Pilote L, Hahn JA, Zolopa AJ, Burke M, Chesney M, Moss AR. 2000. Adherence to isoniazid prophylaxis in the homeless: a randomized controlled trial. Arch Intern Med 160:697–702. [PubMed]
101. Tulsky JP, White MC, Dawson C, Hoynes TM, Goldenson J, Schecter G. 1998. Screening for tuberculosis in jail and clinic follow-up after release. Am J Public Health 88:223–226. [PubMed]
102. White MC, Tulsky JP, Goldenson J, Portillo CJ, Kawamura M, Menendez E. 2002. Randomized controlled trial of interventions to improve follow-up for latent tuberculosis infection after release from jail. Arch Intern Med 162:1044–1050. [PubMed]
103. White MC, Tulsky JP, Menendez E, Goldenson J, Kawamura LM. 2005. Incidence of TB in inmates with latent TB infection: 5-year follow-up. Am J Prev Med 29:295–301. [PubMed]
104. Dhillon J, Dickinson JM, Sole K, Mitchison DA. 1996. Preventive chemotherapy of tuberculosis in Cornell model mice with combinations of rifampin, isoniazid, and pyrazinamide. Antimicrob Agents Chemother 40:552–555. [PubMed]
105. Lecoeur HF, Truffot-Pernot C, Grosset JH. 1989. Experimental short-course preventive therapy of tuberculosis with rifampin and pyrazinamide. Am Rev Respir Dis 140:1189–1193. [PubMed]
106. Curry International Tuberculosis Center and California Department of Public Health. 2016. Drug-Resistant Tuberculosis: A Survival Guide for Clinicians, 3rd ed. Curry International Tuberculosis Center, Oakland, CA. http://www.currytbcenter.ucsf.edu/products/view/drug-resistant-tuberculosis-survival-guide-clinicians-3rd-edition. Accessed 20 December 2016.
107. Polesky A, Farber HW, Gottlieb DJ, Park H, Levinson S, O’Connell JJ, McInnis B, Nieves RL, Bernardo J. 1996. Rifampin preventive therapy for tuberculosis in Boston’s homeless. Am J Respir Crit Care Med 154:1473–1477. [PubMed]
108. Villarino ME, Ridzon R, Weismuller PC, Elcock M, Maxwell RM, Meador J, Smith PJ, Carson ML, Geiter LJ. 1997. Rifampin preventive therapy for tuberculosis infection: experience with 157 adolescents. Am J Respir Crit Care Med 155:1735–1738. [PubMed]
109. Cook PP, Maldonado RA, Yarnell CT, Holbert D. 2006. Safety and completion rate of short-course therapy for treatment of latent tuberculosis infection. Clin Infect Dis 43:271–275. [PubMed]
110. Haley CA, Stephan S, Vossel LF, Sherfy EA, Laserson KF, Kainer MA. 2008. Successful use of rifampicin for Hispanic foreign-born patients with latent tuberculosis infection. Int J Tuberc Lung Dis 12:160–167. [PubMed]
111. Lardizabal A, Passannante M, Kojakali F, Hayden C, Reichman LB. 2006. Enhancement of treatment completion for latent tuberculosis infection with 4 months of rifampin. Chest 130:1712–1717. [PubMed]
112. Menzies D, Dion MJ, Rabinovitch B, Mannix S, Brassard P, Schwartzman K. 2004. Treatment completion and costs of a randomized trial of rifampin for 4 months versus isoniazid for 9 months. Am J Respir Crit Care Med 170:445–449. [PubMed]
113. Menzies D, Long R, Trajman A, Dion MJ, Yang J, Al Jahdali H, Memish Z, Khan K, Gardam M, Hoeppner V, Benedetti A, Schwartzman K. 2008. Adverse events with 4 months of rifampin therapy or 9 months of isoniazid therapy for latent tuberculosis infection: a randomized trial. Ann Intern Med 149:689–697. [PubMed]
114. Page KR, Sifakis F, Montes de Oca R, Cronin WA, Doherty MC, Federline L, Bur S, Walsh T, Karney W, Milman J, Baruch N, Adelakun A, Dorman SE. 2006. Improved adherence and less toxicity with rifampin vs isoniazid for treatment of latent tuberculosis: a retrospective study. Arch Intern Med 166:1863–1870. [PubMed]
115. Ziakas PD, Mylonakis E. 2009. 4 months of rifampin compared with 9 months of isoniazid for the management of latent tuberculosis infection: a meta-analysis and cost-effectiveness study that focuses on compliance and liver toxicity. Clin Infect Dis 49:1883–1889. [PubMed]
116. Forget EJ, Menzies D. 2006. Adverse reactions to first-line antituberculosis drugs. Expert Opin Drug Saf 5:231–249. [PubMed]
117. Girling DJ, Hitze KL. 1977. Adverse reactions to rifampicin in antituberculosis regimens. J Antimicrob Chemother 3:115–132.
118. Grosset J, Leventis S. 1983. Adverse effects of rifampin. Rev Infect Dis 5(Suppl 3):S440–S450. [PubMed]
119. Aquinas M, Allan WG, Horsfall PA, Jenkins PK, Hung-Yan W, Girling D, Tall R, Fox W. 1972. Adverse reactions to daily and intermittent rifampicin regimens for pulmonary tuberculosis in Hong Kong. BMJ 1:765–771. [PubMed]
120. Singapore Tuberculosis Service/British Medical Research Council. 1977. Controlled trial of intermittent regimens of rifampin plus isoniazid for pulmonary tuberculosis in Singapore. The results up to 30 months. Am Rev Respir Dis 116:807–820. [PubMed]
121. American Academy of Pediatrics. 2015. Tuberculosis, p 805–831. In Pickering LK, Baker CJ, Kimberlin DW, Long SS (ed), Red Book: 2015 Report of the Committee on Infectious Diseases, 30th ed. American Academy of Pediatrics, Elk Grove Village, IL.
122. den Boon S, Matteelli A, Getahun H. 2016. Rifampicin resistance after treatment for latent tuberculous infection: a systematic review and meta-analysis. Int J Tuberc Lung Dis 20:1065–1071. [PubMed]
123. Ashkin D, Julien J, Lauzardo M, Hollender E. 2006. Consider rifampin BUT be cautious. Chest 130:1638–1640. [PubMed]
124. Chapuis L, Ji B, Truffot-Pernot C, O’Brien RJ, Raviglione MC, Grosset JH. 1994. Preventive therapy of tuberculosis with rifapentine in immunocompetent and nude mice. Am J Respir Crit Care Med 150:1355–1362. [PubMed]
125. Miyazaki E, Chaisson RE, Bishai WR. 1999. Analysis of rifapentine for preventive therapy in the Cornell mouse model of latent tuberculosis. Antimicrob Agents Chemother 43:2126–2130. [PubMed]
126. Zhang T, Zhang M, Rosenthal IM, Grosset JH, Nuermberger EL. 2009. Short-course therapy with daily rifapentine in a murine model of latent tuberculosis infection. Am J Respir Crit Care Med 180:1151–1157. [PubMed]
127. Sterling TR, Moro RN, Borisov AS, Phillips E, Shepherd G, Adkinson NF, Weis S, Ho C, Villarino ME, Tuberculosis Trials Consortium. 2015. Flu-like and other systemic drug reactions among persons receiving weekly rifapentine plus isoniazid or daily isoniazid for treatment of latent tuberculosis infection in the PREVENT Tuberculosis study. Clin Infect Dis 61:527–535. [PubMed]
128. Martínez E, Collazos J, Mayo J. 1999. Hypersensitivity reactions to rifampin. Pathogenetic mechanisms, clinical manifestations, management strategies, and review of the anaphylactic-like reactions. Medicine (Baltimore) 78:361–369.
129. Dutt AK, Moers D, Stead WW. 1983. Undesirable side effects of isoniazid and rifampin in largely twice-weekly short-course chemotherapy for tuberculosis. Am Rev Respir Dis 128:419–424. [PubMed]
130. Motion S, Humphries MJ, Gabriel SM. 1989. Severe ‘flu’-like symptoms due to isoniazid—a report of three cases. Tubercle 70:57–60. [PubMed]
131. Pandit S, Choudhury S, Das A, Datta S, Das SK. 2013. Isoniazid-induced flu-like syndrome: a rare side effect. Lung India 30:61–63. [PubMed]
132. Bliven-Sizemore EE, Sterling TR, Shang N, Benator D, Schwartzman K, Reves R, Drobeniuc J, Bock N, Villarino ME, TB Trials Consortium. 2015. Three months of weekly rifapentine plus isoniazid is less hepatotoxic than nine months of daily isoniazid for LTBI. Int J Tuberc Lung Dis 19:1039–1044, i–v. [PubMed]
133. Villarino ME, Scott NA, Weis SE, Weiner M, Conde MB, Jones B, Nachman S, Oliveira R, Moro RN, Shang N, Goldberg SV, Sterling TR, International Maternal Pediatric and Adolescents AIDS Clinical Trials Group, Tuberculosis Trials Consortium. 2015. Treatment for preventing tuberculosis in children and adolescents: a randomized clinical trial of a 3-month, 12-dose regimen of a combination of rifapentine and isoniazid. JAMA Pediatr 169:247–255. [PubMed]
134. Cruz AT, Starke JR. 2016. Safety and adherence for 12 weekly doses of isoniazid and rifapentine for pediatric tuberculosis infection. Pediatr Infect Dis J 35:811–813. [PubMed]
135. Cruz AT, Ahmed A, Mandalakas AM, Starke JR. 2013. Treatment of latent tuberculosis infection in children. J Pediatric Infect Dis Soc 2:248–258. [PubMed]
136. Graham SM. 10 December 2016. The management of infection with Mycobacterium tuberculosis in young children post-2015: an opportunity to close the policy practice gap. Expert Rev Respir Med doi:10.1080/17476348.2016.1267572.
137. Sterling TR, Scott NA, Miro JM, Calvet G, La Rosa A, Infante R, Chen MP, Benator DA, Gordin F, Benson CA, Chaisson RE, Villarino ME, Tuberculosis Trials Consortium, the AIDS Clinical Trials Group for the PREVENT TB Trial (TBTC Study 26ACTG 5259). 2016. Three months of weekly rifapentine and isoniazid for treatment of Mycobacterium tuberculosis infection in HIV-coinfected persons. AIDS 30:1607–1615. [PubMed]
138. Ena J, Valls V. 2005. Short-course therapy with rifampin plus isoniazid, compared with standard therapy with isoniazid, for latent tuberculosis infection: a meta-analysis. Clin Infect Dis 40:670–676. [PubMed]
139. Spyridis NP, Spyridis PG, Gelesme A, Sypsa V, Valianatou M, Metsou F, Gourgiotis D, Tsolia MN. 2007. The effectiveness of a 9-month regimen of isoniazid alone versus 3- and 4-month regimens of isoniazid plus rifampin for treatment of latent tuberculosis infection in children: results of an 11-year randomized study. Clin Infect Dis 45:715–722. [PubMed]
140. Lobue P, Menzies D. 2010. Treatment of latent tuberculosis infection: an update. Respirology 15:603–622. [PubMed]
141. McNeill L, Allen M, Estrada C, Cook P. 2003. Pyrazinamide and rifampin vs isoniazid for the treatment of latent tuberculosis: improved completion rates but more hepatotoxicity. Chest 123:102–106. [PubMed]
142. Ijaz K, Jereb JA, Lambert LA, Bower WA, Spradling PR, McElroy PD, Iademarco MF, Navin TR, Castro KG. 2006. Severe or fatal liver injury in 50 patients in the United States taking rifampin and pyrazinamide for latent tuberculosis infection. Clin Infect Dis 42:346–355. [PubMed]
143. Ramappa V, Aithal GP. 2013. Hepatotoxicity related to anti-tuberculosis drugs: mechanisms and management. J Clin Exp Hepatol 3:37–49. [PubMed]
144. Sotgiu G, Matteelli A, Getahun H, Girardi E, Sañé Schepisi M, Centis R, Migliori GB. 2015. Monitoring toxicity in individuals receiving treatment for latent tuberculosis infection: a systematic review versus expert opinion. Eur Respir J 45:1170–1173. [PubMed]
145. Charles P Felton National Tuberculosis Center. 2005. Adherence to Treatment for Latent Tuberculosis Infection: a Manual for Health Care Providers. Charles P Felton National Tuberculosis Center, New York, NY.
146. Alsdurf H, Hill PC, Matteelli A, Getahun H, Menzies D. 2016. The cascade of care in diagnosis and treatment of latent tuberculosis infection: a systematic review and meta-analysis. Lancet Infect Dis 16:1269–1278. [PubMed]
147. Colson PW, Franks J, Sondengam R, Hirsch-Moverman Y, El-Sadr W. 2010. Tuberculosis knowledge, attitudes, and beliefs in foreign-born and US-born patients with latent tuberculosis infection. J Immigr Minor Health 12:859–866. [PubMed]
148. Colson PW, Hirsch-Moverman Y, Bethel J, Vempaty P, Salcedo K, Wall K, Miranda W, Collins S, Horsburgh CR, Tuberculosis Epidemiologic Studies Consortium. 2013. Acceptance of treatment for latent tuberculosis infection: prospective cohort study in the United States and Canada. Int J Tuberc Lung Dis 17:473–479. [PubMed]
149. Centers for Disease Control and Prevention. 2003. Transmission of Mycobacterium tuberculosis associated with failed completion of treatment for latent tuberculosis infection—Chickasaw County, Mississippi, June 1999–March 2002. MMWR Morb Mortal Wkly Rep 52:222–224. [PubMed]
150. Fiske CT, Yan FX, Hirsch-Moverman Y, Sterling TR, Reichler MR, Tuberculosis Epidemiologic Studies Consortium Task Order 2 Team. 2014. Risk factors for treatment default in close contacts with latent tuberculous infection. Int J Tuberc Lung Dis 18:421–427. [PubMed]
151. Li J, Munsiff SS, Tarantino T, Dorsinville M. 2010. Adherence to treatment of latent tuberculosis infection in a clinical population in New York City. Int J Infect Dis 14:e292–e297. [PubMed]
152. Moro RN, Borisov AS, Saukkonen J, Khan A, Sterling TR, Villarino ME, Scott NA, Shang N, Kerrigan A, Goldberg SV. 2016. Factors associated with noncompletion of latent tuberculosis infection treatment: experience from the PREVENT TB trial in the United States and Canada. Clin Infect Dis 62:1390–1400. [PubMed]
153. Shukla SJ, Warren DK, Woeltje KF, Gruber CA, Fraser VJ. 2002. Factors associated with the treatment of latent tuberculosis infection among health-care workers at a midwestern teaching hospital. Chest 122:1609–1614. [PubMed]
154. Munro SA, Lewin SA, Smith HJ, Engel ME, Fretheim A, Volmink J. 2007. Patient adherence to tuberculosis treatment: a systematic review of qualitative research. PLoS Med 4:e238. [PubMed]
155. Bock NN, Metzger BS, Tapia JR, Blumberg HM. 1999. A tuberculin screening and isoniazid preventive therapy program in an inner-city population. Am J Respir Crit Care Med 159:295–300. [PubMed]
156. Moss AR, Hahn JA, Tulsky JP, Daley CL, Small PM, Hopewell PC. 2000. Tuberculosis in the homeless. A prospective study. Am J Respir Crit Care Med 162:460–464. [PubMed]
157. Shieh FK, Snyder G, Horsburgh CR, Bernardo J, Murphy C, Saukkonen JJ. 2006. Predicting non-completion of treatment for latent tuberculous infection: a prospective survey. Am J Respir Crit Care Med 174:717–721. [PubMed]
158. Parsyan AE, Saukkonen J, Barry MA, Sharnprapai S, Horsburgh CR, Jr. 2007. Predictors of failure to complete treatment for latent tuberculosis infection. J Infect 54:262–266. [PubMed]
159. Chaisson RE, Barnes GL, Hackman J, Watkinson L, Kimbrough L, Metha S, Cavalcante S, Moore RD. 2001. A randomized, controlled trial of interventions to improve adherence to isoniazid therapy to prevent tuberculosis in injection drug users. Am J Med 110:610–615.
160. National Tuberculosis Controllers Association, Centers for Disease Control and Prevention. 2005. Guidelines for the investigation of contacts of persons with infectious tuberculosis. Recommendations from the National Tuberculosis Controllers Association and CDC. MMWR Recommend Rep 54(RR-15):1–47.
161. Lobato MN, Sun SJ, Moonan PK, Weis SE, Saiman L, Reichard AA, Feja K, Zero Tolerance for Pediatric TB Study Group. 2008. Underuse of effective measures to prevent and manage pediatric tuberculosis in the United States. Arch Pediatr Adolesc Med 162:426–431. [PubMed]
162. Nolan CM, Roll L, Goldberg SV, Elarth AM. 1997. Directly observed isoniazid preventive therapy for released jail inmates. Am J Respir Crit Care Med 155:583–586. [PubMed]
163. Holland DP, Sanders GD, Hamilton CD, Stout JE. 2009. Costs and cost-effectiveness of four treatment regimens for latent tuberculosis infection. Am J Respir Crit Care Med 179:1055–1060. [PubMed]
164. Powell DA. 2008. Latent tuberculosis needs attention. Arch Pediatr Adolesc Med 162:489–490. [PubMed]
165. Coly A, Morisky D. 2004. Predicting completion of treatment among foreign-born adolescents treated for latent tuberculosis infection in Los Angeles. Int J Tuberc Lung Dis 8:703–710. [PubMed]
166. Goldberg SV, Wallace J, Jackson JC, Chaulk CP, Nolan CM. 2004. Cultural case management of latent tuberculosis infection. Int J Tuberc Lung Dis 8:76–82. [PubMed]
167. Jackson JC, Chaulk CP. 2004. Assessing culture, context, power differences, and psychological development when delivering health care to foreign-born adolescents. Int J Tuberc Lung Dis 8:687–688. [PubMed]
168. Menzies D, Dion MJ, Francis D, Parisien I, Rocher I, Mannix S, Schwartzman K. 2005. In closely monitored patients, adherence in the first month predicts completion of therapy for latent tuberculosis infection. Int J Tuberc Lung Dis 9:1343–1348. [PubMed]
169. Kwara A, Herold JS, Machan JT, Carter EJ. 2008. Factors associated with failure to complete isoniazid treatment for latent tuberculosis infection in Rhode Island. Chest 133:862–868. [PubMed]
170. Aspler A, Long R, Trajman A, Dion MJ, Khan K, Schwartzman K, Menzies D. 2010. Impact of treatment completion, intolerance and adverse events on health system costs in a randomised trial of 4 months rifampin or 9 months isoniazid for latent TB. Thorax 65:582–587. [PubMed]
171. Shepardson D, MacKenzie WR. 2014. Update on cost-effectiveness of a 12-dose regimen for latent tuberculous infection at new rifapentine prices. Int J Tuberc Lung Dis 18:751. [PubMed]
172. Diel R, Loddenkemper R, Sotgiu G, Migliori GB. 2013. Cost-effectiveness of treating latent tuberculous infection: a step towards elimination? Int J Tuberc Lung Dis 17:1515. [PubMed]
173. Moore DA. 2016. What can we offer to 3 million MDRTB household contacts in 2016? BMC Med 14:64. [PubMed]
174. Fraser A, Paul M, Attamna A, Leibovici L. 2006. Drugs for preventing tuberculosis in people at risk of multiple-drug-resistant pulmonary tuberculosis. Cochrane Database Syst Rev 2006(2):CD005435. [PubMed]
175. Schaaf HS, Vermeulen HA, Gie RP, Beyers N, Donald PR. 1999. Evaluation of young children in household contact with adult multidrug-resistant pulmonary tuberculosis cases. Pediatr Infect Dis J 18:494–500. [PubMed]
176. Lou HX, Shullo MA, McKaveney TP. 2002. Limited tolerability of levofloxacin and pyrazinamide for multidrug-resistant tuberculosis prophylaxis in a solid organ transplant population. Pharmacotherapy 22:701–704. [PubMed]
177. Papastavros T, Dolovich LR, Holbrook A, Whitehead L, Loeb M. 2002. Adverse events associated with pyrazinamide and levofloxacin in the treatment of latent multidrug-resistant tuberculosis. CMAJ 167:131–136. [PubMed]
178. Ridzon R, Meador J, Maxwell R, Higgins K, Weismuller P, Onorato IM. 1997. Asymptomatic hepatitis in persons who received alternative preventive therapy with pyrazinamide and ofloxacin. Clin Infect Dis 24:1264–1265. [PubMed]
179. Sterling TR. 2016. Fluoroquinolones for the treatment and prevention of multidrug-resistant tuberculosis. Int J Tuberc Lung Dis 20:S42–S47. [PubMed]
180. Williams K, Minkowski A, Amoabeng O, Peloquin CA, Taylor D, Andries K, Wallis RS, Mdluli KE, Nuermberger EL. 2012. Sterilizing activities of novel combinations lacking first- and second-line drugs in a murine model of tuberculosis. Antimicrob Agents Chemother 56:3114–3120. [PubMed]
181. Diacon AH, Donald PR, Pym A, Grobusch M, Patientia RF, Mahanyele R, Bantubani N, Narasimooloo R, De Marez T, van Heeswijk R, Lounis N, Meyvisch P, Andries K, McNeeley DF. 2012. Randomized pilot trial of eight weeks of bedaquiline (TMC207) treatment for multidrug-resistant tuberculosis: long-term outcome, tolerability, and effect on emergence of drug resistance. Antimicrob Agents Chemother 56:3271–3276. [PubMed]
182. Zhang T, Li SY, Williams KN, Andries K, Nuermberger EL. 2011. Short-course chemotherapy with TMC207 and rifapentine in a murine model of latent tuberculosis infection. Am J Respir Crit Care Med 184:732–737. [PubMed]
183. Jick SS, Lieberman ES, Rahman MU, Choi HK. 2006. Glucocorticoid use, other associated factors, and the risk of tuberculosis. Arthritis Rheum 55:19–26. [PubMed]
184. Mount FW, Ferebee SH. 1962. The effect of isoniazid prophylaxis on tuberculosis morbidity among household contacts of previously known cases of tuberculosis. Am Rev Respir Dis 85:821–827. [PubMed]
185. Fox GJ, Dobler CC, Marais BJ, Denholm JT. 18 November 2016. Preventive therapy for latent tuberculosis infection—the promise and the challenges. Int J Infect Dis doi:10.1016/j.ijid.2016.11.006. [PubMed]
186. Migliori GB, Zellweger JP, Abubakar I, Ibraim E, Caminero JA, De Vries G, D’Ambrosio L, Centis R, Sotgiu G, Menegale O, Kliiman K, Aksamit T, Cirillo DM, Danilovits M, Dara M, Dheda K, Dinh-Xuan AT, Kluge H, Lange C, Leimane V, Loddenkemper R, Nicod LP, Raviglione MC, Spanevello A, Thomsen VØ, Villar M, Wanlin M, Wedzicha JA, Zumla A, Blasi F, Huitric E, Sandgren A, Manissero D. 2012. European Union standards for tuberculosis care. Eur Respir J 39:807–819. [PubMed]
187. Gilroy SA, Rogers MA, Blair DC. 2000. Treatment of latent tuberculosis infection in patients aged =35 years. Clin Infect Dis 31:826–829. [PubMed]
188. Gershon AS, McGeer A, Bayoumi AM, Raboud J, Yang J. 2004. Health care workers and the initiation of treatment for latent tuberculosis infection. Clin Infect Dis 39:667–672. [PubMed]
189. Nuzzo JB, Golub JE, Chaulk P, Shah M. 2015. Analysis of latent tuberculosis infection treatment adherence among refugees and other patient groups referred to the Baltimore City Health Department TB clinic, February 2009–March 2011. J Immigr Minor Health 17:56–65. [PubMed]
190. Morano JP, Walton MR, Zelenev A, Bruce RD, Altice FL. 2013. Latent tuberculosis infection: screening and treatment in an urban setting. J Community Health 38:941–950. [PubMed]
191. Goswami ND, Gadkowski LB, Piedrahita C, Bissette D, Ahearn MA, Blain ML, Østbye T, Saukkonen J, Stout JE. 2012. Predictors of latent tuberculosis treatment initiation and completion at a U.S. public health clinic: a prospective cohort study. BMC Public Health 12:468. [PubMed]
192. Hovell M, Blumberg E, Gil-Trejo L, Vera A, Kelley N, Sipan C, Hofstetter CR, Marshall S, Berg J, Friedman L, Catanzaro A, Moser K. 2003. Predictors of adherence to treatment for latent tuberculosis infection in high-risk Latino adolescents: a behavioral epidemiological analysis. Soc Sci Med 56:1789–1796.
193. Berg J, Blumberg EJ, Sipan CL, Friedman LS, Kelley NJ, Vera AY, Hofstetter CR, Hovell MF. 2004. Somatic complaints and isoniazid (INH) side effects in Latino adolescents with latent tuberculosis infection (LTBI). Patient Educ Couns 52:31–39.
194. Bastos ML, Menzies D, Belo MT, Teixeira EG, de Abreu ST, Antas PR, Trajman A. 2013. Changes in QuantiFERON®-TB Gold In-Tube results during treatment for tuberculous infection. Int J Tuberc Lung Dis 17:909–916. [PubMed]
195. Hirsch-Moverman Y, Colson PW, Bethel J, Franks J, El-Sadr WM. 2013. Can a peer-based intervention impact adherence to the treatment of latent tuberculous infection? Int J Tuberc Lung Dis 17:1178–1185. [PubMed]
196. Young H, Wessolossky M, Ellis J, Kaminski M, Daly JS. 2009. A retrospective evaluation of completion rates, total cost, and adverse effects for treatment of latent tuberculosis infection in a public health clinic in central Massachusetts. Clin Infect Dis 49:424–427. [PubMed]
197. White MC, Gournis E, Kawamura M, Menendez E, Tulsky JP. 2003. Effect of directly observed preventive therapy for latent tuberculosis infection in San Francisco. Int J Tuberc Lung Dis 7:30–35. [PubMed]
198. Morisky DE, Ebin VJ, Malotte CK, Coly A, Kominski G. 2003. Assessment of tuberculosis treatment completion in an ethnically diverse population using two data sources. Implications for treatment interventions. Eval Health Prof 26:43–58. [PubMed]
199. LoBue PA, Moser KS. 2003. Use of isoniazid for latent tuberculosis infection in a public health clinic. Am J Respir Crit Care Med 168:443–447. [PubMed]
200. Chang AH, Polesky A, Bhatia G. 2013. House calls by community health workers and public health nurses to improve adherence to isoniazid monotherapy for latent tuberculosis infection: a retrospective study. BMC Public Health 13:894. [PubMed]
201. Chang SH, Eitzman SR, Nahid P, Finelli ML. 2014. Factors associated with failure to complete isoniazid therapy for latent tuberculosis infection in children and adolescents. J Infect Public Health 7:145–152. [PubMed]
202. Rennie TW, Bothamley GH, Engova D, Bates IP. 2007. Patient choice promotes adherence in preventive treatment for latent tuberculosis. Eur Respir J 30:728–735. [PubMed]
203. Lee AM, Mennone JZ, Jones RC, Paul WS. 2002. Risk factors for hepatotoxicity associated with rifampin and pyrazinamide for the treatment of latent tuberculosis infection: experience from three public health tuberculosis clinics. Int J Tuberc Lung Dis 6:995–1000. [PubMed]
204. Hirsch-Moverman Y, Bethel J, Colson PW, Franks J, El-Sadr W. 2010. Predictors of latent tuberculosis infection treatment completion in the United States: an inner city experience. Int J Tuberc Lung Dis 14:1104–1111. [PubMed]
205. Kominski GF, Varon SF, Morisky DE, Malotte CK, Ebin VJ, Coly A, Chiao C. 2007. Costs and cost-effectiveness of adolescent compliance with treatment for latent tuberculosis infection: results from a randomized trial. J Adolesc Health 40:61–68. [PubMed]
206. Codecasa LR, Murgia N, Ferrarese M, Delmastro M, Repossi AC, Casali L, Besozzi G, Ferrara G, Raviglione MC. 2013. Isoniazid preventive treatment: predictors of adverse events and treatment completion. Int J Tuberc Lung Dis 17:903–908. [PubMed]
207. Fresard I, Bridevaux PO, Rochat T, Janssens JP. 2011. Adverse effects and adherence to treatment of rifampicin 4 months vs isoniazid 6 months for latent tuberculosis: a retrospective analysis. Swiss Med Wkly 141:w13240. [PubMed]
208. Cruz AT, Starke JR. 2012. Increasing adherence for latent tuberculosis infection therapy with health department-administered therapy. Pediatr Infect Dis J 31:193–195. [PubMed]
209. Vinnard C, Gopal A, Linkin DR, Maslow J. 2013. Isoniazid toxicity among an older veteran population: a retrospective cohort study. Tuberc Res Treat 2013:549473. [PubMed]
210. Kan B, Kalin M, Bruchfeld J. 2013. Completing treatment for latent tuberculosis: patient background matters. Int J Tuberc Lung Dis 17:597–602. [PubMed]
211. Cass AD, Talavera GA, Gresham LS, Moser KS, Joy W. 2005. Structured behavioral intervention to increase children’s adherence to treatment for latent tuberculosis infection. Int J Tuberc Lung Dis 9:415–420. [PubMed]
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/content/journal/microbiolspec/10.1128/microbiolspec.TNMI7-0039-2016
2017-04-14
2017-11-19

Abstract:

There are approximately 56 million people who harbor that may progress to active tuberculosis (TB) at some point in their lives. Modeling studies suggest that if only 8% of these individuals with latent TB infection (LTBI) were treated annually, overall global incidence would be 14-fold lower by 2050 compared to incidence in 2013, even in the absence of additional TB control measures. This highlights the importance of identifying and treating latently infected individuals, and that this intervention must be scaled up to achieve the goals of the Global End TB Strategy. The efficacy of LTBI treatment is well established, and the most commonly used regimen is 9 months of daily self-administered isoniazid. However, its use has been hindered by limited provider awareness of the benefits, concern about potential side effects such as hepatotoxicity, and low rates of treatment completion. There is increasing evidence that shorter rifamycin-based regimens are as effective, better tolerated, and more likely to be completed compared to isoniazid. Such regimens include four months of daily self-administered rifampin monotherapy, three months of once weekly directly observed isoniazid-rifapentine, and three months of daily self-administered isoniazid-rifampin. The success of LTBI treatment to prevent additional TB disease relies upon choosing an appropriate regimen individualized to the patient, monitoring for potential adverse clinical events, and utilizing strategies to promote adherence. Safer, more cost-effective, and more easily completed regimens are needed and should be combined with interventions to better identify, engage, and retain high-risk individuals across the cascade from diagnosis through treatment completion of LTBI.

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FIGURE 1

The spectrum of TB, from infection to active (pulmonary) TB disease. Although TB disease can be viewed as a dynamic continuum from infection to active infectious disease, patients are categorized as having either LTBI or active TB disease for simplicity in clinical and public health settings. Individuals can advance or reverse positions, depending on changes in host immunity and comorbidities. Exposure to can result in the elimination of the pathogen, either because of innate immune responses or because of acquired T cell immunity. Individuals who have eliminated the infection via innate immune responses or acquired immune response without T cell priming or memory (indicated by an asterisk) can have negative TST or IGRA results. Some individuals eliminate the pathogen but retain a strong memory T cell response and are positive on the TST or the IGRA. These individuals do not benefit from LTBI treatment. If the pathogen is not eliminated, bacteria persist in a quiescent or latent state that can be detected as positive TST or IGRA results; these tests elicit T cell responses against antigens. These patients would benefit from receiving one of the recommended LTBI preventive therapy regimens (mostly 6 to 9 months of isoniazid). Patients with subclinical TB might not report symptoms but are culture positive (but generally smear negative because of the low bacillary load). Patients with active TB disease experience symptoms such as cough, fever, and weight loss, and the diagnosis can usually be confirmed with sputum smear, culture and molecular tests. Patients with active TB disease might sometimes be negative on the TST or the IGRA because of anergy that is induced by the disease itself or immunosuppression caused by comorbid conditions, such as HIV infection or malnutrition. Individuals with subclinical or active TB disease should receive one of the recommended treatment regimens for active TB disease, which consist of an intensive phase with four drugs, followed by a longer continuation phase with two drugs. Reprinted from reference 13 , with permission.

Source: microbiolspec April 2017 vol. 5 no. 2 doi:10.1128/microbiolspec.TNMI7-0039-2016
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FIGURE 2

LTBI pretreatment clinical evaluation and counseling. Dotted lines signify management according to physician’s discretion. INR, international normalized ratio; PTT, partial thromboplastin time. DILI, drug-induced liver injury. Reprinted with permission of the American Thoracic Society ( 87 ).

Source: microbiolspec April 2017 vol. 5 no. 2 doi:10.1128/microbiolspec.TNMI7-0039-2016
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FIGURE 3

Monitoring for hepatotoxicity during LTBI treatment. Dotted lines signify management according to physician’s discretion. ALT, alanine aminotransferase; AST, aspartate aminotransferase; BeAg, Hepatitis B e antigen; Bili, bilirubin; HAV, hepatitis A virus; HepBcAb, hepatitis B core antibody; HepBsAg, hepatitis B virus surface antigen; ULN, upper limit of normal. Reprinted with permission of the American Thoracic Society ( 87 ).

Source: microbiolspec April 2017 vol. 5 no. 2 doi:10.1128/microbiolspec.TNMI7-0039-2016
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FIGURE 4

TB case rates in the Bethel Isoniazid Studies population according to the number of months that isoniazid was taken in the combined programs. Dots represent observed values; dashed line, the calculated curve ( = + /); and dotted lines, the calculated values based on the first four and the last five observations ( = + ). Reprinted with permission of the International Union Against Tuberculosis and Lung Disease. © The Union ( 21 ).

Source: microbiolspec April 2017 vol. 5 no. 2 doi:10.1128/microbiolspec.TNMI7-0039-2016
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FIGURE 5

Effectiveness of three regimens for treatment of LTBI in elderly Chinese men with silicosis. Based on 503 patients at 1 year, 474 at 2 years, 418 at 3 years, 367 at 4 years, and 304 at 5 years who received their regimen without known interruption. The axis shows the months from start of the LTBI treatment regimen. The axis shows the percentage of patients who developed TB disease. HR3, isoniazid and rifampin for 3 months; H6, isoniazid for 6 months; Pl, placebo; R3, rifampin for 3 months ( 140 ). Reprinted with permission of the American Thoracic Society ( 64 ).

Source: microbiolspec April 2017 vol. 5 no. 2 doi:10.1128/microbiolspec.TNMI7-0039-2016
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Tables

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TABLE 1

Risk factors for the development of active TB among persons infected with ( 28 )

Source: microbiolspec April 2017 vol. 5 no. 2 doi:10.1128/microbiolspec.TNMI7-0039-2016
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TABLE 2

Placebo-controlled studies of isoniazid efficacy for treatment of LTBI

Source: microbiolspec April 2017 vol. 5 no. 2 doi:10.1128/microbiolspec.TNMI7-0039-2016
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TABLE 3

Regimens for latent TB treatment, according to pooled efficacy, risk of hepatotoxicity, adverse events, and drug interactions

Source: microbiolspec April 2017 vol. 5 no. 2 doi:10.1128/microbiolspec.TNMI7-0039-2016
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TABLE 4

Current guidelines for the treatment of latent tuberculosis infection

Source: microbiolspec April 2017 vol. 5 no. 2 doi:10.1128/microbiolspec.TNMI7-0039-2016
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TABLE 5

Overview of determinants of LTBI treatment initiation, adherence, and completion in the general population diagnosed with LTBI

Source: microbiolspec April 2017 vol. 5 no. 2 doi:10.1128/microbiolspec.TNMI7-0039-2016
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TABLE 6

Specific treatment options for drug-resistant TB dependent on susceptibility of source case isolate

Source: microbiolspec April 2017 vol. 5 no. 2 doi:10.1128/microbiolspec.TNMI7-0039-2016

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