Treatment of latent tuberculosis infection in HIV-uninfected adults
- C Robert Horsburgh, Jr, MD, MUS
C Robert Horsburgh, Jr, MD, MUS
- Professor of Epidemiology, Biostatistics and Medicine
- Boston University School of Public Health
Treatment of individuals with active tuberculosis (TB) is the first priority for TB control; an important second priority is identification and treatment of individuals with latent TB infection (LTBI). The World Health Organization (WHO) recommends that LTBI treatment be included as part of the TB control program for high income or upper middle income countries with an estimated TB incidence rate of less than 100 per 100,000 population per year .
In most individuals, Mycobacterium tuberculosis infection is contained initially by host defenses, and the infection remains in a prolonged, suppressed state termed "latency" . However, latent infection has the potential to develop into active infection (termed "active disease") at any time. Identification and treatment of LTBI greatly reduces the likelihood of reactivation and so has potential to protect the health of the individuals as well as the public by reducing the number of potential sources of infection [3,4].
Following LTBI treatment, the durability of protection against reactivation is variable and depends upon regional prevalence of TB and risk for reexposure. LTBI treatment may confer lifelong protection against disease; among Alaskan Eskimos, for example, the protective effect of isoniazid prophylaxis has been shown to persist for more than 19 years .
Treatment of LTBI should be initiated only once active TB has been excluded . The approach to treatment of LTBI in HIV-uninfected patients will be reviewed here. LTBI in children and diagnostic testing for LTBI in HIV-uninfected patients are discussed in detail separately, as is management of LTBI for patients with HIV or receiving tumor necrosis factor-alpha inhibitors. (See "Diagnosis of latent tuberculosis infection (tuberculosis screening) in HIV-uninfected adults" and "Treatment of latent tuberculosis infection in HIV-infected adults" and "Tumor necrosis factor-alpha inhibitors and mycobacterial infections" and "Latent tuberculosis infection in children".)
WHOM TO TREAT
The goal of testing for latent tuberculosis infection (LTBI) is to identify individuals who are at increased risk for the development of tuberculosis and therefore would benefit from treatment of LTBI. Only those who would benefit from treatment should be tested, so a decision to test presupposes a decision to treat if the test is positive. This is discussed further separately. (See "Diagnosis of latent tuberculosis infection (tuberculosis screening) in HIV-uninfected adults".)
- Getahun H, Matteelli A, Abubakar I, et al. Management of latent Mycobacterium tuberculosis infection: WHO guidelines for low tuberculosis burden countries. Eur Respir J 2015; 46:1563.
- Gideon HP, Flynn JL. Latent tuberculosis: what the host "sees"? Immunol Res 2011; 50:202.
- Targeted tuberculin testing and treatment of latent tuberculosis infection. This official statement of the American Thoracic Society was adopted by the ATS Board of Directors, July 1999. This is a Joint Statement of the American Thoracic Society (ATS) and the Centers for Disease Control and Prevention (CDC). This statement was endorsed by the Council of the Infectious Diseases Society of America. (IDSA), September 1999, and the sections of this statement. Am J Respir Crit Care Med 2000; 161:S221.
- Horsburgh CR Jr, Rubin EJ. Clinical practice. Latent tuberculosis infection in the United States. N Engl J Med 2011; 364:1441.
- Comstock GW, Baum C, Snider DE Jr. Isoniazid prophylaxis among Alaskan Eskimos: a final report of the bethel isoniazid studies. Am Rev Respir Dis 1979; 119:827.
- Getahun H, Matteelli A, Chaisson RE, Raviglione M. Latent Mycobacterium tuberculosis infection. N Engl J Med 2015; 372:2127.
- Ena J, Valls V. Short-course therapy with rifampin plus isoniazid, compared with standard therapy with isoniazid, for latent tuberculosis infection: a meta-analysis. Clin Infect Dis 2005; 40:670.
- Centers for Disease Control and Prevention (CDC), American Thoracic Society. 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 2003; 52:735.
- From the Centers for Disease Control and Prevention. Update: Fatal and severe liver injuries associated with Rifampin and Pyrazinamide for latent tuberculosis infection, and revisions in American Thoracic Society/CDC recommendations--United States, 2001. JAMA 2001; 286:1445.
- McElroy PD, Ijaz K, Lambert LA, et al. National survey to measure rates of liver injury, hospitalization, and death associated with rifampin and pyrazinamide for latent tuberculosis infection. Clin Infect Dis 2005; 41:1125.
- Ijaz K, Jereb JA, Lambert LA, et al. Severe or fatal liver injury in 50 patients in the United States taking rifampin and pyrazinamide for latent tuberculosis infection. Clin Infect Dis 2006; 42:346.
- Centers for Disease Control and Prevention (CDC). Impact of a shortage of first-line antituberculosis medication on tuberculosis control - United States, 2012-2013. MMWR Morb Mortal Wkly Rep 2013; 62:398.
- Centers for Disease Control and Prevention. Emergency Preparedness and Response. http://emergency.cdc.gov/HAN/han00340.asp (Accessed on July 16, 2013).
- Centers for Disease Control and Prevention. Tuberculosis. http://www.cdc.gov/tb/ (Accessed on July 16, 2013).
- Jasmer RM, Nahid P, Hopewell PC. Clinical practice. Latent tuberculosis infection. N Engl J Med 2002; 347:1860.
- Smieja MJ, Marchetti CA, Cook DJ, Smaill FM. Isoniazid for preventing tuberculosis in non-HIV infected persons. Cochrane Database Syst Rev 2000; :CD001363.
- Efficacy of various durations of isoniazid preventive therapy for tuberculosis: five years of follow-up in the IUAT trial. International Union Against Tuberculosis Committee on Prophylaxis. Bull World Health Organ 1982; 60:555.
- Comstock GW. How much isoniazid is needed for prevention of tuberculosis among immunocompetent adults? Int J Tuberc Lung Dis 1999; 3:847.
- Nolan CM, Goldberg SV, Buskin SE. Hepatotoxicity associated with isoniazid preventive therapy: a 7-year survey from a public health tuberculosis clinic. JAMA 1999; 281:1014.
- Byrd RB, Horn BR, Solomon DA, Griggs GA. Toxic effects of isoniazid in tuberculosis chemoprophylaxis. Role of biochemical monitoring in 1,000 patients. JAMA 1979; 241:1239.
- Mitchell JR, Zimmerman HJ, Ishak KG, et al. Isoniazid liver injury: clinical spectrum, pathology, and probable pathogenesis. Ann Intern Med 1976; 84:181.
- OESTREICHER R, DRESSLER SH, MIDDLEBROOK G. Peripheral neuritis in tuberculous patients treated with isoniazid. Am Rev Tuberc 1954; 70:504.
- 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 1992; 145:36.
- Villarino ME, Ridzon R, Weismuller PC, et al. Rifampin preventive therapy for tuberculosis infection: experience with 157 adolescents. Am J Respir Crit Care Med 1997; 155:1735.
- Menzies D, Long R, Trajman A, et al. Adverse events with 4 months of rifampin therapy or 9 months of isoniazid therapy for latent tuberculosis infection: a randomized trial. Ann Intern Med 2008; 149:689.
- Aspler A, Long R, Trajman A, et al. 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 2010; 65:582.
- Young H, Wessolossky M, Ellis J, et al. 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 2009; 49:424.
- Sterling TR, Villarino ME, Borisov AS, et al. Three months of rifapentine and isoniazid for latent tuberculosis infection. N Engl J Med 2011; 365:2155.
- Sterling TR, Moro RN, Borisov AS, et al. 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 2015; 61:527.
- Stennis NL, Burzynski JN, Herbert C, et al. Treatment for Tuberculosis Infection With 3 Months of Isoniazid and Rifapentine in New York City Health Department Clinics. Clin Infect Dis 2016; 62:53.
- Centers for Disease Control and Prevention (CDC). Recommendations for use of an isoniazid-rifapentine regimen with direct observation to treat latent Mycobacterium tuberculosis infection. MMWR Morb Mortal Wkly Rep 2011; 60:1650.
- Whalen CC, Johnson JL, Okwera A, et al. A trial of three regimens to prevent tuberculosis in Ugandan adults infected with the human immunodeficiency virus. Uganda-Case Western Reserve University Research Collaboration. N Engl J Med 1997; 337:801.
- Sharma SK, Sharma A, Kadhiravan T, Tharyan P. 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; :CD007545.
- Stagg HR, Zenner D, Harris RJ, et al. Treatment of latent tuberculosis infection: a network meta-analysis. Ann Intern Med 2014; 161:419.
- Polesky A, Farber HW, Gottlieb DJ, et al. Rifampin preventive therapy for tuberculosis in Boston's homeless. Am J Respir Crit Care Med 1996; 154:1473.
- Khan K, Muennig P, Behta M, Zivin JG. Global drug-resistance patterns and the management of latent tuberculosis infection in immigrants to the United States. N Engl J Med 2002; 347:1850.
- Lardizabal A, Passannante M, Kojakali F, et al. Enhancement of treatment completion for latent tuberculosis infection with 4 months of rifampin. Chest 2006; 130:1712.
- Reichman LB, Lardizabal A, Hayden CH. Considering the role of four months of rifampin in the treatment of latent tuberculosis infection. Am J Respir Crit Care Med 2004; 170:832.
- Ziakas PD, Mylonakis E. 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 2009; 49:1883.
- Fraser A, Paul M, Attamna A, Leibovici L. Drugs for preventing tuberculosis in people at risk of multiple-drug-resistant pulmonary tuberculosis. Cochrane Database Syst Rev 2006; :CD005435.
- Schaaf HS, Vermeulen HA, Gie RP, et al. Evaluation of young children in household contact with adult multidrug-resistant pulmonary tuberculosis cases. Pediatr Infect Dis J 1999; 18:494.
- Schaaf HS, Gie RP, Kennedy M, et al. Evaluation of young children in contact with adult multidrug-resistant pulmonary tuberculosis: a 30-month follow-up. Pediatrics 2002; 109:765.
- Management of persons exposed to multidrug-resistant tuberculosis. MMWR Recomm Rep 1992; 41:61.
- Younossian AB, Rochat T, Ketterer JP, et al. High hepatotoxicity of pyrazinamide and ethambutol for treatment of latent tuberculosis. Eur Respir J 2005; 26:462.
- Bamrah S, Brostrom R, Dorina F, et al. Treatment for LTBI in contacts of MDR-TB patients, Federated States of Micronesia, 2009-2012. Int J Tuberc Lung Dis 2014; 18:912.
- Nahid P, Dorman SE, Alipanah N, et al. 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 2016; 63:e147.
- Centers for Disease Control and Prevention (CDC). Severe isoniazid-associated liver injuries among persons being treated for latent tuberculosis infection - United States, 2004-2008. MMWR Morb Mortal Wkly Rep 2010; 59:224.
- Saukkonen JJ, Cohn DL, Jasmer RM, et al. An official ATS statement: hepatotoxicity of antituberculosis therapy. Am J Respir Crit Care Med 2006; 174:935.
- Menzies D, Dion MJ, Rabinovitch B, et al. Treatment completion and costs of a randomized trial of rifampin for 4 months versus isoniazid for 9 months. Am J Respir Crit Care Med 2004; 170:445.
- Page KR, Sifakis F, Montes de Oca R, et al. Improved adherence and less toxicity with rifampin vs isoniazid for treatment of latent tuberculosis: a retrospective study. Arch Intern Med 2006; 166:1863.
- Menzies D, Dion MJ, Francis D, et al. In closely monitored patients, adherence in the first month predicts completion of therapy for latent tuberculosis infection. Int J Tuberc Lung Dis 2005; 9:1343.
- World Health Organization. Guidelines on the management of latent tuberculosis infection. WHO, Geneva 2015.
- Hoppe LE, Kettle R, Eisenhut M, et al. Tuberculosis--diagnosis, management, prevention, and control: summary of updated NICE guidance. BMJ 2016; 352:h6747.
- WHOM TO TREAT
- TREATMENT REGIMENS
- Isoniazid and rifapentine
- Isoniazid and rifampin
- SELECTING A REGIMEN
- General approach
- Treatment of drug-resistant LTBI
- Continuation of LTBI treatment after presumptive treatment for TB disease
- Interrupted LTBI therapy
- SUBSEQUENT MANAGEMENT
- INTERNATIONAL GUIDELINES
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS