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Chapter 6 : Treatment of Latent Tuberculosis Infection

Author: Connie A. Haley1
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Affiliations: 1: Division of Infectious Diseases and Institute for Global Health, Vanderbilt University Medical Center, Nashville, TN 37203
Content Type: Monograph
Publication Year: 2011

Category: Clinical Microbiology; Bacterial Pathogenesis

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Abstract:

This chapter focuses on the treatment of persons with latent tuberculosis infection (LTBI) to prevent future development of TB disease. The identification and treatment of persons with LTBI constitute an essential component of TB elimination through two fundamental mechanisms. The first is the individual clinical benefit conferred through the prevention of morbidity and mortality associated with active TB disease. The second benefit is gained at the population level through the prevention of spread of infection within the community and the associated reduction in health care spending. Prior to the initiation of treatment, all persons with evidence of LTBI should be evaluated for the presence of pulmonary and extrapulmonary TB disease, including a thorough review for TB symptoms, a clinical examination, and a chest radiograph. Specific LTBI treatment regimens are summarized in this chapter according to their effectiveness and level of tolerability. Adverse effects of LTBI treatment drugs such as isoniazid, rifampin and pyrazinamide are also listed in this chapter. To ensure that the maximal benefit of LTBI therapy is achieved, adherence to treatment should be monitored closely for all patients at the recommended monthly clinical visits. Cost-effectiveness is an important consideration for public health programs when determining the most appropriate LTBI treatment regimen to use for targeted testing and LTBI treatment outreach activities. Choosing the most appropriate LTBI regimen, clinical monitoring for potential adverse events, and utilization of adherence-promoting strategies to ensure completion are critical elements for the success of LTBI treatment to prevent additional TB disease.

Citation: Haley C. 2011. Treatment of Latent Tuberculosis Infection, p 83-106. In Schlossberg D (ed), Tuberculosis and Nontuberculous Mycobacterial Infections, Sixth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817138.ch6
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Treatment of Latent Tuberculosis Infection
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Citation: Haley C. 2011. Treatment of Latent Tuberculosis Infection, p 83-106. In Schlossberg D (ed), Tuberculosis and Nontuberculous Mycobacterial Infections, Sixth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817138.ch6
/content/10.1128/9781555817138.ch06.ch06fig01
Figure 1.
LTBI pretreatment clinical evaluation and counseling. Dotted lines signify management according to physician’s discretion. ALT, alanine aminotransferase; INR, international normalized ratio; PTT, partial thromboplastin time. Reprinted with permission of the American Thoracic Society ( ).
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10.1128/9781555817138/f0086-01.gif
Image of Figure 1.
Figure 1.

LTBI pretreatment clinical evaluation and counseling. Dotted lines signify management according to physician’s discretion. ALT, alanine aminotransferase; INR, international normalized ratio; PTT, partial thromboplastin time. Reprinted with permission of the American Thoracic Society ( ).

Citation: Haley C. 2011. Treatment of Latent Tuberculosis Infection, p 83-106. In Schlossberg D (ed), Tuberculosis and Nontuberculous Mycobacterial Infections, Sixth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817138.ch6
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Figure 2.
Monitoring for hepatotoxicity during LTBI treatment. Dotted lines signify management according to physician’s discretion. ALT, alanine aminotransferase; AST, aspartate aminotransferase; HAV, hepatitis A virus; HCV, hepatitis C virus; HepBsAg, hepatitis B surface antigen. Reprinted with permission of the American Thoracic Society ( ).
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10.1128/9781555817138/f0087-01.gif
Image of Figure 2.
Figure 2.

Monitoring for hepatotoxicity during LTBI treatment. Dotted lines signify management according to physician’s discretion. ALT, alanine aminotransferase; AST, aspartate aminotransferase; HAV, hepatitis A virus; HCV, hepatitis C virus; HepBsAg, hepatitis B surface antigen. Reprinted with permission of the American Thoracic Society ( ).

Citation: Haley C. 2011. Treatment of Latent Tuberculosis Infection, p 83-106. In Schlossberg D (ed), Tuberculosis and Nontuberculous Mycobacterial Infections, Sixth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817138.ch6
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Figure 3.
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 by permission of the ( ).
10.1128/9781555817138/f0089-01_thmb.gif
10.1128/9781555817138/f0089-01.gif
Image of Figure 3.
Figure 3.

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 by permission of the ( ).

Citation: Haley C. 2011. Treatment of Latent Tuberculosis Infection, p 83-106. In Schlossberg D (ed), Tuberculosis and Nontuberculous Mycobacterial Infections, Sixth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817138.ch6
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Figure 4.
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 ( ). Reprinted with permission of the American Thoracic Society ( ).
10.1128/9781555817138/f0093-01_thmb.gif
10.1128/9781555817138/f0093-01.gif
Image of Figure 4.
Figure 4.

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 ( ). Reprinted with permission of the American Thoracic Society ( ).

Citation: Haley C. 2011. Treatment of Latent Tuberculosis Infection, p 83-106. In Schlossberg D (ed), Tuberculosis and Nontuberculous Mycobacterial Infections, Sixth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817138.ch6
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Tables

Treatment of Latent Tuberculosis Infection
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Citation: Haley C. 2011. Treatment of Latent Tuberculosis Infection, p 83-106. In Schlossberg D (ed), Tuberculosis and Nontuberculous Mycobacterial Infections, Sixth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817138.ch6
/content/10.1128/9781555817138.ch06.ch06table01
Table 1.
Relative risk of reactivation TB among persons with medical conditions that impair immune control of
Generic image for table
Table 1.

Relative risk of reactivation TB among persons with medical conditions that impair immune control of

Citation: Haley C. 2011. Treatment of Latent Tuberculosis Infection, p 83-106. In Schlossberg D (ed), Tuberculosis and Nontuberculous Mycobacterial Infections, Sixth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817138.ch6
/content/10.1128/9781555817138.ch06.ch06table02
Table 2.
Placebo-controlled studies of isoniazid efficacy for treatment of LTBI
Generic image for table
Table 2.

Placebo-controlled studies of isoniazid efficacy for treatment of LTBI

Citation: Haley C. 2011. Treatment of Latent Tuberculosis Infection, p 83-106. In Schlossberg D (ed), Tuberculosis and Nontuberculous Mycobacterial Infections, Sixth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817138.ch6
/content/10.1128/9781555817138.ch06.ch06table03
Table 3.
Regimens for the treatment of LTBI
Generic image for table
Table 3.

Regimens for the treatment of LTBI

Citation: Haley C. 2011. Treatment of Latent Tuberculosis Infection, p 83-106. In Schlossberg D (ed), Tuberculosis and Nontuberculous Mycobacterial Infections, Sixth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817138.ch6
/content/10.1128/9781555817138.ch06.ch06table04
Table 4.
Adverse effects of LTBI treatment drugs
Generic image for table
Table 4.

Adverse effects of LTBI treatment drugs

Citation: Haley C. 2011. Treatment of Latent Tuberculosis Infection, p 83-106. In Schlossberg D (ed), Tuberculosis and Nontuberculous Mycobacterial Infections, Sixth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817138.ch6
/content/10.1128/9781555817138.ch06.ch06table05
Table 5.
Predictors of adherence to LTBI medications
Generic image for table
Table 5.

Predictors of adherence to LTBI medications

Citation: Haley C. 2011. Treatment of Latent Tuberculosis Infection, p 83-106. In Schlossberg D (ed), Tuberculosis and Nontuberculous Mycobacterial Infections, Sixth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817138.ch6
/content/10.1128/9781555817138.ch06.ch06table06
Table 6.
Challenges of treatment adherence and possible solutions in patients with LTBI
Generic image for table
Table 6.

Challenges of treatment adherence and possible solutions in patients with LTBI

Citation: Haley C. 2011. Treatment of Latent Tuberculosis Infection, p 83-106. In Schlossberg D (ed), Tuberculosis and Nontuberculous Mycobacterial Infections, Sixth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817138.ch6
/content/10.1128/9781555817138.ch06.ch06table07
Table 7.
Treatment of MDR LTBI
Generic image for table
Table 7.

Treatment of MDR LTBI

Citation: Haley C. 2011. Treatment of Latent Tuberculosis Infection, p 83-106. In Schlossberg D (ed), Tuberculosis and Nontuberculous Mycobacterial Infections, Sixth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817138.ch6

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