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Chapter 6 : Treatment of Latent Tuberculosis Infection

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Abstract:

The World Health Organization (WHO) has recently reported that the global tuberculosis (TB) epidemic is larger than previously projected, with an estimated 10.4 million new (incident) cases occurring in 2015 ( ). It has thus become clear that the WHO End TB Strategy targets of a 90% reduction in TB incidence and a 95% reduction in TB deaths by 2035 can be achieved only by combining the effective detection and treatment of active TB with measures to prevent new infection with and to eradicate existing latent TB infections (LTBI) ( ). Recent estimates indicate that approximately 1.7 billion people, nearly one-quarter of the world’s population, are latently infected with and are at risk of progression to active TB without treatment ( ). Moreover, an estimated 11% of those are likely infected with an isoniazid-resistant strain. With ongoing transmission of and a high rate of reactivation from LTBI to active TB, a heightened global commitment to the identification and treatment of infected persons is thus critical for achievement of TB elimination ( ).

Citation: Haley C. 2017. Treatment of Latent Tuberculosis Infection, p 67-100. In Schlossberg D (ed), Tuberculosis and Nontuberculous Mycobacterial Infections, Seventh Edition. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.TNMI7-0039-2016
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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 , with permission.

Citation: Haley C. 2017. Treatment of Latent Tuberculosis Infection, p 67-100. In Schlossberg D (ed), Tuberculosis and Nontuberculous Mycobacterial Infections, Seventh Edition. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.TNMI7-0039-2016
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Image of Figure 2
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 ( ).

Citation: Haley C. 2017. Treatment of Latent Tuberculosis Infection, p 67-100. In Schlossberg D (ed), Tuberculosis and Nontuberculous Mycobacterial Infections, Seventh Edition. ASM Press, Washington, DC. 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 ( ).

Citation: Haley C. 2017. Treatment of Latent Tuberculosis Infection, p 67-100. In Schlossberg D (ed), Tuberculosis and Nontuberculous Mycobacterial Infections, Seventh Edition. ASM Press, Washington, DC. 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 ( ).

Citation: Haley C. 2017. Treatment of Latent Tuberculosis Infection, p 67-100. In Schlossberg D (ed), Tuberculosis and Nontuberculous Mycobacterial Infections, Seventh Edition. ASM Press, Washington, DC. 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 ( ). Reprinted with permission of the American Thoracic Society ( ).

Citation: Haley C. 2017. Treatment of Latent Tuberculosis Infection, p 67-100. In Schlossberg D (ed), Tuberculosis and Nontuberculous Mycobacterial Infections, Seventh Edition. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.TNMI7-0039-2016
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