Treatment of Latent Tuberculosis Infection
- Author: Connie A. Haley1
- Editor: David Schlossberg2
-
VIEW AFFILIATIONS HIDE AFFILIATIONSAffiliations: 1: Division of Infectious Diseases and Southeast National Tuberculosis Center, University of Florida, Gainesville, FL 32611; 2: Philadelphia Health Department, Philadelphia, PA
-
Received 24 December 2016 Accepted 05 January 2017 Published 14 April 2017
- Correspondence: Connie A. Haley, [email protected]
2017_small.jpg)
-
Abstract:
There are approximately 56 million people who harbor Mycobacterium tuberculosis 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.




Treatment of Latent Tuberculosis Infection, Page 1 of 2
< Previous page | Next page > /docserver/preview/fulltext/microbiolspec/5/2/TNMI7-0039-2016-1.gif /docserver/preview/fulltext/microbiolspec/5/2/TNMI7-0039-2016-2.gif

References

Article metrics loading...
Abstract:
There are approximately 56 million people who harbor Mycobacterium tuberculosis 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.

Full text loading...
Figures

Click to view
FIGURE 1
The spectrum of TB, from Mycobacterium tuberculosis infection to active (pulmonary) TB disease. Although TB disease can be viewed as a dynamic continuum from Mycobacterium tuberculosis 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 M. tuberculosis 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 M. tuberculosis 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.

Click to view
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 ).

Click to view
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 ).

Click to view
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 (y = a + b/x); and dotted lines, the calculated values based on the first four and the last five observations (y = a + bx). Reprinted with permission of the International Union Against Tuberculosis and Lung Disease. © The Union ( 21 ).

Click to view
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 x axis shows the months from start of the LTBI treatment regimen. The y 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 ).
Tables

Click to view

Click to view
TABLE 2
Placebo-controlled studies of isoniazid efficacy for treatment of LTBI a

Click to view
TABLE 3
Regimens for latent TB treatment, according to pooled efficacy, risk of hepatotoxicity, adverse events, and drug interactions

Click to view
TABLE 4
Current guidelines for the treatment of latent tuberculosis infection a

Click to view
TABLE 5
Overview of determinants of LTBI treatment initiation, adherence, and completion in the general population diagnosed with LTBI a

Click to view
TABLE 6
Specific treatment options for drug-resistant TB dependent on susceptibility of source case isolate a
Supplemental Material
No supplementary material available for this content.