Draft Recommendation Statement
Latent Tuberculosis Infection: Screening
September 06, 2016
|Adults who are at increased risk for tuberculosis||The USPSTF recommends screening for latent tuberculosis infection (LTBI) in populations that are at increased risk.||B|
Tuberculosis remains an important preventable disease in the United States. The precise prevalence rate of LTBI in the United States is difficult to determine; however, based on 2011–2012 National Health and Nutrition Examination Survey data, estimated prevalence is 4.7% to 5.0%.1 Tuberculosis is spread through respiratory transmission. Approximately 30% of persons exposed to Mycobacterium tuberculosis will develop LTBI, and, if untreated, approximately 5% to 10% of these persons will progress to active tuberculosis disease or reactivation of tuberculosis.2-5 Rates of progression may be higher in persons with certain risk factors or medical conditions. An important strategy to reduce the transmission, morbidity, and mortality of active tuberculosis disease is the identification and treatment of LTBI to prevent its progression to active disease. Traditionally, prevention of tuberculosis has fallen to public health systems; however, more recently, screening for LTBI has become a relevant primary care issue.
The USPSTF found adequate evidence that accurate screening tests are available to detect LTBI. Screening tests include the Mantoux tuberculin skin test (TST) and interferon-gamma release assays (IGRAs); both are moderately sensitive and highly specific.
Benefits of Early Detection and Treatment
The USPSTF found no studies that evaluated the direct benefits of screening for LTBI. The USPSTF found adequate evidence that treatment of LTBI with regimens recommended by the Centers for Disease Control and Prevention (CDC) decreases progression to active tuberculosis; the magnitude of this benefit is moderate.
Harms of Early Detection and Treatment
The USPSTF found no direct evidence on the harms of screening for LTBI. The USPSTF found adequate evidence that the magnitude of harms of treatment of LTBI with CDC-recommended regimens is small. The primary harm of treatment is hepatotoxicity.
The USPSTF concludes with moderate certainty that the net benefit of screening for LTBI in persons who are at increased risk for tuberculosis is moderate.
Patient Population Under Consideration
This recommendation applies to asymptomatic adults age 18 years and older who are at increased risk for tuberculosis (see the “Assessment of Risk” section for more information). It does not apply to adults with symptoms of tuberculosis or children or adolescents.
Assessment of Risk
Populations that are at increased risk for LTBI based on increased prevalence of active disease and increased risk of exposure include persons who were born in, or are former residents of, countries with increased tuberculosis prevalence and persons who live in, or have lived in, high-risk congregate settings (such as homeless shelters and correctional facilities).
In 2014, among persons of known national origin, 66.5% of all active tuberculosis cases in the United States were among foreign-born persons, and the case rate among foreign-born persons was 13.4 times higher than among U.S.-born persons (15.3 vs. 1.1 cases per 100,000 persons).6 More than half of all foreign-born persons in the United States with active tuberculosis come from five countries: Mexico, the Philippines, Vietnam, India, and China.6 Additionally, the CDC has identified foreign-born persons from Haiti and Guatemala as important contributors to active tuberculosis cases in the United States.7 The World Health Organization (WHO) recently updated its list of countries with a high burden of tuberculosis to include the top 20 countries with the highest absolute numbers of cases, plus an additional 10 countries with the most severe burden in terms of case rate per capita8 (available at www.who.int/tb/country/en/).
Persons who live in, or have lived in, high-risk congregate settings also have a higher prevalence rate of active tuberculosis and increased risk for exposure. Among persons age 15 years and older with active tuberculosis, 5.5% were homeless within the past year, 2.2% were long-term care facility residents, and 4.2% were in a correctional facility at the time of diagnosis.6 Published prevalence rates of LTBI in these settings vary widely, depending on the type of test used, the TST threshold used to define the presence of LTBI, and the population studied. Estimates range from 23.1% to 87.6% among prisoners and from 18.6% to 79.8% among persons who are homeless.2, 9
Other populations that are at increased risk for LTBI or progression to active disease include persons who are immunosuppressed (including persons living with HIV; patients receiving immunosuppressive medications, such as chemotherapy or tumor necrosis factor-alpha inhibitors; and persons receiving an organ transplant) and patients with silicosis (a lung disease). However, given that screening in these populations may be considered standard care as part of disease management or indicated prior to the use of certain medications, the USPSTF did not review evidence on screening in these populations. Persons who are contacts of persons with active tuberculosis, as well as health care workers and workers in high-risk congregate settings, may also be at increased risk of exposure. Since screening in these populations is conducted as part of public health10 or employee health11, 12 surveillance, the USPSTF also did not review the evidence in these populations. Clinicians seeking further information on testing for tuberculosis in these populations can refer to the “Useful Resources” section.
Two types of screening tests for LTBI are currently available in the United States—TST and IGRA. TST requires intradermal placement of purified protein derivative and interpretation of response 48 to 72 hours later. IGRA requires a single venous blood sample and laboratory processing within 8 to 30 hours after collection. Two types of IGRAs are currently approved by the U.S. Food and Drug Administration: T-SPOT®.TB (Oxford Immunotec Global PLC, Marlborough, MA) and QuantiFERON®-TB Gold In-Tube (Qiagen, Germantown, MD). Numerous patient and systems factors may influence the selection of a screening test.13 The CDC recommends screening with either TST or IGRA. IGRA tests may be preferred for persons who have received a Bacillus Calmette–Guérin vaccination or persons who may be unlikely to return for TST interpretation. Additional information on the use and interpretation of TST and IGRA is available at www.cdc.gov/tb/publications/factsheets/testing/tb_testing.htm.
The USPSTF found no evidence on the optimal frequency of screening for LTBI. Depending on specific risk factors, screening frequency could range from one-time only screening in persons who are at low risk for future exposure to annual screening in those who are at continued risk of exposure.
Currently, the CDC recommends four different treatment regimens for LTBI (www.cdc.gov/tb/topic/treatment/ltbi.htm). Medications include rifampin, isoniazid, or isoniazid plus rifapentine, and treatment duration ranges from 3 to 9 months. If a nondaily dosing regimen is offered, the CDC recommends directly observed therapy.
Additional Approaches to Prevention
The public health system plays an essential role in the control and elimination of tuberculosis. Clinicians are required to report cases of active tuberculosis to their local health department. As outlined by local and state public health laws, local health departments investigate and ensure treatment of active tuberculosis cases and perform contact tracing and medical surveillance of contacts.
Occupational health services also play an important role in the prevention and control of tuberculosis. Certain work settings (health care settings, correctional facilities, and other high-risk congregate housing settings) may pose a higher risk of tuberculosis exposure, and employers often play an important role in preventing exposure in employees and performing medical surveillance of employees for tuberculosis exposure.
Clinicians seeking guidance on tuberculosis management in persons living with HIV can find additional information at https://aidsinfo.nih.gov/guidelines/html/4/adult-and-adolescent-oi-prevention-and-treatment-guidelines/325/tb. Clinicians seeking information on medical surveillance of contacts of active tuberculosis cases can contact their local health department, review their local public health law, or review guidance from the CDC at www.cdc.gov/tb/publications/guidelines/list_date.htm. Information for public health tuberculosis programs can be found at www.cdc.gov/tb/programs/default.htm.
Clinicians seeking information on medical surveillance of health care workers, or employees working in high-risk settings, can consult the following resources: www.cdc.gov/tb/topic/infectioncontrol/default.htm, www.cdc.gov/tb/topic/populations/correctional/default.htm, and www.osha.gov/SLTC/tuberculosis/standards.html. Clinicians seeking guidance on screening for LTBI in children can find more information on the American Academy of Pediatrics’ Bright Futures Web site at https://brightfutures.aap.org/Pages/default.aspx. Guidance on tuberculosis and pregnancy is available at www.cdc.gov/tb/topic/populations/pregnancy/default.htm.
Screening with the TST requires that patients return in 48 to 72 hours for interpretation of results. When placing a TST, clinicians should plan with patients accordingly to ensure they can return in time, and that the facility is able to interpret the test results within the proper time frame.14 Screening with an IGRA requires only a single venous blood sample, and the patient does not need to return for interpretation of results. However, clinicians should be aware of processing requirements for blood samples and ensure that venous blood samples are drawn and able to reach the laboratory for processing within the appropriate time frame (8 to 30 hours, depending on the test).15
Research Needs and Gaps
Further research that evaluates risk assessment tools to determine efficient ways of identifying candidates for LTBI testing and treatment is needed. Additional research on how often LTBI screening should be performed in different subpopulations is also needed. The USPSTF identified no studies of LTBI screening or treatment in pregnant women and the potential effects on the fetus; this represents an important gap in the literature that needs further research. Additionally, more studies to help clarify if certain screening methods are preferred for certain risk groups are also needed.
Burden of Disease
Tuberculosis causes substantial health burden globally. Approximately one third of the world’s population is infected with tuberculosis, with 9.6 million persons estimated to have fallen sick from tuberculosis and 1.5 million related deaths occurring worldwide in 2014.8 In the United States, there were 9,412 new active cases of tuberculosis reported in 2014, which corresponds to an incidence rate of 3.0 cases per 100,000 persons.6 In 2013, there were 555 deaths from tuberculosis in the United States.16 In 2014, one half of all tuberculosis cases occurred in four states: California, Texas, New York, and Florida. Asians represented the largest percentage of total cases (32%), followed by Hispanics (29%), African Americans (21%), and whites (13%); American Indian or Alaska Natives and Native Hawaiian or other Pacific Islanders each represented 1% of cases.17 Incidence rates of active tuberculosis may be higher in populations that are at increased risk due to greater likelihood of exposure to tuberculosis, such as persons who have resided in countries with a high tuberculosis burden or have a greater likelihood of progression from LTBI to active disease, such as persons who are immunosuppressed.
Scope of Review
The USPSTF commissioned a systematic review of the evidence on screening for LTBI. Evidence dating from the inception of searched databases was included. The review focused on evidence on screening for LTBI in asymptomatic adults who are seen in primary care settings. It did not include evidence on screening in persons for whom LTBI screening would be considered management of a specific condition (such as HIV infection), public health surveillance (i.e., tracing contacts of persons with active tuberculosis disease), or surveillance of employees working in high-risk settings or screening that is indicated prior to the use of specific immunosuppressive medications.
Accuracy of Screening Tests
There is no direct test for the diagnosis of latent infection with M. tuberculosis. Diagnosis of LTBI is based on medical history, physical examination, screening test results, and exclusion of active tuberculosis disease. In the absence of a reference standard for detection of LTBI, screening test performance is based on detection of disease in persons with known active tuberculosis and nondetection of disease in populations that are at low risk for the disease and presumed not to have LTBI or active tuberculosis.
The USPSTF identified 66 good- or fair-quality studies that provided information on the accuracy and reliability of screening tests for LTBI.2 For studies reporting on sensitivity, eight were conducted in countries with a high burden of tuberculosis, 29 were conducted in intermediate-burden countries, 10 were conducted in low-burden countries, and three included a mix of low- to intermediate-burden countries. For studies reporting on specificity, three were conducted in intermediate-burden countries, 14 were conducted in low-burden countries, and one was conducted in both an intermediate- and low-burden country. When using a positive threshold of 10 mm, TST has moderate sensitivity and high specificity for detection of LTBI. Based on pooled analyses of studies reviewed by the USPSTF, when using a positive threshold of 10 mm, TST has sensitivity of 79% (k=11; n=988) and specificity of 97% (k=9; n=9,651).2 Pooled analyses of the T-SPOT.TB test (a type of IGRA) indicate sensitivity of 90% (k=16; n=984) and specificity of 95% (k=5; n=1,810). Pooled analyses of the QuantiFERON-TB test (another type of IGRA) indicate sensitivity of 80% (k=24; n=2,321) and specificity of 97% (k=4; n=2,053). The USPSTF identified no studies that evaluated the accuracy and reliability of sequential screening strategies.
Effectiveness of Early Detection and Treatment
The USPSTF identified no randomized, controlled trials that compared screening to no screening to provide direct evidence of the benefit of screening for LTBI on health outcomes, such as rates of active tuberculosis disease, disease-specific or all-cause mortality, or tuberculosis transmission. Three good- or fair-quality trials (n=35,563) conducted in Canada, Brazil, Saudi Arabia, Spain, Czechoslovakia, Finland, Germany, Hungary, Poland, Romania, and Yugoslavia provided evidence on the benefits of treatment of LTBI.2 Trials evaluated treatment with isoniazid,18 rifampin,19 and rifapentine plus isoniazid.20 The best evidence on the effectiveness of treatment was from the International Union Against Tuberculosis (IUAT) trial. This good-quality randomized, controlled trial was conducted in seven European countries (Czechoslovakia, Finland, Germany, Hungary, Poland, Romania, and Yugoslavia ) among participants with fibrotic pulmonary lesions but not active tuberculosis. The trial was published in 1982, included 27,830 participants, and evaluated treatment with daily isoniazid. It found that at 5 years, the relative risk (RR) of progression to active tuberculosis was 0.35 (95% CI, 0.24 to 0.52) for treatment with isoniazid (300 mg daily for 24 weeks) compared to placebo. Although not statistically significant, the trial reported fewer deaths due to tuberculosis among participants receiving treatment with isoniazid (0 vs. 3 deaths in the placebo group; RR, 0.14 [95% CI, 0.01 to 2.78]). The other two treatment trials compared 1) rifampin to isoniazid and found zero deaths in either group, and 2) rifapentine plus isoniazid to isoniazid alone and found that the combination therapy was noninferior in preventing progression to active tuberculosis. None of the treatment studies reported on transmission rates of tuberculosis.
Potential Harms of Screening and Treatment
The USPSTF identified no studies that directly reported on the harms of screening. Potential harms include stigma associated with screening and diagnostic workup and treatment of false-positive results. Five good- or fair-quality studies (n=36,043) conducted in the United States, Canada, Saudi Arabia, Brazil, Spain, Czechoslovakia, Finland, Germany, Hungary, Poland, Romania, and Yugoslavia reported on the harms of treatment.2, 18-22 Interventions evaluated included isoniazid, rifampin, and rifapentine plus isoniazid. The most consistently reported harm was hepatotoxicity. The only study that assessed harms of treatment versus placebo was the IUAT trial,18 which found an RR of 4.59 for hepatotoxicity at 5 years with isoniazid (300 mg for 24 weeks) versus placebo (95% CI, 2.03 to 10.39). The IUAT trial also reported more deaths from hepatotoxicity with treatment with isoniazid than with placebo, although this finding was not statistically significant (0.14 vs. 0 deaths per 1,000 persons; calculated RR, 2.35 [95% CI, 0.12 to 45.46]). The other trials compared either rifampin19, 21, 22 or rifapentine plus isoniazid20 to isoniazid. Meta-analysis of three trials of rifampin compared to isoniazid found a higher RR for hepatoxicity with isoniazid (RR, 3.29 [95% CI, 1.72 to 6.28]).2 None of these three trials, which were more recent than the IUAT trial, reported any deaths from hepatotoxicity. The one study that reported on hepatotoxicity of rifapentine plus isoniazid versus isoniazid alone found a nonsignificant reduced RR of 0.90 (95% CI, 0.75 to 1.08) for grade 3 or 4 hepatotoxicity with rifapentine plus isoniazid. There was also a nonsignificant reduced RR of death from hepatotoxicity with rifapentine plus isoniazid versus isoniazid alone (RR, 0.83 [95% CI, 0.51 to 1.35]). A few studies also reported on gastrointestinal adverse events. Compared to placebo, participants treated with isoniazid had a higher risk of medication discontinuation due to gastrointestinal adverse events (RR, 1.33 [95% CI, 1.01 to 1.75]).18 Compared to rifampin, treatment with isoniazid had a nonsignificant increased RR of gastrointestinal adverse events (RR, 1.60 [95% CI, 0.76 to 3.40]) in two studies.2 All five studies also reported on discontinuation of treatment due to adverse events. Compared to placebo, treatment with isoniazid had an RR of discontinuation of 1.50 (95% CI, 1.18 to 1.89).18 Pooling results from the three studies on isoniazid versus rifampin found a nonsignificant increased risk of discontinuation with isoniazid (RR, 1.61 [95% CI, 0.57 to 4.57]).2 The study of rifapentine plus isoniazid versus isoniazid alone found an increased risk of discontinuation with rifapentine plus isoniazid (RR, 1.28 [95% CI, 1.03 to 1.59]).20
Estimate of Magnitude of Net Benefit
Overall, the USPSTF found adequate evidence that accurate screening tests for LTBI are available, treatment of LTBI provides a moderate health benefit in preventing progression to active disease, and the harms of screening and treatment are small. The USPSTF has moderate certainty that screening for LTBI in persons who are at increased risk for infection provides a moderate net benefit. The USPSTF estimates that if a hypothetical cohort of 100,000 asymptomatic adults who are at increased risk for tuberculosis (such as persons born in, or former residents of, high-prevalence countries) were screened, 52 to 146 active tuberculosis cases would be prevented, 7 to 67 cases of hepatotoxicity would occur (depending on type of treatment), and 111 persons would discontinue treatment due to adverse events. The number needed to treat to prevent 1 case of LTBI from progressing to active tuberculosis would range from 111 to 314 (depending on the patient’s risk for progression), and the number needed to harm to cause 1 case of hepatotoxicity from treatment would range from 279 to 2,531 (depending on treatment type). These estimates are based on prevalence data from the 2011–2012 National Health and Nutrition Examination Survey1 and numerous assumptions about screening sensitivity and specificity (such as using TST with a 10 mm threshold for a positive diagnosis) and potential benefits of treatment (such as estimated efficacy of treatment with 24 weeks of isoniazid, based on IUAT trial findings). For further information on the assumptions used, please see the corresponding evidence review.2
How Does Evidence Fit With Biological Understanding?
Tuberculosis disease is caused by M. tuberculosis, which is spread through airborne transmission when a person with active pulmonary tuberculosis coughs or sneezes. When inhaled, a person can either clear M. tuberculosis; develop active disease (primary tuberculosis disease), which may be infectious; or develop latent infection (LTBI), which is asymptomatic and not infectious. LTBI can later reactivate and progress to active tuberculosis disease. Approximately 30% of persons exposed to active M. tuberculosis will develop LTBI. Further, approximately 5% to 10% of persons with a positive TST will experience reactivation of LTBI and progress to active tuberculosis disease.2-5
The USPSTF last issued a recommendation on screening for tuberculosis in 1996. At that time, the USPSTF recommended screening for tuberculosis infection with TST in asymptomatic, high-risk persons (A recommendation), and consideration of Bacillus Calmette–Guérin vaccination for selected high-risk individuals only (B recommendation). Given the changes in the epidemiology of the disease, the development of newer screening technologies, and newer methods for developing evidence-based recommendations, the USPSTF decided to update the topic and issue a recommendation using its current methodology and considering all of the available evidence, including studies published prior to 1996.
In 2005, the CDC, American Thoracic Society, and the Infectious Diseases Society of America issued joint guidelines recommending that clinicians screen for LTBI only among high-risk populations and when treatment is feasible.23 In its 2013 “Guide for Primary Health Care Providers,” the CDC recommended targeted testing for tuberculosis among high-risk populations only.7 The CDC identifies persons at risk for developing tuberculosis as those who have an increased likelihood of exposure to persons with tuberculosis disease (known close contacts of a person with infectious tuberculosis disease, persons who have immigrated from tuberculosis-endemic regions of the world, and persons who work or reside in facilities or institutions with those who are at high risk for tuberculosis) or persons with clinical conditions or other factors associated with an increased risk of progression from LTBI to tuberculosis disease (HIV infection, injection drug use, radiographic evidence of prior healed tuberculosis, low body weight, or other medical conditions). Further information on targeted testing is available at www.cdc.gov/tb/publications/ltbi/targetedtesting.htm.
WHO also recently issued guidelines on the management of LTBI. For high-income countries with an estimated tuberculosis incidence of less than 100 cases per 100,000 population (such as the United States), it recommends systematic testing and treatment of LTBI among persons living with HIV, adult and child contacts of pulmonary tuberculosis cases, patients initiating antitumor necrosis factor treatment, patients receiving dialysis, patients preparing for an organ or hematologic transplant, and patients with silicosis. Either IGRA or TST should be used. It recommends considering systematic testing and treatment among prisoners, health workers, immigrants from high-burden countries, persons who are homeless, and illicit drug users. Either IGRA or TST should be used. It does not recommend systematic testing for LTBI among persons who have diabetes, engage in harmful alcohol use, smoke tobacco, or are underweight, unless they are already included in the above recommendations.24 Further information is available at www.who.int/tb/en/.
1. Miramontes R, Hill AN, Yelk Woodruff RS, Lambert LA, Navin TR, Castro KG, et al. Tuberculosis infection in the United States: prevalence estimates from the National Health and Nutrition Examination Survey, 2011-2012. PLoS One. 2015;10(11):e0140881.
2. Kahwati LC, Feltner C, Halpern M, Woodell CL, Boland E, Amick HR, et al. Screening for Latent Tuberculosis Infection in Adults: An Evidence Review for the U.S. Preventive Services Task Force. Evidence Synthesis No. 142. AHRQ Publication No. 14-05212-EF-1. Rockville, MD: Agency for Healthcare Research and Quality; 2016.
3. Grzybowski S, Barnett GD, Styblo K. Contacts of cases of active pulmonary tuberculosis. Bull Int Union Tuberc. 1975;50(1):90-106.
4. Marks SM, Taylor Z, Qualls NL, Shrestha-Kuwahara RJ, Wilce MA, Nguyen CH. Outcomes of contact investigations of infectious tuberculosis patients. Am J Respir Crit Care Med. 2000;162(6):2033-8.
5. American Thoracic Society. Targeted tuberculin testing and treatment of latent tuberculosis infection. Am J Respir Crit Care Med. 2000;161(4 pt 2):S221-47.
6. Scott C, Kirking HL, Jeffries C, Price SF, Pratt R; Centers for Disease Control and Prevention (CDC). Tuberculosis trends--United States, 2014. Morb Mortal Wkly Rep. 2015;64(10):265-9.
7. Centers for Disease Control and Prevention. Latent Tuberculosis Infection: A Guide for Primary Health Care Providers. Atlanta: Centers for Disease Control and Prevention; 2013.
8. World Health Organization. Global Tuberculosis Report 2015. 20th ed. Geneva, Switzerland: World Health Organization; 2015.
9. Getahun H, Matteelli A, Chaisson RE, Raviglione M. Latent Mycobacterium tuberculosis infection. N Engl J Med. 2015;372(22):2127-35.
10. National Tuberculosis Controllers Association; Centers for Disease Control and Prevention (CDC). Guidelines for the investigation of contacts of persons with infectious tuberculosis. Recommendations from the National Tuberculosis Controllers Association and CDC. MMWR Recomm Rep. 2005;54(RR-15):1-47.
11. Jensen PA, Lambert LA, Iademarco MF, Ridzon R; CDC. Guidelines for preventing the transmission of Mycobacterium tuberculosis in health-care settings, 2005. MMWR Recomm Rep. 2005;54(RR-17):1-141.
12. Occupational Safety and Health Administration. Enforcement Procedures and Scheduling for Occupational Exposure to Tuberculosis. Directive No. CPL 02-02-078. Washington, DC: Occupational Safety and Health Administration; 2015.
13. Collins LF, Geadas C, Ellner JJ. Diagnosis of latent tuberculosis infection: too soon to pull the plug on the tuberculin skin test. Ann Intern Med. 2016;164(2):122-4.
14. Centers for Disease Control and Prevention. Fact Sheet: Tuberculin Skin Testing. 2012. http://www.cdc.gov/tb/publications/factsheets/testing/skintesting.htm. Accessed February 23, 2016.
15. Centers for Disease Control and Prevention. Fact Sheet: Interferon-Gamma Release Assays (IGRAs)—Blood Tests for TB Infection. 2012. http://www.cdc.gov/tb/publications/factsheets/testing/igra.htm. Accessed February 23, 2016.
16. Centers for Disease Control and Prevention. Fact Sheet: Trends in Tuberculosis, 2014. 2015. http://www.cdc.gov/tb/publications/factsheets/statistics/tbtrends.htm. Accessed February 23, 2016.
17. Centers for Disease Control and Prevention. Reported Tuberculosis in the United States, 2014. 2014. http://www.cdc.gov/tb/statistics/reports/2014/default.htm. Accessed February 23, 2016.
18. International Union Against Tuberculosis Committee on Prophylaxis. Efficacy of various durations of isoniazid preventive therapy for tuberculosis: five years of follow-up in the IUAT trial. Bull World Health Organ. 1982;60(4):555-64.
19. Menzies D, Long R, Trajman A, Dion MJ, Yang J, Al Jahdali H, 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(10):689-97.
20. Sterling TR, Villarina ME, Borisov AS, Shang N, Gordin F, Bliven-Sizemore E, et al. Three months of rifapentine and isoniazid for latent tuberculosis infection. N Engl J Med. 2011;365(23):2155-66.
21. Menzies D, Dion MJ, Rabinovitch B, Mannix S, Brassard P, Schwartzman K. 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(4):445-9.
22. White MC, Tulsky JP, Lee JR, Chen L, Goldenson J, Spetz J, Kawamura LM. Isoniazid vs. rifampin for latent tuberculosis infection in jail inmates: toxicity and adherence. J Correct Health Care. 2012;18(2):131-42.
23. Taylor Z, Nolan CM, Blumberg HM; American Thoracic Society; Centers for Disease Control and Prevention; Infectious Diseases Society of America. Controlling tuberculosis in the United States. Recommendations from the American Thoracic Society, CDC, and the Infectious Diseases Society of America. MMWR Recomm Rep. 2005;54(RR-12):1-81.
24. World Health Organization. Guidelines on the Management of Latent Tuberculosis Infection. Geneva, Switzerland: World Health Organization; 2015.