Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Current Pulmonology Reports
Published in: Current Pulmonology Reports 4/2013

01-12-2013 | Respiratory Infections (CL Daley, Section Editor)

Diagnosis and treatment of latent tuberculosis infection: an update

Authors: Anna K. Person, April C. Pettit, Timothy R. Sterling

Published in: Current Pulmonology Reports | Issue 4/2013

Login to get access

Abstract

It is estimated that more than two billion people have latent M. tuberculosis infection, and this population serves as an important reservoir for future tuberculosis cases. Prevalence estimates are limited by difficulties in diagnosing the infection, including the lack of an ideal test, and an incomplete understanding of latency. Current tests include the tuberculin skin test and two interferon-γ release assays: QuantiFERON Gold In-Tube and T-SPOT.TB. This update focuses on recent publications regarding the ability of these tests to predict tuberculosis disease, their reproducibility over serial tests, and discordance between tests. We also discuss recent advances in the treatment of latent M. tuberculosis infection, including the three-month regimen of once-weekly rifapentine plus isoniazid, and prolonged isoniazid therapy for HIV-infected persons living in high-tuberculosis-incidence settings. We provide an update on the tolerability of the three-month regimen.
Literature
1.
Daley CL, Small PM, Schecter GF, et al. An outbreak of tuberculosis with accelerated progression among persons infected with the human immunodeficiency virus. An analysis using restriction-fragment-length polymorphisms. N Engl J Med. 1992;326(4):231–5.PubMedCrossRef
2.
Dye C, Scheele S, Dolin P, et al. Consensus statement. Global burden of tuberculosis: estimated incidence, prevalence, and mortality by country. WHO Global Surveillance and Monitoring Project. JAMA. 1999;282(7):677–86.PubMedCrossRef
3.
Bennett DE, Courval JM, Onorato I, et al. Prevalence of tuberculosis infection in the United States population: the national health and nutrition examination survey, 1999–2000. Am J Respir Crit Care Med. 2008;177(3):348–55.PubMedCrossRef
4.
Smieja MJ, Marchetti CA, Cook DJ, et al. Isoniazid for preventing tuberculosis in non-HIV infected persons. Cochrane Database Syst Rev. 2000;2, CD001363.PubMed
5.
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. pages S221–47.
6.
Mazurek GH, Jereb J, Vernon A, et al. Updated guidelines for using Interferon Gamma Release Assays to detect Mycobacterium tuberculosis infection - United States, 2010. MMWR Recomm Rep. 2010. pages 1–25.
7.
Diagnostic Standards and Classification of Tuberculosis in Adults and Children. This official statement of the American Thoracic Society and the Centers for Disease Control and Prevention was adopted by the ATS Board of Directors, July 1999. This statement was endorsed by the Council of the Infectious Disease Society of America, September 1999. Am J Respir Crit Care Med. 2000. pages 1376–95.
8.
Villarino ME, Burman W, Wang YC, et al. Comparable specificity of 2 commercial tuberculin reagents in persons at low risk for tuberculous infection. JAMA. 1999;281(2):169–71.PubMedCrossRef
9.
Blumberg HM, White N, Parrott P, et al. False-positive tuberculin skin test results among health care workers. JAMA. 2000;283(21):2793.PubMedCrossRef
10.
Gillenwater KA, Sapp SC, Pearce K, et al. Increase in tuberculin skin test converters among health care workers after a change from Tubersol to Aplisol. Am J Infect Control. 2006;34(10):651–4.PubMedCrossRef
11.
Grabau JC, Hughes SE, Foster EA, et al. False-positive tuberculin skin tests in a state prison system. Int J Tuberc Lung Dis. 2003;7(1):93–7.PubMed
12.
Mehta SR, MacGruder C, Looney D, et al. Differences in tuberculin reactivity as determined in a veterans administration employee health screening program. Clin Vaccine Immunol. 2009;16(4):541–3.PubMedCrossRef
13.
Centers for Disease Control and Prevention CDC. National shortage of purified-protein derivative tuberculin products. MMWR Morb Mortal Wkly Rep. 2013;62(16):312.
14.
Jensen PA, Lambert LA, Iademarco MF, et al. CDC. Guidelines for preventing the transmission of Mycobacterium tuberculosis in health-care settings, 2005. MMWR Recomm Rep. 2005. pages 1–141.
15.
16.
17.
•• Diel R, Loddenkemper R, Nienhaus A. Predictive value of interferon-γ release assays and tuberculin skin testing for progression from latent TB infection to disease state: a meta-analysis. Chest. 2012;142(1):63–75. Meta-analysis of 28 studies evaluating PPV or NPV for progression to active TB. Excluded those who had received preventive therapy. For high-risk individuals in particular, there was a suggestion of higher PPV for the IGRAs evaluated compared with TST.PubMedCrossRef
18.
• Rangaka MX, Wilkinson KA, Glynn JR, et al. Predictive value of interferon-γ release assays for incident active tuberculosis: a systematic review and meta-analysis. Lancet Infect Dis. 2012;12(1):45–55. This was a systematic review and meta-analysis assessing the ability of IGRAs and TST to predict development of active TB. Those who had taken preventive therapy were not excluded and several “in-house” IGRAs were included. When positive IGRAs were compared with positive TSTs, only modest, non-significant differences in IRR for incident tuberculosis were seen.PubMedCrossRef
19.
Pai M, Joshi R, Dogra S, et al. Serial testing of health care workers for tuberculosis using interferon-gamma assay. Am J Respir Crit Care Med. 2006;174(3):349–55.PubMedCrossRef
20.
Menzies D, Pai M, Comstock G. Meta-analysis: new tests for the diagnosis of latent tuberculosis infection: areas of uncertainty and recommendations for research. Ann Intern Med. 2007;146(5):340–54.PubMedCrossRef
21.
•• Fong KS, Tomford JW, Teixeira L, et al. Challenges of interferon-γ release assay conversions in serial testing of health-care workers in a TB control program. Chest. 2012;142(1):55–62. Retrospective chart review of health-care workers receiving QuantiFERON Gold In-Tube testing for screening at a US hospital. Several health care workers with no known TB exposure found to have low-positive IGRA results; several later had reversion. Reveals how a single “cut-point” for positivity on serial testing may lead to conversions and/or reversions of unclear clinical significance.PubMedCrossRef
22.
• Park JS, Lee JS, Kim MY, et al. Monthly follow-ups of interferon-γ release assays among health-care workers in contact with patients with TB. Chest. 2012;142(6):1461–8. Study of 49 healthcare workers in S. Korea who were contacts with patients with active TB. They were followed for one year with monthly QuantiFERON TB Gold In-Tube assays. Frequent fluctuations around the single “cut-point” were seen; 52 % had conversions and/or reversions when a single cut-point of 0.35 IU mL −1 was used. Demonstrates difficulty in interpreting test with a single cut-point when used serially.PubMedCrossRef
23.
Rafiza S, Rampal KG. Serial testing of Malaysian health care workers with QuantiFERON®-TB Gold In-Tube. Int J Tuberc Lung Dis. 2012;16(2):163–8.PubMedCrossRef
24.
Ringshausen FC, Schablon A, Nienhaus A. Interferon-gamma release assays for the tuberculosis serial testing of health care workers: a systematic review. J Occup Med Toxicol. 2012;7(1):6.PubMedCrossRef
25.
Zwerling A, van den Hof S, Scholten J, et al. Interferon-gamma release assays for tuberculosis screening of healthcare workers: a systematic review. Thorax. 2012;67(1):62–70.PubMedCrossRef
26.
Pai M. Serial testing with TB interferon-γ release assays: toward a nuanced understanding. Chest. 2012;142(6):1366–7.PubMedCrossRef
27.
Daley CL, Reves RR, Beard MA, et al. A summary of meeting proceedings on addressing variability around the cut point in serial interferon-γ release assay testing. Infect Control Hosp Epidemiol. 2013;34(6):625–30.PubMedCrossRef
28.
Loddenkemper R, Diel R, Nienhaus A. To repeat or not to repeat-that is the question: serial testing of health-care workers for TB infection. Chest. 2012;142(1):10–1.PubMedCrossRef
29.
Trajman A, Steffen RE, Menzies D. Interferon-gamma release assays versus tuberculin skin testing for the diagnosis of latent tuberculosis infection: an overview of the evidence. Pulm Med. 2013;2013:601737.PubMed
30.
Pai M. Systematic review: T-cell–based assays for the diagnosis of latent tuberculosis infection: an update. Ann Intern Med. 2008;149(3):177.PubMedCrossRef
31.
Garrett D, Katz D, Chideya S. Prospective comparison of the tuberculin skin test and interferon gamma release assays in diagnosing infection with mycobacterium tuberculosis and in predicting progression to tuberculosis. [Internet]. 2013 [cited 2013 Jul 14]. Available from: http://​clinicaltrials.​gov/​ct2/​show/​NCT01622140 NLM
32.
•• Mancuso JD, Mazurek GH, Tribble D, et al. Discordance among commercially available diagnostics for latent tuberculosis infection. Am J Respir Crit Care Med. 2012;185(4):427–34. US military recruits received simultaneous testing with QuantiFERON-TB Gold In-Tube, T-SPOT.TB, and TST. No differences were seen in specificities among the three tests and 77 % of those with a positive test were positive for one test only. The lower the risk of TB, the lower the quantitative results on IGRA testing and the more likely just one test would be positive.PubMedCrossRef
33.
Gran G, Aßmus J, Dyrhol-Riise AM. Screening for latent tuberculosis in Norwegian health care workers: high frequency of discordant tuberculin skin test positive and interferon-gamma release assay negative results. BMC Public Health. 2013;13(1):353.PubMedCrossRef
34.
Weinfurter P, Blumberg HM, Goldbaum G, et al. Predictors of discordant tuberculin skin test and QuantiFERON®-TB Gold In-Tube results in various high-risk groups. Int J Tuberc Lung Dis. 2011;15(8):1056–61.PubMedCrossRef
35.
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;60:1650–3.
36.
• Martinson NA, Barnes GL, Moulton LH, et al. New regimens to prevent tuberculosis in adults with HIV infection. N Engl J Med. 2011;365(1):11–20. Conducted among HIV-infected persons in South Africa, this study revealed no significant difference in the protective effect of four regimens: three months of once-weekly isoniazid + rifapentine (directly observed), three months of twice-weekly isoniazid + rifampin (directly observed), six months of daily isoniazid (self-administered), and up to six years of daily isoniazid (self-administered). Continuous isoniazid was poorly tolerated.PubMedCrossRef
37.
•• Sterling TR, Villarino ME, Borisov AS, et al. Three months of rifapentine and isoniazid for latent tuberculosis infection. N Engl J Med. 2011;365(23):2155–66. This study conducted in low and medium tuberculosis-incidence countries revealed that three months of once-weekly isoniazid + rifapentine (directly observed) was at least as effective as nine months of daily isoniazid (self-administered). The tolerability of both regimens was similar.PubMedCrossRef
38.
Villarino ME, Scott N, Weis S, et al. Tolerability among children of three months of once-weekly rifapentine + INH (3HP) vs. 9 months of daily INH (9H) for treatment of latent tuberculosis infection. IMPAACT and the TB Trials Consortium. October 20, 2012, San Diego, CA, Presentation # 1323. Presented at IDWeek 2012, a Joint Meeting of IDSA, SHEA, HIVMA, and PIDS.
39.
Sterling TR, Benson CA, Shang N, et al. Tolerability among HIV-infected persons of three months of once-weekly rifapentine + INH (3HP) vs. 9 months of daily INH (9H) for treatment of latent tuberculosis infection. AIDS Clinical Trials Group, and the Tuberculosis Trials Consortium. Presented at the International AIDS Society Conference. July 2012. Washington, DC.
40.
Presented at the International Union Against TB and Lung Disease International Conference. November 2012.
41.
Quigley MA, Mwinga A, Hosp M, et al. Long-term effect of preventive therapy for tuberculosis in a cohort of HIV-infected Zambian adults. AIDS. 2001;15(2):215–22.PubMedCrossRef
42.
Johnson JL, Okwera A, Hom DL, et al. Duration of efficacy of treatment of latent tuberculosis infection in HIV-infected adults. AIDS. 2001;15(16):2137–47.PubMedCrossRef
43.
• Samandari T, Agizew TB, Nyirenda S, et al. 6-month versus 36-month isoniazid preventive treatment for tuberculosis in adults with HIV infection in Botswana: a randomised, double-blind, placebo-controlled trial. Lancet. 2011;377(9777):1588–98. This was a study of the effect of prolonged isoniazid treatment among HIV-infected persons in Botswana (an area of high risk for M. tuberculosis re-infection). Among TST-positive persons the risk of mortality was a factor of three lower for those who received 36INH compared with 6INH.PubMedCrossRef
44.
World Health Organization. Guidelines for intensified tuberculosis case-finding and isoniazid preventive therapy for people living with HIV in resource-constrained settings. Geneva: WHO. 2011.
45.
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(20):398–400.
Metadata
Title
Diagnosis and treatment of latent tuberculosis infection: an update
Authors
Anna K. Person
April C. Pettit
Timothy R. Sterling
Publication date
01-12-2013
Publisher
Springer US
Published in
Current Pulmonology Reports / Issue 4/2013
Electronic ISSN: 2199-2428
DOI
https://doi.org/10.1007/s13665-013-0064-y

Other articles of this Issue 4/2013

Current Pulmonology Reports 4/2013 Go to the issue

Interstitial Lung Disease (G Tino, Section editor)

GERD and idiopathic pulmonary fibrosis: cause or effect

Interstitial Lung Disease (G Tino, Section editor)

Idiopathic pulmonary fibrosis co-morbidity: thromboembolic disease and coronary artery disease

Allergy and Immunology (SP Peters and JJ Oppenheimer, Section editors)

The small airways in asthma

Respiratory Infections (CL Daley, Section Editor)

Management of drug-resistant tuberculosis

Interstitial Lung Disease (G Tino, Section editor)

Combined pulmonary fibrosis and emphysema

Interstitial Lung Disease (G Tino, Section editor)

Lung cancer in idiopathic pulmonary fibrosis
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits