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Tuberculosis

Screening for Latent Tuberculosis Infection in AdultsUpdated Evidence Report and Systematic Review for the US Preventive Services Task Force

To identify the key insights or developments described in this article

1 Credit CME

JAMA

Published Online: May 2, 2023

US Preventive Services Task Force

Article Information and Disclosures

Daniel E. Jonas, MD, MPH^1,2;

Sean R. Riley, MA, MSc^1,2;

Lindsey C. Lee, PharmD²;

Cory P. Coffey, PharmD, BCACP, BCPP²;

Shu-Hua Wang, MD, PharmD, MPH&TM^2,3;

Gary N. Asher, MD, MPH^1,4;

Anne M. Berry, MD, MPH^4,5;

Niketa Williams, MD, MS, MPH^4,6;

Casey Balio, PhD^1,7;

Christiane E. Voisin, MSLS^1,2;

Leila C. Kahwati, MD, MPH^1,8

Author Affiliations

¹RTI International–University of North Carolina at Chapel Hill Evidence-based Practice Center, Research Triangle Park
²Department of Internal Medicine, The Ohio State University College of Medicine, Columbus
³Global One Health Initiative, The Ohio State University, Columbus
⁴Department of Family Medicine, University of North Carolina at Chapel Hill
⁵Department of Family Medicine and Community Health, Duke University, Durham, North Carolina
⁶North Carolina Department of Health and Human Services, Division of Public Health, Raleigh
⁷Center for Rural Health Research, East Tennessee State University, Johnson City
⁸RTI International, Research Triangle Park, North Carolina

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Abstract

Importance Latent tuberculosis infection (LTBI) can progress to active tuberculosis disease, causing morbidity and mortality.

Objective To review the evidence on benefits and harms of screening for and treatment of LTBI in adults to inform the US Preventive Services Task Force (USPSTF).

Data Sources PubMed/MEDLINE, Cochrane Library, and trial registries through December 3, 2021; references; experts; literature surveillance through January 20, 2023.

Study Selection English-language studies of LTBI screening, LTBI treatment, or accuracy of the tuberculin skin test (TST) or interferon-gamma release assays (IGRAs). Studies of LTBI screening and treatment for public health surveillance or disease management were excluded.

Data Extraction and Synthesis Dual review of abstracts, full-text articles, and study quality; qualitative synthesis of findings; meta-analyses conducted when a sufficient number of similar studies were available.

Main Outcomes and Measures Screening test accuracy; development of active tuberculosis disease, transmission, quality of life, mortality, and harms.

Results A total of 113 publications were included (112 studies; N = 69 009). No studies directly evaluated the benefits and harms of screening. Pooled estimates for sensitivity of the TST were 0.80 (95% CI, 0.74-0.87) at the 5-mm induration threshold, 0.81 (95% CI, 0.76-0.87) at the 10-mm threshold, and 0.60 (95% CI, 0.46-0.74) at the 15-mm threshold. Pooled estimates for sensitivity of IGRA tests ranged from 0.81 (95% CI, 0.79-0.84) to 0.90 (95% CI, 0.87-0.92). Pooled estimates for specificity of screening tests ranged from 0.95 to 0.99. For treatment of LTBI, a large (n = 27 830), good-quality randomized clinical trial found a relative risk (RR) for progression to active tuberculosis at 5 years of 0.35 (95% CI, 0.24-0.52) for 24 weeks of isoniazid compared with placebo (number needed to treat, 112) and an increase in hepatotoxicity (RR, 4.59 [95% CI, 2.03-10.39]; number needed to harm, 279). A previously published meta-analysis reported that multiple regimens were efficacious compared with placebo or no treatment. Meta-analysis found greater risk for hepatotoxicity with isoniazid than with rifampin (pooled RR, 4.22 [95% CI, 2.21-8.06]; n = 7339).

Conclusions and Relevance No studies directly evaluated the benefits and harms of screening for LTBI compared with no screening. TST and IGRAs were moderately sensitive and highly specific. Treatment of LTBI with recommended regimens reduced the risk of progression to active tuberculosis. Isoniazid was associated with higher rates of hepatotoxicity than placebo or rifampin.

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Article Information

Accepted for Publication: March 1, 2023.

Corresponding Author: Daniel E. Jonas, MD, MPH, Department of Internal Medicine, The Ohio State University College of Medicine, 2050 Kenny Rd, Columbus, OH 43215 (Daniel.jonas@osumc.edu).

Author Contributions: Dr Jonas had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Jonas, Wang, Berry, Williams, Voisin, Kahwati.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Jonas, Riley, Lee, Coffey, Wang, Asher, Berry, Williams, Voisin, Kahwati.

Critical revision of the manuscript for important intellectual content: Jonas, Riley, Balio, Kahwati.

Statistical analysis: Jonas, Riley, Lee, Coffey, Kahwati.

Obtained funding: Jonas, Kahwati.

Administrative, technical, or material support: Jonas, Riley, Asher, Voisin.

Supervision: Jonas, Kahwati.

Conflict of Interest Disclosures: None reported.

Funding/Support: This research was funded under contract 75Q80120D00007, Task Order 75Q80120F32001, from the Agency for Healthcare Research and Quality (AHRQ), US Department of Health and Human Services, under a contract to support the US Preventive Services Task Force (USPSTF).

Role of the Funder/Sponsor: Investigators worked with USPSTF members and AHRQ staff to develop the scope, analytic framework, and KQs for this review. AHRQ had no role in study selection, quality assessment, or synthesis. AHRQ staff provided project oversight, reviewed the evidence review to ensure that the analysis met methodological standards, and distributed the draft for public comment and review by federal partners. Otherwise, AHRQ had no role in the conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript findings. The opinions expressed in this document are those of the authors and do not reflect the official position of AHRQ or the US Department of Health and Human Services.

Additional Contributions: We gratefully acknowledge the following individuals for their contributions to this project, including AHRQ staff (Sheena Harris, MD, MPH; Tina Fan, MD, MPH; and Tracy Wolff, MD, MPH) and RTI International–University of North Carolina Evidence-based Practice Center staff (Roberta C. Wines, MPH; Sharon Barrell, MA; Jessica Burch; and Teyonna Downing), who received compensation for their role in this project. The USPSTF members, expert consultants, peer reviewers, and federal partner reviewers did not receive financial compensation for their contributions.

Additional Information: A draft version of the full evidence report underwent external peer review from 4 content experts (Ned Calonge, MD, MPH, Colorado Trust; John Bernardo, MD, Boston University School of Medicine; Pennan Barry, MD, MPH, University of California, San Francisco, California Department of Public Health; Jon Warkentin, MD, Vanderbilt Tuberculosis Center) and federal partner reviewers from the US Centers for Disease Control and Prevention. Comments from reviewers were presented to the USPSTF during its deliberation of the evidence and were considered in preparing the final evidence review.

Editorial Disclaimer: This evidence report is presented as a document in support of the accompanying USPSTF Recommendation Statement. It did not undergo additional peer review after submission to JAMA.

AMA CME Accreditation Information

Credit Designation Statement: The American Medical Association designates this Journal-based CME activity activity for a maximum of 1.00  AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to:

1.00 Medical Knowledge MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program;;
1.00 Self-Assessment points in the American Board of Otolaryngology – Head and Neck Surgery’s (ABOHNS) Continuing Certification program;
1.00 MOC points in the American Board of Pediatrics’ (ABP) Maintenance of Certification (MOC) program;
1.00 Lifelong Learning points in the American Board of Pathology’s (ABPath) Continuing Certification program; and
1.00 credit toward the CME [and Self-Assessment requirements] of the American Board of Surgery’s Continuous Certification program

It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting MOC credit.