Diagnosis of Tuberculosis in Adults and Children

Publication Date: December 8, 2016
Last Updated: December 16, 2022

Testing for TB Disease

The panel recommends that acid-fast bacilli (AFB) smear microscopy be performed, rather than no AFB smear microscopy, in all patients suspected of having pulmonary TB. (S, M)
  • Remarks: False-negative results are sufficiently common that a negative AFB smear result does not exclude pulmonary TB. Similarly, false-positive results are sufficiently common that a positive AFB smear result does not confirm pulmonary TB. Testing of 3 specimens is considered the normative practice in the United States and is strongly recommended by the Centers for Disease Control and Prevention and the National Tuberculosis Controllers Association in order to improve sensitivity given the pervasive issue of poor sample quality. Providers should request a sputum volume of ≥3 mL, but the optimal volume is 5–10 mL. Concentrated respiratory specimens and fluorescence microscopy are preferred.
620
The panel suggests that both liquid and solid mycobacterial cultures be performed, rather than either culture method alone, for every specimen obtained from an individual with suspected TB disease. (C, L)
  • Remarks: The conditional qualifier applies to performance of both liquid and solid culture methods on all specimens. At least liquid culture should be done on all specimens since culture is the gold standard microbiologic test for the diagnosis of TB disease. The isolate recovered should be identified according to the Clinical and Laboratory Standards Institute guidelines and the American Society for Microbiology Manual of Clinical Microbiology.
620
The panel suggests performing a diagnostic nucleic acid amplification test (NAAT), rather than not performing a NAAT, on the initial respiratory specimen from patients suspected of having pulmonary TB. (C, L)
  • Remarks: In AFB smear-positive patients, a negative NAAT makes TB disease unlikely. In AFB smear-negative patients with an intermediate to high level of suspicion for disease, a positive NAAT can be used as presumptive evidence of TB disease, but a negative NAAT cannot be used to exclude pulmonary TB. Appropriate NAAT include the Hologic Amplified Mycobacteria Tuberculosis Direct (MTD) test (San Diego, California) and the Cepheid Xpert Mtb/RIF test (Sunnyvale, California).
620
The panel recommends performing rapid molecular drug susceptibility testing for rifampin with or without isoniazid using the respiratory specimens of persons who are either AFB smear positive or Hologic Amplified MTD positive and who meet one of the following criteria:
  • have been treated for tuberculosis in the past
  • were born in or have lived for ≥1 year in a foreign country with at least a moderate tuberculosis incidence (≥20 per 100,000) or a high primary multidrug-resistant tuberculosis prevalence (≥2%)
  • are contacts of patients with multidrug-resistant tuberculosis, or
  • are HIV infected.
(S, M)
  • Remarks: This recommendation specifically addresses patients who are Hologic Amplified MTD positive because the Hologic Amplified MTD NAAT only detects TB and not drug resistance. It is not applicable to patients who are positive for types of NAAT that detect drug resistance, including many line probe assays and Cepheid Xpert Mtb/RIF.
620
The panel suggests mycobacterial culture of respiratory specimens for all children suspected of having pulmonary TB. (C, M)
  • Remarks: In a low incidence setting like the United States, it is unlikely that a child identified during a recent contact investigation of a close adult/adolescent contact with contagious TB was, in fact, infected by a different individual with a strain with a different susceptibility pattern. Therefore, under some circumstances, microbiological confirmation may not be necessary for children with uncomplicated pulmonary TB identified through a recent contact investigation if the source case has drug-susceptible TB.
620
The panel suggests sputum induction rather than flexible bronchoscopic sampling as the initial respiratory sampling method for adults with suspected pulmonary TB who are either unable to expectorate sputum or whose expectorated sputum is AFB smear microscopy negative. (C, L)
620
The panel suggests flexible bronchoscopic sampling, rather than no bronchoscopic sampling, in adults with suspected pulmonary TB from whom a respiratory sample cannot be obtained via induced sputum. (C, VL)
  • Remarks: In the committee members’ clinical practices, bronchoalveolar lavage (BAL) plus brushings alone are performed for most patients. However, for patients in whom a rapid diagnosis is essential, transbronchial biopsy is also performed.
620
The panel suggests that postbronchoscopy sputum specimens be collected from all adults with suspected pulmonary TB who undergo bronchoscopy. (C, L)
  • Remarks: Postbronchoscopy sputum specimens are used to perform AFB smear microscopy and mycobacterial cultures.
620
The panel suggests flexible bronchoscopic sampling, rather than no bronchoscopic sampling, in adults with suspected miliary TB and no alternative lesions that are accessible for sampling whose induced sputum is AFB smear microscopy negative or from whom a respiratory sample cannot be obtained via induced sputum. (C, VL)
  • Remarks: Bronchoscopic sampling in patients with suspected miliary TB should include bronchial brushings and/or transbronchial biopsy, as the yield from washings is substantially less and the yield from BAL unknown. For patients in whom it is important to provide a rapid presumptive diagnosis of tuberculosis (ie, those who are too sick to wait for culture results), transbronchial biopsies are both necessary and appropriate.
620
The panel suggests that cell counts and chemistries be performed on amenable fluid specimens collected from sites of suspected extrapulmonary TB. (C, VL)
  • Remarks: Specimens that are amenable to cell counts and chemistries include pleural, cerebrospinal, ascitic, and joint fluids.
620
The panel suggests that adenosine deaminase levels be measured, rather than not measured, on fluid collected from patients with suspected pleural TB, TB meningitis, peritoneal TB, or pericardial TB. (C, L)
620
The panel suggests that free IFN-γ levels be measured, rather than not measured, on fluid collected from patients with suspected pleural TB or peritoneal TB. (C, L)
620
The panel suggests that AFB smear microscopy be performed, rather than not performed, on specimens collected from sites of suspected extrapulmonary TB. (C, VL)
  • Remarks: A positive result can be used as evidence of extrapulmonary TB and guide decision making because false-positive results are unlikely. However, a negative result may not be used to exclude TB because false-negative results are exceedingly common.
620
The panel recommends that mycobacterial cultures be performed, rather than not performed, on specimens collected from sites of suspected extrapulmonary TB. (S, L)
  • Remarks: A positive result can be used as evidence of extrapulmonary TB and guide decision making because false-positive results are unlikely. However, a negative result may not be used to exclude TB because false-negative results are exceedingly common.
620
The panel suggests that NAAT be performed, rather than not performed, on specimens collected from sites of suspected extrapulmonary TB. (C, VL)
  • Remarks: A positive NAAT result can be used as evidence of extrapulmonary TB and guide decision making because false-positive results are unlikely. However, a negative NAAT result may not be used to exclude TB because false-negative results are exceedingly common. At present, NAAT testing on specimens other than sputum is an off-label use of the test.
620
The panel suggests that histological examination be performed, rather than not performed, on specimens collected from sites of suspected extrapulmonary TB. (C, VL)
  • Remarks: Both positive and negative results should be interpreted in the context of the clinical scenario because neither false-positive nor false-negative results are rare.
620
The panel recommends a culture isolate from each mycobacterial culture-positive patient be submitted to a regional genotyping laboratory for genotyping. (S, VL)
620

Recommendation Grading

Overview

Title

Diagnosis of Tuberculosis in Adults and Children

Authoring Organizations

American Thoracic Society

Centers for Disease Control and Prevention

Infectious Diseases Society of America

Publication Month/Year

December 8, 2016

Last Updated Month/Year

October 4, 2024

Supplemental Implementation Tools

Document Type

Guideline

External Publication Status

Published

Country of Publication

US

Target Patient Population

Individuals infected with Mycobacterium tuberculosis (Mtb)

Target Provider Population

Clinicians in high-resource countries with a low incidence of tuberculosis (TB) disease and latent tuberculosis infection (LTBI)

PICO Questions

  1. Should an IGRA or a TST be performed in individuals 5 years or older who are likely to be infected with Mtb, who have a low or intermediate risk of disease progression, and in whom it has been decided that testing for LTBI is warranted?

  2. Should an IGRA or a TST be performed in individuals 5 years or older who are likely to be infected with Mtb, who have a high risk of progression to disease, and in whom it has been decided that testing for LTBI is warranted?

  3. Should an IGRA or a TST be performed in individuals 5 years or older who are unlikely to be infected with Mtb, but in whom it has been decided that testing for LTBI is warranted?

  4. Should an IGRA or a TST be performed in healthy children <5 years of age in whom it has been decided that testing for LTBI is warranted?

  5. Should AFB smear microscopy be performed in persons suspected of having pulmonary TB?

  6. Should both liquid and solid mycobacterial cultures be performed in persons suspected of having pulmonary TB?

  7. Should NAAT be performed on the initial respiratory specimen in persons suspected of having pulmonary TB?

  8. Should rapid molecular drug susceptibility testing for isoniazid and rifampin be performed as part of the initial diagnostic evaluation for all patients suspected of having pulmonary TB or only in selected subgroups?

  9. Should respiratory specimens be collected from children with suspected pulmonary TB disease?

  10. Should sputum induction or flexible bronchoscopic sampling be the initial respiratory sampling method for adults with suspected pulmonary TB who are either unable to expectorate sputum or whose expectorated sputum is AFB smear microscopy negative?

  11. Should flexible bronchoscopic sampling be performed in adults with suspected pulmonary TB from whom a respiratory sample cannot be obtained via induced sputum?

  12. Should post-bronchoscopy sputum specimens be collected from adults with suspected pulmonary TB?

  13. Should flexible bronchoscopic sampling be performed in adults with suspected miliary TB and no alternative lesions that are accessible for sampling whose induced sputum is AFB smear microscopy negative or from whom a respiratory sample cannot be obtained via induced sputum?

  14. Should cell counts and chemistries be performed on amenable (ie, liquid) specimens collected from sites of suspected extrapulmonary TB?

  15. Should adenosine deaminase (ADA) and free IFN-γ levels be measured on specimens collected from sites of suspected extrapulmonary TB?

  16. Should AFB smear microscopy be performed on specimens collected from sites of suspected extrapulmonary TB?

  17. Should mycobacterial cultures be performed on specimens collected from sites of suspected extrapulmonary TB?

  18. Should NAAT be performed on specimens collected from sites of suspected extrapulmonary TB?

  19. Should histological examination be performed on specimens collected from sites of suspected extrapulmonary TB?

  20. Should genotyping be performed on a culture isolate from culture-positive patients with TB?

Inclusion Criteria

Male, Female, Adolescent, Adult, Child, Infant, Older adult

Health Care Settings

Ambulatory, Hospital, Laboratory services, Outpatient

Intended Users

Nurse, nurse practitioner, physician, physician assistant

Scope

Diagnosis, Assessment and screening

Diseases/Conditions (MeSH)

D014376 - Tuberculosis, D014397 - Tuberculosis, Pulmonary, D055985 - Latent Tuberculosis, D059425 - Interferon-gamma Release Tests

Keywords

tuberculosis, interferon-gamma release assays (IGRAs), TB, TB, tb, IGRA, latent tuberculosis infection, pulmonary tuberculosis, extrapulmonary tuberculosis, TST, Tuberculosis

Source Citation

David M. Lewinsohn, Michael K. Leonard, Philip A. LoBue, David L. Cohn, Charles L. Daley, Ed Desmond, Joseph Keane, Deborah A. Lewinsohn, Ann M. Loeffler, Gerald H. Mazurek, Richard J. O’Brien, Madhukar Pai, Luca Richeldi, Max Salfinger, Thomas M. Shinnick, Timothy R. Sterling, David M. Warshauer, Gail L. Woods, Official American Thoracic Society/Infectious Diseases Society of America/Centers for Disease Control and Prevention Clinical Practice Guidelines: Diagnosis of Tuberculosis in Adults and Children, Clinical Infectious Diseases, Volume 64, Issue 2, 15 January 2017, Pages e1–e33, https://doi.org/10.1093/cid/ciw694

Supplemental Methodology Resources

Data Supplement