Mycobacterium tuberculosis - Tuberculosis

  • Diagnosis
  • Screening
  • Monitoring
  • Background
  • Pediatrics
  • Lab Tests
  • References
  • Related Topics

Laboratory Testing

Differential Diagnosis

  • Screening recommendations
    • Screen for latent TB in populations at increased risk (AAFP, 2016; CDC, 2013; USPSTF, 2016)
    • Screen for latent TB in populations at increased risk and when treatment is feasible (CDC, ATS, IDSA, 2005)
  • Two types of screening tests for latent TB available in the U.S. – CDC generally recommends screening with either test but not both (USPSTF, 2016)
    • Tuberculin skin test (TST)
      • Targeted tuberculin testing for latent TB infection for foreign-born persons entering the U.S. within the past 5 years
      • False positives in patients previously vaccinated with BCG or exposed to NTM
      • False negatives
        • Immunocompromised state
        • Severe illness
      • Requires patients return 48-72 hrs post administration of test for interpretation of results
    • Interferon-gamma release assay (eg, QuantiFERON Gold)
      • Should not be used in patients with active disease symptoms
      • May be preferable for persons who have received a bacillus Calmette-Guérin (BCG) vaccination or persons who may be unlikely to return for TST interpretation
      • May be used instead of PPD
      • Should not be used in children <5 years
  • Sputum culture
    • Follow up treatment with repeat cultures of sputum
    • 3-month culture may be predictive of relapse, if positive

Mycobacterium tuberculosis (TB), as well as other nontuberculosis mycobacteria (NTM), can be infectious agents in humans.

Clinical Background

Epidemiology

  • High-incidence countries where children have contact with TB-positive adults – 30-40% risk for TB in child

Clinical Presentation

  • Much higher rate of progression to active disease
  • Cough typical in infants; fever common in adolescents
  • 25-35% have extrapulmonary presentation
    • 3 typical forms
      • Cervical adenitis
      • Miliary disease – most common in <2-3 years or immunocompromised
      • CNS disease – meningitis typically develops 3-6 months after primary infection; 50% are <2 years
    • Risk highest in infants, adolescents, immunocompromised children
  • Reactivation disease most common in adolescents
  • Congenital
    • Infants born to mothers who have disseminated disease
    • Failure to thrive in first 3 months (most common symptom)
    • Other – hepatomegaly, peripheral lymphadenopathy, respiratory distress

Diagnosis

Indications for Testing

  • Clinical suspicion for disease

Laboratory Testing

  • Concentrated acid-fast bacilli smear
    • Not as sensitive as culture;  positive in 10-15%
    • Difficult to obtain sputum in children; may need to use early morning gastric aspiration
  • Culture
    • Yield positive in 20-30%
    • Best specimen is early morning gastric aspirate
    • Gastric lavage has better yield than pulmonary lavage – 3 samples best on sequential mornings
      • Requires hospitalization and fasting
    • Single hypertonic saline-induced sputum specimen may produce some bacteriologic yield as gastric aspirate
    • Highest yield in cavitary disease
  • Nuclear acid amplification test (NAAT)  – variable sensitivities may be good in children for rapid test if positive
  • QuantiFERON Gold
    • Unable to distinguish between active and latent disease
    • Better than tuberculin skin test
    • Cannot be used in children <5 years (highest yield of indeterminate results)
  • Tuberculin skin test
    • Test of choice in children <5 years
    • Rarely positive in congenital disease

Imaging Studies

  • Chest x-ray
    • Enlarged perihilar and peritracheal nodes most common in children <5 years
    • Effusions unusual in children 3-5 years
    • Adult disease at age 8-10 years with apical segment involvement

Differential Diagnosis

Monitoring

  • Refer to Monitoring section
Tests generally appear in the order most useful for common clinical situations. Click on number for test-specific information in the ARUP Laboratory Test Directory.

Acid-Fast Bacillus (AFB) Culture and AFB Stain 0060152
Method: Stain/Culture/Identification/Susceptibility

Recommended Use 

Gold standard test for diagnosing the presence of mycobacteria organisms

Specimen from any suspected site, including sputum, CSF, tissue, urine, and other body fluid or gastric aspirate

Susceptibility will be performed on organisms isolated from a sterile source and isolates of Mycobacterium chelonae, M. abscesses, M. fortuitum complex, M. immunogenum, M. mucogenicum; susceptibility testing will be performed by request only on M. kansaii and M. marinum; susceptibility testing of M. gordonae is inappropriate

Limitations 

Mycobacteria are slow growing organisms; culture requires several weeks

Follow-up 

DNA probes are available for M. tuberculosis complex (MTBC) and M. avium-intracellulare complex as indicated

Other species require DNA sequencing or different molecular techniques for identification

For drug susceptibilities, refer to Antimicrobial Susceptibility - AFB Mycobacteria test

Mycobacterium tuberculosis Complex Detection and Rifampin Resistance by PCR 2010775
Method: Qualitative Polymerase Chain Reaction

Recommended Use 

Panel includes PCR testing to detect M. tuberculosis isolates and determine possible resistance to rifampin treatment

Test may be ordered for client-processed specimens; refer to specimen requirements

QuantiFERON-TB Gold In-Tube 0051729
Method: Cell Culture/Semi-Quantitative Enzyme-Linked Immunosorbent Assay

Recommended Use 

Aid in the detection of latent disease among persons at increased risk for tuberculosis

Positive predictive value is less in low-risk populations

Test may be used in persons who have received BCG vaccine

Limitations 

Do not use alone to diagnose or exclude TB or to assess possible latent disease; result interpretation requires a combination of epidemiological, historical, medical, and diagnostic findings

Negative result does not completely rule out TB infection; positive result does not differentiate active from latent TB

Acid-Fast Bacillus (AFB) Identification 0060999
Method: Identification. Methods may include biochemical, mass spectrometry, nucleic acid probe, polymerase chain reaction, or sequencing.

Recommended Use 

Identify mycobacterial isolates, including requests for speciation within the M. tuberculosis complex.

Acid-Fast Bacillus (AFB) Culture and AFB Stain with Reflex to Mycobacterium Tuberculosis Complex Detection and Rifampin Resistance by PCR 0060738
Method: Stain/Culture

Recommended Use 

Comprehensive panel includes acid-fast bacillus culture and stain

Positive smears reflex to PCR amplification of MTBC species and rifampin resistance

Limitations 

Available for respiratory specimens only

Low-level false-positive results can occur in specimens with high concentration of mycobacteria other than M. tuberculosis

Negative result does not exclude M. tuberculosis

Blood Culture, Acid-Fast Bacillus (AFB) 0060060
Method: Continuous Monitoring Blood Culture/Identification

Recommended Use 

Order for AFB culture of blood or bone marrow specimen

Acid-Fast Bacillus (AFB) Identification with Reflex to Susceptibility 0060997
Method: Identification/Susceptibility. Methods may include biochemical, mass spectrometry, nucleic acid probe, polymerase chain reaction, or sequencing.

Recommended Use 

Order for M. tuberculosis complex speciation and susceptibility testing.

Limitations 

Susceptibility testing may not be performed on all isolates (varies by species)

Antimicrobial Susceptibility, AFB/Mycobacteria 0060217
Method: Macrobroth Dilution/Microbroth Dilution

Recommended Use 

Order for susceptibility of clinically significant isolates of M. tuberculosis complex, M. kansasii, M. avium-intracellulare complex, M. fortuitum complex, M. abscessus complex, M. chelonae, M. immunogenum, and any isolate from a significant source

Antimicrobial Susceptibility, AFB/Mycobacterium tuberculosis Primary Panel 0060347
Method: Broth Macrodilution

Recommended Use 

Order when phenotypic drug susceptibility testing is required for M. tuberculosis treatment

For genotypic (DNA sequencing) resistance testing, refer to TB drug resistance by sequencing test

Mycobacterium tuberculosis Drug Resistance by Sequencing 2011713
Method: Polymerase Chain Reaction/Sequencing

Recommended Use 

Order for rapid identification of mutations associated with drug resistance for M. tuberculosis treatment

For phenotypic drug susceptibility testing, refer to the antimicrobial susceptibility, AFB/TB primary panel

Guidelines

Clinical Preventive Service Recommendation: Tuberculosis Infection, Asymptomatic Adults. American Academy of Family Physicians. [Accessed: Dec 2016]

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. Am J Respir Crit Care Med. 2000; 161(4 Pt 1): 1376-95. PubMed

Mazurek GH, Jereb J, Vernon A, LoBue P, Goldberg S, Castro K, IGRA Expert Committee, Centers for Disease Control and Prevention (CDC). Updated guidelines for using Interferon Gamma Release Assays to detect Mycobacterium tuberculosis infection - United States, 2010. MMWR Recomm Rep. 2010; 59(RR-5): 1-25. PubMed

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. PubMed

US Preventive Services Task Force, Bibbins-Domingo K, Grossman DC, Curry SJ, Bauman L, Davidson KW, Epling JW, Garcia FA, Herzstein J, Kemper AR, Krist AH, Kurth AE, Landefeld S, Mangione CM, Phillips WR, Phipps MG, Pignone MP. Screening for Latent Tuberculosis Infection in Adults: US Preventive Services Task Force Recommendation Statement JAMA. 2016; 316(9): 962-9. PubMed

General References

Balasingham SV, Davidsen T, Szpinda I, Frye SA, Tønjum T. Molecular diagnostics in tuberculosis: basis and implications for therapy. Mol Diagn Ther. 2009; 13(3): 137-51. PubMed

Cruz AT, Starke JR. Pediatric tuberculosis. Pediatr Rev. 2010; 31(1): 13-25; quiz 25-6. PubMed

Deangelis TM, Miller A. Diagnosis of multiple sclerosis. Handb Clin Neurol. 2014; 122: 317-42. PubMed

Diel R, Goletti D, Ferrara G, Bothamley G, Cirillo D, Kampmann B, Lange C, Losi M, Markova R, Migliori GB, Nienhaus A, Ruhwald M, Wagner D, Zellweger JP, Huitric E, Sandgren A, Manissero D. Interferon-γ release assays for the diagnosis of latent Mycobacterium tuberculosis infection: a systematic review and meta-analysis. Eur Respir J. 2011; 37(1): 88-99. PubMed

El-Sadr WM, Tsiouris SJ. HIV-associated tuberculosis: diagnostic and treatment challenges. Semin Respir Crit Care Med. 2008; 29(5): 525-31. PubMed

Glassroth J. Pulmonary disease due to nontuberculous mycobacteria. Chest. 2008; 133(1): 243-51. PubMed

Kahwati LC, Feltner C, Halpern M, Woodell CL, Boland E, Amick HR, Weber RP, Jonas DE. Primary Care Screening and Treatment for Latent Tuberculosis Infection in Adults: Evidence Report and Systematic Review for the US Preventive Services Task Force JAMA. 2016; 316(9): 970-83. PubMed

Karussis D. The diagnosis of multiple sclerosis and the various related demyelinating syndromes: a critical review. J Autoimmun. 2014; 48-49: 134-42. PubMed

Lawn SD. Diagnosis of pulmonary tuberculosis. Curr Opin Pulm Med. 2013; 19(3): 280-8. PubMed

Miranda C, Tomford W, Gordon SM. Interferon-gamma-release assays: Better than tuberculin skin testing? Cleve Clin J Med. 2010; 77(9): 606-11. PubMed

Schlossberg D. Acute tuberculosis. Infect Dis Clin North Am. 2010; 24(1): 139-46. PubMed

Shingadia D. The diagnosis of tuberculosis. Pediatr Infect Dis J. 2012; 31(3): 302-5. PubMed

Sia IG, Wieland ML. Current concepts in the management of tuberculosis. Mayo Clin Proc. 2011; 86(4): 348-61. PubMed

Zar HJ, Connell TG, Nicol M. Diagnosis of pulmonary tuberculosis in children: new advances. Expert Rev Anti Infect Ther. 2010; 8(3): 277-88. PubMed

References from the ARUP Institute for Clinical and Experimental Pathology®

Aldous WK, Pounder JI, Cloud JL, Woods GL. Comparison of six methods of extracting Mycobacterium tuberculosis DNA from processed sputum for testing by quantitative real-time PCR. J Clin Microbiol. 2005; 43(5): 2471-3. PubMed

Anderson BL, Welch RJ, Litwin CM. Assessment of three commercially available serologic assays for detection of antibodies to Mycobacterium tuberculosis and identification of active tuberculosis. Clin Vaccine Immunol. 2008; 15(11): 1644-9. PubMed

Cloud JL, Carroll KC, Cohen S, Anderson CM, Woods GL. Interpretive criteria for use of AccuProbe for identification of Mycobacterium avium complex directly from 7H9 broth cultures. J Clin Microbiol. 2005; 43(7): 3474-8. PubMed

Cloud JL, Hoggan K, Belousov E, Cohen S, Brown-Elliott BA, Mann L, Wilson R, Aldous W, Wallace RJ, Woods GL. Use of the MGB Eclipse system and SmartCycler PCR for differentiation of Mycobacterium chelonae and M. abscessus. J Clin Microbiol. 2005; 43(8): 4205-7. PubMed

Cloud JL, Meyer JJ, Pounder JI, Jost KC, Sweeney A, Carroll KC, Woods GL. Mycobacterium arupense sp. nov., a non-chromogenic bacterium isolated from clinical specimens. Int J Syst Evol Microbiol. 2006; 56(Pt 6): 1413-8. PubMed

Cloud JL, Neal H, Rosenberry R, Turenne CY, Jama M, Hillyard DR, Carroll KC. Identification of Mycobacterium spp. by using a commercial 16S ribosomal DNA sequencing kit and additional sequencing libraries. J Clin Microbiol. 2002; 40(2): 400-6. PubMed

Cloud JL, Shutt C, Aldous W, Woods G. Evaluation of a modified gen-probe amplified direct test for detection of Mycobacterium tuberculosis complex organisms in cerebrospinal fluid. J Clin Microbiol. 2004; 42(11): 5341-4. PubMed

Cooksey RC, de Waard JH, Yakrus MA, Toney SR, Da Mata O, Nowicki S, Sohner K, Koch E, Petti CA, Morey RE, Srinivasan A. Mycobacterium cosmeticum, Ohio and Venezuela. Emerg Infect Dis. 2007; 13(8): 1267-9. PubMed

Jazrawi A, Jones M, Kfoury AG, Fisher PW, Gilbert EM, Bader F, Pombo D, Hanson KE, Stehlik J. Tuberculosis in a solid-organ transplant recipient: modern-day implications. J Heart Lung Transplant. 2009; 28(2): 191-3. PubMed

Lozier BK, Haven TR, Astill ME, Hill HR. Detection of acetylcholine receptor modulating antibodies by flow cytometry Am J Clin Pathol. 2015; 143(2): 186-92; quiz 305. PubMed

Lu J, Grenache DG. Development of a rapid, microplate-based kinetic assay for measuring adenosine deaminase activity in body fluids. Clin Chim Acta. 2012; 413(19-20): 1637-40. PubMed

Neal H, Cloud JL, Pounder JI, Page SR, Woods GL. Sequence variant for internal transcribed spacer region of Mycobacterium abscessus. J Clin Microbiol. 2005; 43(12): 6214. PubMed

Odell ID, Cloud JL, Seipp M, Wittwer CT. Rapid species identification within the Mycobacterium chelonae-abscessus group by high-resolution melting analysis of hsp65 PCR products. Am J Clin Pathol. 2005; 123(1): 96-101. PubMed

Pounder JI, Aldous WK, Woods GL. Comparison of real-time polymerase chain reaction using the Smart Cycler and the Gen-Probe amplified Mycobacterium tuberculosis direct test for detection of M. tuberculosis complex in clinical specimens. Diagn Microbiol Infect Dis. 2006; 54(3): 217-22. PubMed

Simmon KE, Low YY, Brown-Elliott BA, Wallace RJ, Petti CA. Phylogenetic analysis of Mycobacterium aurum and Mycobacterium neoaurum with redescription of M. aurum culture collection strains. Int J Syst Evol Microbiol. 2009; 59(Pt 6): 1371-5. PubMed

Simmon KE, Pounder JI, Greene JN, Walsh F, Anderson CM, Cohen S, Petti CA. Identification of an emerging pathogen, Mycobacterium massiliense, by rpoB sequencing of clinical isolates collected in the United States. J Clin Microbiol. 2007; 45(6): 1978-80. PubMed

Taggart EW, Hill HR, Ruegner RG, Litwin CM. Evaluation of an in vitro assay for interferon gamma production in response to the Mycobacterium tuberculosis-synthesized peptide antigens ESAT-6 and CFP-10 and the PPD skin test. Am J Clin Pathol. 2006; 125(3): 467-73. PubMed

Taggart EW, Hill HR, Ruegner RG, Martins TB, Litwin CM. Evaluation of an in vitro assay for gamma interferon production in response to Mycobacterium tuberculosis infections. Clin Diagn Lab Immunol. 2004; 11(6): 1089-93. PubMed

Wallace RJ, Brown-Elliott BA, Brown J, Steigerwalt AG, Hall L, Woods G, Cloud J, Mann L, Wilson R, Crist C, Jost KC, Byrer DE, Tang J, Cooper J, Stamenova E, Campbell B, Wolfe J, Turenne C. Polyphasic characterization reveals that the human pathogen Mycobacterium peregrinum type II belongs to the bovine pathogen species Mycobacterium senegalense. J Clin Microbiol. 2005; 43(12): 5925-35. PubMed

Medical Reviewers

Barker, Adam, PhD, Medical Director, Microbiology, Assistant Director, ARUP Institute of Clinical & Experimental Pathology®; Assistant Professor of Clinical Pathology, University of Utah

Last Update: September 2017