Mycobacterium tuberculosis - TB

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

Laboratory Testing

Differential Diagnosis

  • TB skin testing
    • 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
  • QuantiFERON Gold – if latent TB infection suspected
    • Should not be used in patients with active disease symptoms
    • Unaffected by previous BCG
    • 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

  • See Monitoring tab

Indications for Laboratory Testing

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/Susceptiblity

Limitations

Mycobacteria are slow growing organisms; culture requires several weeks

Follow Up

DNA probes are available for MTB complex 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

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

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

Mycobacterium tuberculosis Complex Speciation 0060771
Method: Qualitative Polymerase Chain Reaction

Limitations

NTM may have indeterminate patterns of the genomic deletions used as targets in this assay

Changes in DNA sequence at the primer annealing sites may affect genomic deletion pattern determination and speciation

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

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

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.

Limitations

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

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

Additional Tests Available

Acid-Fast Bacillus (AFB) Stain Only 0060151
Method: Auramine O Stain

Comments

Monitor respiratory specimens on previously diagnosed patients

Should not be ordered without culture in previously undiagnosed patients

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

Comments

Identification of acid-fast organisms (AFB) isolated in pure culture

Blood Culture, AFB and Fungal 0060024
Method: Continuous Monitoring Blood Culture/Identification

Adenosine Deaminase, CSF 2006098
Method: Quantitative Spectrophotometry

Adenosine Deaminase, Peritoneal Fluid 2006101
Method: Quantitative Spectrophotometry

Adenosine Deaminase, Pleural Fluid 2006096
Method: Quantitative Spectrophotometry

Adenosine Deaminase, Pericardial Fluid 2009357
Method: Quantitative Spectrophotometry

Chylomicron Screen, Body Fluid 0098457
Method: Qualitative Electrophoresis

Guidelines

General References

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

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

Deangelis T, 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 G, Nienhaus A, Ruhwald M, Wagner D, Zellweger J, 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 W, Tsiouris S. 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

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

Miranda C, Tomford W, Gordon S. 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 I, Wieland M. Current concepts in the management of tuberculosis. Mayo Clin Proc. 2011; 86(4): 348-61. PubMed

Zar H, Connell T, 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 W, Pounder J, Cloud J, Woods G. 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 B, Welch R, Litwin C. 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 J, Carroll K, Cohen S, Anderson C, Woods G. 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 J, Hoggan K, Belousov E, Cohen S, Brown-Elliott B, Mann L, Wilson R, Aldous W, Wallace R, Woods G. 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 J, Meyer J, Pounder J, Jost K, Sweeney A, Carroll K, Woods G. 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 J, Neal H, Rosenberry R, Turenne C, Jama M, Hillyard D, Carroll K. 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 J, 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 R, de Waard J, Yakrus M, Toney S, Da Mata O, Nowicki S, Sohner K, Koch E, Petti C, Morey R, Srinivasan A. Mycobacterium cosmeticum, Ohio and Venezuela. Emerg Infect Dis. 2007; 13(8): 1267-9. PubMed

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

Lu J, Grenache D. 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 J, Pounder J, Page S, Woods G. Sequence variant for internal transcribed spacer region of Mycobacterium abscessus. J Clin Microbiol. 2005; 43(12): 6214. PubMed

Odell I, Cloud J, Seipp M, Wittwer C. 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 J, Aldous W, Woods G. 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 K, Low Y, Brown-Elliott B, Wallace R, Petti C. 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 K, Pounder J, Greene J, Walsh F, Anderson C, Cohen S, Petti C. 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 E, Hill H, Ruegner R, Litwin C. 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 E, Hill H, Ruegner R, Martins T, Litwin C. 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 R, Brown-Elliott B, Brown J, Steigerwalt A, Hall L, Woods G, Cloud J, Mann L, Wilson R, Crist C, Jost K, Byrer D, 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

Last Update: January 2016