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Disease Categories > Infectious Disease > Mycobacteria

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Mycobacterium tuberculosis - TB

Mycobacteria belong to the family Mycobacteriaceae and the order Actinomycetales. Mycobacterium tuberculosis as well as other non-tuberculosis species can be infectious agents in humans.

Mycobacterium tuberculosis

Epidemiology
- Prevalence
  - 8-9 million new cases occur per year
  - 3-4 million cases of infectious pulmonary disease (smear positive)
Organism
- Mycobacterium tuberculosis – rod-shaped aerobic bacterium with acid-fast staining properties
- Mycobacterium tuberculosis complex (MTB) – M. tuberculosis, M. bovis, M. africanum M. microti and others
  - Transmission is via inhalation of droplet nuclei
Risk factors
- Once the patient has been infected, the risks for developing active tuberculosis (TB) for the development of active TB include:
  - Comorbidity present (AIDS, immunosuppression, fibrotic lung disease, chronic renal failure, diabetes mellitus)
  - Recent tuberculosis infection (<1 year)
  - Malnutrition, alcoholism
  - Fibrotic lesions on chest X-ray
Clinical Presentation
- Primary disease
  - Ranges from mild, self-limited illness to severe disseminated disease
- Post primary disease
  - Reactivation of latent infection
  - Moderate to severe, progressive and often fatal disease
- Extrapulmonary TB
  - Gastrointestinal disease
  - Genitourinary
  - Lymphadenitis
  - Meningitis, central nervous system tuberculoma
  - Miliary
  - Pericarditis
  - Pleural disease
  - Skeletal (Pott disease)
- TB in patients with HIV
  - Extrapulmonary disease is common
  - Atypical chest X-ray findings
  - Delays in diagnosis and treatment are common
  - Increased risk of reactivation of latent disease and rapid progression of newly acquired infection
Diagnosis
- Laboratory testing
  - Based on AFB smear, culture and nucleic acid amplification testing
  - Susceptibility testing is mandatory
  - Latent M. tuberculosis – Interferon alpha release assays (QuantiFERON®)

Nontuberculous (atypical) mycobacteria

Epidemiology
- Transmission via cutaneous, inhalation, or parenteral routes
  - Widely distributed in water, soil and animal species
Organisms
- Nontuberculous organisms
  - M. avium complex, M. kansasii, M. fortuitum, M. abscessus, M. chelonae, M. marinum, M. haemophilum
- Rare new organisms
  - M.nebraskerise, M. parmense, M. saskat-chewanense, M. arupense, M. caprae, M. colombiense, M. florentium, M. montefiorense
- Pathogenicity and clinical significance vary with species and host
  - Asymptomatic infections are common
Clinical Presentation
- Cutaneous – M. fortuitum, M. abscessus, M. chelonae, M. marinum, M. haemophilum
  - Nodular or ulcerating chronic lesions that fail to respond to standard antimicrobial therapy
  - Lymphadenitis - M. avium complex, especially in children
- Pulmonary – M. avium complex, M. kansasii, M. abscessus
  - Immunocompromised and immunocompetent hosts
  - Increased in elderly and patients with underlying pulmonary disease
  - Bronchiectatic, nodular or cavitary disease
- Disseminated
  - Weight loss, fever, fatigue, lymphadenopathy, hepatosplenomegaly, gastrointestinal complaints
  - Usually immunocompromised patients (advanced HIV, transplant)
- Other (catheter-related, skeletal)
Diagnosis
- Laboratory testing
  - Concentrated AFB smear
    - Traditional standard screening method (sputum)
    - Not as sensitive as culture (requires approximately 10⁴ bacilli/mL sputum for detection)
    - Not specific for Mycobacterium tuberculosis complex
- Mycobacterial culture
  - Most sensitive test for detection of mycobacteria (gold standard)
  - Slow (2-8 weeks)
  - Should be performed on any specimen for which Mycobacteria are a consideration
- Nucleic acid amplified testing (NAAT)
  - Emerging recommended method for rapid, sensitive and specific detection of MTB complex
  - Less sensitive than culture
- Adenosine deaminase (ADA)
  - Adjunctive test for use in the evaluation of suspected extrapulmonary tuberculosis involving body cavities (or CSF)
  - Reported sensitivity and specificity vary
    - Meta-analysis derived summary receiver operator curves (ROC) from pleural fluid: sensitivity 92%; specificity 92%
  - Not specific for tuberculosis
  - AFB culture should always be performed

Indications for Ordering

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

Test Name and Number	Recommended Use	Limitations	Follow Up
AFB Culture (Includes AFB Stain 0060151) 0060152 Method: Standard reference procedures for stain and culture. Identification of AFB is ordered and billed separately. DNA probes are available for M. tuberculosis complex and M. avium-intracellulare complex as indicated. DNA sequencing and other molecular techniques are used for identification of other mycobacteria species. For drug susceptibilities, refer to Antimicrobial Susceptibility - AFB Mycobacteria (0060217).	Gold standard, most sensitive test for diagnosing mycobacteria Use for detection in sputum, tissues, urine and other body fluids	Time to detection (mycobacteria are slow growing organisms)	DNA probes are available for M. tuberculosis complex and M. avium-intracellulare complex as indicated. DNA sequencing and other molecular techniques are used for identification of other mycobacteria species. For drug susceptibilities, refer to Antimicrobial Susceptibility - AFB Mycobacteria (0060217)
Mycobacterium tuberculosis Amplified Direct Detection 0060095 Method: Transcription Mediated Amplification (Gen-Probe®)	Order as adjunct to AFB culture in untreated patients with smear-positive and smear-negative respiratory samples Rapid,sensitive and specific detection of MTB complex from respiratory specimens	AFB culture should always be ordered with this test Low level false-positive results can occur in specimens with high concentration of Mycobacteria other than M. tuberculosis A negative result does not exclude M. tuberculosis infection
Quantiferon®-TB Gold In Tube	Detect latent TB infections among persons who are at increased risk for TB Specific for M. tuberculosis, not nontuberculous mycobacteria or the BCG vaccine
QuantiFERON®-TB Gold (Local Clients Only) 0051231 Method: Cell Culture/Enzyme-Linked Immunosorbent Assay	Detect latent TB infections among persons at increased risk for TB Specific for M. tuberculosis; not nontuberculous mycobacteria or the BCG vaccine	Time sensitive test The ability of the QuantiFERON®-TB Gold assay to predict the progression of latent tuberculosis infection to active tuberculosis has not been evaluated
Mycobacterium tuberculosis Complex Speciation 0060771 Method: Polymerase Chain Reaction	Identify species of the M. tuberculosis complex (M. tuberculosis, M. bovis, M. bovis BCG-vaccine strain, M. africanum, M. microti, M. caprae) to species level by comparing genomic deletion patterns	Non-tuberculous mycobacteria 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
Mycobacterium tuberculosis Antibody, IgG by ELISA 0051698 Method: Enzyme-Linked Immunosorbent Assay	Order this rapid serologic assay when clinical symptoms and the possibility of exposure indicate MTB infection Detect IgG antibodies against MTB in patients with active infection Monitor the success of therapeutic intervention Differentiate active and latent cases of TB Can also be used in previously BCG vaccinated individuals since the antigens utilized are not present in Mycobacterium bovis	Not intended for use as a screening assay Results should be interpreted in conjunction with PPD or QuantiFERON® testing as well as the complete history of the patient Assay has not been validated for use on patients with HIV/TB co-infection and is not recommended for this population
AFB Culture (Includes AFB Stain 0060151) with Reflex to Mycobacterium tuberculosis Amplified Direct Detection (0060095) 0060738 Method: Standard reference procedures for stain and culture. Identification of AFB is ordered and billed separately. DNA probes are available for M. tuberculosis complex and M. avium-intracellulare complex as indicated. DNA sequencing and other molecular techniques are used for identification of other mycobacteria species. For drug susceptibilities, refer to Antimicrobial Susceptibility - AFB Mycobacteria (0060217). For AFB stain positive respiratory specimens, Mycobacterium tuberculosis Amplified Direct Detection (0060095) will be added at an additional charge.	Single order test incorporating culture and stain with reflex to amplified testing for MTB complex when smear positive	Available for respiratory specimens only Low-level false-positive results can occur in specimens with high concentration of mycobacteria other than M. tuberculosis A negative result does not exclude M. tuberculosis
Blood Culture, AFB 0060060 Method: Bactec® 9240, continuous monitoring systems. Standard reference procedures for identification of positive cultures.	Order for AFB culture of blood or bone marrow specimen
Mycobacterium tuberculosis Amplified Detection , CSF 0060063 Method: Transcription Mediated Amplification (Gen-Probe®)	Amplified test offers rapid and specific detection of MTB complex from cerebrospinal fluid (CSF)	AFB culture should always be ordered with test The Mycobacterium tuberculosis Amplified Direct test does not differentiate among members of the MTB complex Low level false-positive results can occur in specimens with high concentration of mycobacteria other than M. tuberculosis (rare in CSF) Limited sensitivity A negative result does not exclude the possibility of isolating MTB from the specimen (e.g. culture)
AFB Identification with Reflex to Susceptibility 0060997 Method: Standard reference procedures for identification and susceptibility testing of AFB. DNA probes available for M. tuberculosis complex and M. avium-intracellulare complex. DNA sequencing and other molecular techniques are used for other mycobacteria species.	Identification of acid-fast organisms (AFB) isolated in pure culture with reflex susceptibility testing if indicated	Susceptibility testing may not be performed on all isolates (varies by species)
Antimicrobial Susceptibility - AFB/Mycobacteria 0060217 Method: Varies with organism identification	Availability: a. M. tuberculosis primary panel b. M. avium complex panel c. Rapidly Growing Nontuberculous Mycobacteria panel d. Atypical Mycobacteria panel

Additional Tests Available

Click on number for test-specific information in the ARUP Laboratory Test Directory

Test Name and Number	Comments
AFB Stain Only 0060151 Method: Auramine O Stain	Monitor respiratory specimens on previously diagnosed patients Should not be ordered without culture in previously undiagnosed patients
AFB Identification 0060999 Method: Standard reference procedures for identification of AFB. DNA probes available for M. tuberculosis complex and M. avium-intracellulare complex. DNA sequencing and other molecular techniques are used for other mycobacteria species.	Identification of acid-fast organisms (AFB) isolated in pure culture
Blood Culture, AFB & Fungal 0060024 Method: Bactec® 9240, continuous monitoring systems. Standard reference procedures for identification of positive cultures.

Additional Information

The laboratory should be notified when the presence of Mycobacterium genavense is suspected as this organism will not grow on media routinely used for Mycobacterial isolation.

Guidelines

Controlling tuberculosis in the United States. Recommendations from the American Thoracic Society, CDC, and the Infectious Diseases Society of America. American Thoracic Society - Medical Specialty Society. Centers for Disease Control and Prevention - Federal Government Agency [U.S.] Infectious Diseases Society of America - Medical Specialty Society. 2005 Nov 4. 81 pages. NGC:004660 (Link to NGC)

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;161(4 Pt 1):1376-1395. (Link to PubMed)

Guidelines for preventing the transmission of Mycobacterium tuberculosis in health-care settings, 2005. Centers for Disease Control and Prevention - Federal Government Agency [U.S.]. 2005 Dec 30. 142 pages. (Link to NGC)

Jereb JA. Progressing toward tuberculosis elimination in low-incidence areas of the United States. Recommendations of the Advisory Council for the Elimination of Tuberculosis. MMWR Recomm Rep. 2002;51(RR-5):1-14. (Link to PubMed)

General References

Dinnes J, Deeks J, Kunst H, Gibson A, Cummins E, Waugh N, Drobniewski F, Lalvani A. A systematic review of rapid diagnostic tests for the detection of tuberculosis infection. Health Technol Assess. 2007;11(3):1-196. (Link to PubMed)

Goto,M., Noguchi,Y., Koyama,H., Hira,K., Shimbo,T., Fukui,T. Diagnostic value of adenosine deaminase in tuberculous pleural effusion: a meta-analysis. Ann Clin Biochem. 2003;40(Pt 4):374-81. (Link to PubMed)

Harries AD, Dye C. Tuberculosis. Ann Trop Med Parasitol. 2006;100(5-6):415-431. (Link to PubMed)

Havlir DV, Barnes PF. Tuberculosis in patients with human immunodeficiency virus infection. N Engl J Med. 1999;340(5):367-373. (Link to PubMed)

Jasmer RM, Nahid P, Hopewell PC. Clinical practice. Latent tuberculosis infection. N Engl J Med. 2002;347(23):1860-1866. (Link to PubMed)

Kanaujia GV, Lam PK, Perry S, Brusasca PN, Catanzaro A, Gennaro ML. Integration of microscopy and serodiagnostic tests to screen for active tuberculosis. Int J Tuberc Lung Dis.. 2005;9(10):1120-6. (Link to PubMed)

Lalvani A. Diagnosing tuberculosis infection in the 21st century: new tools to tackle an old enemy. Chest. 2007;131(6):1898-1906. (Link to PubMed)

Maartens G, Wilkinson RJ. Tuberculosis. Lancet. 2007;370(9604):2030-2043. (Link to PubMed)

Marais BJ, Graham SM, Cotton MF, Beyers N. Diagnostic and management challenges for childhood tuberculosis in the era of HIV. J Infect Dis. 2007;196 Suppl 1:S76-S85. (Link to PubMed)

Palomino JC. Newer diagnostics for tuberculosis and multi-drug resistant tuberculosis. Curr Opin Pulm Med. 2006;12(3):172-178. (Link to PubMed)

Perkins MD, Cunningham J. Facing the crisis: improving the diagnosis of tuberculosis in the HIV era. J Infect Dis. 2007;196 Suppl 1:S15-S27. (Link to PubMed)

Quast TM, Browning RF. Pathogenesis and clinical manifestations of pulmonary tuberculosis. Dis Mon. 2006;52(11-12):413-419. (Link to PubMed)

Richeldi L. An update on the diagnosis of tuberculosis infection. Am J Respir Crit Care Med. 2006;174(7):736-742. (Link to PubMed)

Sharma SK, Mohan A, Sharma A, Mitra DK. Miliary tuberculosis: new insights into an old disease. Lancet Infect Dis. 2005;5(7):415-430. (Link to PubMed)

Small PM, Fujiwara PI. Management of tuberculosis in the United States. N Engl J Med. 2001;345(3):189-200. (Link to PubMed)

Stout JE. Evaluation and management of patients with pulmonary nontuberculous mycobacterial infections. Expert Rev Anti Infect Ther. 2006;4(6):981-993. (Link to PubMed)

Tortoli E. The new mycobacteria: an update. FEMS Immunol Med Microbiol. 2006;48(2):159-178. (Link to PubMed)

Yew WW, Leung CC. Update in tuberculosis 2006. Am J Respir Crit Care Med. 2007;175(6):541-546. (Link to 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):2471-2473. (Link to 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):3474-3478. (Link to PubMed)

Cloud JL, Hoggan K, Belousov E, Cohen S, Brown-Elliott BA, Mann L, Wilson R, Aldous W, Wallace RJ Jr, 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):4205-4207. (Link to PubMed)

Cloud JL, Meyer JJ, Pounder JI, Jost KC Jr, 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):1413-1418. (Link to 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):400-406. (Link to 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):5341-5344. (Link to 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):1267-1269. (Link to 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-. (Link to 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. (Link to 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):217-222. (Link to 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):1978-1980. (Link to 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):467-473. (Link to 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):1089-1093. (Link to PubMed)

Wallace RJ Jr, Brown-Elliott BA, Brown J, Steigerwalt AG, Hall L, Woods G, Cloud J, Mann L, Wilson R, Crist C, Jost KC Jr, 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):5925-5935. (Link to PubMed)

Reviewed by

Carney, Heather, M.D. Assistant Medical Director, Transfusion Services at ARUP Laboratories; Pathology, University of Utah

Petti, Cathy A., M.D. Medical Director, Infectious Diseases at ARUP Laboratories; Assistant Professor, Pathology and Medicine, University of Utah

Comprehensive Review: March 2008
Last Update: July 2008