Transmission

• Mycobacterium tuberculosis (Mtb) is transmitted from person to person via the airborne route. Several factors determine the probability of Mtb transmission:
  1. Infectiousness of the source patient: A positive sputum smear for acid-fast bacilli (AFB) or a cavity on chest radiograph are strongly associated with infectiousness.
  2. Host susceptibility of the contact.
  3. Duration of exposure of the contact to the source patient.
  4. The environment in which the exposure takes place. A small, poorly ventilated space provides the highest risk.
  5. Infectiousness of the Mtb strain.
• Those who are household contacts and are exposed to patients who are smear positive have higher rates of both infection and disease.
• Medical procedures that generate aerosols of respiratory secretions, such as sputum induction and bronchoscopy, entail significant risk for Mtb transmission unless proper precautions are taken.

Testing for Latent Tuberculosis Infection (LTBI)

See page 11 for an explanation of the Recommendation Grading.

• The panel recommends performing an interferon-γ release assay (IGRA) rather than a tuberculin skin test (TST) in individuals ≥5 years of age who meet the following criteria (S-M):
  • are likely to be infected with Mtb
  • have a low or intermediate risk of disease progression
  • it has been decided that testing for LTBI is warranted and
  • either have a history of BCG vaccination or are unlikely to return to have their TST read.

  Remarks: A TST is an acceptable alternative, especially in situations where an IGRA is not available, too costly, or too burdensome.

• The panel suggests performing an IGRA rather than a TST in all other individuals ≥5 years of age 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 (C-M).

  Remarks: A TST is an acceptable alternative, especially in situations where an IGRA is not available, too costly, or too burdensome.

There are insufficient data to recommend a preference for either a TST or an IGRA as the first-line diagnostic test in individuals ≥5 years of age who are likely to be infected with Mtb, who have a high risk of progression to disease, and in whom it has been determined that diagnostic testing for LTBI is warranted.

• Guidelines recommend that persons at low risk for Mtb infection and disease progression NOT be tested for Mtb infection. The Panel concurs with this recommendation. However, it also recognizes that such testing may be obliged by law or credentialing bodies. If diagnostic testing for LTBI is performed in individuals who are unlikely to be infected with Mtb despite guidelines to the contrary:
  • The panel suggests performing an IGRA instead of a TST in individuals ≥5 years of age (C-L).

  Remarks: A TST is an acceptable alternative in settings where an IGRA is unavailable, too costly, or too burdensome.

  • The panel suggests a second diagnostic test if the initial test is positive in individuals ≥5 years of age (C-VL).

  Remarks: The confirmatory test may be either an IGRA or a TST. When such testing is performed, the person is considered infected only if both tests are positive.

• The panel suggests performing a TST rather than an IGRA in healthy children <5 years of age for whom it has been decided that diagnostic testing for LTBI is warranted (C-VL).
  • Remarks: In situations in which an IGRA is deemed the preferred diagnostic test, some experts are willing to use IGRAs in children >3 years of age.

The preceding recommendations are summarized in Figures 1 and 2.
While both IGRA and TST testing provide evidence for infection with Mtb, they cannot distinguish active from latent tuberculosis. Therefore, the diagnosis of active TB must be excluded prior to embarking on treatment for LTBI. This is typically done by determining whether or not symptoms suggestive of TB disease are present, performing a chest radiograph and, if radiographic signs of active tuberculosis (eg, airspace opacities, pleural effusions, cavities, or changes on serial radiographs) are seen, then sampling is performed and the patient managed accordingly.

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.

• 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.

• 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).

• 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 (S-M):
  • 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.

  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.

• 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.

• 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).
• 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.

• 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.

• 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.

• 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.

• 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).
• 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).
• 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.

• 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.

• 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.

• 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.

• The panel recommends a culture isolate from each mycobacterial culture-positive patient be submitted to a regional genotyping laboratory for genotyping (S-VL).

Table 1. Essential Laboratory Tests for the Detection of Mtb

Figure 1. Paradigm for Evaluation of Those with LTBI Based on Risk of Infection, Risk of Progression to Tuberculosis, and Benefit of Therapy

Figure 2. Summary of Recommendations for Testing for LTBI

Grading of Recommendations, Assessment, Development, and Evaluation (GRADE)-Based Recommendations

Abbreviations

CXR, chest radiograph; HIV, human immunodeficiency virus; HPLC, high-performance liquid chromatography; IGRA, interferon-γ release assay; LTBI, latent tuberculosis infection; Mtb, Mycobacterium tuberculosis; RR, relative risk; TB, tuberculosis; TST, tuberculin skin test

Source

Lewinsohn DM, Leonard MK, LoBue PA, Cohn DL, Daley CL, Desmond E, Keane J, Lewinsohn DA, Loeffler AM, Mazurek GH, O'Brien RJ, Pai M, Richeldi L, Salfinger M, Shinnick TM, Sterling TR, Warshauer DM, Woods GL. 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. Clin Infect Dis. 2017; 64(2):e1-e33.

The guidelines were a cooperative effort among the American Thoracic Society, Centers for Disease Control and Prevention, and Infectious Diseases Society of America