Report of an Expert Consultation on the Uses of Nucleic Acid Amplification Tests for the Diagnosis of Tuberculosis

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General Recommendations of the Expert Panel:

  1. All U.S. clinicians and public health TB programs should have access to molecular tests to aid in the diagnosis of TB. NAA testing for TB should become standard practice for TB suspects.
  2. NAA testing should be performed on a respiratory specimen from each patient with signs and symptoms of active pulmonary TB disease for whom a diagnosis of TB is being considered (i.e., TB suspect), but has not been established.
    1. NAA testing does not replace the need for AFB smear and culture. All current guidelines and recommendations for culture-based testing should remain in effect, especially recommended turn around times for culture and DST.
    2. A single positive NAA test result can support the diagnosis of TB in a patient for whom there is a reasonable index of suspicion. This result should trigger reporting to public health officials, initiation of treatment if not already started, and intensified efforts to obtain an isolate for drug susceptibility testing.
    3. In a patient with little suspicion of having active TB, a single positive NAA test result should be viewed with suspicion (i.e., a possible false-positive result) and interpreted in the same way as a single culture-positive result, i.e., by correlating the results with other diagnostic findings.
    4. A single negative NAA test result should never be used as a definitive test to exclude TB, especially in suspects with a moderate to high clinical suspicion of TB. Rather, the negative NAA test result should be used as additional information to aid in making clinical decisions to expedite a work-up for an alternative diagnosis or to prevent unnecessary use of TB treatment in suspects with a low clinical suspicion.
    5. Specimens may contain inhibitors. Testing for inhibitors should be considered for specimens that are AFB-smear positive and NAA test-negative. Each laboratory should establish the rate of inhibition to determine if routine testing for inhibitors is necessary. If inhibition testing is not performed on NAA test-negative specimens, it should be noted on the laboratory report.
    6. If the clinician is inexperienced with the diagnosis and treatment TB, consultation with a TB expert should be obtained with respect to the interpretation of NAA test results in the context of other diagnostic evidence.
  3. It is recommended that the appropriate work group consider amending the guidelines for ‘Controlling the Transmission of TB in Health Care Settings 2005’ section on ‘Suspected TB Disease’ to: ‘For patients placed under airborne precautions because of suspected infectious TB disease of the lungs, airway, or larynx, airborne precautions can be discontinued when infectious TB disease is considered unlikely and either 1) another diagnosis is made that explains the clinical syndrome, 2) the patient has three negative AFB sputum smear results,’ or 3) the patient has a sputum specimen that has a negative NAA test result and two additional sputum specimens that are AFB-smear negative. ‘Each of the three consecutive sputum specimens should be collected in 8–24-hour intervals, and at least one specimen should be an early morning specimen because respiratory secretions pool overnight. Generally, this method will allow patients with negative sputum smear results to be released from airborne precautions in 2 days.’
    Note: this recommendation does not apply to patients with a suspicion for TB that is high enough to start TB medication. For these patients, release from isolation requires clinical response to treatment, usually four to seven days of treatment in addition to three negative specimens by sputum AFB smears or NAA testing as outlined above.
  4. NAA testing should be treated as a priority test.
    1. Health care providers should be provided with clear instructions for the collection of quality specimens and encouraged to collect an adequate volume (5-10ml).
    2. The processed diagnostic specimen must be suspended in sufficient volume to ensure adequate samples for NAA testing, AFB-smear microscopy, and culture.
  5. The interval from specimen collection to the time that the laboratory report is communicated to the treating clinician must be as brief as possible. Laboratories and programs should track this performance measure.
    1. Specimens must be delivered promptly to the laboratory that does the NAA testing.
    2. Specimens must be tested promptly in the laboratory, preferably on the day received (i.e., without introducing significant delays by batching specimens).
    3. The results of NAA tests should be available within 48 hours of specimen collection.
    4. Laboratorians should treat an initial positive NAA test result as a critical test value. They must immediately report NAA test results to the health care provider and be available for consultation as to appropriate test interpretation and possible need for follow-up testing.
    5. Laboratorians should immediately report initial positive NAA test results to public health authorities for earlier interventions and possibly earlier engagement of a TB expert in the management of the patient.
  6. For laboratories that do not have sufficient resources for NAA testing or sufficient test volume for NAA testing without adding delays from batching, specimens for NAA testing should be referred promptly to laboratories that have demonstrated proficiency in the test and can provide timely results (e.g., within 24–48hrs).
  7. Laboratories performing NAA testing should participate in a NAA proficiency testing program (e.g., WSLH PT [Wisconsin State Laboratory of Hygiene Proficiency Testing], CAP [College of American Pathologists], or other accredited program).
  8. The number and types of NAA tests, commercial sources, FDA-approved tests, and validated ASR tests should be increased.
  9. Research is needed to improve specimen processing, referral processes, testing algorithms, NAA test performance and ease-of-use, utility for diagnosing extrapulmonary and pediatric TB, and regulatory quality trials.
  10. The expert panel endorses the recommendations under consideration in the proposed revision of the ‘Diagnostic Standards and Classification of Tuberculosis in Adults and Children’ supporting the routine use of molecular methods for detection of drug resistance directly in AFB smear-positive sputum sediments for TB patients who are suspected of having drug-resistant disease or are from a region or population with a high prevalence of drug resistance.