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Rapid Diagnosis of Pulmonary Tuberculosis
Abstract & Commentary
By Stan Deresinski, MD, FACP, Clinical Professor of Medicine, Stanford, Associate Chief of Infectious Diseases, Santa Clara Valley Medical Center, is Editor for Infectious Disease Alert.
Source: CDC. Updated guidelines for the use of nucleic acid amplification test in the diagnosis of tuberculosis. MMWR. 2009;58:7-10.
Synopsis: Nucleic acid amplification (NAA) testing should be performed on at least one respiratory specimen from each patient with signs and symptoms of pulmonary TB for whom a diagnosis of TB is being considered but has not yet been established, and for whom the test result would alter case management or TB control activities.
Nucleic acid tests (NAA) for the diagnosis of pulmonary tuberculosis (TB) have had FDA approval for more than a decade, but their use has been limited, at least in part because of a frequent lack of availability in local laboratories. In addition, previously published guidelines gave less than enthusiastic promotion to their use. The CDC has now updated these guidelines for the second time, and their enthusiasm for the test has ballooned.
A major problem in the diagnosis of pulmonary TB is the frequent delay involved. While acid fast smears can have a rapid turnaround time, they are relatively insensitive when compared to culture and, furthermore, lack specificity at a time when the incidence of pulmonary infection with non-tuberculous mycobacteria (NTM) is apparently growing. Culture is specific and sensitive but may require as long as six weeks. In the interval, some patients with tuberculosis may not receive therapy and others with NTM may receive inappropriate therapy. Furthermore, these shortcomings of classical techniques have adverse effects on contact tracing, both in and out of the hospital.
The sensitivity of NAA with AFB smear-positive respiratory samples is > 95%, and is 50%-90% with smear-negative samples from patients whose cultures subsequently prove to be culture-positive. In each case, the infection is automatically identified by NAA as being due to Mycobacterium tuberculosis rather than NTM.
Because the positive predictive value of the test is < 50% in patients with a low pretest probability of having tuberculosis, NAA tests should not be requested in such patients. On the other hand, a single negative NAA cannot be use to exclude TB in patients with a moderate or high pretest probability of the infection.
Having reviewed the available information, the panel has now recommended that, rather than being a secondary test, NAA testing should become standard practice in the United States. They state that the test should be utilized in the diagnostic evaluation of each patient with suspected pulmonary tuberculosis and for whom the test result would affect either management of the patient or TB control activities, or both. They recommend the following approach:
The panel also recommends that all clinicians and public health TB programs have access to NAA testing for TB in order to shorten the time-to-diagnosis from weeks to days. NAA results should be available within 48 hours of specimen collection, and the laboratory should treat the result as a critical value, with immediate reporting to both the clinician and the public health department.
The panel makes no recommendations regarding the use of NAA on non-respiratory specimens, but does acknowledge that "evidence exists for the use of such testing in individual cases." It also makes no recommendations for the use of molecular tests for the detection of drug resistance (no such tests have as yet received FDA approval in the United States). It does, however, indicate that a proposed guideline revision "is likely to support the use of molecular DSTs (diagnostic susceptibility tests) for AFB smear-positive sputum specimens from TB patients who are suspected to have drug-resistant disease or who are from a region or population with a high prevalence of drug resistance."
Overall, as the document indicates, the appropriate use of NAA for the rapid diagnosis of pulmonary TB has the potential to result in earlier initiation of treatment, with resultant improved clinical outcomes, more expeditious interruption of transmission, and more effective public health interventions. It may also lead to reduced inappropriate use of antibacterials, including fluoroquinolones, which could otherwise lead to difficulty in culture recovery of TB and to fluoroquinolone resistance. It also prevents unnecessary isolation and contact investigation, as well as inappropriate therapy in hospitalized patients who prove to have NTM infection.