Performance of Nucleic Acid Amplification Tests for Diagnosis of Tuberculosis in a Large Urban Setting

Bureau of Tuberculosis Control, New York City Department of Health of Mental Hygiene, New York 10013, USA.
Clinical Infectious Diseases (Impact Factor: 8.89). 07/2009; 49(1):46-54. DOI: 10.1086/599037
Source: PubMed


A diagnosis of tuberculosis (TB) relies on acid-fast bacilli (AFB) smear and culture results. Two rapid tests that use nucleic acid amplification (NAA) have been approved by the US Food and Drug Administration for the diagnosis of TB based on detection of Mycobacterium tuberculosis from specimens obtained from the respiratory tract. We evaluated the performance of NAA testing under field conditions in a large urban setting with moderate TB prevalence.
The medical records of patients with suspected TB during 2000-2004 were reviewed. Analysis was restricted to the performance of NAA on specimens collected within 7 days after the initiation of treatment for TB. The assay's sensitivity, specificity, and positive and negative predictive values (PPV and NPV, respectively) were evaluated.
The proportion of patients with confirmed or suspected TB whose respiratory tract specimens were tested by use of NAA increased from 429 (12.9%) of 3334 patients in 2000 to 527 (15.6%) of 3386 patients in 2004; NAA testing among patients whose respiratory tract specimens tested positive for AFB increased from 415 (43.6%) of 952 patients in 2000 to 487 (55.5%) of 877 patients in 2004 (P < .001 for both trends). Of the 16,511 patients being evaluated for pulmonary TB, 4642 (28.1%) had specimens that tested positive for AFB on smear. Of those 4642 patients, 2241 (48.3%) had NAA performed on their specimens. Of those 2241 patients, 1279 (57.1%) had positive test results. Of those 1279 patients, 1262 (98.7%) were confirmed to have TB. For 1861 (40.1%) of the 4642 patients whose specimens tested positive for AFB on smear, the NAA test had a sensitivity of 96.0%, a specificity of 95.3%, a PPV of 98.0%, and an NPV of 90.9%. For 158 patients whose specimens tested negative for AFB on smear, the NAA test had a sensitivity of 79.3%, a specificity of 80.3%, a PPV of 83.1%, and an NPV of 76.0%, respectively. For the 215 specimens that tested positive for AFB by smear, we found a sensitivity, specificity, PPV, and NPV of 97.5%, 93.6%, 95.1%, and 96.8%, respectively. A high-grade smear was associated with a better test performance.
NAA testing was helpful for determining whether patients whose specimens tested positive for AFB on smear had TB or not. This conclusion supports the use of this test for early diagnosis of pulmonary and extrapulmonary TB.

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    • "Newer, highly sensitive nucleic acid amplification techniques have provided new opportunities for earlier diagnosis of patient with active TB [5]. A number of polymerase chain reaction (PCR) assays are currently in use in clinical laboratories, often as part of routine diagnostic work-up [6, 7]. GeneXpert MTB/RIF (Cepheid, Sunnyvale, CA, USA) is a real-time PCR system that demands minimal technical expertise which has been validated for clinical use in both respiratory and non-respiratory clinical samples [8]. "
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    ABSTRACT: GeneXpert MTB/RIF is a real-time PCR assay with established diagnostic performance in pulmonary and extra-pulmonary forms of tuberculosis. The aim of this study was to assess the contribution of GeneXpert MTB/RIF assay to the management of patients with any form of active tuberculosis in a single large tertiary center in Saudi Arabia, with a special focus on the impact on time to start of antituberculous therapy compared with Ziehl-Neelsen (ZN) smears and mycobacterial cultures. Clinical, radiological and laboratory records for all patients who were commenced on antituberculous therapy between March 2011 and February 2013 were retrospectively reviewed. A total of 140 patients were included, 38.6% of which had pulmonary tuberculosis. GeneXpert MTB/RIF was requested for only 39.2% of patients and was the only reason for starting antituberculous therapy for only 12.1%. The median time to a positive GeneXpert MTB/RIF result was 0 days (IQR 3) compared with 0 day (IQR 1) for smear microscopy (P > 0.999) and 22 days (IQR 21) for mycobacterial cultures (P < 0.001). No patients discontinued antituberculous therapy because of a negative GeneXpert MTB/RIF result. In a setting wherein physicians are highly experienced in the diagnosis and treatment of tuberculosis, GeneXpert MTB/RIF was remarkably under-utilized and had only a limited impact on decisions related to starting or stopping antituberculous therapy. Cost-effectiveness and clinical utility of routine testing of all smear-negative clinical samples submitted for tuberculosis investigations by GeneXpert MTB/RIF warrant further study.
    03/2014; 46(1):30-4. DOI:10.3947/ic.2014.46.1.30
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    • "First and second samples were then tested for acid-fast bacilli (AFB) by smear and culture. The third specimen was subjected to a nucleic acid amplification assay for M. tuberculosis[14,15]. When multiple pulmonary infiltrates were visible on chest radiography, bronchial washing was performed at the segment exhibiting the most severe abnormalities. "
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    ABSTRACT: Flexible bronchoscopy with bronchial washing is a useful procedure for diagnosis of pulmonary tuberculosis (TB), when a patient cannot produce sputum spontaneously or when sputum smears are negative. However, the benefit of gaining serial bronchial washing specimens for diagnosis of TB has not yet been studied. Therefore, we conducted a retrospective study to determine the diagnostic utility of additional bronchial washing specimens for the diagnosis of pulmonary TB in suspected patients. A retrospective analysis was performed on 174 patients [sputum smear-negative, n=95 (55%); lack of sputum specimen, n=79 (45%)] who received flexible bronchoscopy with two bronchial washing specimens with microbiological confirmation of pulmonary TB in Samsung Medical Center, between January, 2010 and December, 2011. Pulmonary TB was diagnosed by first bronchial washing specimen in 141 patients (81%) out of 174 enrolled patients, and an additional bronchial washing specimen established diagnosis exclusively in 22 (13%) patients. Smear for acid-fast bacilli (AFB) was positive in 46 patients (26%) for the first bronchial washing specimen. Thirteen patients (7%) were positive only on smear of an additional bronchial washing specimen. Combined smear positivity of the first and second bronchial washing specimens was significantly higher compared to first bronchial washing specimen alone [Total cases: 59 (34%) vs. 46 (26%), p 0.001; cases for smear negative sputum: 25 (26%) vs. 18 (19%), p=0.016; cases for poor expectoration: 34 (43%) vs. 28 (35%), p=0.031]. The diagnostic yield determined by culture was also significantly higher in combination of the first and second bronchial washing specimens compared to the first bronchial washing. [Total cases: 163 (94%) vs. 141 (81%), p 0.001; cases for smear negative sputum: 86 (91%) vs. 73 (77%), p 0.001; cases for poor expectoration: 77 (98%) vs. 68 (86%), p=0.004]. Obtaining an additional bronchial washing specimen could be a beneficial and considerable option for diagnosis of TB in patients with smear-negative sputum or who cannot produce sputum samples.
    BMC Infectious Diseases 08/2013; 13(1):404. DOI:10.1186/1471-2334-13-404 · 2.61 Impact Factor
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    ABSTRACT: ASTUDY of the noise characteristics of a general purpose silicon diode (type 1 N645) was made to determine whether excessive r-f noise is correlated with high failure rates. The selection of the abnormally high noise diodes was made by monitoring the noise level across the diode as it was excited with an a-c voltage within the diode maximum ratings. Mechanical stress in the form of impacts within the rated value was applied simultaneously to aggravate structural imperfections. Noise measurements at 25 mc were used for the recognition of weaknesses and early failure. The forward and reverse characteristics were obtained for the diodes exhibiting high r-f noise. These were compared with the characteristics of diodes exhibiting normal r-f noise. In the forward direction, no difference was obtained; in the reverse biased condition, the average leakage current of all the noisy diodes was considerably higher than the average of the quiet group. In addition it was noted that the r-f noise level of the diodes was almost inversely proportional to the avalanche breakdown voltage. The diodes were also tested for 1/f noise; 35% of the r-f noisy diodes also exhibited high 1/f noise, whereas only 1.2% of the diodes having normal r-f noise exhibited high I/f noise. The noise spectrum taken on a number of the silicon diodes indicates that the 1/f noise extends into the megacycle region.
    Physics of Failure in Electronics, 1964. Third Annual Symposium on the; 10/1964
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