10 research outputs found
Clinical diagnostic utility of IP-10 and LAM antigen levels for the diagnosis of tuberculous pleural effusions in a high burden setting
Background: Current tools for the diagnosis of tuberculosis pleural effusions are sub-optimal. Data about the value of new
diagnostic technologies are limited, particularly, in high burden settings. Preliminary case control studies have identified
IFN-γ-inducible-10kDa protein (IP-10) as a promising diagnostic marker; however, its diagnostic utility in a day-to-day clinical
setting is unclear. Detection of LAM antigen has not previously been evaluated in pleural fluid.
Methods: We investigated the comparative diagnostic utility of established (adenosine deaminase [ADA]), more recent
(standardized nucleic-acid-amplification-test [NAAT]) and newer technologies (a standardized LAM mycobacterial antigendetection
assay and IP-10 levels) for the evaluation of pleural effusions in 78 consecutively recruited South African
tuberculosis suspects. All consenting participants underwent pleural biopsy unless contra-indicated or refused. The
reference standard comprised culture positivity for M. tuberculosis or histology suggestive of tuberculosis.
Principal Findings: Of 74 evaluable subjects 48, 7 and 19 had definite, probable and non-TB, respectively. IP-10 levels were
significantly higher in TB vs non-TB participants (p<0.0001). The respective outcomes [sensitivity, specificity, PPV, NPV %]
for the different diagnostic modalities were: ADA at the 30 IU/L cut-point [96; 69; 90; 85], NAAT [6; 93; 67; 28], IP-10 at the
28,170 pg/ml ROC-derived cut-point [80; 82; 91; 64], and IP-10 at the 4035 pg/ml cut-point [100; 53; 83; 100]. Thus IP-10,
using the ROC-derived cut-point, missed ~20% of TB cases and mis-diagnosed ~20% of non-TB cases. By contrast, when a
lower cut-point was used a negative test excluded TB. The NAAT had a poor sensitivity but high specificity. LAM antigendetection
was not diagnostically useful.
Conclusion: Although IP-10, like ADA, has sub-optimal specificity, it may be a clinically useful rule-out test for tuberculous
pleural effusions. Larger multi-centric studies are now required to confirm our findings
Clinical diagnostic utility of IP-10 and LAM antigen levels for the diagnosis of tuberculous pleural effusions in a high burden setting
BACKGROUND: Current tools for the diagnosis of tuberculosis pleural effusions are sub-optimal. Data about the value of new diagnostic technologies are limited, particularly, in high burden settings. Preliminary case control studies have identified IFN-γ-inducible-10kDa protein (IP-10) as a promising diagnostic marker; however, its diagnostic utility in a day-to-day clinical setting is unclear. Detection of LAM antigen has not previously been evaluated in pleural fluid. METHODS: We investigated the comparative diagnostic utility of established (adenosine deaminase [ADA]), more recent (standardized nucleic-acid-amplification-test [NAAT]) and newer technologies (a standardized LAM mycobacterial antigen-detection assay and IP-10 levels) for the evaluation of pleural effusions in 78 consecutively recruited South African tuberculosis suspects. All consenting participants underwent pleural biopsy unless contra-indicated or refused. The reference standard comprised culture positivity for M. tuberculosis or histology suggestive of tuberculosis. Principal FINDINGS: Of 74 evaluable subjects 48, 7 and 19 had definite, probable and non-TB, respectively. IP-10 levels were significantly higher in TB vs non-TB participants (p<0.0001). The respective outcomes [sensitivity, specificity, PPV, NPV %] for the different diagnostic modalities were: ADA at the 30 IU/L cut-point [96; 69; 90; 85], NAAT [6; 93; 67; 28], IP-10 at the 28,170 pg/ml ROC-derived cut-point [80; 82; 91; 64], and IP-10 at the 4035 pg/ml cut-point [100; 53; 83; 100]. Thus IP-10, using the ROC-derived cut-point, missed ∼20% of TB cases and mis-diagnosed ∼20% of non-TB cases. By contrast, when a lower cut-point was used a negative test excluded TB. The NAAT had a poor sensitivity but high specificity. LAM antigen-detection was not diagnostically useful. CONCLUSION: Although IP-10, like ADA, has sub-optimal specificity, it may be a clinically useful rule-out test for tuberculous pleural effusions. Larger multi-centric studies are now required to confirm our findings
Quantitative lung T cell responses aid the rapid diagnosis of pulmonary tuberculosis
Background: The diagnosis of smear-negative pulmonary tuberculosis (TB) is problematic. There are limited data on the profile of alveolar TB antigen-specific T cells, and their utility for the rapid immunodiagnosis of pulmonary TB is unclear.
Methods: Antigen-specific interferon γ (IFNγ) responses to the RD-1 antigens ESAT-6 and CFP-10 (T-SPOT.TB and QuantiFERON-TB-Gold-In-Tube), heparin-binding haemagglutinin and purified protein derivative were evaluated, using alveolar lavage cells, in 91 consecutively recruited South African patients suspected of having TB.
Results: Of 85 evaluable patients (29% HIV+), 24, 11, 48 and 2 had definite TB, probable TB, non-TB and an uncertain diagnosis, respectively. Between 34% (T-SPOT.TB) and 41% (QuantiFERON-TB-Gold-In-Tube) of all test results were inconclusive. Failure of the positive control was significantly higher with the QuantiFERON-TB-Gold-In-Tube than with T-SPOT.TB (85% vs 46% of inconclusive results; p = 0.001). Using staphylococcal enterotoxin B, compared with phytohaemagglutinin, substantially reduced failure of the positive control (25% to 3%; p = 0.02). In evaluable samples, when the definite and non-TB groups were used for outcome analysis, the percentage sensitivity, specificity, positive predictive value and negative predictive value for T-SPOT.TB (≥20 spots/million alveolar mononuclear cells) and QuantiFERON-TB-Gold-In-Tube (0.35 IU/ml) were 89, 94, 89 and 94% (n = 55) and 55, 86, 77 and 69% (n = 46), respectively. Rapid diagnosis of TB was achieved more frequently with T-SPOT.TB than with smear microscopy (14/24 (58%) vs. 7/24 (29%) of definite TB cases; p = 0.02). Heparin-binding haemagluttinin and purified protein derivative alveolar lymphocyte IFNγ responses had poor performance outcomes.
Conclusion: Provided evaluable results are obtained, the RD-1, but not the heparin-binding haemagglutinin or purified protein derivative, alveolar lymphocyte IFNγ ELISPOT response is a useful rapid immunodiagnostic test for TB. However, test utility in high-burden settings may be limited by the high proportion of inconclusive results
Scatter-plot (left panel) showing IP-10 levels in patients with pleural tuberculosis versus non-tuberculosis controls.
<p>The area under the ROC curve was 0.82.</p
Performance outcomes of ADA, microbiological investigations, a nucleic-acid-amplification-test [NAAT] and unstimulated IFN-γ levels for the diagnosis of TB pleural effusion in 74 TB suspects using the <i>definite and non-TB</i> groups.
<p>( ; ) = 95% CI.</p>**<p>Cut-point used in day-to-day clinical practice in Cape Town, South Africa, where the test guides the institution of anti-TB treatment.</p><p>AUC = area under the ROC curve.</p>***<p>AUC-derived cut-point.</p>#<p>cut-point with a high NPV.</p><p>RLU = relative light units detectable using a luminometer.</p
Individual and incremental value of different test combinations.
*<p> = 47 iu/l cut-point and non-asterisked values refer to the 30 iu/l cut-point.</p>$<p> = maximal clinical score. Unless, otherwise stated all IP-10 outcomes refer to the 28170 pg/ml cut-point.</p
Performance outcomes of ADA, microbiological investigations, a nucleic-acid-amplification-test [NAAT] and unstimulated IFN-γ levels for the diagnosis of TB pleural effusion in 74 TB suspects when the <i>definite and probable TB groups are combined</i>.
<p>( ; ) = 95% CI.</p>**<p>Cut-point used in day-to-day clinical practice in Cape Town, South Africa, where the test guides the institution of anti-TB treatment.</p><p>AUC = area under the ROC curve.</p>***<p>AUC-derived cut-point.</p>#<p>cut-point with a high NPV.</p><p>RLU = relative light units detectable using a luminometer.</p
Scatter-plots (left panel) and area under the ROC (right panel) of a standardized nucleic-acid amplification test using pleural fluid from patients with tuberculous (TB) and non-tuberculous (non-TB) effusions.
<p>Area under the ROC values are shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0004689#pone-0004689-t001" target="_blank">table 1</a>. Positive (culture and amplification) and negative controls (culture and amplification) from 6 independent runs are shown.</p
Summary and flow chart of the established and newer technologies evaluated.
<p>Summary and flow chart of the established and newer technologies evaluated.</p