Improved diagnostic evaluation of suspected tuberculosis.
BACKGROUND
The role of new T-cell-based blood tests for tuberculosis in the diagnosis of active tuberculosis is unclear.


OBJECTIVE
To compare the performance of 2 interferon-gamma assays and tuberculin skin testing in adults with suspected tuberculosis.


METHODS
Prospective study conducted in routine practice.


METHODS
2 urban hospitals in the United Kingdom.


METHODS
389 adults, predominantly of South Asian and black ethnicity, with moderate to high clinical suspicion of active tuberculosis.


METHODS
Tuberculin skin testing, the enzyme-linked immunospot assay (ELISpot) incorporating early secretory antigenic target-6 and culture filtrate protein-10 (standard ELISpot), and ELISpot incorporating a novel antigen, Rv3879c (ELISpot(PLUS)) were performed during diagnostic assessment by independent persons who were blinded to results of the other test.


METHODS
Sensitivity, specificity, predictive values, and likelihood ratios.


RESULTS
194 patients had a final diagnosis of active tuberculosis, of which 79% were culture-confirmed. Sensitivity for culture confirmed and highly probable tuberculosis was 89% (95% CI, 84% to 93%) with ELISpot(PLUS), 85% (CI, 79% to 90%) with standard ELISpot, 79% (CI, 72% to 85%) with 15-mm threshold tuberculin skin testing, and 83% (CI, 77% to 89%) with stratified thresholds of 15 and 10 mm in vaccinated and unvaccinated patients, respectively. The ELISpot(PLUS) assay was more sensitive than tuberculin skin testing with 15-mm cutoff points (P = 0.01) but not with stratified cutoff points (P = 0.10). The ELISpot(PLUS) assay had 4% higher diagnostic sensitivity than standard ELISpot (P = 0.02). Combined sensitivity of ELISpot(PLUS) and tuberculin skin testing was 99% (CI, 95% to 100%), conferring a negative likelihood ratio of 0.02 (CI, 0 to 0.06) when both test results were negative.


CONCLUSIONS
Local standards for tuberculin skin testing differed from others used internationally. The study sample included few immunosuppressed patients.


CONCLUSIONS
The ELISpot(PLUS) assay is more sensitive than standard ELISpot and, when used in combination with tuberculin skin testing, enables rapid exclusion of active infection in patients with moderate to high pretest probability of tuberculosis.
Dosanjh
Davinder P S
DP
Tuberculosis Immunology Group, Imperial College London, London, United Kingdom.
Hinks
Timothy S C
TS
Innes
John A
JA
Deeks
Jonathan J
JJ
Pasvol
Geoffrey
G
Hackforth
Sarah
S
Varia
Hansa
H
Millington
Kerry A
KA
Gunatheesan
Rubamalar
R
Guyot-Revol
Valerie
V
Lalvani
Ajit
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000942:Antigens, Bacterial / Q000276:immunology; D001426:Bacterial Proteins / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods*; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D014374:Tuberculin Test; D014376:Tuberculosis / Q000175:diagnosis*
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C117940:CFP-10 protein, Mycobacterium tuberculosis; C093276:ESAT-6 protein, Mycobacterium tuberculosis; C527546:rv3879c antigen, Mycobacterium tuberculosis; D007371:Interferon-gamma