Longitudinal assessment of an ELISPOT test for Mycobacterium tuberculosis infection.
BACKGROUND
Very little longitudinal information is available regarding the performance of T cell-based tests for Mycobacterium tuberculosis infection. To address this deficiency, we conducted a longitudinal assessment of the enzyme-linked immunosorbent spot test (ELISPOT) test in comparison to the standard tuberculin skin test (TST).


RESULTS
In tuberculosis (TB) contacts we repeated ELISPOT tests 3 mo (n = 341) and 18 mo (n = 210) after recruitment and TSTs at 18 mo (n = 130). We evaluated factors for association with conversion and reversion and investigated suspected cases of TB. Of 207 ELISPOT-negative contacts, 51 (24.6%) had 3-mo ELISPOT conversion, which was associated with a positive recruitment TST (odds ratio [OR] 2.2, 95% confidence interval [CI] 1.0-5.0, p = 0.048) and negatively associated with bacillus Calmette-Guérin (BCG) vaccination (OR 0.5, 95% CI 0.2-1.0, p = 0.06). Of 134 contacts, 54 (40.2%) underwent 3-mo ELISPOT reversion, which was less likely in those with a positive recruitment TST (OR 0.3, 95% CI 0.1-0.8, p = 0.014). Between 3 and 18 mo, 35/132 (26.5%) contacts underwent ELISPOT conversion and 28/78 (35.9%) underwent ELISPOT reversion. Of the 210 contacts with complete results, 73 (34.8%) were ELISPOT negative at all three time points; 36 (17.1%) were positive at all three time points. Between recruitment and 18 mo, 20 (27%) contacts had ELISPOT conversion; 37 (50%) had TST conversion, which was associated with a positive recruitment ELISPOT (OR 7.2, 95% CI 1.4-37.1, p = 0.019); 18 (32.7%) underwent ELISPOT reversion; and five (8.9%) underwent TST reversion. Results in 13 contacts diagnosed as having TB were mixed, but suggested higher TST sensitivity.


CONCLUSIONS
Both ELISPOT conversion and reversion occur after M. tuberculosis exposure. Rapid ELISPOT reversion may reflect M. tuberculosis clearance or transition into dormancy and may contribute to the relatively low reported ELISPOT conversion rate. Therefore, a negative ELISPOT test for M. tuberculosis infection should be interpreted with caution.
Hill
Philip C
PC
Bacterial Diseases Programme, Medical Research Council Laboratories, Banjul, The Gambia. phill@mrc.gm
Brookes
Roger H
RH
Fox
Annette
A
Jackson-Sillah
Dolly
D
Jeffries
David J
DJ
Lugos
Moses D
MD
Donkor
Simon A
SA
Adetifa
Ifedayo M
IM
de Jong
Bouke C
BC
Aiken
Alex M
AM
Adegbola
Richard A
RA
McAdam
Keith P
KP
D000293:Adolescent; D000328:Adult; D000368:Aged; D000942:Antigens, Bacterial / Q000276:immunology; D001426:Bacterial Proteins / Q000276:immunology; D015331:Cohort Studies; D016358:Contact Tracing; D004269:DNA, Bacterial / Q000235:genetics; D016208:Databases, Factual; D004797:Enzyme-Linked Immunosorbent Assay; D005188:False Negative Reactions; D005260:Female; D005500:Follow-Up Studies; D005714:Gambia / Q000453:epidemiology; D006801:Humans; D007371:Interferon-gamma / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology / Q000302:isolation & purification*; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013183:Sputum / Q000382:microbiology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D013997:Time Factors; D014374:Tuberculin Test; D014376:Tuberculosis / Q000175:diagnosis* / Q000453:epidemiology / Q000276:immunology / Q000382:microbiology
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C117940:CFP-10 protein, Mycobacterium tuberculosis; D004269:DNA, Bacterial; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D007371:Interferon-gamma