Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comparative Study
. 2007 Jun;4(6):e192.
doi: 10.1371/journal.pmed.0040192.

Longitudinal assessment of an ELISPOT test for Mycobacterium tuberculosis infection

Philip C Hill  1 , Roger H Brookes, Annette Fox, Dolly Jackson-Sillah, David J Jeffries, Moses D Lugos, Simon A Donkor, Ifedayo M Adetifa, Bouke C de Jong, Alex M Aiken, Richard A Adegbola, Keith P McAdam
Affiliations
Comparative Study

Longitudinal assessment of an ELISPOT test for Mycobacterium tuberculosis infection

Philip C Hill et al. PLoS Med. 2007 Jun.

Abstract

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).

Methods and findings: 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.

PubMed Disclaimer

Conflict of interest statement

Competing Interests: RHB has a patent relating to ex vivo ELISPOT licensed through Oxford University.

Figures

Figure 1
Figure 1. Study Profile: Recruitment and 3-Mo ELISPOT Conversion and Reversion
Figure 2
Figure 2. Study Profile: 3-Mo and 18-Mo ELISPOT Results
Figure 3
Figure 3. Study Profile: Recruitment and 18-Mo ELISPOT and TST Conversion and Reversion
See this image and copyright information in PMC

Comment in

References

    1. Ewer K, Deeks J, Alvarez L, Bryant G, Waller S, et al. Comparison of T-cell-based assay with tuberculin skin test for diagnosis of Mycobacterium tuberculosis infection in a school tuberculosis outbreak. Lancet. 2003;361:1168–1173. - PubMed
    1. Hill PC, Brookes RH, Fox A, Fielding K, Jeffries DJ, et al. Large-scale evaluation of enzyme-linked immunospot assay and skin test for diagnosis of Mycobacterium tuberculosis infection against a gradient of exposure in The Gambia. Clin Infect Dis. 2004;38:966973. - PubMed
    1. Ferrara G, Losi M, D'Amico R, Roversi P, Piro R, et al. Use in routine clinical practice of two commercial blood tests for diagnosis of infection with Mycobacterium tuberculosis: A prospective study. Lancet. 2006;367:1328–1334. - PubMed
    1. Ewer K, Millington KA, Deeks JJ, Alvarez L, Bryant G, et al. Dynamic antigen-specific T-cell responses after point-source exposure to Mycobacterium tuberculosis . Am J Respir Crit Care Med. 2006;174:831–839. - PubMed
    1. Wilkinson KA, Kon OM, Newton SM, Meintjes G, Davidson RN, et al. Effect of treatment of latent tuberculosis infection on the T cell response to Mycobacterium tuberculosis antigens. J Infect Dis. 2006;193:354–359. - PubMed

Publication types

MeSH terms

Substances