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Journal of Clinical Microbiology, May 2005, p. 2070-2074, Vol. 43, No. 5
0095-1137/05/$08.00+0     doi:10.1128/JCM.43.5.2070-2074.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

ESAT-6/CFP-10 Fusion Protein and Peptides for Optimal Diagnosis of Mycobacterium tuberculosis Infection by Ex Vivo Enzyme-Linked Immunospot Assay in The Gambia

Philip C. Hill,1* Dolly Jackson-Sillah,1 Annette Fox,1 Kees L. M. C. Franken,2 Moses D. Lugos,1 David J. Jeffries,1 Simon A. Donkor,1 Abdulrahman S. Hammond,1 Richard A. Adegbola,1 Tom H. M. Ottenhoff,2 Michel R. Klein,2 and Roger H. Brookes1

Tuberculosis Division, Bacterial Diseases Programme, Medical Research Council Unit, Banjul, The Gambia,1 Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands2

Received 13 December 2004/ Returned for modification 18 January 2005/ Accepted 24 January 2005

Overlapping peptides of Mycobacterium tuberculosis antigens ESAT-6 and CFP-10 offer increased specificity over the purified protein derivative skin test when they were used in an ex vivo enzyme-linked immunospot (ELISPOT) assay for gamma interferon detection for the diagnosis of M. tuberculosis infection from recent exposure. We assessed whether equivalent results could be obtained for a fusion protein of the two antigens and whether a combined readout would offer increased sensitivity in The Gambia. We studied the ELISPOT assay results for 488 household contacts of 88 sputum smear-positive tuberculosis (TB) cases. The proportions of subjects positive by each test and by the tests combined were assessed across an exposure gradient, defined according to sleeping proximity to a TB case. Eighty-eight (18%) subjects were positive for CFP-10 peptides, 148 (30%) were positive for ESAT-6 peptides, 161 (33%) were positive for both peptides, and 168 (34%) were positive for the fusion protein; 188 (39%) subjects had either a positive result for a peptide or a positive result for the fusion protein. There was reasonable agreement between the peptide and the protein results (kappa statistic = 0.78) and no significant discordance (P = 0.38). There was a strong correlation between the fusion protein and combined peptide spot counts (r = 0.9), and responses to the peptide and the proteins all increased significantly according to M. tuberculosis exposure. The proportion of subjects positive for either the pool of peptides or the fusion protein offered maximum sensitivity, being significantly higher than the proportion of subjects positive for ESAT-6 peptides alone (P = 0.007). A fusion protein of ESAT-6 and CFP-10 is equivalent to overlapping peptides for the diagnosis of latent M. tuberculosis infection. Use of a combination of peptides and fusion protein offers improved sensitivity.

* Corresponding author. Mailing address: MRC Labs, P.O. Box 273, Banjul, The Gambia. Phone: 00220 4494072. Fax: 00220 4496513. E-mail: phill{at}mrc.gm.

Journal of Clinical Microbiology, May 2005, p. 2070-2074, Vol. 43, No. 5
0095-1137/05/$08.00+0     doi:10.1128/JCM.43.5.2070-2074.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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