ESAT-6 and CFP-10 can be combined to reduce the cost of testing for Mycobacterium tuberculosis infection, but CFP-10 responses associate with active disease.
Commercial tests measuring IFN-gamma responses to ESAT-6 and CFP-10 are available for diagnosing Mycobacterium tuberculosis infection. Measures that minimize cost and complexity will facilitate their application in less-developed countries. We investigated whether overlapping peptides representing both ESAT-6 and CFP-10 are required to detect M. tuberculosis infection in a high TB-burden country, and whether they can be combined in a single pool. ESAT-6 and CFP-10 peptides were compared in IFN-gamma enzyme-linked immunospot (ELISPOT) in 183 HIV-negative smear-positive TB cases and 1673 HIV-negative household contacts. Separate peptide pools for each antigen were compared with a combined pool in 498 contacts. Forty per cent of responsive contacts recognized both antigens, 51% only ESAT-6 and 10% only CFP-10, whereas 56% of responsive cases recognized both antigens, 30% only ESAT-6 and 13% only CFP-10. Accordingly, CFP-10 response rates were higher for TB cases (odds ratio 2.409, P<0.001). Low purified protein derivative response rates indicated that responses to CFP-10 only were non-specific in contacts. Agreement between peptides in separate versus combined pools was good (kappa=0.758, r=0.840). Therefore a combined ESAT-6/CFP-10 peptide pool provided maximum sensitivity and efficiency, but CFP-10 was mainly required to detect active disease.
Fox
Annette
A
Tuberculosis Division, Bacterial Diseases Programme, Medical Research Council (UK) Laboratories, Banjul, The Gambia. afox@pacific.net.au
Jeffries
David J
DJ
Hill
Philip C
PC
Hammond
Abdulrahman S
AS
Lugos
Moses D
MD
Jackson-Sillah
Dolly
D
Donkor
Simon A
SA
Owiafe
Patrick K
PK
McAdam
Keith P W J
KP
Brookes
Roger H
RH
D000293:Adolescent; D000328:Adult; D000942:Antigens, Bacterial / Q000032:analysis*; D001426:Bacterial Proteins / Q000032:analysis*; D002648:Child; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods*; D005260:Female; D005714:Gambia; D006801:Humans; D008297:Male; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D012680:Sensitivity and Specificity; D014374:Tuberculin Test; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis* / Q000635:transmission
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C117940:CFP-10 protein, Mycobacterium tuberculosis; C093276:ESAT-6 protein, Mycobacterium tuberculosis