Using ELISPOT to expose false positive skin test conversion in tuberculosis contacts.
BACKGROUND
Repeat tuberculin skin tests may be false positive due to boosting of waned immunity to past mycobacterial exposure. We evaluated whether an ELISPOT test could identify tuberculosis (TB) contacts with boosting of immunity to non-tuberculous mycobacterial exposure.


RESULTS
We conducted tuberculin and ELISPOT tests in 1665 TB contacts: 799 were tuberculin test negative and were offered a repeat test after three months. Those with tuberculin test conversion had an ELISPOT, chest X-ray and sputum analysis if appropriate. We compared converters with non-converters, assessed the probability of each of four combinations of ELISPOT results over the two time points and estimated boosting with adjustment for ELISPOT sensitivity and specificity. 704 (72%) contacts had a repeat tuberculin test; 176 (25%) had test conversion, which increased with exposure to a case (p = 0.002), increasing age (p = 0.0006) and BCG scar (p = 0.06). 114 tuberculin test converters had ELISPOT results: 16(14%) were recruitment positive/follow-up positive, 9 (8%) positive/negative, 34 (30%) negative/positive, and 55 (48%) were negative/negative. There was a significant non-linear effect of age for ELISPOT results in skin test converters (p = 0.038). Estimates of boosting ranged from 32%-41% of skin test converters with increasing age. Three converters were diagnosed with TB, two had ELISPOT results: both were positive, including one at recruitment.


CONCLUSIONS
We estimate that approximately one third of tuberculin skin test conversion in Gambian TB case contacts is due to boosting of immunity to non-tuberculous mycobacterial exposure. Further longitudinal studies are required to confirm whether ELISPOT can reliably identify case contacts with tuberculin test conversion that would benefit most from prophylactic treatment.
Hill
Philip C
PC
Bacterial Diseases Programme, Medical Research Council Unit, Banjul, The Gambia. phill@mrc.gm
Jeffries
David J
DJ
Brookes
Roger H
RH
Fox
Annette
A
Jackson-Sillah
Dolly
D
Lugos
Moses D
MD
Donkor
Simon A
SA
de Jong
Bouke C
BC
Corrah
Tumani
T
Adegbola
Richard A
RA
McAdam
Keith P
KP
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001500:BCG Vaccine / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods*; D005006:Ethnicity; D005189:False Positive Reactions; D005260:Female; D005714:Gambia; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology; D012680:Sensitivity and Specificity; D013183:Sputum / Q000382:microbiology; D014374:Tuberculin Test; D014376:Tuberculosis / Q000175:diagnosis* / Q000382:microbiology / Q000517:prevention & control; D055815:Young Adult
D001500:BCG Vaccine