title: Using ELISPOT to expose false positive skin test conversion in tuberculosis contacts.
abstract: 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.
authors.affiliation: Bacterial Diseases Programme, Medical Research Council Unit, Banjul, The Gambia. phill@mrc.gm
authors.forename: Philip C
authors.initials: PC
authors.lastname: Hill
authors.forename: David J
authors.initials: DJ
authors.lastname: Jeffries
authors.forename: Roger H
authors.initials: RH
authors.lastname: Brookes
authors.forename: Annette
authors.initials: A
authors.lastname: Fox
authors.forename: Dolly
authors.initials: D
authors.lastname: Jackson-Sillah
authors.forename: Moses D
authors.initials: MD
authors.lastname: Lugos
authors.forename: Simon A
authors.initials: SA
authors.lastname: Donkor
authors.forename: Bouke C
authors.initials: BC
authors.lastname: de Jong
authors.forename: Tumani
authors.initials: T
authors.lastname: Corrah
authors.forename: Richard A
authors.initials: RA
authors.lastname: Adegbola
authors.forename: Keith P
authors.initials: KP
authors.lastname: McAdam
mesh_terms: 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
chemical_list: D001500:BCG Vaccine