Abstract
BackgroundRepeat 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.Methodology/Principal FindingsWe 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/SignificanceWe 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.
Highlights
The period of highest risk for developing tuberculosis (TB) is in the first year after exposure to Mycobacterium tuberculosis.[1]
Individuals most likely to be in this group are those who have a negative test for M. tuberculosis infection, exposure to a TB case and subsequent test conversion
The British National Institute for Health and Clinical Excellence (NICE) published recommendations suggesting that the traditional tuberculin test and an interferon-gamma test be used in a two-step manner – the tuberculin test as a screening tool and an interferon-gamma test as confirmation.[3]
Summary
The period of highest risk for developing tuberculosis (TB) is in the first year after exposure to Mycobacterium tuberculosis.[1]. Conversion of the traditional tuberculin skin test can be confounded by the ‘booster’ phenomenon, whereby an initial tuberculin injection causes recall of waned cell-mediated immunity to previous, largely non-tuberculous, mycobacterial exposure. It is our view that such a twostep approach may be most appropriate when trying to distinguish true tuberculin skin test conversion from that due to the booster phenomenon, at least in relation to previous non-tuberculous exposure. Repeat tuberculin skin tests may be false positive due to boosting of waned immunity to past mycobacterial exposure. 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
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