Can Tb Readings Give a False Positive
Thorax. 2006 February; 61(ii): 180.
Repeated tuberculin testing does non induce false positive ELISPOT results
Keywords: tuberculosis, tuberculin skin examination, ELISPOT, boosting, screening
The Enzyme Linked ImmunoSpot (ELISPOT) is a new rapid T cell based blood test (otherwise known every bit an interferon‐γ assay) for the diagnosis of latent tuberculosis infection.1 ,2 ,3 The commercially available form of the analysis, T‐SPOT® TB (Oxford Immunotec, Abingdon, Uk) has European regulatory approval as an in vitro diagnostic test and is increasingly being used in clinical practice. The exam is based on the enumeration of interferon‐γ producing T cells which are specific for two highly antigenic proteins, early secretory antigenic target‐6 (ESAT‐half-dozen) and culture filtrate protein 10 (CFP‐ten).1 These proteins are expressed by Mycobacterium tuberculosis just are absent from M bovis BCG vaccine. Hence, the examination does not give false positive results in BCG vaccinated individuals.1 ,two ,iii
ESAT‐6 and CFP‐10 are, all the same, independent inside tuberculin purified protein derivative (PPD). Since ELISPOT is a highly sensitive method for measuring even low numbers of antigen specific T cells,4 concerns have been raised as to whether repeated tuberculin skin tests might induce T cell responses to these specific antigens, resulting in false positive ELISPOT results.
As T‐SPOT® TB enters clinical practice, it may initially be used by some people in conjunction with the tuberculin skin test. Information technology is therefore of import to know whether false positive ELISPOT results are induced past tuberculin testing. The following results strongly suggest that this is not the case.
The results reported here are from a 2 twelvemonth follow upwardly of a group of people with potential point source exposure to multidrug resistant tuberculosis on a maternity unit in Modena University Infirmary, Italy.five Forty four BCG unvaccinated subjects were negative at initial screening by tuberculin pare test and ELISPOT, three months after the signal source exposure ceased. All participants had negative results on serological testing for HIV infection. Tuberculin skin tests were administered and read by two experienced chest physicians using five units of PPD‐S injected intradermally almost 2 hours after blood was fatigued for ELISPOT assays. The ELISPOT assays were performed and scored, every bit previously described,five by two technicians without knowledge of personal identifiers. All these individuals underwent repeated testing by peel test and ELISPOT at 9, fifteen and 24 months after the point exposure. At 24 months all 44 individuals remained ELISPOT negative, although three had become positive with the tuberculin skin test (fig 1 ). Thus, inoculation of three PPD skin tests over a 21 month period in 44 initially ELISPOT negative individuals did non induce any false positive ELISPOT results.
Effigy 1 Fourth dimension grade of development of positive Mantoux results in the three participants who became tuberculin pare exam (TST) positive as a consequence of repeated skin testing.
These results evidence that repeated tuberculin skin testing over fourth dimension does non induce a T cell response to ESAT‐half dozen or CFP‐10 resulting in simulated positive ELISPOT results. Our findings suggest that this new interferon‐γ blood assay could be used in association with the standard PPD skin test without whatever reduction in its high diagnostic specificity. Given the high sensitivity of the ELISPOT assay for detecting even depression numbers of antigen specific T cells, the absenteeism of a detectable response to ESAT‐six and CFP‐10 suggests that T cells specific for these antigens were not induced by repeated inoculation of PPD. This is consistent with the observation that ESAT‐six has very poor immunogenicity when administered as a candidate vaccine, unless inoculated with powerful adjuvants.6 This is in stark contrast to its potent immunogenicity when presented to the immune organisation during natural M tuberculosis infection; indeed, ESAT‐6 is the strongest known target of T prison cell responses during tuberculosis infection.
Our results too propose that T‐SPOT® TB could be especially useful in distinguishing true latent tuberculosis infection from simulated positive tuberculin skin test results that have arisen through "boosting". Boosting occurs in people who undergo repeated tuberculin skin tests (such equally healthcare workers) and causes false positive pare examination results in uninfected people. This miracle is a major problem in tuberculosis screening programmes for healthcare workers, prisoners, and other groups at persistent take a chance of tuberculosis exposure, and was almost certainly the reason why iii individuals in our study developed positive skin test results afterwards repeated testing. Our findings suggest that T‐SPOT® TB will maintain its high specificity fifty-fifty in individuals with false positive skin examination results due to boosting from repeated tuberculin testing. Thus, use of T‐SPOT® TB could enhance our ability to screen for latent tuberculosis infection even in populations who accept already been repeatedly screened by the peel examination.
Footnotes
This piece of work was supported by the Wellcome Trust and Azienda Ospedaliera Policlinico di Modena.
Competing interests: AL is a named inventor on patents relating to T jail cell based diagnosis filed past the University of Oxford. Regulatory blessing and commercialisation of ELISPOT (T‐SPOT TB) has been undertaken by a spin out visitor of the University of Oxford (Oxford Immunotec Ltd), in which AL has a share of equity and to which he acts as scientific advisor in a non‐executive capacity. KE is a named inventor on a patent application relating to the awarding of ELISPOT filed by the Academy of Oxford. The University of Oxford has a share of equity in Oxford Immunotec Ltd.
The report was approved by the Modena research ideals committee and each study participant provided written informed consent.
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Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2104569/
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