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Serial T-SPOT.TB responses in Tanzanian adolescents: Transient, persistent and irregular conversions
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Serial T-SPOT.TB responses in Tanzanian adolescents: Transient, persistent and irregular conversions
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Journal Article
Serial T-SPOT.TB responses in Tanzanian adolescents: Transient, persistent and irregular conversions
2022
Overview
T-SPOT.TB assays were performed manually on healthy adolescents during a tuberculosis vaccine trial in Tanzania at 5 intervals over 3 years. Assay results were defined as negative, positive, borderline or invalid. Subsequently, microtiter plates were analyzed by an automated reader to obtain quantitative counts of spot forming cells (SFCs) for the present analysis. 3387 T-SPOT.TB samples were analyzed from 928 adolescents; manual and automated assay results were 97% concordant. Based on the quantitative results 143 (15%) participants were prevalent IGRA-positives at baseline, were ineligible for further study. Among the remaining IGRA-negative participants, the annual rate of IGRA conversion was 2·9%. Among 43 IGRA converters with repeat assays 12 (28%) were persistent converters, 16 (37%) were transient converters, and 15 (35%) comprised a new category defined as irregular converters ([greater than or equal to]2 different subsequent results). ESAT-6 and CFP-10 responses were higher in prevalent than incident positives: 53 vs 36 for CFP-10 (p < 0·007); 44 vs 34 for ESAT-6 (p = 0·12). Definitions of IGRA conversion, reversion, and persistence depend critically on the frequency of testing. Multiple shifts in categories among adolescents in a TB-endemic country may represent multiple infections, variable host responses in subclinical infection, or assay variation. These findings should to be considered in the design and interpretation of TB vaccine trials based on prevention of infection. Household contact studies could determine whether even transient IGRA conversion might represent exposure to an active case of M. tuberculosis disease.
Publisher
Public Library of Science,Public Library of Science (PLoS)
Subject
