Serial testing for tuberculosis: can we make sense of T cell assay conversions and reversions?

Abstract

The authors discuss a new study, which they say is a valuable addition to the existing literature on the performance of interferon gamma release assays in serial testing for TB infection.

Figure 1. A Schematic of the Postulated Correlation between Bacterial Load, T Cell Response, and Clinical Outcome

Initial infection might be controlled at its onset with minimal bacterial replication (measured as colony-forming units [CFU]) and induction of ESAT-6 responses (A and D). In such cases, the T cell response may be below the diagnostic cut-off. However, in most cases, initial bacterial replication reaches a point at which it induces an ESAT-6-specific IFNγ response to increase above the established cut-off value (infection threshold), enabling the diagnosis of an individual as latently infected (B and E). In most cases, individuals control the infection, resulting in latent infection, but some develop active TB disease associated with progressive bacterial replication. This is accompanied by increasing and strong ESAT-6 responses and, as hypothesized here, an incipient (higher) disease cut-off value may predict subsequent development of progressive disease (C and F). Reproduced with permission from [13].