Figure - PMC

Skip to main content

View full-text article in PMC

. Author manuscript; available in PMC: 2013 May 1.

Published in final edited form as: Drug Discov Today. 2011 Dec 20;17(9-10):514–521. doi: 10.1016/j.drudis.2011.12.013

Fig. 1 — A. In this model after initial exposure, the bacillus may be eliminated by innate immune mechanisms (mucocillary, neutrophil, macrophage etc.). Once infection is established and an acquired immune response has been generated IGRA or TST may become positive. Infection may be eliminated by the acquired immune response but if antigen specific effector memory persists TST or IGRA may remain positive and it is possible a degree of protection from reinfection may be present. Over time memory responses may wane resulting in reversion of TST or IGRA. In these scenarios in which the bacillus was eliminated no further treatment would be required but prophylactic vaccination may further reduce risk of re infection. If the bacillus is controlled but not eliminated by the acquired immune response the individual may enter a state of quiescent infection in which both symptoms and culturable bacilli are absent and with a greater proportion of bacilli in a dormant rather than replicative state. Immunosuppression (e.g. HIV infection or anti TNF therapy) during this state may lead to rapid progression to active disease. The dynamic nature of this state may result in fluctuation in bacillary load and metabolic state of bacilli with a probability of the immune system regaining control reducing as bacillary load increases, if bacilli are culturable and symptoms and signs absent this would be regarded as a sub-clinical state. Optimal treatment regimens for infection with regard to duration of treatment, number of drugs and mechanism of active of drugs would vary according to bacillary load and proportion of bacilli in dormant state.

B. Shows for a hypothetical group of people exposed to TB, a prediction of how the proportion of individuals in the proposed infection states might vary in the years following single exposure (graph depicts all exposed individuals over time).

Fig. 1 — A. In this model after initial exposure, the bacillus may be eliminated by innate immune mechanisms (mucocillary, neutrophil, macrophage etc.). Once infection is established and an acquired immune response has been generated IGRA or TST may become positive. Infection may be eliminated by the acquired immune response but if antigen specific effector memory persists TST or IGRA may remain positive and it is possible a degree of protection from reinfection may be present. Over time memory responses may wane resulting in reversion of TST or IGRA. In these scenarios in which the bacillus was eliminated no further treatment would be required but prophylactic vaccination may further reduce risk of re infection. If the bacillus is controlled but not eliminated by the acquired immune response the individual may enter a state of quiescent infection in which both symptoms and culturable bacilli are absent and with a greater proportion of bacilli in a dormant rather than replicative state. Immunosuppression (e.g. HIV infection or anti TNF therapy) during this state may lead to rapid progression to active disease. The dynamic nature of this state may result in fluctuation in bacillary load and metabolic state of bacilli with a probability of the immune system regaining control reducing as bacillary load increases, if bacilli are culturable and symptoms and signs absent this would be regarded as a sub-clinical state. Optimal treatment regimens for infection with regard to duration of treatment, number of drugs and mechanism of active of drugs would vary according to bacillary load and proportion of bacilli in dormant state.

B. Shows for a hypothetical group of people exposed to TB, a prediction of how the proportion of individuals in the proposed infection states might vary in the years following single exposure (graph depicts all exposed individuals over time).