Cardona hypothesises that the bacilli is not in a state of suspension rather it maintains a presence by very slowly growing and replicating (reinfecting), a process which normally will decrease over time, but not a lifetime as previously thought. This can be demonstrated by using T-cell Interferon-Gamma Release Assay (TIGRA), a test which can distinguish between effector T-cells and memory T-cells;
At the present time, this hypothesis can be carefully proved using the new LTBI diagnostic tools. TIGRA techniques support the concept that growing bacilli are constantly present in LTBI, as postulated in the dynamic hypothesis. TIGRAs may detect the IFN-y released by effector lymphocytes (with an approximate half-life of 3 days) after identifying macrophages that present antigens (included in the ESAT-6 complex) produced by growing bacilliThe significance of the presence of effector and/or memory T-cells is explained clearly in the FAQ on the Cellestis website
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Background: It has been traditionally postulated that individuals, once infected by Mycobacterium tuberculosis, will retain throughout their entire lifetime latent bacilli which will remain dormant in old lesions. This bacillus would then be the source of a later reactivation of active tuberculosis (TB), with the aid of resuscitation factors. Unfortunately, the presence of these bacilli can only be predicted by indirect immunological methods, such as the tuberculin skin test (TST) or T cell interferon–gamma release assays. Other evidence shows that a 9-month isoniazid treatment of TST+ individuals converting to TB reduces the incidence of TB by approximately 90%.
Questions: Taking into account this widely accepted framework, I suggest that there are at least three relevant questions to answer:
(1) How can dormant bacilli remain in the lungs for an entire lifetime, taking into account constant cellular turnover and the healing of damaged tissues?
(2) What provides the resuscitation factor to dormant bacilli, assuming that these latent bacilli are indeed present inside old lesions?
(3) Why can a 9-month treatment with isoniazid eliminate dormant bacilli? As isoniazid is active only against growing
bacilli, and thus is only able to destroy them after reactivation of latent bacilli, this treatment should have to be provided for life if the traditionally accepted postulate is correct.
Hypothesis: For a better understanding of latent TB infection. I propose a hypothesis that describes a dynamic scenario of constant endogenous reinfection with M. tuberculosis which explains the efficacy of the current standard of treatment. If this hypothesis is true, new strategies for the management of TB may arise.
Infection 2009
DOI 10.1007/s15010-008-8087-y
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