A dynamic reinfection hypothesis of latent tuberculosis infection.

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.