Latent Tuberculosis: Two Centuries of Confusion.

The term latent tuberculosis (TB) was coined two centuries ago to describe post-mortem tuberculous pathology in the absence of ante-mortem tuberculosis manifestations. However, the meaning of the term has changed with each passing century, engendering confusion. In the early 20th century, with the advent of microbiological assays for live tubercle bacteria, latent TB switched from the host to refer to the bacteria from post-mortem tissues of nontuberculous hosts. Then in the late 20th century, the definition of latent TB infection returned to the host, this time referring to those with immunoreactivity to Mycobacterium tuberculosis antigens. Based on this new definition, latent TB infection is unique among bacterial infectious diseases, in that supportive evidence of the infection state is sought by the absence of the causative bacterium and its clinical manifestations. The use of indirect bedside and laboratory tests to denote infection creates clinical and research confusion, as the tests for immunoreactivity suffer from recognized limitations in sensitivity and specificity. We propose that the concept of latent TB infection be separated from that of tuberculous immunoreactivity in the interest of correct diagnosis and focused treatment, correct formulation and interpretation of research questions and better allocation of programmatic resources for TB elimination. To this end, we suggest new terminology to course-correct our thinking about tuberculous infection (TBI) which is subdivided into tuberculous infection-no disease (TBInd) and the long-accepted term for the disease, tuberculosis (TB).