Tuberculosis most commonly presents as a
pulmonary disease, in which
infection, persistence, and induction of transmissible pathology all occur in the lungs. If viewed as a
pulmonary disease, enlarged lymph nodes represent reactive
adenitis, and extrapulmonary forms of
tuberculosis (including lymphatic
tuberculosis) are not transmissible, hence representing an evolutionary dead-end for the pathogen. In an alternative theory, Mycobacterium tuberculosis passes asymptomatically through the lungs and rapidly establishes a chronic lymphatic
infection. After a period of weeks to decades secondary lung pathology develops, ultimately allowing transmission to occur. Evidence that supports this lymphatic model includes historical descriptions of human
tuberculosis from the preantibiotic era, analogy with other mycobacterial
infections, observations of
tuberculosis in non-human hosts, and experimental models of
tuberculosis disease. At a fundamental level, a lymphocentric model proposes that spread of organisms outside the lung parenchyma is essential to induce adaptive immunity, which is crucial for the generation of transmissible pathology. Furthermore, a lymphatic model could explain why the lesion associated with primary
infection (Ghon focus) is anatomically separated from the most common site of reactivation disease (the apex). More practically, an alternative perspective that classes
tuberculosis as a
lymphatic disease might affect strategies for preclinical and clinical assessment of novel diagnostics, drugs, and
vaccines.