|Behr, Marcel -|
Submitted to: Lancet Infectious Diseases
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: August 27, 2013
Publication Date: March 1, 2014
Repository URL: http://handle.nal.usda.gov/10113/58867
Citation: Behr, M., Waters, W.R. 2014. Is tuberculosis a lymphatic disease with a pulmonary portal. Lancet Infectious Diseases. 14(3):250-255. Interpretive Summary: Despite highly successful eradication efforts in several countries, tuberculosis of cattle remains a serious health concern worldwide. In addition, an outbreak of tuberculosis in white-tailed deer in Michigan and continued importation of tuberculous cattle from Mexico have seriously hindered eradication efforts within the United States. Elsewhere, wildlife reservoirs including Eurasian badgers in the UK, brushtailed possums in New Zealand, wild boar in Spain, and cape buffalo in southern Africa seriously hinder control efforts. Without new strategies, eradication and control of bovine tuberculosis will be impossible. Thus, improved techniques such as vaccination are needed for prevention of tuberculosis in cattle. Tuberculosis in cattle is very similar to tuberculosis in humans. The two diseases have many similarities. In this article, a perspective is provided on the nature of tuberculosis as it affects cattle, wildlife, and humans. Insights are provided into future research opportunities, given a fresh perspective on the nature and course of the disease. This article provides insight into the nature of the host/pathogen relationship of tuberculosis.
Technical Abstract: Tuberculosis (TB) is commonly viewed as a pulmonary disease, in which infection, persistence, induction of pathology and bacterial expulsion all occur in the lungs. In this model, enlarged lymph nodes represent reactive adenitis and spread of organisms to extrapulmonary sites results in a non-transmissible disease which is an evolutionary dead-end for the pathogen. Based on this paradigm, TB research aims to understand the metabolic and immunologic pressures experienced by Mycobacterium tuberculosis in the lung with the ultimate goal of developing improved tools to diagnose, treat or prevent pulmonary disease. This pulmonary model contrasts with an alternative, lympho-centric paradigm in which M. tuberculosis passes through the lungs to establish a lymphatic infection, following which it ultimately induces secondary lung pathology in order for transmission to occur. Considerations that support this lymphatic model include historical descriptions of human TB from the pre-antibiotic era, analogy with other mycobacterial infections, observations on TB in non-human hosts and experimental models of TB disease. At a fundamental level, a lympho-centric model proposes that spread of organisms outside the lung parenchyma is essential for the induction of adaptive immunity, itself necessary for inducing the pathology required for transmission. This model suggests that clinical latency may present in the face of an active lymphatic infection, without an evident focus of pulmonary pathology. Furthermore, a lymphatic model offers an explanation for why the site of entry (Ghon locus) is anatomically separated from the most common site of reactivation disease (the apex). On a more practical level, an alternative perspective that considers TB as a lymphatic disease can influence strategies towards the development of novel diagnostics, drugs and vaccines. “A striking example of a difference in tissue susceptibility is provided by the freer multiplication of the bacillus in the lymph nodes draining a site of primary infection than in the infected site itself” Arnold Rich, the Pathogenesis of Tuberculosis, 1944 (1).