The minipig as an animal model to study Mycobacterium tuberculosis infection and natural transmission

Authors: RAMOS, LAYLAA - Colorado State University; OBREGON-HENAO, ANDRES - Colorado State University; HENAO-TAMAYO, MARCELA - Colorado State University; BOWEN, RICHARD - Colorado State University; Lunney, Joan; GONZALEZ-JUARRERO, MERCEDES - Colorado State University

Submitted to: Tuberculosis
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/11/2017
Publication Date: 7/18/2017
Citation: Ramos, L., Obregon-Henao, A., Henao-Tamayo, M., Bowen, R., Lunney, J.K., Gonzalez-Juarrero, M. 2017. The minipig as an animal model to study Mycobacterium tuberculosis infection and natural transmission. Tuberculosis. 106:91-98.

Interpretive Summary: Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), kills or debilitates more people between 15-59 years of age than any other disease in the world. Drug-susceptible TB is curable, but nowadays cases of multiple and extensively drug resistant TB are on the rise. The disease often affects the lungs, however, only 5-15% of infected individuals progress to active TB. Studies in infants and children with TB are few, even though this age group accounts for more than 20% of TB cases in high burden countries. In this article, we show evidence that minipigs provide benefits for the study of human adult, adolescent and infant TB. Two-month old minipigs (representing human infants) and six-month old minipigs (representing adolescents) were infected via the aerosol route with a hyper-virulent clinical strain of Mtb and monitored for 11 or 36 weeks post-challenge, respectively. Our results affirm that minipigs are experimental hosts of Mtb infection. The pathology developed in pig lungs and lymph nodes resembles pathological findings described in human TB. Importantly, within communities of Mtb infected minipigs, natural transmission does occur. Thus, the minipig should be a good animal model to study Mycobacterium tuberculosis infection and natural transmission, as well as to test for potential use of the minipig for TB vaccine and drug efficacy testing.

Technical Abstract: Infants and children with tuberculosis (TB) account for more than 20% of cases in endemic countries. Current animal models study TB during adulthood but animal models for adolescent and infant TB are scarce. Here we propose that minipigs can be used as an animal model to study adult, adolescent and infant TB including natural transmission. Two-month old minipigs (representing infant age in humans) and six-month old minipigs (representing adolescence in humans) were infected via the aerosol route with hyper-virulent clinical strain W-Beijing Mycobacterium tuberculosis (Mtb) HN878 and were monitored for 11 or 36 weeks post-challenge, respectively. In the same studies groups of infected and unchallenged animals were housed together. Viable bacteria were recovered from pulmonary and thoracic lymph nodes from both infected and their initially unchallenged natural contacts. Bacillary load, gross lesions and histopathology revealed similarities to the spectrum of disease observed in human TB. The study did not reach terminal end point, thus it was not possible to annotate definitive clinical symptoms of active TB. Minipigs are experimental hosts of Mtb HN878, and the pathology developed in their lungs and lymph nodes resembles pathological findings described in human TB. Importantly, within communities of Mtb infected minipigs natural transmission occurs.