The progression from primary Mycobacterium tuberculosis infection to diseas
e is usually slow in humans. The aim of this study was to develop and chara
cterize a mouse model for slowly progressive primary tuberculosis, using th
e intraperitoneal (i.p.) route of infection, and to compare it with our pre
viously described model of latent M, tuberculosis infection. B6D2F1 hybrid
mice inoculated with 1.5 x 10(6) colony-forming units (CFUs) of M, tubercul
osis H37Rv were followed-up for 70 weeks. Lungs, livers and spleens were ex
amined for bacillary growth, histopathological changes and mycobacterial an
tigens (MPT64, ManLAM and multiple antigens of M. tuberculosis), by immunoh
istochemical staining. The infection was found to pass through three distin
ctive phases. During phase 1, mice were healthy despite development of smal
l granulomas and an increasing number of bacilli in the lungs. During phase
2, mice were unwell but mortality was low. The count of M, tuberculosis an
d the granuloma size stabilized. The granulomas contained an increasing pop
ulation of large, vacuolated macrophages. During phase 3, mice became morib
und and died rapidly, but the M. tuberculosis count remained relatively sta
ble. The inflammatory infiltrates filled approximate to 80% of the lung par
enchyma and the lesions were not well demarcated. Rapidly progressing infla
mmation, rather than an increase in the M. tuberculosis count, seems to con
tribute more to mortality.