The aim of the study mas to establish a reproducible murine model for
latent tuberculosis. We propose an operational definition of latent mu
rine tuberculosis as a stable Mycobacterium tuberculosis count in lung
s and spleens without clinical signs or obvious histopathological chan
ges in the lungs over a long period of time and without spontaneous re
activation of disease. B6D2F1Bom mice mere inoculated with a wide rang
e of Mycobacterium tuberculosis doses intraperitoneally or intravenous
ly and followed for a long period to determine suitable conditions to
produce latent infection. No anti-tuberculosis drug treatment mas used
. Microbiological and histopathological studies mere carried out, Cort
icosterone challenge was used to reactivate the latent infection. Mice
infected with 4 x 10(4) and 4 x 10(5) bacilli i,p. were followed up t
o 107 weeks without spontaneous reactivation. The present model is dis
cussed in comparison with previous latent tuberculosis mouse models as
well as the possible mechanisms of shift to stationary phase from mul
tiplying bacilli.