INTRODUCTION e rabbit was rst used by Medlar and Sasano as a model for tuberculosis in 1935. ese authors compared the lung lesions induced in response to infection with three dierently virulent strains of Mycobacterium bovis BCG. ey described “a variety of (lung) lesions … similar to those, known to occur in the human tuberculosis lung” (Medlar and Sasano, 1935). e lesions were characterized as showing “localization, progression, cavitation, bronchogenic spread and retrogression.” ese studies suggested that the type of disease induced in infected rabbits is a function of the balance between the resistance of the host and the virulence of the pathogen. Max B. Lurie, and later Lurie and Dannenberg, extensively characterized the rabbit response to infection with M. bovis Ravenel or Mycobacterium tuberculosis (MTB) H37Rv, drawing many analogies to the progression of

CONTENTS Introduction 107 Inoculum and Route of Inoculation 108 Features 108

Bacillary Load in the Lungs of Infected Rabbits 108 Gross Pathology 109 Histopathology 109

Strengths of is Animal Model 123 Shortcomings 129 References 129


human disease (Lurie, 1928, 1932; Lurie et al., 1950, 1952; Dannenberg, 1994; Converse et al., 1998). Depending on the dose of infecting organisms and the mycobacterial strain, Lurie and Dannenberg observed either mild infection that was controlled by the rabbit immune response (usually caused by MTB H37Rv infection), or severe progressive disease, oen with formation of necrotizing granulomas with and without cavities (usually caused by M. bovis Ravenel infection). Consequently, rabbits were considered relatively resistant to MTB compared to M. bovis Ravenel, suggesting the development of a robust protective acquired immune response to infection with the human pathogen (Lurie, 1964; Dannenberg, 2001, 2006). Taken together, these studies demonstrated that the rabbit can be used as an excellent model for tuberculosis infection, mimicking all forms of human disease.