INTRODUCTION Nonhuman primates (NHPs), generally macaques, have been used for decades as a model of tuberculosis, for drug and vaccine studies (Good, 1968). ere is a long history of “natural” Mycobacterium tuberculosis (MTB) or M. bovis infections in captive nonhuman primates, although rigorous screening practices have brought this under control. e nonhuman

CONTENTS Introduction 83 Inoculum and Route of Infection 84 Features 84

Acute (Early) 84 Chronic 86 Latent 93

Variations 93 Tuberculous Pneumonia 93 Cavitation 93 Suppurative Granulomas 98 Miliary Disease 98 Endobronchial Disease 98 Reactivation (Postprimary) Disease 98

Strengths of is Animal Model 103 Shortcomings 103 References 103


primate is genetically close to humans, and most human immunologic reagents are cross-reactive with macaques, which facilitates the use of this model for studying tuberculosis. Our studies (Capuano et al., 2003; Flynn et al., 2005; Lin et al., 2009), and those of others (Langermans et al., 2001, 2005; Chen et al., 2009; Verreck et al., 2009), have demonstrated that macaques recapitulate all manifestations of human MTB infection. is includes presentation of both latent and active infection, as well as reactivation tuberculosis. e pathology and granuloma structures observed are remarkably similar to those in human tuberculosis (Figure 6.2).