The objective of this study was to characterize the rhesus macaque (RM) as a model for inhalational
brucellosis in support of the U.S. Food and Drug Administration's (FDA) Animal Rule. The pathophysiology of chronic Brucella melitensis
aerosol infection was monitored in two phases that each occurred over an 8-week time period; dose escalation (8 RMs; targeted doses of 5.0E+03, 5.0E+04, or 5.0E+05 CFU/animal or the unchallenged control) and natural history (12 RMs; targeted dose of 2.50E+05 CFU/animal or the unchallenged control). RMs given an
aerosol challenge with B. melitensis developed undulating
fevers (6/6 phase I; 8/9 phase II), positive enriched blood cultures (5/10; phase II), and bacterial burdens in tissues starting 14 to 21 days postchallenge (6/6 phase I; 10/10 phase II). In addition, 80% (8/10; phase II) of infected RMs seroconverted 14 to 21 days postchallenge. RMs developed elevations in certain liver
enzymes and had an increased inflammatory response by 3 weeks postchallenge as shown by increases in
C-reactive protein (6/8) and
neopterin (4/8), which correlated with the onset of a
fever. As early as 14 days postchallenge, positive liver biopsy specimens were detected (2/8), and ultrasound imaging showed the development of
splenomegaly. Finally, histopathologic examination found lesions attributed to
Brucella infection in the liver, kidney, lung, and/or spleen of all animals. The
disease progression observed with the RMs in this study is analogous to human
brucellosis pathophysiology. Thus, the results from this study support the use of the RM as an animal model for inhalational
brucellosis to evaluate the efficacy of novel
vaccines and
therapeutics against B. melitensis.