Pathology
meningeal lesions, anthrax, hemorrhage
INFILTRATE, ANTHRAX, HEMORRHAGE, INFLAMMATION
All gross lesions observed in non-surviving NHPs were typical of inhalation anthrax in cynomolgus macaques [Control animals had a greater incidence and/or severity of parenchymal organ lesions than did ANTHRASIL-treated animals. When present, meningeal lesions in IGIV-treated control animals were largely confined to minimal to mild hemorrhage, with no evidence of inflammatory infiltrate. In contrast, the subset of ANTHRASIL-treated non-surviving animals exhibited a dose-dependent increase in the incidence and severity of inflammatory lesions in the brain/meninges compared to IGIV-treated control animals. In addition, non-surviving ANTHRASIL-treated animals had more numerous and widespread bacteria observed in the brain, while bacteria in the brain of non-surviving IGIV-treated control animals were often confined to blood vessels or the immediate perivascular space. Similar observations of increased incidence and severity of brain lesions (hemorrhage and bacteria) in cynomolgus macaques have been reported in animals treated with monoclonal antibodies against PA [While the survival rates were greater in ANTHRASIL-treated cynomolgus macaques compared to IGIV-treated controls, a high percentage of non-survivors in ANTHRASIL-treated groups, exhibited lesions characterized by a mixed accumulation of neutrophils and fibrin in the meningeal space, typical of an acute immune reaction that developed hours to days after the onset of local bacterial invasion. This appeared to be dose-dependent, with 27% (3 of 11) of 7.5 U/kg dose, 66% (6 of 9) of 15 U/kg dose and 100% (5 of 5) of 30 U/kg dose of non-surviving ANTHRASIL-treated animals exhibiting lesions resulting from neutrophilic or fibrin inflammation. Of the IGIV control animals that succumbed, 53% were documented to have bacteria found in the brain, and 80% exhibited hemorrhage, but none showed inflammatory lesions. The cause of these findings could not be determined.