Pathology of Inhalational Francisella tularensis spp. tularensis SCHU S4 Infection in African Green Monkeys (Chlorocebus aethiops)

Abstract

Tularemia, caused by Francisella tularensis, is a sporadic zoonotic disease with the potential to be an agent of biowarfare or bioterrorism. We describe here the gross, histologic, immunohistochemical, and ultrastructural findings in a group of 5 African green monkeys (AGMs) that received an average inhaled dose of 729 colony-forming units of F. tularensis and died or were euthanatized between days 7 and 11 post infection. Clinical changes were evident by 48 hours post infection, and key physiologic abnormalities included increases in body temperature, heart rate, peak cardiac pressure, and mean blood pressure. Prominent gross changes in all cases included numerous pinpoint to 1-cm, well-demarcated, necrotic foci present consistently in the lungs, mediastinal lymph nodes, and spleen but also seen in the heart, mediastinum, diaphragm, liver, urinary bladder, urethra, and mesentery. The lungs, mediastinal lymph nodes, and spleen were most severely affected, with as much as 50% of the tissue replaced by necrotic foci. Histologic changes in all tissues consisted of well-delineated foci of necrosis and neutrophilic and histiocytic inflammation, with varying amounts of hemorrhage, edema, fibrin, and vasculitis. Some lesions were immature pyogranulomas. Strong immunoreactivity was identified primarily within macrophages. Ultrastructurally, bacteria were present within cytoplasmic vacuoles of alveolar macrophages, many of which were degenerate. In summary, AGMs infected with F. tularensis by aerosol develop lethal multisystemic disease that particularly targets the lungs and lymphoid tissues. Thus, AGMs should serve as a suitable and reliable animal model for further studies of tularemia.