Clinical Characterization of Aerosolized Francisella tularensis Infection in Cynomolgus macaques

The disease progression and pathogenesis of tularemia was examined in three species of NHPs (African green monkey (AGM), cynomolgus macaque (CM), rhesus macaque (RM)) exposed to aerosolized Francisella tularensis in a previous study. Based on the similarity of infectious dose, clinical symptoms and...

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Bibliographic Details
Main Authors: Nalca, Aysegul, Frick,Ondraya M, Livingston,Virginia A, Whitehouse,Chris A, Erwin-Cohen,Rebecca A, Porter,Aimee I, Alves,Derron A
Format: Report
Language:English
Subjects:
animal models
BACTERIAL AEROSOLS
bacterial load
blood
cm (Cynomolgus macaques)
DEOXYRIBONUCLEIC ACIDS
dna (DEOXYRIBONUCLEIC ACIDS)
Francisella tularensis
HISTOLOGY
immunohistochemistry
infectious diseases
inhalational tularemia
MACAQUE MONKEYS
medical countermeasures
Medicine and Medical Research
Microbiology
necropsy
OBSERVATION
PATHOGENESIS
Pathology
RADIO TELEMETRY
SIGNS AND SYMPTOMS
Statistical analysis
SURVIVAL
tissues
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Summary:The disease progression and pathogenesis of tularemia was examined in three species of NHPs (African green monkey (AGM), cynomolgus macaque (CM), rhesus macaque (RM)) exposed to aerosolized Francisella tularensis in a previous study. Based on the similarity of infectious dose, clinical symptoms and disease progression with human tularemia, the CM was the most appropriate animal species to develop an animal model to test potential medical countermeasures against inhalational tularemia. In this study, the disease pathogenesis of inhalational tularemia was investigated after exposing cynomolgus macaques to target doses of 50, 500 or 5000 CFU of aerosolized F. tularensis SCHU S4. Survival was challenge dose dependent with target doses of 500 CFU (range of 134 to 749 CFU) and 5000 CFU (range of 1177 CFU to 5860 CFU) causing 100 lethality by Days 17 and 8 respectively. Target doses of 50 CFU (range of 10 CFU to 110 CFU) resulted in 20 survival. Comparable to respiratory tularemia infection in humans, infection of cynomolgus macaques with aerosolized SCHU S4 resulted in fever, anorexia, increased white blood cell (WBC) counts, increased liver enzymes, and pathology typical of infection with F. tularensis regardless of the challenge dose. These results indicated that F. tularensis-infected cynomolgus monkeys have similar clinical profiles as seen in humans and are reliable animal models to test medical countermeasures against aerosolized F. tularensis. Frontiers in Microbiology , 01 Jan 0001, 01 Jan 0001,