title: Comparison of experimental respiratory tularemia in three nonhuman primate species.
abstract: Tularemia is a zoonotic disease caused by Francisella tularensis, which is transmitted to humans most commonly by contact with infected animals, tick bites, or inhalation of aerosolized bacteria. F. tularensis is highly infectious via the aerosol route; inhalation of as few as 10-50 organisms can cause pneumonic tularemia. Left untreated, the pneumonic form has more than >30% case-fatality rate but with early antibiotic intervention can be reduced to 3%. This study compared tularemia disease progression across three species of nonhuman primates [African green monkey (AGM), cynomolgus macaque (CM), and rhesus macaque (RM)] following aerosolized F. tularensis Schu S4 exposure. Groups of the animals exposed to various challenge doses were observed for clinical signs of infection and blood samples were analyzed to characterize the disease pathogenesis. Whereas the AGMs and CMs succumbed to disease following challenge doses of 40 and 32 colony forming units (CFU), respectively, the RM lethal dose was 276,667 CFU. Following all challenge doses that caused disease, the NHPs experienced weight loss, bacteremia, fever as early as 4 days post exposure, and tissue burden. Necrotizing-to-pyogranulomatous lesions were observed most commonly in the lung, lymph nodes, spleen, and bone marrow. Overall, the CM model consistently manifested pathological responses similar to those resulting from inhalation of F. tularensis in humans and thereby most closely emulates human tularemia disease. The RM model displayed a higher tolerance to infection and survived exposures of up to 15,593 CFU of aerosolized F. tularensis.
authors.affiliation: Center for Aerobiological Sciences, U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD 21702, USA.
authors.forename: Audrey R
authors.initials: AR
authors.lastname: Glynn
authors.affiliation: Pathology Division, U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD 21702, USA.
authors.forename: Derron A
authors.initials: DA
authors.lastname: Alves
authors.affiliation: Center for Aerobiological Sciences, U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD 21702, USA.
authors.forename: Ondraya
authors.initials: O
authors.lastname: Frick
authors.affiliation: Center for Aerobiological Sciences, U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD 21702, USA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Erwin-Cohen
authors.affiliation: Center for Aerobiological Sciences, U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD 21702, USA.
authors.forename: Aimee
authors.initials: A
authors.lastname: Porter
authors.affiliation: Biostatistics Division, U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD 21702, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Norris
authors.affiliation: Bacteriology Division of U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD 21702, USA.
authors.forename: David
authors.initials: D
authors.lastname: Waag
authors.affiliation: Center for Aerobiological Sciences, U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD 21702, USA. Electronic address: aysegul.nalca@us.army.mil.
authors.forename: Aysegul
authors.initials: A
authors.lastname: Nalca
mesh_terms: D000336:Aerosols; D000818:Animals; D058491:Bacterial Load; D002522:Chlorocebus aethiops / Q000382:microbiology; D004195:Disease Models, Animal; D018450:Disease Progression; D005604:Francisella tularensis / Q000472:pathogenicity*; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D008252:Macaca fascicularis / Q000382:microbiology; D008253:Macaca mulatta / Q000382:microbiology; D013154:Spleen / Q000382:microbiology / Q000473:pathology; D014406:Tularemia / Q000382:microbiology / Q000473:pathology
chemical_list: D000336:Aerosols
keywords: Aerosol; Animal model; Francisella tularensis; Inhalation; Nonhuman primate; Tularemia