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Article

The Natural History of Aerosolized Francisella tularensis Infection in Cynomolgus Macaques

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Veterinary Medicine Division, U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), Frederick, MD 21702, USA
2
Naval Medical Research Center, Undersea Medicine Department, Silver Spring, MD 20910, USA
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Molecular and Translational Sciences Division, U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), Frederick, MD 21702, USA
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Office of Research, Center for Veterinary Medicine, U.S. Food and Drug Administration, Laurel, MD 20708, USA
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Pathology Division, U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), Frederick, MD 21702, USA
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Veterinary Services and Public Health Sanitation Directorate, Army Public Health Center, Aberdeen Proving Ground, MD 21010, USA
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Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA 15261, USA
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Core Support Directorate, U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), Frederick, MD 21702, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Bonto Faburay
Pathogens 2021, 10(5), 597; https://doi.org/10.3390/pathogens10050597
Received: 3 March 2021 / Revised: 26 April 2021 / Accepted: 7 May 2021 / Published: 13 May 2021
(This article belongs to the Special Issue Translation of Pre-clinical Francisella tularensis Research)
Tularemia is a severe, zoonotic infection caused by the Gram-negative bacterium Francisella tularensis. Inhalation results in a rapid, severe bacterial pneumonia and sepsis, which can be lethal. Because the cynomolgus macaque is the accepted nonhuman primate model for tularemia, we conducted a natural history study of pneumonic tularemia by exposing macaques to target inhaled doses of 50, 500, or 5000 colony forming units (CFU) of F. tularensis subsp. tularensis SCHU S4. Two animals within the 50 CFU group (calculated doses of 10 and 11 CFU) survived the challenge, while the remainder succumbed to infection. Exposure of cynomolgus macaques to aerosolized SCHU S4 resulted in fever, anorexia, increased white blood cell counts, lymphopenia, thrombocytopenia, increased liver enzymes, alterations in electrocardiogram (ECG), and pathological changes typical of infection with F. tularensis, regardless of the challenge dose. Blood pressure dropped during the febrile phase, particularly as temperature began to drop and macaques succumbed to the disease. ECG analysis indicated that in 33% of the macaques, heart rate was not elevated during the febrile phase (Faget’s sign; pulse-temperature disassociation), which has been reported in a similar percentage of human cases. These results indicated that infection of cynomolgus macaques with aerosolized F. tularensis results in similar disease progression and outcome as seen in humans, and that cynomolgus macaques are a reliable animal model to test medical countermeasures against aerosolized F. tularensis. View Full-Text
Keywords: Francisella tularensis; tularemia; aerosol; animal model; cynomolgus macaque Francisella tularensis; tularemia; aerosol; animal model; cynomolgus macaque
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MDPI and ACS Style

Frick, O.M.; Livingston, V.A.; Whitehouse, C.A.; Norris, S.L.; Alves, D.A.; Facemire, P.R.; Reed, D.S.; Nalca, A. The Natural History of Aerosolized Francisella tularensis Infection in Cynomolgus Macaques. Pathogens 2021, 10, 597. https://doi.org/10.3390/pathogens10050597

AMA Style

Frick OM, Livingston VA, Whitehouse CA, Norris SL, Alves DA, Facemire PR, Reed DS, Nalca A. The Natural History of Aerosolized Francisella tularensis Infection in Cynomolgus Macaques. Pathogens. 2021; 10(5):597. https://doi.org/10.3390/pathogens10050597

Chicago/Turabian Style

Frick, Ondraya M., Virginia A. Livingston, Chris A. Whitehouse, Sarah L. Norris, Derron A. Alves, Paul R. Facemire, Douglas S. Reed, and Aysegul Nalca. 2021. "The Natural History of Aerosolized Francisella tularensis Infection in Cynomolgus Macaques" Pathogens 10, no. 5: 597. https://doi.org/10.3390/pathogens10050597

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