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Published on: July 6, 2016
Characterization of Coxiella burnetii infection in cynomolgus macaques
Nancy A Twenhafel1, David N Dyer1, Ondraya M Frick1
1U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, MD, USA.
Abstract:
Q fever, caused by Coxiella burnetii, leads to debilitating human infections that are often recalcitrant to antibiotics. The development of new medical countermeasures is critical, as the only available vaccine has significant limitations that prevent its widespread or rapid use. To address this, we characterized aerosol C. burnetii infection in 16 cynomolgus macaques (Macaca fascicularis), providing the first detailed pathological description of Q fever pneumonia in a nonhuman primate model. Following exposure, all animals developed clinical signs consistent with human Q fever, including sustained fever, respiratory distress, and weight loss. Clinical pathology revealed hematological changes and evidence of systemic inflammation, including elevated C-reactive protein. Although clinical signs resolved by day 28, significant pathology persisted, including granulomatous interstitial pneumonia, pleuritis, carditis, hepatitis, and nephritis. Infection was confirmed in tissues using immunohistochemistry and electron microscopy. The cynomolgus macaque model faithfully replicates key features of human Q fever, validating its utility for studying disease pathogenesis and serving as a pivotal model for evaluating next-generation vaccines and therapies.
Insights
Q fever, a debilitating infection caused by Coxiella burnetii, requires new treatments. A cynomolgus macaque model accurately mimics human Q fever, aiding vaccine and therapy development.
Area of Science:
- Infectious Diseases
- Pathology
- Veterinary Medicine
Background:
- Q fever is a debilitating zoonotic infection caused by Coxiella burnetii, often resistant to antibiotics.
- Current vaccines for Q fever have significant limitations, hindering widespread use.
- New medical countermeasures are urgently needed to combat Q fever.
Purpose of the Study:
- To characterize aerosol Coxiella burnetii infection in cynomolgus macaques.
- To provide a detailed pathological description of Q fever pneumonia in a nonhuman primate model.
- To validate the cynomolgus macaque as a model for studying Q fever pathogenesis and evaluating new therapies.
Main Methods:
- 16 cynomolgus macaques were exposed to aerosolized Coxiella burnetii.
- Clinical signs, clinical pathology, and hematological changes were monitored.
- Tissue samples were analyzed using immunohistochemistry and electron microscopy for infection confirmation.
Main Results:
- All macaques exhibited clinical signs consistent with human Q fever, including fever, respiratory distress, and weight loss.
- Systemic inflammation and elevated C-reactive protein were observed.
- Persistent pathology included granulomatous interstitial pneumonia, pleuritis, carditis, hepatitis, and nephritis.
Conclusions:
- The cynomolgus macaque model effectively replicates key features of human Q fever.
- This model is validated for studying Q fever pathogenesis.
- It serves as a pivotal model for evaluating next-generation Q fever vaccines and therapies.
