Primary pneumonic plague in the African Green monkey as a model for treatment efficacy evaluation
R Colby Layton1, Trevor Brasel, Andrew Gigliotti
1Lovelace Respiratory Research Institute, Albuquerque, NM, USA.
Background:
Primary pneumonic plague is rare among humans, but treatment efficacy may be tested in appropriate animal models under the FDA 'Animal Rule'.
Methods:
Ten African Green monkeys (AGMs) inhaled 44-255 LD(50) doses of aerosolized Yersinia pestis strain CO92. Continuous telemetry, arterial blood gases, chest radiography, blood culture, and clinical pathology monitored disease progression.
Results:
Onset of fever, >39°C detected by continuous telemetry, 52-80 hours post-exposure was the first sign of systemic disease and provides a distinct signal for treatment initiation. Secondary endpoints of disease severity include tachypnea measured by telemetry, bacteremia, extent of pneumonia imaged by chest x-ray, and serum lactate dehydrogenase enzyme levels.
Conclusions:
Inhaled Y. pestis in the AGM results in a rapidly progressive and uniformly fatal disease with fever and multifocal pneumonia, serving as a rigorous test model for antibiotic efficacy studies.
Insights
African Green monkeys exposed to aerosolized Yersinia pestis developed rapidly fatal pneumonic plague. Fever onset reliably signals disease progression, establishing this model for testing antibiotic treatments.
Area of Science:
- Microbiology
- Infectious Diseases
- Veterinary Medicine
Background:
- Primary pneumonic plague is a rare but severe human disease.
- The FDA 'Animal Rule' permits testing treatment efficacy in animal models.
- Developing a suitable animal model is crucial for plague research.
Purpose of the Study:
- To establish and validate a Yersinia pestis-induced pneumonic plague model in African Green monkeys (AGMs).
- To identify reliable indicators of disease onset and progression for treatment efficacy studies.
Main Methods:
- Ten AGMs inhaled aerosolized Yersinia pestis strain CO92 at doses of 44-255 LD(50).
- Disease progression was monitored using continuous telemetry, arterial blood gases, chest radiography, blood cultures, and clinical pathology.
Main Results:
- Fever onset (>39°C), detected by telemetry 52-80 hours post-exposure, was the earliest sign of systemic disease.
- Secondary indicators of severity included tachypnea, bacteremia, pneumonia extent on radiography, and elevated lactate dehydrogenase.
Conclusions:
- Inhaled Yersinia pestis infection in AGMs causes rapidly progressive, uniformly fatal pneumonic plague.
- This model, characterized by fever and multifocal pneumonia, is suitable for rigorous antibiotic efficacy testing.
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