Primary pneumonic plague in the African Green monkey as a model for treatment efficacy evaluation.
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.
Layton
R Colby
RC
Lovelace Respiratory Research Institute, Albuquerque, NM, USA.
Brasel
Trevor
T
Gigliotti
Andrew
A
Barr
Edward
E
Storch
Steven
S
Myers
Leslie
L
Hobbs
Charles
C
Koster
Frederick
F
D000818:Animals; D016470:Bacteremia; D002522:Chlorocebus aethiops; D004195:Disease Models, Animal; D004562:Electrocardiography; D005260:Female; D005334:Fever; D006339:Heart Rate; D001239:Inhalation; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008168:Lung / Q000382:microbiology / Q000473:pathology; D008297:Male; D008992:Monkey Diseases / Q000382:microbiology*; D010930:Plague / Q000175:diagnosis / Q000503:physiopathology / Q000662:veterinary*; D013902:Radiography, Thoracic / Q000662:veterinary; D056152:Respiratory Rate; D013686:Telemetry; D015010:Yersinia pestis / Q000302:isolation & purification
D007770:L-Lactate Dehydrogenase