Milestones in progression of primary pneumonic plague in cynomolgus macaques.
Vaccines against primary pneumonic plague, a potential bioweapon, must be tested for efficacy in well-characterized nonhuman primate models. Telemetered cynomolgus macaques (Macaca fascicularis) were challenged by the aerosol route with doses equivalent to approximately 100 50% effective doses of Yersinia pestis strain CO92 and necropsied at 24-h intervals postexposure (p.e.). Data for telemetered heart rates, respiratory rates, and increases in the temperature greater than the diurnal baseline values identified the onset of the systemic response at 55 to 60 h p.e. in all animals observed for at least 70 h p.e. Bacteremia was detected at 72 h p.e. by a Yersinia 16S rRNA-specific quantitative reverse transcription-PCR and was detected later by the culture method at the time of moribund necropsy. By 72 h p.e. multilobar pneumonia with diffuse septal inflammation consistent with early bacteremia was established, and all lung tissues had a high bacterial burden. The levels of cytokines or chemokines in serum were not significantly elevated at any time, and only the interleukin-1beta, CCL2, and CCL3 levels were elevated in lung tissue. Inhalational plague in the cynomolgus macaque inoculated by the aerosol route produces most clinical features of the human disease, and in addition the disease progression mimics the disease progression from the anti-inflammatory phase to the proinflammatory phase described for the murine model. Defined milestones of disease progression, particularly the onset of fever, tachypnea, and bacteremia, should be useful for evaluating the efficacy of candidate vaccines.
Koster
Frederick
F
Lovelace Respiratory Research Institute, Albuquerque, New Mexico 87108, USA. fkoster@LRRI.org
Perlin
David S
DS
Park
Steven
S
Brasel
Trevor
T
Gigliotti
Andrew
A
Barr
Edward
E
Myers
Leslie
L
Layton
Robert C
RC
Sherwood
Robert
R
Lyons
C R
CR
D000818:Animals; D016470:Bacteremia / Q000382:microbiology; D001831:Body Temperature; D018925:Chemokines / Q000097:blood; D016207:Cytokines / Q000097:blood; D018450:Disease Progression; D004562:Electrocardiography; D005260:Female; D006339:Heart Rate; D008168:Lung / Q000382:microbiology / Q000473:pathology; D008252:Macaca fascicularis; D008297:Male; D008992:Monkey Diseases / Q000276:immunology / Q000382:microbiology* / Q000473:pathology / Q000503:physiopathology; D010930:Plague / Q000276:immunology / Q000382:microbiology* / Q000473:pathology / Q000503:physiopathology; D056152:Respiratory Rate; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015010:Yersinia pestis / Q000276:immunology
D018925:Chemokines; D016207:Cytokines
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