Clinical and Pathologic Features of Cynomolgus Macaques (Macaca Fascicularis) Infected With Aerosolized Yersinia Pestis

Comp Med. 2008 Feb;58(1):68-75.

Abstract

Since the anthrax attacks of 2001, the emphasis on developing animal models of aerosolized select agent pathogens has increased. Many scientists believe that nonhuman primate models are the most appropriate to evaluate pulmonary response to, vaccines for, and treatments for select agents such as Yersinia pestis (Y. pestis), the causative agent of plague. A recent symposium concluded that the cynomolgus macaque (Macaca fascicularis) plague model should be characterized more fully. To date, a well-characterized cynomolgus macaque model of pneumonic plague using reproducible bioaerosols of viable Y. pestis has not been published. In the current study, methods for creating reproducible bioaerosols of viable Y. pestis strain CO92 (YpCO92) and pneumonic plague models were evaluated in 22 Indonesian-origin cynomolgus macaques. Five macaques exposed to doses lower than 250 CFU remained free of any indication of plague infection. Fifteen macaques developed fever, lethargy, and anorexia indicative of clinical plague. The 2 remaining macaques died without overt clinical signs but were plague-positive on culture and demonstrated pathology consistent with plague. The lethal dose of plague in humans is reputedly less than 100 organisms; in this study, 66 CFU was the dose at which half of the macaques developed fever and clinical signs (ED(50)), The Indonesian cynomolgus macaque reproduces many aspects of human pneumonic plague and likely will provide an excellent model for studies that require a macaque model.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aerosols
  • Animals
  • Anticonvulsants / pharmacology
  • Anticonvulsants / toxicity
  • Appetite / drug effects
  • Bacterial Vaccines / administration & dosage
  • Bacterial Vaccines / therapeutic use*
  • Body Temperature / drug effects
  • Chlorocebus aethiops / microbiology
  • GABA Modulators / pharmacology
  • GABA Modulators / toxicity
  • Macaca fascicularis / microbiology*
  • Macaca mulatta / microbiology
  • Motor Activity / drug effects
  • Plague / immunology
  • Plague / microbiology*
  • Plague / veterinary*
  • Plague Vaccine / therapeutic use*
  • Species Specificity
  • Tiletamine / pharmacology
  • Tiletamine / toxicity
  • Yersinia pestis / pathogenicity*
  • Zolazepam / pharmacology
  • Zolazepam / toxicity

Substances

  • Aerosols
  • Anticonvulsants
  • Bacterial Vaccines
  • GABA Modulators
  • Plague Vaccine
  • Tiletamine
  • Zolazepam