Remote monitoring of the progression of primary pneumonic plague in Brown Norway rats in high-capacity, high-containment housing
Autor: | Eric A. Coate, Mark R. Ellersieck, Deborah M. Fine, Kristen N. Peters, Paul E. Anderson, Deborah M. Anderson, Andrew G. Kocsis |
---|---|
Rok vydání: | 2014 |
Předmět: |
Male
Microbiology (medical) Pneumonic plague Yersinia pestis Motor Activity Biology Bubonic plague Article Body Temperature Heart Rate medicine Animals Immunology and Allergy Inhalation Exposure Plague Biodefense General Immunology and Microbiology Incidence (epidemiology) General Medicine Containment of Biohazards medicine.disease biology.organism_classification Rats Natural history Clinical trial Disease Models Animal Infectious Diseases Remote Sensing Technology Immunology Female Lethality |
Zdroj: | Pathogens and Disease. 71:265-275 |
ISSN: | 2049-632X |
DOI: | 10.1111/2049-632x.12176 |
Popis: | Development of new vaccines, diagnostics, and therapeutics for biodefense or other relatively rare infectious diseases is hindered by the lack of naturally occurring human disease on which to conduct clinical trials of efficacy. To overcome this experimental gap, the U.S. Food and Drug Administration established the Animal Rule, in which efficacy testing in two well-characterized animal models that closely resemble human disease may be accepted in lieu of large-scale clinical trials for diseases with limited natural human incidence. In this report, we evaluated the Brown Norway rat as a model for pneumonic plague and describe the natural history of clinical disease following inhalation exposure to Yersinia pestis. In high-capacity, high-containment housing, we monitored temperature, activity, heart rate, and rhythm by capturing electronic impulses transmitted from abdominal telemeter implants. Using this system, we show that reduced activity and development of fever are sensitive indications of disease progression. Furthermore, we identified heart arrhythmias as contributing factors to the rapid progression to lethality following the fever response. Together, these data validate the Brown Norway rat as an experimental model for human pneumonic plague and provide new insight that may ultimately lead to novel approaches in postexposure treatment of this devastating infection. |
Databáze: | OpenAIRE |
Externí odkaz: |