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PloS one
2015;10 (9): e0138843.

Dose Response of MARV/Angola Infection in Cynomolgus Macaques following IM or Aerosol Exposure.

Sara C Johnston, Kenny L Lin, Nancy A Twenhafel, Jo Lynne W Raymond, Joshua D Shamblin, Suzanne E Wollen, Carly B Wlazlowski, Eric R Wilkinson, Miriam A Botto, Arthur J Goff
Author Information
  1. Sara C Johnston: Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, 21702, United States of America.
  2. Kenny L Lin: Nonclinical Development Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, 21702, United States of America.
  3. Nancy A Twenhafel: Pathology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, 21702, United States of America.
  4. Jo Lynne W Raymond: Pathology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, 21702, United States of America.
  5. Joshua D Shamblin: Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, 21702, United States of America.
  6. Suzanne E Wollen: Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, 21702, United States of America.
  7. Carly B Wlazlowski: Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, 21702, United States of America.
  8. Eric R Wilkinson: Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, 21702, United States of America.
  9. Miriam A Botto: Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, 21702, United States of America.
  10. Arthur J Goff: Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, 21702, United States of America.
PMID: 26413900 DOI: 10.1371/journal.pone.0138843

Abstract

Marburg virus infection in humans causes a hemorrhagic disease with a high case fatality rate. Countermeasure development requires the use of well-characterized animal models that mimic human disease. To further characterize the cynomolgus macaque model of MARV/Angola, two independent dose response studies were performed using the intramuscular or aerosol routes of exposure. All animals succumbed at the lowest target dose; therefore, a dose effect could not be determined. For intramuscular-exposed animals, 100 PFU was the first target dose that was not significantly different than higher target doses in terms of time to disposition, clinical pathology, and histopathology. Although a significant difference was not observed between aerosol-exposed animals in the 10 PFU and 100 PFU target dose groups, 100 PFU was determined to be the lowest target dose that could be consistently obtained and accurately titrated in aerosol studies.

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MeSH Term

Aerosols
Animals
Injections, Intramuscular
Kaplan-Meier Estimate
Macaca fascicularis
Marburg Virus Disease
Marburgvirus
RNA, Viral
Temperature

Chemicals

Aerosols
RNA, Viral
Journal Article Research Support, Non-U.S. Gov't

Word Cloud

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