title: Euthanasia assessment in ebola virus infected nonhuman primates.
abstract: Multiple products are being developed for use against filoviral infections. Efficacy for these products will likely be demonstrated in nonhuman primate models of filoviral disease to satisfy licensure requirements under the Animal Rule, or to supplement human data. Typically, the endpoint for efficacy assessment will be survival following challenge; however, there exists no standardized approach for assessing the health or euthanasia criteria for filovirus-exposed nonhuman primates. Consideration of objective criteria is important to (a) ensure test subjects are euthanized without unnecessary distress; (b) enhance the likelihood that animals exhibiting mild or moderate signs of disease are not prematurely euthanized; (c) minimize the occurrence of spontaneous deaths and loss of end-stage samples; (d) enhance the reproducibility of experiments between different researchers; and (e) provide a defensible rationale for euthanasia decisions that withstands regulatory scrutiny. Historic records were compiled for 58 surviving and non-surviving monkeys exposed to Ebola virus at the US Army Medical Research Institute of Infectious Diseases. Clinical pathology parameters were statistically analyzed and those exhibiting predicative value for survival are reported. These findings may be useful for standardization of objective euthanasia assessments in rhesus monkeys exposed to Ebola virus and may serve as a useful approach for other standardization efforts.
authors.affiliation: US Army Medical Research Institute for Infectious Diseases, 1425 Porter St., Fort Detrick, MD 21702, USA. travis.k.warren.ctr@mail.mil.
authors.forename: Travis K
authors.initials: TK
authors.lastname: Warren
authors.affiliation: US Army Medical Research Institute for Infectious Diseases, 1425 Porter St., Fort Detrick, MD 21702, USA. john.c.trefry.ctr@mail.mil.
authors.forename: John C
authors.initials: JC
authors.lastname: Trefry
authors.affiliation: US Army Medical Research Institute for Infectious Diseases, 1425 Porter St., Fort Detrick, MD 21702, USA. shannon.t.marko.mil@mail.mil.
authors.forename: Shannon T
authors.initials: ST
authors.lastname: Marko
authors.affiliation: US Army Medical Research Institute for Infectious Diseases, 1425 Porter St., Fort Detrick, MD 21702, USA. taylor.b.chance.mil@mail.mil.
authors.forename: Taylor B
authors.initials: TB
authors.lastname: Chance
authors.affiliation: US Army Medical Research Institute for Infectious Diseases, 1425 Porter St., Fort Detrick, MD 21702, USA. jay.b.wells.ctr@mail.mil.
authors.forename: Jay B
authors.initials: JB
authors.lastname: Wells
authors.affiliation: US Army Medical Research Institute for Infectious Diseases, 1425 Porter St., Fort Detrick, MD 21702, USA. william.d.pratt4.civ@mail.mil.
authors.forename: William D
authors.initials: WD
authors.lastname: Pratt
authors.affiliation: US Army Medical Research Institute for Infectious Diseases, 1425 Porter St., Fort Detrick, MD 21702, USA. joshua.johnson@nih.gov.
authors.forename: Joshua C
authors.initials: JC
authors.lastname: Johnson
authors.affiliation: US Army Medical Research Institute for Infectious Diseases, 1425 Porter St., Fort Detrick, MD 21702, USA. eric.m.mucker.ctr@mail.mil.
authors.forename: Eric M
authors.initials: EM
authors.lastname: Mucker
authors.affiliation: US Army Medical Research Institute for Infectious Diseases, 1425 Porter St., Fort Detrick, MD 21702, USA. sarah.l.norris2.civ@mail.mil.
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Norris
authors.affiliation: US Army Medical Research Institute for Infectious Diseases, 1425 Porter St., Fort Detrick, MD 21702, USA. mark.chappell@usuhs.edu.
authors.forename: Mark
authors.initials: M
authors.lastname: Chappell
authors.affiliation: US Army Medical Research Institute for Infectious Diseases, 1425 Porter St., Fort Detrick, MD 21702, USA. john.m.dye1.civ@mail.mil.
authors.forename: John M
authors.initials: JM
authors.lastname: Dye
authors.affiliation: US Army Medical Research Institute for Infectious Diseases, 1425 Porter St., Fort Detrick, MD 21702, USA. anna.honko@nih.gov.
authors.forename: Anna N
authors.initials: AN
authors.lastname: Honko
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical / Q000379:methods; D037901:Euthanasia, Animal; D000882:Haplorhini; D019142:Hemorrhagic Fever, Ebola / Q000473:pathology* / Q000628:therapy; D018419:Primate Diseases / Q000473:pathology* / Q000628:therapy; D016019:Survival Analysis