Humane Endpoints for Infectious Disease Animal Models

Olfert, Ernest D.; Godson, Dale L.

doi:10.1093/ilar.41.2.99

Cited by 63 publications

(58 citation statements)

References 24 publications

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“…Hp and serum amyloid A belong to major APP in cows, acid glycoprotein and α 1 antiprotease are moderate APP and fibrinogen and α 2 -macroglobulin -minor APP in this species (Olfert & Godson, 2000). Moreover, APP are more sensitive to the inflammatory process than blood analysis, which is now recommended as a diagnostic marker for the assessment of inflammation.…”

Section: Discussionmentioning

confidence: 99%

Field study on plasma haptoglobin concentrations and total milk somatic cell counts in cows with untreated and treated mastitis

Georgieva¹,

Vasilev²,

Karadaev³

et al. 2018

BJVM

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Section: Discussionmentioning

confidence: 99%

Field study on plasma haptoglobin concentrations and total milk somatic cell counts in cows with untreated and treated mastitis

Georgieva¹,

Vasilev²,

Karadaev³

et al. 2018

BJVM

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“…The second, related, concern is the paucity of concrete, published data defining accurate humane endpoints in some of the controversial models for shock and inflammatory events including trauma, burns, and sepsis. General guidelines (13)(14)(15) describing how to determine humane endpoints for various models, including those that involve pain or infectious disease, may be loosely applied to trauma/burn and sepsis models, respectively. More specific information on endpoints for lethal models employing endotoxins and specific microbial agents may also prove helpful (see Table 1).…”

Section: The Pros and Cons Of Humane Endpoints In Shock Researchmentioning

confidence: 99%

“…As suggested by Olfert and Godson (15), early endpoints "should be based on scientifically valid values of variables, not just honest judgments based on an appreciation of the distress and pain the animal may be experiencing". The decision-making may also involve the facility veterinarians as well as technicians and husbandry staff (7,13,15,22,28,29). These individuals, who observe both the normal and abnormal course of events in animal models on a daily basis, can be invaluable.…”

Section: Establishing Endpointsmentioning

confidence: 99%

Humane Endpoints in Shock Research

Nemzek¹,

Hong

Minard

et al. 2004

Shock

140

114

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In biomedical research using animal models, the phrase "humane endpoints" refers to predetermined criteria used to judge when the research animals should be humanely euthanized. The intended goal of humane endpoints is to minimize the distress or suffering of research animals; however, if applied incorrectly, this well-intended concept could lead to premature decisions and inaccurate data, resulting in a waste of animal life. A concensus on specific endpoints for shock and inflammation research is not available but several biochemical, physical and behavioral parameters have been suggested for other research models. In addition, the authors have found, in the studies presented here, that increasing body weight, decreased body temperature, and inability to ambulate are important parameters in a model of cecal ligation and puncture. However, it is clear that the applicability of these endpoints may change with the model of disease, intensity of insults, experimental treatments and other factors. Consequently, humane endpoints should be assigned cautiously and preferably after preliminary studies to prevent aberrant research results. In order to accomplish this, investigators must become aware of certain concepts including: when to implement endpoints, what endpoints to consider, and how to establish the endpoints for their studies. Equipped with the basic principles of humane endpoints, investigators can make informed decisions that meet current standards of animal care while still achieving the scientific goals of their research studies.

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“…Although changes in the physical appearance of a rodent, including piloerection and a hunched posture, are indicators of distress (4,5,14), researchers are reluctant to use such observations as a surrogate for death, on the basis that the subjectivity of these measurements would likely compromise the scientific outcomes of their research. Alternatively, a decrease of 4°C or more in core body temperature is an important sign of deterioration in an animal's condition following challenge with an infectious agent and has therefore been regarded as a more reliable and objective measure (11,16,18).…”

mentioning

confidence: 99%

Novel Murine Model of Pneumococcal Pneumonia: Use of Temperature as a Measure of Disease Severity To Compare the Efficacies of Moxifloxacin and Levofloxacin

Bast

Yue

Chen

et al. 2004

Antimicrob Agents Chemother

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Surface temperature measured by an infrared temperature-scanning thermometer was used to evaluate disease severity and predict imminent death in a murine model of pneumococcal pneumonia. We showed that a decrease in temperature was associated with increasing severity of disease and concomitant histological changes and also that a temperature of 30°C or less was a predictor of death. Furthermore, viable bacterial counts in the lungs of mice euthanized at a temperature of < 30°C were not significantly different from those seen in the lungs of mice allowed to die without intervention. These data support temperature change as a more subtle indicator of outcome than death and demonstrate that this could be used as a reliable end point for euthanasia. To test the utility of our model in a drug trial, we examined the efficacies of moxifloxacin and levofloxacin by using temperature as a measure of disease severity prior to and during treatment. Regardless of the antibiotic used, mice assessed as moderately ill (temperature > 32°C) at the start of treatment had better clinical and bacteriological outcomes than mice assessed as severely ill (temperature < 32°C). However, moxifloxacin offered better protection and greater bacterial clearance than did levofloxacin in all infected mice independent of disease severity. This model not only allows a more subtle evaluation of drug efficacy but also ensures a better degree of standardization and a more humane approach to drug efficacy studies involving animals.

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Humane Endpoints for Infectious Disease Animal Models

Cited by 63 publications

References 24 publications

Field study on plasma haptoglobin concentrations and total milk somatic cell counts in cows with untreated and treated mastitis

Field study on plasma haptoglobin concentrations and total milk somatic cell counts in cows with untreated and treated mastitis

Humane Endpoints in Shock Research

Novel Murine Model of Pneumococcal Pneumonia: Use of Temperature as a Measure of Disease Severity To Compare the Efficacies of Moxifloxacin and Levofloxacin

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