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Humane Endpoint: Example from a Murine Model of Disseminated Sporotrichosis

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Abstract

Vertebrate animal models are essential in research; however, efforts need to be made to decrease animal suffering as much as possible. It could be useful to determine humane endpoints that could serve as surrogates for a fatal outcome. We address this issue with respect to infectious diseases. We propose a humane endpoint for studies of Sporothrix brasiliensis infection. BALB/c mice were inoculated subcutaneously in the footpad. To define a humane endpoint, we considered two groups: animals who died during the experiment, and those euthanized at the end of the experiment. The groups were compared for colony-forming units (CFU) in internal organs, clinical condition, and body weight. Thirteen (22%) animals died before the end of the experiment due to the progression of local infection to severe and disseminated sporotrichosis. Analyzing data of the groups, we propose the following future criteria for euthanasia as a humane endpoint: neurological impairment OR necrosis of the footpad OR loss of ≥ 20% body weight AND moderate to severe dehydration. In view of the current global epidemiological impact of zoonotic sporotrichosis caused by S. brasiliensis, our data could facilitate the utility of models used to study the disease, particularly therapy.

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Acknowledgements

The authors are grateful to the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES – postgraduate scholarships), Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS; number 21/2551-0001974-3 and 23/2551-0000503-4), and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPQ 316067/2021-0 and undergraduate scholarship).

Funding

This research was funded by Fundação de Amparo à pesquisa do Estado do Rio Grande do Sul (FAPERGS), grant number 19/2551-0001922-0 (PqG 2019—edital 05/2019).

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Author notes

  1. Vanice Rodrigues Poester and Lívia Silveira Munhoz have contribute equally to the manuscript.

Authors and Affiliations

  1. Programa de Pós-Graduação Em Ciências da Saúde, Faculdade de Medicina (FAMED), Universidade Federal Do Rio Grande (FURG), Rio Grande, Rio Grande do Sul (RS), Brazil

    Vanice Rodrigues Poester, Lívia Silveira Munhoz, Mariana Rodrigues Trápaga, Bruna Muradás Esperon & Melissa Orzechowski Xavier

  2. California Institute for Medical Research, San Jose, USA

    David A. Stevens

  3. Division of Infectious Diseases and Geographic Medicine, Stanford University Medical School, Stanford, USA

    David A. Stevens

  4. Foundation for Research in Infectious Diseases, P.O. Box 2734, Saratoga, 95070, USA

    David A. Stevens

  5. Laboratório de Micologia, Faculdade de Medicina, Universidade Federal Do Rio Grande, Campus Saúde. Visconde de Paranaguá 102, Centro, Rio Grande, RS, 96201-900, Brasil

    Vanice Rodrigues Poester, Lívia Silveira Munhoz, Mariana Rodrigues Trápaga, Bruna Muradás Esperon & Melissa Orzechowski Xavier

Authors
  1. Vanice Rodrigues Poester
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  2. Lívia Silveira Munhoz
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  3. Mariana Rodrigues Trápaga
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  4. Bruna Muradás Esperon
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  5. David A. Stevens
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  6. Melissa Orzechowski Xavier
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Contributions

Conceptualization: Vanice Rodrigues Poester; Lívia Silveira Munhoz, and David A. Stevens; Methodology: Vanice Rodrigues Poester, Lívia Silveira Munhoz, Mariana Rodrigues Trápaga, Bruna Muradás Esperon, and Melissa Orzechowski Xavier; Formal analysis: Vanice Rodrigues Poester, Lívia Silveira Munhoz, Mariana Rodrigues Trápaga, Bruna Muradás Esperon, and Melissa Orzechowski Xavier; Writing—original draft preparation: Vanice Rodrigues Poester; Lívia Silveira Munhoz, and David A. Stevens; Writing—review and editing: David A. Stevens and Melissa Orzechowski Xavier. All authors have read and agreed to the published version of the manuscript.

Corresponding authors

Correspondence to Vanice Rodrigues Poester, David A. Stevens or Melissa Orzechowski Xavier.

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Conflict of interest

All authors declare that they have no conflicts of interest pertaining to this work.

Ethical Approval

All procedures were conducted according to the National Institutes of Health Animal and Care Guidelines and the Animal Use Ethics Committee of the FURG approved the project (process number CEUA-FURG P046/2019).

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Poester, V.R., Munhoz, L.S., Trápaga, M.R. et al. Humane Endpoint: Example from a Murine Model of Disseminated Sporotrichosis. Curr Microbiol 81, 175 (2024). https://doi.org/10.1007/s00284-024-03692-y

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