Skip to main content
SpringerLink
Log in

In Vivo Drug Testing for Experimental Trypanosoma cruzi Infection

  • Chapter
  • First Online:
Chagas Disease

Part of the book series: Birkhäuser Advances in Infectious Diseases ((BAID))

Abstract

Experimental animals have contributed to basic and translational research on Chagas disease. Although many species and models have been used depending on the main experimental objective, there is a lack of uniformity and harmonization in preclinical in vivo studies. This chapter focuses on the description of relevant T. cruzi-infected animal models for drug discovery, and results are discussed in a translational research perspective, while some key concepts are presented in order to choose and establish a suitable animal model of T. cruzi infection to assess new chemotherapies’ efficacy. Also, some strategies related to the 3Rs principles (replacement, reduction, and refinement) are proposed to apply on Chagas disease research to achieve scientific aims while ensuring animal well-being.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Jelicks L, Lisanti M, Machado F, Weiss L, Tanowitz H, Desruisseaux M. Imaging of small-animal models of infectious diseases. Am J Pathol. 2013;182(2):296–304.

    Article  Google Scholar 

  2. Desquesnes M, De Lana M. Veterinary aspects and experimental studies. In: Telleria J, Tibayrenc M, editors. American Trypanosomiasis: one hundred years of research. 1st ed. Amsterdam: Elsevier Inc; 2010. p. 277–318.

    Chapter  Google Scholar 

  3. WHO. Report of the scientific working group on the development and evaluation of animal models for Chagas disease. Geneva: WHO; 1984.

    Google Scholar 

  4. do Canto Cavalheiro M, Leon L. Animal models of Trypanosoma cruzi infection. In: Zak O, Sande MA, editors. Handbook of animal models of infection: experimental models in antimicrobial chemotherapy. 1st ed. London: Academic Press; 1999. p. 801–10.

    Chapter  Google Scholar 

  5. Castro M, Brener Z. Estudo parasitológico e anátomo-patológico da fase aguda da doença de chagas em cães inoculados com duas diferentes cepas do Trypanosoma Cruzi. Rev Soc Bras Med Trop. 1985;18(1):223–9.

    Article  Google Scholar 

  6. Guedes P, Veloso V, Tafuri W, Galvão L, Carneiro C, Lana M, et al. The dog as model for chemotherapy of the Chagas’ disease. Acta Trop. 2002;84(1):9–17.

    Article  CAS  Google Scholar 

  7. Diniz LF, Caldas I, Guedes P, Crepalde G, de Lana M, Carneiro C, et al. Effects of ravuconazole treatment on parasite load and immune response in dogs experimentally infected with Trypanosoma cruzi. Antimicrob Agents Chemother. 2010;54(7):2979–86.

    Article  CAS  Google Scholar 

  8. Chatelain E. Chagas disease drug discovery: toward a new era. J Biomol Screen. 2015;20(1):22–35.

    Article  Google Scholar 

  9. Torrico F, Gascón J, Ribeiro I. E 1224—results of proof-of-concept clinical trial in patients with chronic indeterminate Chagas disease. Washington, DC: American Society of Tropical Medicine and Hygiene, 62nd Annual Meeting; 2013. p. 13.

    Google Scholar 

  10. Jorge T, Castro S. Doença de Chagas: manual para experimentação animal. (Editora FIOCRUZ, Ed.) (1st ed.). Rio de Janeiro. 2000.

    Google Scholar 

  11. Moreno E, Araujo M, Alarcón M, Lugo de Yarbuh A, Araujo S, Borges R. Effects of acute Chagasic infection on gestating Wistar rats. Rev Cient. 2006;16(5):506–16.

    Google Scholar 

  12. Frare E, Santello F, Caetano L, Caldeira J, Toldo M, Prado JJ. Growth hormones therapy in immune response against Trypanosoma cruzi. Res Vet Sci. 2010;88(2):273–8. https://doi.org/10.1016/j.rvsc.2009.10.001.

    Article  CAS  PubMed  Google Scholar 

  13. Kuehn C, Rodrigues Oliveira L, Santos C, Ferreira D, Alonso Toldo M, de Albuquerque S, do Prado JJ. Melatonin and dehydroepiandrosterone combination: does this treatment exert a synergistic effect during experimental Trypanosoma cruzi infection? J Pineal Res. 2009;47(3):253–9.

    Article  CAS  Google Scholar 

  14. Santos C, Loria R, Oliveira L, Kuehn C, Toldo M, Albuquerque S, do Prado JJ. Effects of dehydroepiandrosterone-sulfate (DHEA-S) and benznidazole treatments during acute infection of two different Trypanosoma cruzi strains. Immunobiology. 2010;215(12):980–6. https://doi.org/10.1016/j.imbio.2009.11.002.

    Article  CAS  PubMed  Google Scholar 

  15. Perez A, Fontanella G, Nocito A, Revelli S, Bottasso O. Short treatment with the tumour necrosis factor-alpha blocker infliximab diminishes chronic chagasic myocarditis in rats without evidence of Trypanosoma cruzi reactivation. Clin Exp Immunol. 2009;157(2):291–9.

    Article  CAS  Google Scholar 

  16. Costa S. Mouse as a model for Chagas disease: does mouse represent a good model for Chagas disease? Mem Inst Oswaldo Cruz. 1999;94(Suppl. I):269–72.

    Article  Google Scholar 

  17. Buckner FS. Experimental chemotherapy and approaches to drug discovery for Trypanosoma cruzi infection. Adv Parasitol. 2011;75:89–119.

    Article  Google Scholar 

  18. Chatelain E, Konar N. Translational challenges of animal models in Chagas disease drug development: a review. Drug Des Devel Ther. 2015;19(9):4807–23.

    Article  Google Scholar 

  19. Jelicks L, Tanowitz H. Advances in imaging of animal models of Chagas disease. Adv Parasitol. 2011;75:193–208.

    Article  Google Scholar 

  20. Solana M, Celentano A, Tekiel V, Jones M, González-Cappa S. Trypanosoma cruzi: effect of parasite subpopulation on murine pregnancy outcome. J Parasitol. 2002;88(1):102–6.

    Google Scholar 

  21. Roggero E, Perez A, Tamae-Kakazu M, Piazzon I, Nepomnaschy I, Wietzerbin J, et al. Differential susceptibility to acute Trypanosoma cruzi infection in BALB/c and C57BL/6 mice is not associated with a distinct parasite load but cytokine abnormalities. Clin Exp Immunol. 2002;128(3):421–8.

    Article  CAS  Google Scholar 

  22. Romanha A, Castro S, Soeiro MN, Lannes-Vieira J, Ribeiro I, Talvani A, et al. In vitro and in vivo experimental models for drug screening and development for Chagas disease. Mem Inst Oswaldo Cruz. 2010;105(2):233–8.

    Article  CAS  Google Scholar 

  23. ICLAS-CIOMS. International guiding principles for biomedical research involving animals. Geneva: ICLAS-CIOMS; 2012.

    Google Scholar 

  24. Akle V, Agudelo-Dueñas N, Molina-Rodriguez MA, Kartchner L, Ruth A, González J, Forero-Shelton M. Establishment of larval Zebrafish as an animal model to investigate Trypanosoma cruzi motility in vivo. J Vis Exp. 2017;127:PMID: 28994774.

    Google Scholar 

  25. Buchanan-Kilbey G, Djumpah J, Papadopoulou MV, Bloomer W, Hu L, Wilkinson SR, Ashworth R. Evaluating the developmental toxicity of trypanocidal nitroaromatic compounds on zebrafish. Acta Trop. 2013;128(3):701–5. https://doi.org/10.1016/j.actatropica.2013.07.022.

    Article  CAS  PubMed  Google Scholar 

  26. Smith A, Clutton R, Lilley E, Hansen K, Brattelid T. PREPARE: guidelines for planning animal research and testing. Lab Anim. 2017; https://doi.org/10.1177/0023677217724823.

    Article  Google Scholar 

  27. Festing MFW, Altman DG. Guidelines for the design and statistical analysis of experiments using laboratory animals. ILAR J. 2002;43(4):244–58.

    Article  CAS  Google Scholar 

  28. Pathak RR. Small size sampling. Int J Bas Clin Pharmacol. 2012;1(1):43–4.

    Article  Google Scholar 

  29. Festing M. Inbred strains should replace outbred stocks in toxicology, safety testing, and drug development. Toxicol Pathol. 2010;38:681–90.

    Article  CAS  Google Scholar 

  30. Kilkenny C, Browne WJ, Cuthill IC, Emerson M, Altman DG. Improving bioscience research reporting: the ARRIVE guidelines for reporting animal research. PLoS Biol. 2010;8(6):e1000412.

    Article  Google Scholar 

  31. Munafò MR, Nosek BA, Bishop DVM, Button KS, Chambers CD, Percie du Sert N, et al. A manifesto for reproducible science. Nat Hum Behav. 2017;1:21. https://doi.org/10.1038/s41562-016-0021.

    Article  Google Scholar 

  32. Gulin J, Rocco D, García-Bournissen F. Quality of reporting and adherence to ARRIVE guidelines in animal studies for Chagas disease preclinical drug research: a systematic review. PLoS Negl Trop Dis. 2015;9(11):e0004194.

    Article  Google Scholar 

  33. National Research Council. Guide for the care and use of laboratory animals. 8th ed. Washington, DC: The National Academic Press; 2011.

    Google Scholar 

  34. Gouveia K, Hurst J. Reducing mouse anxiety during handling: effect of experience with handling tunnels. PLoS One. 2013;8(6):e664.

    Article  Google Scholar 

  35. Hurst JL, West RS. Taming anxiety in laboratory mice. Nat Methods. 2010;7:825. https://doi.org/10.1038/nmeth.1500.

    Article  CAS  PubMed  Google Scholar 

  36. Morton DDB, Jennings M, Buckwell A, Ewbank R, Godfrey C, Holgate B, et al. Refining procedures for the administration of substances. Lab Anim. 2001;35(1):1–41. https://doi.org/10.1258/0023677011911345.

    Article  CAS  PubMed  Google Scholar 

  37. Küster T, Zumkehr B, Hermann C, Theurillat R, Thormann W, Gottstein B, Hemphill A. Voluntary ingestion of antiparasitic drugs emulsified in honey represents an alternative to gavage in mice. J Am Assoc Lab Anim Sci. 2012;51(2):219–23.

    PubMed  PubMed Central  Google Scholar 

  38. Zimmer J, Lewis S, Moyer J. Comparison of gavage, water bottle, and a high-moisture diet bolus as dosing methods for quantitative D-xylose administration to B6D2F1 (Mus musculus) mice. Lab Anim. 1993;27(2):164–70. https://doi.org/10.1258/002367793780810423.

    Article  CAS  PubMed  Google Scholar 

  39. Canavaci A, Bustamante J, Padilla A, Perez Brandan C, Simpson L, Xu D, et al. In vitro and in vivo high-throughput assays for the testing of anti-Trypanosoma cruzi compounds. PLoS Negl Trop Dis. 2010;4(7):e740.

    Article  Google Scholar 

  40. Lewis MD, Fortes Francisco A, Taylor MC, Burrell-Saward H, McLatchie AP, Miles M a, Kelly JM. Bioluminescence imaging of chronic Trypanosoma cruzi infections reveals tissue-specific parasite dynamics and heart disease in the absence of locally persistent infection. Cell Microbiol. 2014;16(May):1285–300. https://doi.org/10.1111/cmi.12297.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Francisco AF, Lewis MD, Jayawardhana S, Taylor MC, Kelly JM, Chatelain E, Kelly JM. Limited ability of posaconazole to cure both acute and chronic Trypanosoma cruzi infections revealed by highly sensitive in vivo imaging. Antimicrob Agents Chemother. 2015;59(8):4653–61. https://doi.org/10.1128/AAC.00520-15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Campos J, Hoppe L, Duque T, de Castro S, Oliveira G. Use of non-invasive parameters to evaluate Swiss Webster mice during Trypanosoma cruzi experimental acute infection. J Parasitol. 2016;102(2):280–5.

    Article  CAS  Google Scholar 

  43. Silva D, Castro S, Alves M, Batista WS, Oliveira G. Acute experimental Trypanosoma cruzi infection: establishing a murine model that utilises non-invasive measurements of disease parameters. Mem Inst Oswaldo Cruz. 2012;107(2):211–6.

    Article  Google Scholar 

Download references

Acknowledgment

Dr. Facundo García-Bournissen for the critical review of the manuscript.

Author information

Authors and Affiliations

  1. Servicio de Parasitología y Enfermedad de Chagas, Hospital de Niños “Ricardo Gutiérrez”, Buenos Aires, Argentina

    Julián Ernesto Nicolás Gulin

  2. Instituto Multidisciplinario de Investigación en Patologías Pediátricas (IMIPP-GCBA), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina

    Julián Ernesto Nicolás Gulin

Authors
  1. Julián Ernesto Nicolás Gulin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Julián Ernesto Nicolás Gulin .

Editor information

Editors and Affiliations

  1. Servicio de Parasitología y Enfermedad de Chagas, Hospital de Niños “Ricardo Gutiérrez”, Buenos Aires, Argentina

    Jaime Marcelo Altcheh

  2. Servicio de Parasitología y Enfermedad de Chagas, Hospital de Niños “Ricardo Gutiérrez”, Buenos Aires, Argentina

    Hector Freilij

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Gulin, J.E.N. (2019). In Vivo Drug Testing for Experimental Trypanosoma cruzi Infection. In: Altcheh, J., Freilij, H. (eds) Chagas Disease. Birkhäuser Advances in Infectious Diseases. Springer, Cham. https://doi.org/10.1007/978-3-030-00054-7_15

Download citation

Publish with us

Policies and ethics

Search

Navigation