Lab Anim Res.  2020 Dec;36(4):356-362. 10.1186/s42826-020-00071-z.

Refining drug administration in a murine model of acute infection with Trypanosoma cruzi

Affiliations
  • 1Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas (IMIPP), Hospital de Niños “Dr. Ricardo Gutiérrez”, CONICET- GCBA, Gallo 1330, 1425 Buenos Aires, Argentina
  • 2Servicio de Parasitología y Enfermedad de Chagas, Hospital de Niños “Dr. Ricardo Gutiérrez”. Ministerio de Salud. GCBA, Buenos Aires, Argentina

Abstract

Background
In animal research, “refinement” refers to modifications of husbandry or experimental procedures to enhance animal well-being and minimize or eliminate pain and distress. Evaluation of drug efficacy in mice models, such as those used to study Trypanosoma cruzi infection, require prolonged drug administration by the oral route (e.g. for 20 consecutive days). However, the orogastric gavage method can lead to significant discomfort, upper digestive or respiratory tract lesions, aspiration pneumonia and even accidental death. The aim of this work was to evaluate the effect of two administration methods (conventional oral gavage vs. a refined method using a disposable tip and automatic pipette) on the efficacy of benznidazole in a murine model of T. cruzi infection.
Results
Both administration methods led to a rapid and persistent reduction in parasitaemia. Absence of T. cruzi DNA (evaluated by real-time PCR) in blood, cardiac and skeletal muscle confirmed that treatment efficacy was not influenced by the administration method used.
Conclusions
The proposed refined method for long-term oral drug administration may be a suitable strategy for assessing drug efficacy in mice models of Chagas disease and can be applied to similar murine infection models to reduce animal discomfort.

Keyword

Chagas disease animal models; Chronic treatment - Oral administration; Preclinical drug research; Refinement
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