Oral administration of azithromycin ameliorates trypanosomosis in Trypanosoma congolense-infected mice
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Animal trypanosomosis is a devastating parasitic disease that is of economic importance to livestock production. The infection includes animal African trypanosomosis, surra, and dourine. The treatment is based solely on few compounds that were discovered decades ago and which are associated with severe toxicity. Furthermore, it is likely that the parasite has developed resistance towards them. Thus, there is an urgent need for new, accessible, and less toxic drugs. Azithromycin is an antibiotic with documented efficacy against Toxoplasma, Babesia, and Plasmodium. The current study investigated its effects against animal trypanosomes. An in vitro system was used to determine the trypanocidal effects of azithromycin against Trypanosoma congolense, Trypanosoma brucei brucei, and Trypanosoma evansi, and cytotoxicity in Madin-Darby bovine kidney (MDBK) and NIH 3T3 cells. Furthermore, the trypanocidal effects of azithromycin were investigated in T. congolense-infected mice. In vitro, azithromycin had an IC50 of 0.19 ± 0.17; 3.69 ± 2.26; 1.81 ± 1.82 μg/mL against T. congolense, T. b. brucei, and T. evansi, respectively. No cytotoxic effects were observed in MDBK and NIH 3T3 cells. The efficacy of orally administered azithromycin was investigated in short-term and long-term treatment protocols. Although the short-term treatment protocol showed no curative effects, the survival rate of the mice was significantly prolonged (p < 0.001) in comparison to the control group. The long-term treatment yielded satisfying curative effects with doses of 300 and 400 mg/kg achieving 80 and 100% survival, respectively. In conclusion, long-term oral azithromycin treatment has trypanocidal effects against T. congolense.
KeywordsAnimal trypanosomosis Azithromycin Oral administration Trypanosoma congolense
The authors would like to express their gratitude to the Ministry of Education, Culture, Sports, Science and Technology (MEXT) for the financial support granted to this study, which was conducted at Obihiro University of Agriculture and Veterinary Medicine in the National Research Center for Protozoan Diseases. This study was also financially supported by grants from the Japan Society for the Promotion of Science (JSPS) KAKENHI Grant Number 16K18793 (Grants-in-Aid for Young Scientists [B]), the “International Collaborative Research Program for Tackling the NTD (Neglected Tropical Disease) Challenges in African Countries” from the Japan Agency for Medical Research and Development (AMED), and the AMED/JICA SATREPS.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
All procedures performed in studies involving animals were in accordance with the ethical standards of Obihiro University of Agriculture and Veterinary Medicine, Japan, animal committee (approval nos. 28-129 and 28-169).
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