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Activities of artesunate-based combinations and tafenoquine against Babesia bovis in vitro and Babesia microti in vivo

BACKGROUND: Babesiosis represents a veterinary and medical threat, with a need for novel drugs. Artemisinin-based combination therapies (ACT) have been successfully implemented for malaria, a human disease caused by related parasites, Plasmodium spp. The aim of this study was to investigate whether...

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Autores principales: Carvalho, Leonardo J. M., Tuvshintulga, Bunduurem, Nugraha, Arifin B., Sivakumar, Thillaiampalam, Yokoyama, Naoaki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7372749/
https://www.ncbi.nlm.nih.gov/pubmed/32690081
http://dx.doi.org/10.1186/s13071-020-04235-7
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author Carvalho, Leonardo J. M.
Tuvshintulga, Bunduurem
Nugraha, Arifin B.
Sivakumar, Thillaiampalam
Yokoyama, Naoaki
author_facet Carvalho, Leonardo J. M.
Tuvshintulga, Bunduurem
Nugraha, Arifin B.
Sivakumar, Thillaiampalam
Yokoyama, Naoaki
author_sort Carvalho, Leonardo J. M.
collection PubMed
description BACKGROUND: Babesiosis represents a veterinary and medical threat, with a need for novel drugs. Artemisinin-based combination therapies (ACT) have been successfully implemented for malaria, a human disease caused by related parasites, Plasmodium spp. The aim of this study was to investigate whether ACT is active against Babesia in vitro and in vivo. METHODS: Mefloquine, tafenoquine, primaquine, methylene blue and lumefantrine, alone or in combination with artesunate, were tested in vitro against Babesia bovis. Parasite growth was verified using a SYBR green I-based fluorescence assay. Mice infected with Babesia microti were treated with mefloquine or tafenoquine, alone or in combination with artesunate, and parasitemia was verified by microscopy and PCR. RESULTS: All drugs, except lumefantrine, showed in vitro activity against B. bovis, with methylene blue showing the most potent activity (concentration 0.2 μM). Combination with artesunate led to improved activity, with mefloquine showing a striking 20-fold increase in activity. Tafenoquine (10 mg/kg, base), combined or not with artesunate, but not mefloquine, induced rapid clearance of B. microti in vivo by microscopy, but mice remained PCR-positive. Blood from mice treated with tafenoquine alone, but not with tafenoquine-artesunate, was infective for naive mice upon sub-inoculation. CONCLUSIONS: Tafenoquine, and most likely other 8-aminoquinoline compounds, are promising compounds for the development of ACT for babesiosis. [Image: see text]
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spelling pubmed-73727492020-07-21 Activities of artesunate-based combinations and tafenoquine against Babesia bovis in vitro and Babesia microti in vivo Carvalho, Leonardo J. M. Tuvshintulga, Bunduurem Nugraha, Arifin B. Sivakumar, Thillaiampalam Yokoyama, Naoaki Parasit Vectors Research BACKGROUND: Babesiosis represents a veterinary and medical threat, with a need for novel drugs. Artemisinin-based combination therapies (ACT) have been successfully implemented for malaria, a human disease caused by related parasites, Plasmodium spp. The aim of this study was to investigate whether ACT is active against Babesia in vitro and in vivo. METHODS: Mefloquine, tafenoquine, primaquine, methylene blue and lumefantrine, alone or in combination with artesunate, were tested in vitro against Babesia bovis. Parasite growth was verified using a SYBR green I-based fluorescence assay. Mice infected with Babesia microti were treated with mefloquine or tafenoquine, alone or in combination with artesunate, and parasitemia was verified by microscopy and PCR. RESULTS: All drugs, except lumefantrine, showed in vitro activity against B. bovis, with methylene blue showing the most potent activity (concentration 0.2 μM). Combination with artesunate led to improved activity, with mefloquine showing a striking 20-fold increase in activity. Tafenoquine (10 mg/kg, base), combined or not with artesunate, but not mefloquine, induced rapid clearance of B. microti in vivo by microscopy, but mice remained PCR-positive. Blood from mice treated with tafenoquine alone, but not with tafenoquine-artesunate, was infective for naive mice upon sub-inoculation. CONCLUSIONS: Tafenoquine, and most likely other 8-aminoquinoline compounds, are promising compounds for the development of ACT for babesiosis. [Image: see text] BioMed Central 2020-07-20 /pmc/articles/PMC7372749/ /pubmed/32690081 http://dx.doi.org/10.1186/s13071-020-04235-7 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Carvalho, Leonardo J. M.
Tuvshintulga, Bunduurem
Nugraha, Arifin B.
Sivakumar, Thillaiampalam
Yokoyama, Naoaki
Activities of artesunate-based combinations and tafenoquine against Babesia bovis in vitro and Babesia microti in vivo
title Activities of artesunate-based combinations and tafenoquine against Babesia bovis in vitro and Babesia microti in vivo
title_full Activities of artesunate-based combinations and tafenoquine against Babesia bovis in vitro and Babesia microti in vivo
title_fullStr Activities of artesunate-based combinations and tafenoquine against Babesia bovis in vitro and Babesia microti in vivo
title_full_unstemmed Activities of artesunate-based combinations and tafenoquine against Babesia bovis in vitro and Babesia microti in vivo
title_short Activities of artesunate-based combinations and tafenoquine against Babesia bovis in vitro and Babesia microti in vivo
title_sort activities of artesunate-based combinations and tafenoquine against babesia bovis in vitro and babesia microti in vivo
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7372749/
https://www.ncbi.nlm.nih.gov/pubmed/32690081
http://dx.doi.org/10.1186/s13071-020-04235-7
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