Optimization of topical therapy for Leishmania major localized cutaneous leishmaniasis using a reliable C57BL/6 Model.
BACKGROUND: Because topical therapy is easy and usually painless, it is an attractive first-line option for the treatment of localized cutaneous leishmaniasis (LCL). Promising ointments are in the final stages of development. One main objective was to help optimize the treatment modalities of human...
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ftdoajarticles:oai:doaj.org/article:f4eccaa3b1594a639e80def5f5256ab9 2023-05-15T15:14:37+02:00 Optimization of topical therapy for Leishmania major localized cutaneous leishmaniasis using a reliable C57BL/6 Model. Hervé Lecoeur Pierre Buffet Gloria Morizot Sophie Goyard Ghislaine Guigon Geneviève Milon Thierry Lang 2007-01-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0000034 https://doaj.org/article/f4eccaa3b1594a639e80def5f5256ab9 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC2100369?pdf=render https://doaj.org/toc/1935-2735 1935-2735 doi:10.1371/journal.pntd.0000034 https://doaj.org/article/f4eccaa3b1594a639e80def5f5256ab9 PLoS Neglected Tropical Diseases, Vol 1, Iss 2, p e34 (2007) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2007 ftdoajarticles https://doi.org/10.1371/journal.pntd.0000034 2022-12-31T16:26:08Z BACKGROUND: Because topical therapy is easy and usually painless, it is an attractive first-line option for the treatment of localized cutaneous leishmaniasis (LCL). Promising ointments are in the final stages of development. One main objective was to help optimize the treatment modalities of human LCL with WR279396, a topical formulation of aminoglycosides that was recently proven to be efficient and safe for use in humans. METHODOLOGY/PRINCIPAL FINDINGS: C57BL/6 mice were inoculated in the ear with luciferase transgenic L. major and then treated with WR279396. The treatment period spanned lesion onset, and the evolution of clinical signs and bioluminescent parasite loads could be followed for several months without killing the mice. As judged by clinical healing and a 1.5-3 log parasite load decrease in less than 2 weeks, the 94% efficacy of 10 daily applications of WR279396 in mice was very similar to what had been previously observed in clinical trials. When WR279396 was applied with an occlusive dressing, parasitological and clinical efficacy was significantly increased and no rebound of parasite load was observed. In addition, 5 applications under occlusion were more efficient when done every other day for 10 days than daily for 5 days, showing that length of therapy is a more important determinant of treatment efficacy than the total dose topically applied. CONCLUSIONS/SIGNIFICANCE: Occlusion has a significant adjuvant effect on aminoglycoside ointment therapy of experimental cutaneaous leishmaniasis (CL), a concept that might apply to other antileishmanial or antimicrobial ointments. Generated in a laboratory mouse-based model that closely mimics the course of LCL in humans, our results support a schedule based on discontinuous applications for a few weeks rather than several daily applications for a few days. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLoS Neglected Tropical Diseases 1 2 e34 |
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Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
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English |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Hervé Lecoeur Pierre Buffet Gloria Morizot Sophie Goyard Ghislaine Guigon Geneviève Milon Thierry Lang Optimization of topical therapy for Leishmania major localized cutaneous leishmaniasis using a reliable C57BL/6 Model. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
BACKGROUND: Because topical therapy is easy and usually painless, it is an attractive first-line option for the treatment of localized cutaneous leishmaniasis (LCL). Promising ointments are in the final stages of development. One main objective was to help optimize the treatment modalities of human LCL with WR279396, a topical formulation of aminoglycosides that was recently proven to be efficient and safe for use in humans. METHODOLOGY/PRINCIPAL FINDINGS: C57BL/6 mice were inoculated in the ear with luciferase transgenic L. major and then treated with WR279396. The treatment period spanned lesion onset, and the evolution of clinical signs and bioluminescent parasite loads could be followed for several months without killing the mice. As judged by clinical healing and a 1.5-3 log parasite load decrease in less than 2 weeks, the 94% efficacy of 10 daily applications of WR279396 in mice was very similar to what had been previously observed in clinical trials. When WR279396 was applied with an occlusive dressing, parasitological and clinical efficacy was significantly increased and no rebound of parasite load was observed. In addition, 5 applications under occlusion were more efficient when done every other day for 10 days than daily for 5 days, showing that length of therapy is a more important determinant of treatment efficacy than the total dose topically applied. CONCLUSIONS/SIGNIFICANCE: Occlusion has a significant adjuvant effect on aminoglycoside ointment therapy of experimental cutaneaous leishmaniasis (CL), a concept that might apply to other antileishmanial or antimicrobial ointments. Generated in a laboratory mouse-based model that closely mimics the course of LCL in humans, our results support a schedule based on discontinuous applications for a few weeks rather than several daily applications for a few days. |
format |
Article in Journal/Newspaper |
author |
Hervé Lecoeur Pierre Buffet Gloria Morizot Sophie Goyard Ghislaine Guigon Geneviève Milon Thierry Lang |
author_facet |
Hervé Lecoeur Pierre Buffet Gloria Morizot Sophie Goyard Ghislaine Guigon Geneviève Milon Thierry Lang |
author_sort |
Hervé Lecoeur |
title |
Optimization of topical therapy for Leishmania major localized cutaneous leishmaniasis using a reliable C57BL/6 Model. |
title_short |
Optimization of topical therapy for Leishmania major localized cutaneous leishmaniasis using a reliable C57BL/6 Model. |
title_full |
Optimization of topical therapy for Leishmania major localized cutaneous leishmaniasis using a reliable C57BL/6 Model. |
title_fullStr |
Optimization of topical therapy for Leishmania major localized cutaneous leishmaniasis using a reliable C57BL/6 Model. |
title_full_unstemmed |
Optimization of topical therapy for Leishmania major localized cutaneous leishmaniasis using a reliable C57BL/6 Model. |
title_sort |
optimization of topical therapy for leishmania major localized cutaneous leishmaniasis using a reliable c57bl/6 model. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2007 |
url |
https://doi.org/10.1371/journal.pntd.0000034 https://doaj.org/article/f4eccaa3b1594a639e80def5f5256ab9 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 1, Iss 2, p e34 (2007) |
op_relation |
http://europepmc.org/articles/PMC2100369?pdf=render https://doaj.org/toc/1935-2735 1935-2735 doi:10.1371/journal.pntd.0000034 https://doaj.org/article/f4eccaa3b1594a639e80def5f5256ab9 |
op_doi |
https://doi.org/10.1371/journal.pntd.0000034 |
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PLoS Neglected Tropical Diseases |
container_volume |
1 |
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2 |
container_start_page |
e34 |
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1766345055712313344 |