Allopurinol Resistance in Leishmania infantum from Dogs with Disease Relapse.
BACKGROUND:Visceral leishmaniasis caused by the protozoan Leishmania infantum is a zoonotic, life threatening parasitic disease. Domestic dogs are the main peridomestic reservoir, and allopurinol is the most frequently used drug for the control of infection, alone or in combination with other drugs....
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ftdoajarticles:oai:doaj.org/article:72bda54fc82b46acaf14cdb49de44d43 2023-05-15T15:12:42+02:00 Allopurinol Resistance in Leishmania infantum from Dogs with Disease Relapse. Daniel Yasur-Landau Charles L Jaffe Lior David Gad Baneth 2016-01-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0004341 https://doaj.org/article/72bda54fc82b46acaf14cdb49de44d43 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC4711794?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0004341 https://doaj.org/article/72bda54fc82b46acaf14cdb49de44d43 PLoS Neglected Tropical Diseases, Vol 10, Iss 1, p e0004341 (2016) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2016 ftdoajarticles https://doi.org/10.1371/journal.pntd.0004341 2022-12-31T13:31:39Z BACKGROUND:Visceral leishmaniasis caused by the protozoan Leishmania infantum is a zoonotic, life threatening parasitic disease. Domestic dogs are the main peridomestic reservoir, and allopurinol is the most frequently used drug for the control of infection, alone or in combination with other drugs. Resistance of Leishmania strains from dogs to allopurinol has not been described before in clinical studies. METHODOLOGY/PRINCIPAL FINDINGS:Following our observation of clinical disease relapse in dogs under allopurinol treatment, we tested susceptibility to allopurinol of L. infantum isolated from groups of dogs pre-treatment, treated in remission, and with disease relapse during treatment. Promastigote isolates obtained from four treated relapsed dogs (TR group) showed an average half maximal inhibitory concentration (IC50) of 996 μg/mL. A significantly lower IC50 (P = 0.01) was found for isolates from ten dogs before treatment (NT group, 200 μg/mL), as well as for five isolates obtained from treated dogs in remission (TA group, 268 μg/mL). Axenic amastigotes produced from isolates of the TR group also showed significantly higher (P = 0.002) IC50 compared to the NT group (1678 and 671 μg/mL, respectively). The lower sensitivity of intracellular amastigotes from the TR group relative to those from the NT group (P = 0.002) was confirmed using an infected macrophage model (6.3% and 20% growth inhibition, respectively at 300 μg/mL allopurinol). CONCLUSIONS:This is the first study to demonstrate allopurinol resistance in L. infantum and to associate it with disease relapse in the canine host. These findings are of concern as allopurinol is the main drug used for long term control of the disease in dogs, and resistant L. infantum strains may enhance uncontrolled transmission to humans and to other dogs. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 10 1 e0004341 |
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Directory of Open Access Journals: DOAJ Articles |
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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 Daniel Yasur-Landau Charles L Jaffe Lior David Gad Baneth Allopurinol Resistance in Leishmania infantum from Dogs with Disease Relapse. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
BACKGROUND:Visceral leishmaniasis caused by the protozoan Leishmania infantum is a zoonotic, life threatening parasitic disease. Domestic dogs are the main peridomestic reservoir, and allopurinol is the most frequently used drug for the control of infection, alone or in combination with other drugs. Resistance of Leishmania strains from dogs to allopurinol has not been described before in clinical studies. METHODOLOGY/PRINCIPAL FINDINGS:Following our observation of clinical disease relapse in dogs under allopurinol treatment, we tested susceptibility to allopurinol of L. infantum isolated from groups of dogs pre-treatment, treated in remission, and with disease relapse during treatment. Promastigote isolates obtained from four treated relapsed dogs (TR group) showed an average half maximal inhibitory concentration (IC50) of 996 μg/mL. A significantly lower IC50 (P = 0.01) was found for isolates from ten dogs before treatment (NT group, 200 μg/mL), as well as for five isolates obtained from treated dogs in remission (TA group, 268 μg/mL). Axenic amastigotes produced from isolates of the TR group also showed significantly higher (P = 0.002) IC50 compared to the NT group (1678 and 671 μg/mL, respectively). The lower sensitivity of intracellular amastigotes from the TR group relative to those from the NT group (P = 0.002) was confirmed using an infected macrophage model (6.3% and 20% growth inhibition, respectively at 300 μg/mL allopurinol). CONCLUSIONS:This is the first study to demonstrate allopurinol resistance in L. infantum and to associate it with disease relapse in the canine host. These findings are of concern as allopurinol is the main drug used for long term control of the disease in dogs, and resistant L. infantum strains may enhance uncontrolled transmission to humans and to other dogs. |
format |
Article in Journal/Newspaper |
author |
Daniel Yasur-Landau Charles L Jaffe Lior David Gad Baneth |
author_facet |
Daniel Yasur-Landau Charles L Jaffe Lior David Gad Baneth |
author_sort |
Daniel Yasur-Landau |
title |
Allopurinol Resistance in Leishmania infantum from Dogs with Disease Relapse. |
title_short |
Allopurinol Resistance in Leishmania infantum from Dogs with Disease Relapse. |
title_full |
Allopurinol Resistance in Leishmania infantum from Dogs with Disease Relapse. |
title_fullStr |
Allopurinol Resistance in Leishmania infantum from Dogs with Disease Relapse. |
title_full_unstemmed |
Allopurinol Resistance in Leishmania infantum from Dogs with Disease Relapse. |
title_sort |
allopurinol resistance in leishmania infantum from dogs with disease relapse. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2016 |
url |
https://doi.org/10.1371/journal.pntd.0004341 https://doaj.org/article/72bda54fc82b46acaf14cdb49de44d43 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 10, Iss 1, p e0004341 (2016) |
op_relation |
http://europepmc.org/articles/PMC4711794?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0004341 https://doaj.org/article/72bda54fc82b46acaf14cdb49de44d43 |
op_doi |
https://doi.org/10.1371/journal.pntd.0004341 |
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PLOS Neglected Tropical Diseases |
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10 |
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1 |
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e0004341 |
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