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Antimony susceptibility of Leishmania isolates collected over a 30-year period in Algeria
BACKGROUND: In Algeria, the treatment of visceral and cutaneous leishmanioses (VL and CL) has been and continues to be based on antimony-containing drugs. It is suspected that high drug selective pressure might favor the emergence of chemoresistant parasites. Although treatment failure is frequently...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5889277/ https://www.ncbi.nlm.nih.gov/pubmed/29561842 http://dx.doi.org/10.1371/journal.pntd.0006310 |
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author | Eddaikra, Naouel Ait-Oudhia, Khatima Kherrachi, Ihcen Oury, Bruno Moulti-Mati, Farida Benikhlef, Razika Harrat, Zoubir Sereno, Denis |
author_facet | Eddaikra, Naouel Ait-Oudhia, Khatima Kherrachi, Ihcen Oury, Bruno Moulti-Mati, Farida Benikhlef, Razika Harrat, Zoubir Sereno, Denis |
author_sort | Eddaikra, Naouel |
collection | PubMed |
description | BACKGROUND: In Algeria, the treatment of visceral and cutaneous leishmanioses (VL and CL) has been and continues to be based on antimony-containing drugs. It is suspected that high drug selective pressure might favor the emergence of chemoresistant parasites. Although treatment failure is frequently reported during antimonial therapy of both CL and VL, antimonial resistance has never been thoroughly investigated in Algeria. Determining the level of antimonial susceptibility, amongst Leishmania transmitted in Algeria, is of great importance for the development of public health policies. METHODOLOGY/PRINCIPAL FINDINGS: Within the framework of the knowledge about the epidemiology of VL and CL amassed during the last 30 years, we sampled Leishmania isolates to determine their susceptibility to antimony. We analyzed a total of 106 isolates including 88 isolates collected between 1976 and 2013 in Algeria from humans, dogs, rodents, and phlebotomines and 18 collected from dogs in France. All the Algerian isolates were collected in 14 localities where leishmaniasis is endemic. The 50% inhibitory concentrations (IC50) of potassium antimony tartrate (the trivalent form of antimony, Sb(III)) and sodium stibogluconate (the pentavalent form of antimony, Sb(V)) were determined in promastigotes and intramacrophage amastigotes, respectively. The epidemiological cutoff (ECOFF) that allowed us to differentiate between Leishmania species causing cutaneous or visceral leishmaniases that were susceptible (S+) or insusceptible (S-) to the trivalent form of antimony was determined. The computed IC50 cutoff values were 23.83 μg/mL and 15.91 μg/mL for VL and CL, respectively. We report a trend of increasing antimony susceptibility in VL isolates during the 30-year period. In contrast, an increase in the frequency of S- phenotypes in isolates causing CL was observed during the same period. In our study, the emergence of S- phenotypes correlates with the inclusion of L. killicki (syn: L. tropica) isolates that cause cutaneous leishmaniasis and that have emerged in Algeria during the last decade. CONCLUSION/SIGNIFICANCE: Our results provide insight into the spatiotemporal dynamics of Leishmania antimony susceptibility in Algeria. We highlight the need for the future implementation of an effective methodology to determine the antimony susceptibility status of Leishmania isolates to detect the emergence of and prevent the dissemination of drug-resistant strains. |
format | Online Article Text |
id | pubmed-5889277 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-58892772018-04-20 Antimony susceptibility of Leishmania isolates collected over a 30-year period in Algeria Eddaikra, Naouel Ait-Oudhia, Khatima Kherrachi, Ihcen Oury, Bruno Moulti-Mati, Farida Benikhlef, Razika Harrat, Zoubir Sereno, Denis PLoS Negl Trop Dis Research Article BACKGROUND: In Algeria, the treatment of visceral and cutaneous leishmanioses (VL and CL) has been and continues to be based on antimony-containing drugs. It is suspected that high drug selective pressure might favor the emergence of chemoresistant parasites. Although treatment failure is frequently reported during antimonial therapy of both CL and VL, antimonial resistance has never been thoroughly investigated in Algeria. Determining the level of antimonial susceptibility, amongst Leishmania transmitted in Algeria, is of great importance for the development of public health policies. METHODOLOGY/PRINCIPAL FINDINGS: Within the framework of the knowledge about the epidemiology of VL and CL amassed during the last 30 years, we sampled Leishmania isolates to determine their susceptibility to antimony. We analyzed a total of 106 isolates including 88 isolates collected between 1976 and 2013 in Algeria from humans, dogs, rodents, and phlebotomines and 18 collected from dogs in France. All the Algerian isolates were collected in 14 localities where leishmaniasis is endemic. The 50% inhibitory concentrations (IC50) of potassium antimony tartrate (the trivalent form of antimony, Sb(III)) and sodium stibogluconate (the pentavalent form of antimony, Sb(V)) were determined in promastigotes and intramacrophage amastigotes, respectively. The epidemiological cutoff (ECOFF) that allowed us to differentiate between Leishmania species causing cutaneous or visceral leishmaniases that were susceptible (S+) or insusceptible (S-) to the trivalent form of antimony was determined. The computed IC50 cutoff values were 23.83 μg/mL and 15.91 μg/mL for VL and CL, respectively. We report a trend of increasing antimony susceptibility in VL isolates during the 30-year period. In contrast, an increase in the frequency of S- phenotypes in isolates causing CL was observed during the same period. In our study, the emergence of S- phenotypes correlates with the inclusion of L. killicki (syn: L. tropica) isolates that cause cutaneous leishmaniasis and that have emerged in Algeria during the last decade. CONCLUSION/SIGNIFICANCE: Our results provide insight into the spatiotemporal dynamics of Leishmania antimony susceptibility in Algeria. We highlight the need for the future implementation of an effective methodology to determine the antimony susceptibility status of Leishmania isolates to detect the emergence of and prevent the dissemination of drug-resistant strains. Public Library of Science 2018-03-21 /pmc/articles/PMC5889277/ /pubmed/29561842 http://dx.doi.org/10.1371/journal.pntd.0006310 Text en © 2018 Eddaikra et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Eddaikra, Naouel Ait-Oudhia, Khatima Kherrachi, Ihcen Oury, Bruno Moulti-Mati, Farida Benikhlef, Razika Harrat, Zoubir Sereno, Denis Antimony susceptibility of Leishmania isolates collected over a 30-year period in Algeria |
title | Antimony susceptibility of Leishmania isolates collected over a 30-year period in Algeria |
title_full | Antimony susceptibility of Leishmania isolates collected over a 30-year period in Algeria |
title_fullStr | Antimony susceptibility of Leishmania isolates collected over a 30-year period in Algeria |
title_full_unstemmed | Antimony susceptibility of Leishmania isolates collected over a 30-year period in Algeria |
title_short | Antimony susceptibility of Leishmania isolates collected over a 30-year period in Algeria |
title_sort | antimony susceptibility of leishmania isolates collected over a 30-year period in algeria |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5889277/ https://www.ncbi.nlm.nih.gov/pubmed/29561842 http://dx.doi.org/10.1371/journal.pntd.0006310 |
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