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In vitro susceptibility to pentavalent antimony in Leishmania infantum strains is not modified during in vitro or in vivo passages but is modified after host treatment with meglumine antimoniate.

Carrió J, Portús M - BMC Pharmacol. (2002)

Bottom Line: In contrast, a significant difference (P < 0.01, t test) was observed between the mean SbV-IC50 values in the stocks obtained before and after treatment of hosts with meglumine antimoniate (4.7 +/- 0.4 mgSbV/L vs. 7.7 +/- 1.5 mgSbV/L).Drug-resistance after drug pressure in experimentally infected dogs increased over repeated drug administration (6.4 +/- 0.5 mgSbV/L after first treatment vs. 8.6 +/- 1.4 mgSbV/L after the second) (P < 0.01, t test).These results confirm previous observations on strains from Leishmania/HIV co-infected patients and indicate the effect of the increasing use of antimony derivatives for treatment of canine leishmaniasis in endemic areas on the emergence of Leishmania antimony-resistant strains.

View Article: PubMed Central - HTML - PubMed

Affiliation: Laboratory of Parasitology, Departament de Microbiologia i Parasitologia Sanitàries, Facultat de Farmàcia, Universitat de Barcelona, 08028 Barcelona, Spain. jcarrio@farmacia.far.ub.es

ABSTRACT

Background: Leishmaniasis is a common parasitic disease in Southern Europe, caused by Leishmania infantum. The failures of current treatment with pentavalent antimonials are partially attributable to the emergence of antimony-resistant Leishmania strains. This study analyses the in vitro susceptibility to pentavalent antimony of intracellular amastigotes from a range of L. infantum strains, derived from the same infected animal, during in vitro and in vivo passages and after host treatment with meglumine antimoniate.

Results: SbV-IC50 values for strains from two distinct isolates from the same host and one stock after two years of culture in NNN medium and posterior passage to hamster were similar (5.0 +/- 0.2; 4.9 +/- 0.2 and 4.4 +/- 0.1 mgSbV/L, respectively). In contrast, a significant difference (P < 0.01, t test) was observed between the mean SbV-IC50 values in the stocks obtained before and after treatment of hosts with meglumine antimoniate (4.7 +/- 0.4 mgSbV/L vs. 7.7 +/- 1.5 mgSbV/L). Drug-resistance after drug pressure in experimentally infected dogs increased over repeated drug administration (6.4 +/- 0.5 mgSbV/L after first treatment vs. 8.6 +/- 1.4 mgSbV/L after the second) (P < 0.01, t test).

Conclusions: These results confirm previous observations on strains from Leishmania/HIV co-infected patients and indicate the effect of the increasing use of antimony derivatives for treatment of canine leishmaniasis in endemic areas on the emergence of Leishmania antimony-resistant strains.

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Flow chart for the origin of L. infantum stocks, derived from the same infected dog, after several in vitro and in vivo passages.
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Figure 1: Flow chart for the origin of L. infantum stocks, derived from the same infected dog, after several in vitro and in vivo passages.

Mentions: The in vitro susceptibility to SbV of two L. infantum strains (MCAN/ES/92/BCN-82 and MCAN/ES/92/BCN-83), simultaneously isolated from bone marrow and lymph node aspirate from the same dog were almost identical (IC50: 5.0 ± 0.2 and 4.9 ± 0.2 mgSbV/L). Also, the SbV-IC50 for MCRI/ES/94/BCN-328 (4.4 ± 0.1 mg/L) was very similar to that of the original strain (BCN-83) (Figure 1), despite repeated in vitro passages and hamster inoculation.


In vitro susceptibility to pentavalent antimony in Leishmania infantum strains is not modified during in vitro or in vivo passages but is modified after host treatment with meglumine antimoniate.

Carrió J, Portús M - BMC Pharmacol. (2002)

Flow chart for the origin of L. infantum stocks, derived from the same infected dog, after several in vitro and in vivo passages.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC113748&req=5

Figure 1: Flow chart for the origin of L. infantum stocks, derived from the same infected dog, after several in vitro and in vivo passages.
Mentions: The in vitro susceptibility to SbV of two L. infantum strains (MCAN/ES/92/BCN-82 and MCAN/ES/92/BCN-83), simultaneously isolated from bone marrow and lymph node aspirate from the same dog were almost identical (IC50: 5.0 ± 0.2 and 4.9 ± 0.2 mgSbV/L). Also, the SbV-IC50 for MCRI/ES/94/BCN-328 (4.4 ± 0.1 mg/L) was very similar to that of the original strain (BCN-83) (Figure 1), despite repeated in vitro passages and hamster inoculation.

Bottom Line: In contrast, a significant difference (P < 0.01, t test) was observed between the mean SbV-IC50 values in the stocks obtained before and after treatment of hosts with meglumine antimoniate (4.7 +/- 0.4 mgSbV/L vs. 7.7 +/- 1.5 mgSbV/L).Drug-resistance after drug pressure in experimentally infected dogs increased over repeated drug administration (6.4 +/- 0.5 mgSbV/L after first treatment vs. 8.6 +/- 1.4 mgSbV/L after the second) (P < 0.01, t test).These results confirm previous observations on strains from Leishmania/HIV co-infected patients and indicate the effect of the increasing use of antimony derivatives for treatment of canine leishmaniasis in endemic areas on the emergence of Leishmania antimony-resistant strains.

View Article: PubMed Central - HTML - PubMed

Affiliation: Laboratory of Parasitology, Departament de Microbiologia i Parasitologia Sanitàries, Facultat de Farmàcia, Universitat de Barcelona, 08028 Barcelona, Spain. jcarrio@farmacia.far.ub.es

ABSTRACT

Background: Leishmaniasis is a common parasitic disease in Southern Europe, caused by Leishmania infantum. The failures of current treatment with pentavalent antimonials are partially attributable to the emergence of antimony-resistant Leishmania strains. This study analyses the in vitro susceptibility to pentavalent antimony of intracellular amastigotes from a range of L. infantum strains, derived from the same infected animal, during in vitro and in vivo passages and after host treatment with meglumine antimoniate.

Results: SbV-IC50 values for strains from two distinct isolates from the same host and one stock after two years of culture in NNN medium and posterior passage to hamster were similar (5.0 +/- 0.2; 4.9 +/- 0.2 and 4.4 +/- 0.1 mgSbV/L, respectively). In contrast, a significant difference (P < 0.01, t test) was observed between the mean SbV-IC50 values in the stocks obtained before and after treatment of hosts with meglumine antimoniate (4.7 +/- 0.4 mgSbV/L vs. 7.7 +/- 1.5 mgSbV/L). Drug-resistance after drug pressure in experimentally infected dogs increased over repeated drug administration (6.4 +/- 0.5 mgSbV/L after first treatment vs. 8.6 +/- 1.4 mgSbV/L after the second) (P < 0.01, t test).

Conclusions: These results confirm previous observations on strains from Leishmania/HIV co-infected patients and indicate the effect of the increasing use of antimony derivatives for treatment of canine leishmaniasis in endemic areas on the emergence of Leishmania antimony-resistant strains.

Show MeSH
Related in: MedlinePlus