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.
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.
Carrió
Jaume
J
Laboratory of Parasitology, Departament de Microbiologia i Parasitologia Sanitàries, Facultat de Farmàcia, Universitat de Barcelona, 08028 Barcelona, Spain. jcarrio@farmacia.far.ub.es
Portús
Montserrat
M
D000818:Animals; D000965:Antimony / Q000737:chemistry; D000981:Antiprotozoal Agents / Q000494:pharmacology / Q000627:therapeutic use*; D004283:Dog Diseases / Q000188:drug therapy* / Q000469:parasitology; D004285:Dogs; D004351:Drug Resistance; D006801:Humans; D018314:Leishmania infantum / Q000187:drug effects*; D007896:Leishmaniasis / Q000188:drug therapy* / Q000662:veterinary; D008536:Meglumine / Q000494:pharmacology / Q000627:therapeutic use*; D000077485:Meglumine Antimoniate; D009942:Organometallic Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D021261:Parasitic Sensitivity Tests
D000981:Antiprotozoal Agents; D009942:Organometallic Compounds; D008536:Meglumine; D000077485:Meglumine Antimoniate; D000965:Antimony