American tegumentary leishmaniasis: Is antimonial treatment outcome related to parasite drug susceptibility?
BACKGROUND
Antimonials are the first drug of choice for the treatment of American tegumentary leishmaniasis (ATL); however, their efficacy is not predictable, and this may be linked to parasite drug resistance. We aimed to characterize the in vitro antimony susceptibility of clinical isolates of Peruvian patients with ATL who were treated with sodium stibogluconate and to correlate this in vitro phenotype with different treatment outcomes.


METHODS
Thirty-seven clinical isolates were obtained from patients with known disease and treatment histories. These isolates were typed, and the susceptibility of intracellular amastigotes to pentavalent (SbV) and trivalent (SbIII) antimonials was determined.


RESULTS
We observed 29 SbV-resistant isolates among 4 species of subgenus Viannia, most of which exhibited primary resistance; isolates resistant only to SbIII; and 3 combinations of in vitro phenotypes: (1) parasites sensitive to both drugs, (2) parasites resistant to both drugs, and (3) parasites resistant to SbV only (the majority of isolates fell into this category). There was no correlation between in vitro susceptibility to both antimonials and the clinical outcome of therapy.


CONCLUSIONS
Antimony insensitivity might occur in a stepwise fashion (first to SbV and then to SbIII). Our data question the definition of true parasite resistance to antimonials. Further studies of treatment efficacy should apply standardized protocols and definitions and should also consider host factors.
Yardley
Vanessa
V
London School of Hygiene and Tropical Medicine, Department of Infectious and Tropical Diseases, London, United Kingdom.
Ortuno
Nimer
N
Llanos-Cuentas
Alejandro
A
Chappuis
Francois
F
Doncker
Simonne De
SD
Ramirez
Luis
L
Croft
Simon
S
Arevalo
Jorge
J
Adaui
Vanessa
V
Bermudez
Hernan
H
Decuypere
Saskia
S
Dujardin
Jean-Claude
JC
D000818:Animals; D000967:Antimony Sodium Gluconate / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000981:Antiprotozoal Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004351:Drug Resistance; D006801:Humans; D007891:Leishmania / Q000187:drug effects* / Q000302:isolation & purification; D016773:Leishmaniasis, Cutaneous / Q000188:drug therapy* / Q000453:epidemiology / Q000469:parasitology; D021261:Parasitic Sensitivity Tests; D010568:Peru / Q000453:epidemiology; D011446:Prospective Studies; D016896:Treatment Outcome
D000981:Antiprotozoal Agents; D000967:Antimony Sodium Gluconate