title: American tegumentary leishmaniasis: Is antimonial treatment outcome related to parasite drug susceptibility?
abstract: 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.
authors.affiliation: London School of Hygiene and Tropical Medicine, Department of Infectious and Tropical Diseases, London, United Kingdom.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Yardley
authors.forename: Nimer
authors.initials: N
authors.lastname: Ortuno
authors.forename: Alejandro
authors.initials: A
authors.lastname: Llanos-Cuentas
authors.forename: Francois
authors.initials: F
authors.lastname: Chappuis
authors.forename: Simonne De
authors.initials: SD
authors.lastname: Doncker
authors.forename: Luis
authors.initials: L
authors.lastname: Ramirez
authors.forename: Simon
authors.initials: S
authors.lastname: Croft
authors.forename: Jorge
authors.initials: J
authors.lastname: Arevalo
authors.forename: Vanessa
authors.initials: V
authors.lastname: Adaui
authors.forename: Hernan
authors.initials: H
authors.lastname: Bermudez
authors.forename: Saskia
authors.initials: S
authors.lastname: Decuypere
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Dujardin
mesh_terms: 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
chemical_list: D000981:Antiprotozoal Agents; D000967:Antimony Sodium Gluconate