title: Antimonial treatment of visceral leishmaniasis: are current in vitro susceptibility assays adequate for prognosis of in vivo therapy outcome?
abstract: In most of the Indian subcontinent, the first line treatment for visceral leishmaniasis (VL) is sodium stibogluconate (SSG), an antimonial drug, but the efficacy of the drug varies according to region. We aimed to characterize the in vitro antimony susceptibility of clinical isolates of Nepalese VL patients, and to correlate this in vitro parasite phenotype to clinical therapy outcome. Thirty-three clinical isolates of L. donovani were taken from patients with known disease history. These isolates were typed and the susceptibility of intracellular amastigotes to pentavalent (SbV) and trivalent (SbIII) antimonials was determined. We observed (i) 22 SbV-resistant isolates out of 33 tested and (ii) 3 SbIII-resistant isolates out of 12 tested. Amongst the latter, there were three combinations of in vitro phenotypes: (i) parasites sensitive (n=4) or (ii) resistant to both drugs (n=3) and (iii) resistant to SbV only (n=5). There was no geographical clustering in terms of in vitro susceptibility. The relation between the in vitro susceptibility to antimonials and the corresponding in vivo treatment outcome was ambiguous. Our results highlight the need to adjust the currently used Leishmania drug susceptibility assays if they are to be used for prognosis of in vivo SSG treatment outcome.
authors.affiliation: B.P. Koirala Institute of Health Sciences, Ghopa, Dharan, Nepal.
authors.forename: Suman
authors.initials: S
authors.lastname: Rijal
authors.forename: Vanessa
authors.initials: V
authors.lastname: Yardley
authors.forename: François
authors.initials: F
authors.lastname: Chappuis
authors.forename: Saskia
authors.initials: S
authors.lastname: Decuypere
authors.forename: Basudha
authors.initials: B
authors.lastname: Khanal
authors.forename: Rupa
authors.initials: R
authors.lastname: Singh
authors.forename: Marleen
authors.initials: M
authors.lastname: Boelaert
authors.forename: Simonne
authors.initials: S
authors.lastname: De Doncker
authors.forename: Simon
authors.initials: S
authors.lastname: Croft
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Dujardin
mesh_terms: D000818:Animals; D000967:Antimony Sodium Gluconate / Q000627:therapeutic use*; D000981:Antiprotozoal Agents / Q000627:therapeutic use*; D004352:Drug Resistance, Microbial; D006801:Humans; D007893:Leishmania donovani / Q000254:growth & development*; D007898:Leishmaniasis, Visceral / Q000188:drug therapy* / Q000469:parasitology; D011379:Prognosis; D016896:Treatment Outcome
chemical_list: D000981:Antiprotozoal Agents; D000967:Antimony Sodium Gluconate