title: Sensitivity of Leishmania braziliensis promastigotes to meglumine antimoniate (glucantime) is higher than that of other Leishmania species and correlates with response to therapy in American tegumentary leishmaniasis.
abstract: The first line drugs for the treatment of leishmaniasis are antimonial derivatives. Poor clinical response may be credited to factors linked to the host, the drug, or the parasite. We determined the sensitivity of Leishmania sp. promastigotes and amastigotes by counting parasites exposed to increasing concentrations of meglumine antimoniate (Glucantime). Leishmania braziliensis promastigotes were significantly more sensitive than those belonging to other species. The sensitivity of L. braziliensis isolates from patients with unfavorable clinical outcome, such as therapeutic failure or relapse, was significantly lower than those from patients who had clinical cure. Poor clinical response to therapy (therapeutic failure or relapse) was also associated with inadequate antimonial therapy. We also found a significant and positive correlation between promastigotes and intracellular amastigotes with regard to their in vitro susceptibilities to meglumine antimoniate. Our data provide evidence for an association between the sensitivity of promastigotes to antimonials in vitro and clinical response to therapy in American tegumentary leishmaniasis. The high sensitivity of the local L. braziliensis to meglumine antimoniate in vitro provides an explanation for the good clinical response of cutaneous leishmaniasis in the municipality of Rio de Janeiro, Brazil, even when low-dose regimens are employed.
authors.affiliation: Departamento de Imunologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Avenida Brasil 4365, Manguinhos, 21045-900, Rio de Janeiro, RJ, Brazil. azeredocoutinho@ioc.fiocruz.br
authors.forename: Rilza B Gayoso
authors.initials: RB
authors.lastname: Azeredo-Coutinho
authors.forename: Sergio C F
authors.initials: SC
authors.lastname: Mendonça
authors.forename: Heather
authors.initials: H
authors.lastname: Callahan
authors.forename: Andréia C
authors.initials: AC
authors.lastname: Portal
authors.forename: Grögl
authors.initials: G
authors.lastname: Max
mesh_terms: D000818:Animals; D000965:Antimony / Q000494:pharmacology / Q000627:therapeutic use; D000981:Antiprotozoal Agents / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D020128:Inhibitory Concentration 50; D007892:Leishmania braziliensis / Q000187:drug effects*; D016773:Leishmaniasis, Cutaneous / Q000188:drug therapy* / Q000469:parasitology; D008536:Meglumine / Q000494:pharmacology* / Q000627:therapeutic use; D000077485:Meglumine Antimoniate; D009942:Organometallic Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D021261:Parasitic Sensitivity Tests; D016896:Treatment Outcome
chemical_list: D000981:Antiprotozoal Agents; D009942:Organometallic Compounds; D008536:Meglumine; D000077485:Meglumine Antimoniate; D000965:Antimony