title: In vitro drug susceptibility of Leishmania infantum isolated from humans and dogs.
abstract: Visceral leishmaniasis (VL) caused by parasites of Leishmania donovani complex is a severe human disease which often leads to death if left untreated. Domestic dogs are the main reservoir hosts for zoonotic human visceral infection caused by Leishmania infantum. In the absence of effective human and dog vaccines, the only feasible way to treat and control leishmaniasis is through the use of suitable medications. To know the drug susceptibility of human and canine Leishmania strains from Lisbon-Portugal, a study on a panel of strains was conducted by testing the susceptibility of promastigotes and intracellular amastigotes to the common drugs used in canine leishmaniasis (CanL) and human VL (meglumine antimoniate, amphotericin B, miltefosine and allopurinol). Although a high heterogeneity of susceptibilities was obtained to each drug on both axenic promastigote and intracellular amastigote assays, intracellular amastigotes system correlated better with treatment outcome. Parasites isolated from the refractory human case were the least susceptible to the drugs used highlighting that the emergence of cross-resistance to the drugs available for human therapy should not be neglected. Furthermore, parasites isolated from dogs showed low susceptibility to the main drugs used in CanL treatment. Our results focus the importance of reducing/avoiding the emergence and spread of resistant parasites in the canine and human populations, a factor that requires special consideration when dogs are treated using the same available anti-Leishmania drugs for human VL. In addition, efforts should be made in order to standardize the conditions used to test drug susceptibility (methodologies, drug formulations and media) in order to compare results between laboratories.
authors.affiliation: Unidade de Parasitologia Médica, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Lisboa, Portugal. carlamaia@ihmt.unl.pt
authors.forename: Carla
authors.initials: C
authors.lastname: Maia
authors.forename: Mónica
authors.initials: M
authors.lastname: Nunes
authors.forename: Mónica
authors.initials: M
authors.lastname: Marques
authors.forename: Sofia
authors.initials: S
authors.lastname: Henriques
authors.forename: Nuno
authors.initials: N
authors.lastname: Rolão
authors.forename: Lenea
authors.initials: L
authors.lastname: Campino
mesh_terms: D000493:Allopurinol / Q000494:pharmacology; D000666:Amphotericin B / Q000494:pharmacology; D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D003840:Deoxycholic Acid / Q000494:pharmacology; D004197:Disease Reservoirs / Q000469:parasitology*; D004283:Dog Diseases / Q000188:drug therapy / Q000276:immunology / Q000469:parasitology*; D004285:Dogs; D004338:Drug Combinations; D006801:Humans; D007121:Immunocompetence; D016867:Immunocompromised Host; D020128:Inhibitory Concentration 50; D018314:Leishmania infantum / Q000187:drug effects* / Q000302:isolation & purification; D007898:Leishmaniasis, Visceral / Q000188:drug therapy / Q000276:immunology / Q000469:parasitology*; D008536:Meglumine / Q000494:pharmacology; D000077485:Meglumine Antimoniate; D009942:Organometallic Compounds / Q000494:pharmacology; D021261:Parasitic Sensitivity Tests; D010767:Phosphorylcholine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D000981:Antiprotozoal Agents; D004338:Drug Combinations; D009942:Organometallic Compounds; D003840:Deoxycholic Acid; D010767:Phosphorylcholine; C039128:miltefosine; D000493:Allopurinol; D008536:Meglumine; D000077485:Meglumine Antimoniate; D000666:Amphotericin B; C059765:amphotericin B, deoxycholate drug combination
keywords: Chemotherapy; In vitro susceptibility; Leishmania infantum; Portugal; Visceral leishmaniasis