title: Treatment failure in leishmaniasis: drug-resistance or another (epi-) phenotype?
abstract: Two major leishmaniasis treatments have shown a significant decrease in effectiveness in the last few decades, mostly in the Indian subcontinent but also in other endemic areas. Drug resistance of Leishmania correlated only partially to treatment failure (TF) of pentavalent antimonials, and has so far proved not to be important for the increased miltefosine relapse rates observed in the Indian subcontinent. While other patient- or drug-related factors could also have played a role, recent studies identified several parasite features such as infectivity and host manipulation skills that might contribute to TF. This perspective aims to discuss how different parasitic features other than drug resistance can contribute to TF of leishmaniasis and how this may vary between different epidemiological contexts.
authors.affiliation: Molecular Parasitology Unit, Department of Biomedical Sciences, Institute of Tropical Medicine, Nationalestraat 155, 2000 Antwerpen, Belgium.
authors.forename: Manu
authors.initials: M
authors.lastname: Vanaerschot
authors.forename: Franck
authors.initials: F
authors.lastname: Dumetz
authors.forename: Syamal
authors.initials: S
authors.lastname: Roy
authors.forename: Alicia
authors.initials: A
authors.lastname: Ponte-Sucre
authors.forename: Jorge
authors.initials: J
authors.lastname: Arevalo
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Dujardin
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000627:therapeutic use*; D004351:Drug Resistance; D006801:Humans; D007303:Insect Vectors / Q000187:drug effects / Q000469:parasitology; D007891:Leishmania / Q000187:drug effects / Q000254:growth & development / Q000472:pathogenicity*; D007896:Leishmaniasis / Q000188:drug therapy / Q000453:epidemiology / Q000469:parasitology; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011576:Psychodidae / Q000187:drug effects / Q000469:parasitology; D012008:Recurrence; D017211:Treatment Failure
chemical_list: D000981:Antiprotozoal Agents; D010767:Phosphorylcholine; C039128:miltefosine
keywords: drug resistance; leishmania; leishmaniasis; miltefosine; pentavalent antimonials; treatment failure