title: Presence of Leishmania RNA Virus 1 in Leishmania guyanensis Increases the Risk of First-Line Treatment Failure and Symptomatic Relapse.
abstract: Treatment failure and symptomatic relapse are major concerns in American tegumentary leishmaniasis (TL). Such complications are seen frequently in Leishmania guyanensis infections, in which patients respond variously to first-line antileishmanials and are more prone to develop chronic cutaneous leishmaniasis. The factors underlying this pathology, however, are unknown. Recently, we reported that a double-stranded RNA virus, Leishmania RNA virus 1 (LRV1), nested within L. guyanensis parasites is able to exacerbate experimental murine leishmaniasis by inducing a hyperinflammatory response. This report investigates the prevalence of LRV1 in human L. guyanensis infection and its effect on treatment efficacy, as well as its correlation to symptomatic relapses after the completion of first-line treatment. In our cohort of 75 patients with a diagnosis of primary localized American TL, the prevalence of LRV1-positive L. guyanensis infection was elevated to 58%. All patients infected with LRV1-negative L. guyanensis were cured after 1 dose (22 of 31 [71%]) or 2 doses (31 of 31 [100%]) of pentamidine. In contrast, 12 of 44 LRV1-positive patients (27%) presented with persistent infection and symptomatic relapse that required extended therapy and the use of second-line drugs. Finally, LRV1 presence was associated with a significant increase in levels of intra-lesional inflammatory markers. In conclusion, LRV1 status in L. guyanensis infection is significantly predictive (P = .0009) of first-line treatment failure and symptomatic relapse and has the potential to guide therapeutic choices in American TL.
authors.affiliation: Immunologie des leishmanioses, Institut Pasteur de Guyane.
authors.forename: Eliane
authors.initials: E
authors.lastname: Bourreau
authors.affiliation: Ecosystemes Amazoniens et Pathologie Tropicale - EA 3593 - Labex CEBA - Medicine Department, University of French Guiana.
authors.forename: Marine
authors.initials: M
authors.lastname: Ginouves
authors.affiliation: Ecosystemes Amazoniens et Pathologie Tropicale - EA 3593 - Labex CEBA - Medicine Department, University of French Guiana.
authors.forename: Ghislaine
authors.initials: G
authors.lastname: Prévot
authors.affiliation: Department of Biochemistry, University of Lausanne, Epalinges.
authors.forename: Mary-Anne
authors.initials: MA
authors.lastname: Hartley
authors.affiliation: Laboratoire de Parasitologie-Mycologie du CHU de Rennes INSERM U1085-Institut de Recherches en Santé Environnement Travail, Université Rennes 1.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Gangneux
authors.affiliation: Laboratoire de Parasitologie-Mycologie du CHU de Rennes INSERM U1085-Institut de Recherches en Santé Environnement Travail, Université Rennes 1.
authors.forename: Florence
authors.initials: F
authors.lastname: Robert-Gangneux
authors.affiliation: Service de Dermatologie, Centre Hospitalier de Cayenne, French Guiana.
authors.forename: Julie
authors.initials: J
authors.lastname: Dufour
authors.affiliation: Service de Dermatologie, Centre Hospitalier de Cayenne, French Guiana.
authors.forename: Dominique
authors.initials: D
authors.lastname: Sainte-Marie
authors.affiliation: Service de Dermatologie, Centre Hospitalier de Cayenne, French Guiana.
authors.forename: Antoine
authors.initials: A
authors.lastname: Bertolotti
authors.affiliation: French National Reference Center of Leishmaniasis, Laboratory of Parasitology-Mycology, University Montpellier 1 University Hospital of Montpellier CNRS 5290-IRD 224-University Montpellier 1 and 2, MiVEGEC, France.
authors.forename: Francine
authors.initials: F
authors.lastname: Pratlong
authors.affiliation: Department of Biochemistry, University of Lausanne, Epalinges.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Martin
authors.affiliation: Swiss Institute of Bioinformatics, University of Lausanne, Switzerland.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Schütz
authors.affiliation: Ecosystemes Amazoniens et Pathologie Tropicale - EA 3593 - Labex CEBA - Medicine Department, University of French Guiana Service de Dermatologie, Centre Hospitalier de Cayenne, French Guiana.
authors.forename: Pierre
authors.initials: P
authors.lastname: Couppié
authors.affiliation: Department of Biochemistry, University of Lausanne, Epalinges.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Fasel
authors.affiliation: Department of Biochemistry, University of Lausanne, Epalinges.
authors.forename: Catherine
authors.initials: C
authors.lastname: Ronet
mesh_terms: D000328:Adult; D000981:Antiprotozoal Agents / Q000494:pharmacology* / Q000627:therapeutic use; D015331:Cohort Studies; D005260:Female; D006801:Humans; D018334:Leishmania guyanensis / Q000187:drug effects* / Q000821:virology*; D007897:Leishmaniasis, Mucocutaneous / Q000188:drug therapy* / Q000453:epidemiology / Q000821:virology*; D019199:Leishmaniavirus; D008297:Male; D010419:Pentamidine / Q000494:pharmacology / Q000627:therapeutic use; D012008:Recurrence; D017211:Treatment Failure
chemical_list: D000981:Antiprotozoal Agents; D010419:Pentamidine
keywords: L. guyanensis; Leishmania RNA virus; drug treatment; leishmaniasis; mutualism exclusive; pentamidine