title: Early curative applications of the aminoglycoside WR279396 on an experimental Leishmania major-loaded cutaneous site do not impair the acquisition of immunity.
abstract: Topical therapy is an attractive approach for the treatment of Leishmania major cutaneous leishmaniasis (CL). WR279396, an expanded-spectrum aminoglycoside ointment, is now in phase 3 trials. Because the application of a cream is easier than the injection of pentavalent antimony, many patients with CL will likely be treated with WR279396 soon after the onset of a lesion. However, this new therapeutic approach may impair the acquisition of immunity. We evaluated the impact of early topical therapy on acquired immunity in an optimized mouse model of L. major-induced CL. The efficacy of the WR279396 ointment in this model has been established previously. Acquired immunity was defined as the absence of lesions upon reinoculation of the same parasite isolate at a different skin site. Bioluminescence-based follow-up of luciferase-expressing L. major loads was also performed. In this model, the control of L. major loads at the initial inoculation site and the acquisition of immunity are simultaneous (day 22 postinoculation). The clinical and parasitological efficacies of WR279396 applied as early as day 11 postinoculation, i.e., during the L. major multiplication phase, did not impair the acquisition of immunity to a second L. major challenge. This is reassuring from the perspective of the wide deployment of WR279396-based therapy in foci where L. major is endemic.
authors.affiliation: Institut Pasteur, Département de Parasitologie et Mycologie, Unité d'Immunophysiologie et Parasitisme Intracellulaire, 25 Rue du Dr. Roux, Paris 75724 Cedex 15, France.
authors.forename: Hervé
authors.initials: H
authors.lastname: Lecoeur
authors.forename: Pierre A
authors.initials: PA
authors.lastname: Buffet
authors.forename: Geneviève
authors.initials: G
authors.lastname: Milon
authors.forename: Thierry
authors.initials: T
authors.lastname: Lang
mesh_terms: D000279:Administration, Cutaneous; D000617:Aminoglycosides / Q000008:administration & dosage / Q000627:therapeutic use; D000818:Animals; D000981:Antiprotozoal Agents / Q000008:administration & dosage / Q000627:therapeutic use; D020405:Dermis / Q000469:parasitology; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007109:Immunity / Q000276:immunology; D018320:Leishmania major / Q000187:drug effects* / Q000472:pathogenicity; D016773:Leishmaniasis, Cutaneous / Q000188:drug therapy* / Q000276:immunology* / Q000469:parasitology; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D016896:Treatment Outcome
chemical_list: D000617:Aminoglycosides; D000981:Antiprotozoal Agents; C461480:WR279396