Document Detail


Early curative applications of the aminoglycoside WR279396 on an experimental Leishmania major-loaded cutaneous site do not impair the acquisition of immunity.
MedLine Citation:
PMID:  20038619     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Hervé Lecoeur; Pierre A Buffet; Geneviève Milon; Thierry Lang
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-12-28
Journal Detail:
Title:  Antimicrobial agents and chemotherapy     Volume:  54     ISSN:  1098-6596     ISO Abbreviation:  Antimicrob. Agents Chemother.     Publication Date:  2010 Mar 
Date Detail:
Created Date:  2010-02-22     Completed Date:  2010-05-31     Revised Date:  2010-09-02    
Medline Journal Info:
Nlm Unique ID:  0315061     Medline TA:  Antimicrob Agents Chemother     Country:  United States    
Other Details:
Languages:  eng     Pagination:  984-90     Citation Subset:  IM    
Affiliation:
Institut Pasteur, Département de Parasitologie et Mycologie, Unité d'Immunophysiologie et Parasitisme Intracellulaire, 25 Rue du Dr. Roux, Paris 75724 Cedex 15, France.
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MeSH Terms
Descriptor/Qualifier:
Administration, Cutaneous
Aminoglycosides* / administration & dosage,  therapeutic use
Animals
Antiprotozoal Agents* / administration & dosage,  therapeutic use
Dermis / parasitology
Disease Models, Animal
Female
Humans
Immunity / immunology
Leishmania major / drug effects*,  pathogenicity
Leishmaniasis, Cutaneous / drug therapy*,  immunology*,  parasitology
Mice
Mice, Inbred C57BL
Mice, Nude
Treatment Outcome
Chemical
Reg. No./Substance:
0/Aminoglycosides; 0/Antiprotozoal Agents; 0/WR279396

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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