BACKGROUND: Diffuse cutaneous leishmaniasis (DCL), although rare, is profoundly incapacitating. At present there is no successful treatment for this progressive protozoan infection, which is associated with the absence of specific cell-mediated immunity (CMI) to Leishmania. This disease shares features with visceral leishmaniasis (VL), including specific CMI inactivity during active disease and a heavy parasitic burden, but VL responds well to treatment. Miltefosine is the first orally administered drug which has shown efficacy in the treatment of VL; it has not been adequately evaluated in the treatment of DCL. OBJECTIVES: To evaluate the efficacy of miltefosine in the treatment of DCL, using clinical, parasitological, histopathological and immunological criteria. METHODS: Sixteen patients with DCL were treated with miltefosine, 2.0-2.5 mg kg(-1) daily, for variable periods of time (75-218 days). Patients were hospitalized for the first month and evaluated every 2 weeks until the termination of treatment with routine laboratory chemistry, percentage clinical improvement, presence of parasites in skin smears, growth of parasites in culture medium and in hamsters, histopathological characteristics of the granulomas, adverse side-effects, and reactivity to leishmanin skin test antigen. Further cycles of treatment were given in some of these patients, particularly after suspension of treatment was followed by relapse. RESULTS: Patients showed dramatic clinical improvement and reduction in the parasite burden by day 15 after the initiation of treatment, which continued while treatment was maintained. By day 45, 15 patients showed 80-90% clinical improvement. Nevertheless, suspension of treatment was followed by the development of new lesions in all but one patient. Inoculation in hamsters was observed to be the most sensitive technique to detect persisting parasites. Adverse events were very mild. CONCLUSIONS: Miltefosine produced a dramatic clinical and parasitological response in patients with DCL and improvement continued during drug administration, but with a single exception all patients presented new lesions after suspension of treatment. There was no histological or skin test evidence to suggest the development of CMI during treatment, which may be an indispensable criterion for the evaluation of potentially effective drugs against DCL.
BACKGROUND: Diffuse cutaneous leishmaniasis (DCL), although rare, is profoundly incapacitating. At present there is no successful treatment for this progressive protozoan infection, which is associated with the absence of specific cell-mediated immunity (CMI) to Leishmania. This disease shares features with visceral leishmaniasis (VL), including specific CMI inactivity during active disease and a heavy parasitic burden, but VL responds well to treatment. Miltefosine is the first orally administered drug which has shown efficacy in the treatment of VL; it has not been adequately evaluated in the treatment of DCL. OBJECTIVES: To evaluate the efficacy of miltefosine in the treatment of DCL, using clinical, parasitological, histopathological and immunological criteria. METHODS: Sixteen patients with DCL were treated with miltefosine, 2.0-2.5 mg kg(-1) daily, for variable periods of time (75-218 days). Patients were hospitalized for the first month and evaluated every 2 weeks until the termination of treatment with routine laboratory chemistry, percentage clinical improvement, presence of parasites in skin smears, growth of parasites in culture medium and in hamsters, histopathological characteristics of the granulomas, adverse side-effects, and reactivity to leishmanin skin test antigen. Further cycles of treatment were given in some of these patients, particularly after suspension of treatment was followed by relapse. RESULTS:Patients showed dramatic clinical improvement and reduction in the parasite burden by day 15 after the initiation of treatment, which continued while treatment was maintained. By day 45, 15 patients showed 80-90% clinical improvement. Nevertheless, suspension of treatment was followed by the development of new lesions in all but one patient. Inoculation in hamsters was observed to be the most sensitive technique to detect persisting parasites. Adverse events were very mild. CONCLUSIONS:Miltefosine produced a dramatic clinical and parasitological response in patients with DCL and improvement continued during drug administration, but with a single exception all patients presented new lesions after suspension of treatment. There was no histological or skin test evidence to suggest the development of CMI during treatment, which may be an indispensable criterion for the evaluation of potentially effective drugs against DCL.
Authors: Subha Banerjee; June Ghosh; Subha Sen; Rajan Guha; Ranjan Dhar; Moumita Ghosh; Sanchita Datta; Bikramjit Raychaudhury; Kshudiram Naskar; Arun Kumar Haldar; C S Lal; K Pandey; V N R Das; Pradeep Das; Syamal Roy Journal: Infect Immun Date: 2009-03-16 Impact factor: 3.441
Authors: Alejandro Ordaz-Farias; Fania Z Muñoz-Garza; Farah K Sevilla-Gonzalez; Ana Arana-Guajardo; Jorge Ocampo-Candiani; Nancy Treviño-Garza; Ingeborg Becker; Adrian Camacho-Ortiz Journal: Am J Trop Med Hyg Date: 2012-12-12 Impact factor: 2.345
Authors: Andrés F Flórez; Daeui Park; Jong Bhak; Byoung-Chul Kim; Allan Kuchinsky; John H Morris; Jairo Espinosa; Carlos Muskus Journal: BMC Bioinformatics Date: 2010-09-27 Impact factor: 3.169
Authors: Kristina M Bacon; Peter J Hotez; Stephanie D Kruchten; Shaden Kamhawi; Maria Elena Bottazzi; Jesus G Valenzuela; Bruce Y Lee Journal: Vaccine Date: 2012-11-20 Impact factor: 3.641
Authors: Rubén E Varela-M; Janny A Villa-Pulgarin; Edward Yepes; Ingrid Müller; Manuel Modolell; Diana L Muñoz; Sara M Robledo; Carlos E Muskus; Julio López-Abán; Antonio Muro; Iván D Vélez; Faustino Mollinedo Journal: PLoS Negl Trop Dis Date: 2012-04-10