title: Combined topical paromomycin and oral miltefosine treatment of mice experimentally infected with Leishmania (Leishmania) major leads to reduction in both lesion size and systemic parasite burdens.
abstract: OBJECTIVE
  This study aimed to investigate the activity of the combination of topical paromomycin gel and oral miltefosine for the treatment of experimental cutaneous leishmaniasis caused by Leishmania (Leishmania) major.
  
  
  METHODS
  The efficacy of the combination, evaluated by measuring lesion size and parasite burden in the skin and spleen, was assessed in BALB/c mice infected by L. (L.) major. Miltefosine was administered orally at 25 mg/kg/day for 10 days, while 10% paromomycin gel was applied topically twice a day for 10 days.
  
  
  RESULTS
  Treatment of the experimentally infected animals with topical paromomycin + oral miltefosine combination induced a statistically significant reduction in lesion size and parasite burden in the skin, with complete healing of ulcers, as compared with those treated with oral miltefosine or placebo. Furthermore, topical paromomycin + oral miltefosine combination was as effective as topical paromomycin alone to reduce the lesion size and parasite load in lesions. However, the efficacy of the combination was significantly higher than that observed for the other treatments, including topical paromomycin alone, in reducing the parasite burden in spleen.
  
  
  CONCLUSIONS
  The combination of topical paromomycin gel and oral miltefosine provides an enhanced efficacy in the treatment of L. (L.) major-infected mice, thus presenting a significantly higher activity than that observed for the monotherapeutic regimens.
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Federal University Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Marta Gontijo
authors.initials: MG
authors.lastname: Aguiar
authors.forename: Diana Lara
authors.initials: DL
authors.lastname: Silva
authors.forename: Fernando Antônio
authors.initials: FA
authors.lastname: Nunan
authors.forename: Elzíria Aguiar
authors.initials: EA
authors.lastname: Nunan
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Fernandes
authors.forename: Lucas Antônio Miranda
authors.initials: LA
authors.lastname: Ferreira
mesh_terms: D000284:Administration, Oral; D000287:Administration, Topical; D000818:Animals; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005260:Female; D018320:Leishmania major / Q000187:drug effects*; D016773:Leishmaniasis, Cutaneous / Q000188:drug therapy* / Q000469:parasitology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D010303:Paromomycin / Q000008:administration & dosage* / Q000627:therapeutic use*; D010767:Phosphorylcholine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D012867:Skin / Q000469:parasitology / Q000473:pathology; D013154:Spleen / Q000469:parasitology; D016896:Treatment Outcome
chemical_list: D010767:Phosphorylcholine; C039128:miltefosine; D010303:Paromomycin