Combined suboptimal schedules of topical paromomycin, meglumine antimoniate and miltefosine to treat experimental infection caused by Leishmania (Viannia) braziliensis.
OBJECTIVE
This study aimed to evaluate the efficacy of binary combinations of suboptimal schedules of drugs with different administration routes (topical paromomycin, intramuscular meglumine antimoniate and oral miltefosine) to treat animals infected with Leishmania (Viannia) braziliensis.


METHODS
Hamsters were inoculated with L. (V.) braziliensis and after ulceration of lesions, divided into seven groups: untreated control, paromomycin, miltefosine, meglumine antimoniate, meglumine antimoniate + paromomycin, miltefosine + paromomycin and meglumine antimoniate + miltefosine. Meglumine antimoniate and miltefosine were administered at low doses and topical paromomycin at a single daily application regimen. The animals were treated for 20 consecutive days (meglumine antimoniate and/or paromomycin) and/or 10 alternate days (miltefosine). Lesion sizes were determined weekly. Upon completion of treatment, parasites were recovered from skin lesions and spleens and evaluated by limiting dilution assay.


RESULTS
The combinations of a once daily application of paromomycin with low doses of miltefosine or meglumine antimoniate yielded higher efficacies in reducing the parasite load as well as lesion size when compared with any of these drugs administered as monotherapy regimens at the same suboptimal schedules.


CONCLUSIONS
Considering the parameters evaluated, the combinations of a systemic therapy with topical treatment were more effective than monotherapy with each of these drugs. These combinations may represent an alternative combination strategy for the treatment of leishmaniasis caused by L. (V.) braziliensis.
Laboratório de Pesquisas Clínicas-Centro de Pesquisas René Rachou-Fundação Oswaldo Cruz-FIOCRUZ, Belo Horizonte, Minas Gerais, Brazil.
Eliane
E
de Morais-Teixeira
Laboratório de Pesquisas Clínicas-Centro de Pesquisas René Rachou-Fundação Oswaldo Cruz-FIOCRUZ, Belo Horizonte, Minas Gerais, Brazil Department of Pharmaceutics, Faculty of Pharmacy, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Marta Gontijo
MG
Aguiar
Laboratório de Pesquisas Clínicas-Centro de Pesquisas René Rachou-Fundação Oswaldo Cruz-FIOCRUZ, Belo Horizonte, Minas Gerais, Brazil.
Bruna
B
Soares de Souza Lima
Department of Pharmaceutics, Faculty of Pharmacy, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Lucas Antônio Miranda
LA
Ferreira
Laboratório de Pesquisas Clínicas-Centro de Pesquisas René Rachou-Fundação Oswaldo Cruz-FIOCRUZ, Belo Horizonte, Minas Gerais, Brazil ana@cpqrr.fiocruz.br.
Ana
A
Rabello
D000284:Administration, Oral; D000287:Administration, Topical; D000818:Animals; D000981:Antiprotozoal Agents / Q000008:administration & dosage*; D001071:Appointments and Schedules; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination / Q000379:methods; D007273:Injections, Intramuscular; D007892:Leishmania braziliensis / Q000187:drug effects* / Q000302:isolation & purification; D016773:Leishmaniasis, Cutaneous / Q000188:drug therapy* / Q000469:parasitology; D008297:Male; D008536:Meglumine / Q000008:administration & dosage*; D000077485:Meglumine Antimoniate; D008647:Mesocricetus; D009942:Organometallic Compounds / Q000008:administration & dosage*; D010303:Paromomycin / Q000008:administration & dosage*; D010767:Phosphorylcholine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D012867:Skin / Q000469:parasitology; D013154:Spleen / Q000469:parasitology; D016896:Treatment Outcome
D000981:Antiprotozoal Agents; D009942:Organometallic Compounds; D010767:Phosphorylcholine; C039128:miltefosine; D010303:Paromomycin; D008536:Meglumine; D000077485:Meglumine Antimoniate