Oral Miltefosine Plus Topical Paromomycin In American Cutaneous Leishmaniasis
Oral Miltefosine Plus Topical Paromomycin In American Cutaneous Leishmaniasis
Cure rate for L braziliensis bolivian CL has been 70%-80% for standard systemic and local
 monotherapies. It would benefit patients if cure rates could be consistently >90%, so testing
 a combination of two treatments is proposed. The most attractive systemic therapy is the only
 oral agent, miltefosine during 28 days, and the most attractive local therapy is application
 of Paromomycin cream for 28 days.
Cutaneous leishmaniasis (CL) is endemic in the New World from approximately the US-Mexican
 border through Central America and the Northern part of South America down to the level of
 Rio de Janeiro.

 L braziliensis CL is perhaps the most important of these diseases, since its natural cure
 rate is low and it may metastasize, and our group has been evaluating therapies for L
 braziliensis in Bolivia for some time.

 In recent studies at investigator's Bolivian site for the years 2013-2016, the cure rate for
 L braziliensis CL has been 70%-80% for standard systemic and local therapies. Systemic agents
 intramuscular pentavalent antimony cured 80% (114 of 143) and oral miltefosine cured 81% (47
 of 58). Local injections with pentamidine cured 72% (43 of 60); intralesional antimony cured
 70% (21 of 30). In contrast, cryotherapy was ineffective [20% (4 of 20) cured and placebo
 creams cured 17% (5 of 30) in one report and 10% more recently.

 Investigator's have recently evaluated treatment with topical paromomycin cream.
 Paromomycin-in-Aquaphilic had a cure rate of 77.5% (31 of 40 patients) compared to a cure
 rate of only 10% (2 of 20 patients) for the Aquaphilic vehicle alone. This remarkably high
 cure rate, combined with essentially no adverse events (both Paromomycin-Aquaphilic and
 Aquaphilic vehicle had only grade 1 adverse reactions in 5-10% of patients), makes
 Paromomycin-Aquaphilic very attractive for Bolivian CL.

 It would benefit patients if cure rates could be consistently >90%. Since all the individual
 therapies, whether systemic, local injections, or local cream, have an approximately 75% cure
 rate, we propose testing a combination of two treatment. The most attractive systemic therapy
 is the only oral agent, miltefosine, and the most attractive local therapy is simple
 application of Paromomycin cream. Thus the present protocol proposes to evaluate the efficacy
 of miltefosine, 2.5 mg/kg (50 mg tid) for 28 days, plus Paromomycin-Aquaphilic daily for 28
 days. The controls will be the two components of this combination used separately:
 miltefosine alone, Paromomycin-Aquaphilic alone.
Inclusion and exlusion Criteria:

 -  Gender: Male or female

 -  Age: >12 yrs of age

 -  Presentation: 1-to-2 ulcerative lesions, each < 30 mm in largest diameter and with a
 total lesion area <900 mm2.

 -  Parasitology: Parasitological confirmation of the lesion will be made by visualization
 or culture of Leishmania from the biopsy or aspirate of the lesion.

 -  Previous treatment for leishmaniasis:

 -  No specific or putatively specific therapy (Sb, pentamidine, amphotericin B,
 miltefosine, imidazoles, allopurinol) in the last 3 months

 -  Other diseases: No concomitant diseases by history that would be likely in the PI's
 opinion to interact, either positively or negatively, with treatment.