Oral Miltefosine Plus Topical Imiquimod to Treat Cutaneous Leishmaniasis
Oral Miltefosine Plus Topical Imiquimod to Treat Cutaneous Leishmaniasis
Cutaneous leishmaniasis 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.

 Until recently, the standard treatment for the leishmaniases was pentavalent antimony
 (Glucantime or Pentostam). The cure rate for L panamensis in Colombia is 91%-93% [Soto, 1993;
 Velez, 1997], a large study with several formulations of antimony found a combined
 Bolivia-Colombia cure rate of 86% [Soto, 2004b], and in work just completed, the cure rate in
 Palos Blancos, Bolivia is 15 of 16 = 94% [ Soto, manuscript in preparation]. Nevertheless,
 pentavalent antimonials have the disadvantages of multiple injections and mild-moderate
 clinical toxicity [gastrointestinal complaints, liver enzyme elevations, pancreatic enzyme
 elevations], all of which are particularly unpleasant for a moderate clinical problem such as
 cutaneous leishmaniasis.

 The oral agent Miltefosine has now been shown to be as effective as antimony in Colombia and
 Bolivia. In Colombia, the cure rate for miltefosine was 91% [Soto 2004a] and in the
 just-completed trial in Palos Blancos, the cure rate for miltefosine was 32 of 37 = 88 % .
 Side effects seen in patients with cutaneous disease that can be specifically attributed to
 the drug are nausea and vomiting of mild grade in approximately 25% of patients, and
 low-grade elevation of creatinine also in approximately 25% of patients [Soto 2001; Soto
 2004].

 The 6-month cure rate did not reach 100%, and miltefosine was relatively slow to cure
 compared to Sb. 31 of 44 evaluable miltefosine patients (70%) were cured by 1 month after
 therapy, compared to 16 of 16 evaluable Glucantime patients (100%).

 Imiquimod (Aldara; 3M Pharmaceuticals) is a novel immune response-activating compound,
 approved by the FDA for cervical warts, that activates macrophage killing of Leishmania
 species. Combined imiquimod plus Glucantime was used as rescue treatment in 12 patients with
 Peruvian cutaneous leishmaniasis who had previously not responded to Glucantime alone. 90% of
 patients were cured at the 6-month follow-up period [Arevalo, 2001]. In a follow up study
 [Miranda-Verastegui et al, 2005], naïve patients were randomized between the combination of
 Sb plus imiquimod (18 patients) vs Sb plus placebo (20 patients). The cure rate at 1 month
 after therapy was 50% in the imiquimod +Sb group compared to 15% in the placebo+Sb group (p =
 0.02). By 12 months after therapy, the Sb+placebo group had caught up, and the cure rate was
 72%-75% in each group. Local side effects were evaluated. Edema, itching, burning, pain were
 equal in the two groups. There was more erythema in the imiquimod grup (55% of patients)
 compared to the placebo group (25% of patients).

 The Imiquimod studies in neighboring Peru suggest that combination with this immunomodulator
 is capable of decreasing the time to cure, and potentially increasing the cure rate, in
 Andean cutaneous leishmaniasis. The present study will evaluate the combination of oral
 miltefosine plus topical imiquimod for cutaneous leishmaniasis in Bolivia. If in the first
 group of patients, cure rate at 1 month after therapy is appreciably above the 70% historic
 value for miltefosine alone and the cure rate at 6 months is greater than the 88% historic
 value for miltefosine alone, subsequent patients will be randomized between
 miltefosine+imiquimod and miltefosine+placebo cream.
Inclusion Criteria:

 -  Gender: Male or female

 -  Age: >12 yrs of age

 -  Presentation: At least 1 lesion must be ulcerative. No more than 3 lesions.
 Parasitology: Parasitological confirmation of 1 lesion will be made by visualization
 or culture of leishmania from the biopsy or aspirate of the lesion.

 -  No specific or putatively specific therapy (Sb, pentamidine, amphotericin B,
 imidazoles, allopurinol) in the last 6 months

 Exclusion Criteria:

 -  Previous treatment for leishmaniasis

 -  concomitant diseases by history

 -  abnormal complete blood counts (white blood count, hemoglobin, platelet count), values
 of liver transaminases (SGOT), kidney function tests (creatinine).

 -  pregnancy or breastfeeding or not willing to take contraception for 3 months after the
 end of treatment.