Short Course of Intralesional Antimony for Bolivian 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 the cure rate in Palos Blancos, Bolivia is 15 of 16 = 94% [ Soto, 2008]. Nevertheless, pentavalent antimonials have the disadvantages of multiple injections during at least 3 weeks and mild-moderate clinical toxicity: local pain at the site of injections and generalized myalgias and arthralgias that can be severe and responsible for partial or definitive interruption of therapy, gastrointestinal complaints, liver enzyme elevations, pancreatic enzyme elevations and more rarely but with danger for life ventricular repolarization problems [Soto, 2005, Velez 2010], all of which are particularly unpleasant for a localized moderate clinical problem such as cutaneous leishmaniasis that usually is not dangerous for the patient.

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]. Now that cutaneous leishmaniasis is affecting more women at reproductive age, there is a crucial inconvenient because miltefosine can't be taken during pregnancy and breastfeeding; additionally prolonged courses (4 weeks) makes more difficult adherence to therapy and emerge the risk of incomplete treatments or it might be necessary supervised administration during the full course.

For small, single lesions, the side effects and cost of systemic therapy with antimony or miltefosine may outweigh the advantage of cure. For such lesions, targeted local therapy would be attractive if it is effective. The cost of goods will be low, and systemic adverse events would be non-existent.

For these reasons, topical treatment of the leishmaniases is presently the subject of intense worldwide interest, including at a recent [July 2010] PAHO meeting in Colombia. The leading candidates are topical formulations of paromomyin, local heat since cutaneous leishmania are heat-sensitive, local freezing as per any dermatologic lesion, and intralesional injections of antimony. The ability of topical formulations of paromomycin to cure depends on penetration of this divalent cation into the lesion and thus depends on the precise formula for the cream in which the paromomycin is dissolved. Other than the combination of paromomycin plus MBCL in Vaseline, which had minimal efficacy in Colombia [Soto 1998], patented paromomycin-containing creams are under investigation but cannot be obtained except from Pharma. Reports of local thermotherapy have been published, but again the key issue is penetration of the agent [in this case, heat] to the lesion and the best approach is difficult to utilize because it requires a $25,000 machine and exists a risk of infections via electrodes.