Intralesional Antimony for Bolivian Cutaneous Leishmaniasis
Intralesional Antimony for Bolivian Cutaneous Leishmaniasis
Intralesional injection of antimony has been used for L major from Iran with a modest cure
 rate [56%: Asilian 2004]. However, this therapeutic approach has been used for L braziliensis
 from Brazil, with an attractive cure rate after 3 months of 80% [Oliveira-Neto 1997]. Because
 intralesional Sb injections is the local therapy with the best reported cure rate for South
 American L braziliensis disease, the species that causes disease in Bolivia, this pilot study
 of local therapy for bolivian L braziliensis disease will evaluate intralesional Sb therapy.
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.

 Intralesional injection of antimony has also been used for L major from Iran, and also with a
 modest cure rate [56%: Asilian 2004]. However, this therapeutic approach has been used for L
 braziliensis from Brazil, with an attractive cure rate after 3 months of 80% [Oliveira-Neto
 1997]. Because intralesional Sb injections is the local therapy with the best reported cure
 rate for South American L braziliensis disease, the species that causes disease in Bolivia,
 this pilot study of local therapy for bolivian L braziliensis disease will evaluate
 intralesional Sb therapy.

 Cryotherapy has been used as sole therapy for L major from Iran. The cure rate was modest:
 50-60% [Asilian 2004; Layegh 2009]. Nevertheless, cryotherapy may have an attractive cure
 rate against L braziliensis. Therefore, cryotherapy will also be evaluated in this pilot
 study.

 Patients receiving intralesional Sb will be randomized vs vs patients receiving cryotherapy
 and also vs patients receiving an emollient cream Because Il Sb has perhaps more promise than
 cryotherapy, more patients will receive Il Sb (30) than will receive cryotherapy (20) The
 emollient cream may improve host response to the trauma of the parasitic process,
 nevertheless, emollient cream is a placebo treatment in the specifically antiparasitic sense.
 The spontaneous rate of cure is unknown in Bolivia, thus this group will serve to establish
 this key value and permit comparison of the IL Sb rate and the cryotherapy rate to it.
 Although 20 patients will be randomized to the "placebo" group, stopping rules are such that
 if 4 early patients or 6 total patients in this group fail, no further "placebo" patients
 will be entered into the trial.
INCLUSION CRITERIA:

 -  Gender: Male or female

 -  Age: >12 yrs of age

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

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

 EXCLUSION CRITERIA:

 -  Previous treatment for leishmaniasis: therapy with Sb, pentamidine, amphotericin B,
 miltefosine, imidazoles or allopurinol in the last 3 months

 -  Concomitant diseases by history that would be likely in the PI's opinion to interact,
 either positively or negatively, with IL Sb treatment.