Cutaneous Leishmaniasis: Treatment needs and combination therapies

Abstract

There is an increasingly number of cases of cutaneous leishmaniosis (CL) reported worldwide. The ideal treatment for CL should be based on the clinical presentation: local therapies for subjects with small/ few lesions; systemic oral drugs for subjects with numerous or large lesions; whilst subjects with leishmaniasis recidivans, diffuse CL or PKDL should be benefit from using an anti-leishmania drug in combination with an immune response modifier to accelerate and enhance a Th-1 type immune response. Miltefosine is the only oral treatment currently available for treatment of leishmaniasis. In 2014, FDA approved its use for infections caused by L. braziliensis, L. panamensis and L. guyanensis. Despite its limitations due to teratogenicity and gastro-intestinal side effects, miltefosine is a better option than antimonials which are toxic, difficult to administer and its efficacy in many regions is doubtful. Local thermotherapy has also been tested widely. In a meta-analysis of controlled clinical trials comparing thermotherapy with systemic antimonials it was found that the overall efficacy of thermotherapy was 73.9% (95% CI 70.0 - 77.8%) whereas that of systemic antimonials was 72.7% (95% CI 68.7 – 76.6%). Although DNDi and partners have identified several compounds showing activity against Leishmania parasites causing CL, completing the clinical development of at least one of them will take 8-10 years, so the currently available treatments will probably represent the therapeutic arsenal for the coming decade. Hence, DNDi is proposing to explore opportunities to better use the existing approved treatments in combinations, as a short-term solution. The combined use of thermotherapy (one application, 500C for 30 mins) + miltefosine (2.5 mg/kg/day for 21 days) seem to be the best option. The advantages offered by this combination are that a) both approaches are currently recommended for use individually, and there is good information regarding efficacy and safety when used alone; b) combining a topical and a systemic treatment is expected to have an additive effect, since systemic treatment would eliminate circulating parasites or those located in the periphery of the lesion that topical treatment fails to remove; c) it offers the opportunity to increase the current cure rate compared to either treatment used alone and; d) it will reduce the duration and severity of the adverse events associated with 28 days of treatment with miltefosine alone.