What are the current treatments for visceral leishmaniasis & cutaneous leishmaniasis and their limitations?

Existing drugs have serious drawbacks in terms of safety, resistance, stability, and cost. They have low tolerability, long treatment duration, and are difficult to administer.

  • Pentavalent antimonials (sodium stibogluconate – SSG – and meglumine antimoniate): used for VL and CL for over 60 years. Acquired resistance in areas of high prevalence and high transmission. Serious cardiotoxicity leading to death is well documented. In monotherapy, they require a 30-day parenteral treatment for VL. Registered in South East Asia, Latin America, and some Mediterranean and African countries.
  • Amphotericin B deoxycholate: only an alternative treatment for VL in areas with high rates of unresponsiveness to antimonials where no other options are available. Need for hospitalization, constant renal monitoring of patients, 28-day duration of treatment, and infusion-related adverse events are notable drawbacks. Amphotericin B displays dose-limiting toxicity. Registered in South Asian countries and some countries in Africa and Latin America.
  • AmBisome®: a liposomal formulation of amphotericin B, which is much safer and highly efficacious. A single infusion of 10mg/kg has shown a 96.4% cure rate in Asia. However, high cost and the need for a cold chain limit widespread use. Registered for VL in India, USA, and Europe and used as a second-line drug for the treatment of PKDL in East Africa at higher doses than in India and for VL in Brazil. It is also used to treat PKDL cases in Sudan. A donation to WHO facilitates free distribution of AmBisome® to the three countries involved in the elimination strategy in South Asia for primary VL patients, and as a rescue treatment for African VL. It is not properly evaluated for cutaneous leishmaniasis (CL).
  • Miltefosine: oral drug registered for use in India for VL, but is expensive and requires 28-day treatment. Major limitations include low compliance, risk of resistance, and contraindication in pregnancy and mandatory contraception for women of child-bearing age for the duration of therapy and three months beyond. A recent study in Asia indicated an emerging lack of efficacy in monotherapy in the region, probably associated with drug underexposure in children. For CL, currently approved for lesions caused by three Leishmania species. Miltefosine is not registered in many endemic countries and consequently not available.
  • Paromomycin (PM): a low-cost parenteral formulation for VL that requires three weeks of painful intramuscular administration is also highly efficacious in Asia but is associated with some degree of renal and ototoxicity with limited efficacy as monotherapy in East Africa.