Treatment of New World Mucosal Leishmaniasis: Randomized Comparison of Glucantime®, Liposomal Amphotericin B, and Miltefosine.

New World Mucosal Leishmaniasis (ML) is predominantly caused by Leishmania braziliensis. We performed the first randomized trial of the three recommended agents for this disease-intravenous pentavalent antimony (Sb), intravenous liposomal amphotericin B (LAMB), oral miltefosine-with 24-month follow-up. Upon study enrollment, disease was scored by the number of sites (oro-nasal-palate, pharynx, larynx) and degree of disease at each site (maximum score = 60.) Our criterion for "cure" was ≥90% diminution in the enrollment score. Cure rates were 20/40 (50%) for Sb, 18/40 (45%) for LAMB, and 23/40 (57%) for miltefosine. Cure was highly dependent on whether the patient was being treated for the first time (39/55 = 71% cure) or undergoing repeat treatment (22/63 = 35% cure). The primary reason for the low cure rate for repeat patients was laryngeal disease at enrollment. For all patients, naïve patients, and repeat patients, the miltefosine cure rate was highest but not statistically so. A curative score at 2-6 months of follow-up had a predictive value of 94% for cure. It is notable that 14 of the 57 treatment failures (25%) were attributable to relapses occurring more than 24 months after therapy completion. Myalgias/arthralgias/general bodily discomfort occurred for LAMB and Sb patients; diarrhea and motion sickness occurred for miltefosine patients; Electrocardiogram abnormalities (occasionally severe) were seen in LAMB and Sb patients. When choosing a treatment of a ML patient, cure rates in part based on disease location and absence/presence of previous treatment, route of administration, tolerability, and cost should be considered. Patients should be followed for ≥2 years.