Mucosal Leishmaniasis and Miltefosine

To the Editor—Because of its significant morbidity and mortality, mucosal leishmaniasis (ML) is an important endemic disease and a public health problem in underdeveloped countries. The increase in ecological tourism has resulted in the extension of this problem to developed countries. The current treatment for ML depends on the use of toxic compounds; few drugs have emerged over the past 40 years to treat this condition. Pentavalent antimonials are the drug of choice for the treatment of ML, although they have various adverse effects. We recently observed a high rate of cure with amphotericin B colloidal dispersion treatment in few patients who had recurrent disease [1]. In the past 2 decades, more attention has been dedicated to finding oral drugs that might minimize injection-associated complications. Numerous drugs have been tested, such as the antifungal ketoconazole, but the results were similar to those with placebo. Miltefosine, an anticancer compound, has undergone experimental and clinical testing and has been found to be very effective in treating visceral leishmaniasis [2]. The miltefosine trial performed in Colombia and Guatemala was one of the largest placebo-controlled trial studies concerning localized cutaneous leishmaniasis (CL) chemotherapy that has been reported in the Americas [3]. Because CL cures itself in most cases, and because self-cure rates vary with infecting species and geographical region, data from uncontrolled trials are difficult to interpret. In Guatemala, the 6-month intent-to-treat cure rate for miltefosine was 50%; in contrast, it was 20% with placebo. Leishmania braziliensis is highly susceptible to antimonial therapy; generally, >80% and >90% of cases of ML and CL, respectively, are cured [4, 5]. The 50% miltefosine cure rate mentioned above [3] compares unfavorably, therefore, with the historic antimony cure rates. Unfortunately, patients with ML were excluded from these studies, although it might be expected that the response would not be greatly different, because the parasite involved is of the same species [3]. The recently published trial by Soto et al. [6] in Clinical Infectious Diseases showed a 70% response rate for treatment of ML with miltefosine. Considering that treatment of ML is more difficult than treatment of CL, the results of this study seem to be in conflict with previous findings from the same author [3]. Nevertheless, these results reinforce the theory of different clinical responses from distinct geographical areas (e.g., Guatemala and Bolivia). Indeed, the results of therapy with oral miltefosine are very important in the evolution of the treatment of leishmaniasis. We believe that these data should be confirmed by studies performed in other countries to determine the different cure rates observed in different geographical areas of disease. This cure-rate variability can be verified using pentavalent antimonial therapy. An unpublished metaanalysis of CL in Latin America that was presented at a recent convention in Brazil revealed a mean cure rate of 71.3% among 310 Brazilian patients, whereas in Colombia, 91.4% of 432 patients achieved complete healing (P < .05). Mucosal leishmaniasis can be caused by different Leishmania species. There is mounting evidence that different subspecies/strains are responsible for the variability of the cure rate observed in Latin America. Thus, before we consider the use of a new drug as first-line therapy, more studies should be performed in different countries and areas of this continent. The use of miltefosine is a valid option for the treatment of ML, and we propose that a large study be performed in several countries where the disease is endemic. Additional studies are needed to evaluate the efficacy of dosing, costs, and long-term adverse effects associated with this drug. Such studies should also employ longer follow-up periods to determine the frequency of late disease recurrence, which is commonly observed with antimonial therapy. Potential conflicts of interest. F.F.T. and V.S.A.: no conflicts.