A randomized, open-label clinical trial comparing the long-term effects of miltefosine and meglumine antimoniate for mucosal leishmaniasis

Abstract INTRODUCTION: The treatment of mucosal leishmaniasis (ML) is difficult due to the toxicity and route of administration of standard drugs. Miltefosine is an oral agent used for leishmaniasis treatment; however, no data exist regarding its use for ML in Brazil. In this study, we aimed to evaluate the efficacy of miltefosine for ML treatment compared to that of pentavalent antimonial in a pilot study. METHODS: We performed a randomized clinical trial with two parallel groups. The tested intervention consisted of miltefosine 1.3-2 mg/kg/day (two capsules) for 28 days or intravenous 20 mg SbV/kg/day of meglumine antimoniate (N-MA) for 30 days. The final endpoint was defined as complete healing of the lesion four years after treatment. We also analyzed an early endpoint at 90 days after treatment. RESULTS: Forty patients were included in this study: each experimental group comprised 20 patients. Applying a multivariate model in an intention-to-treat analysis, we observed that patients treated with miltefosine had a cure probability 2.08 times greater (95% confidence interval [CI] = 1.03-4.18) than those treated with N-MA at 90 days after treatment. At the final endpoint, we observed no differences in cure probability between miltefosine and N-MA (relative risk = 0.66; 95% CI = 0.33-1.32). With respect to adverse reactions, significant differences between groups were related to gastrointestinal effects, which were more frequent in the miltefosine group. CONCLUSIONS: Miltefosine may be an interesting alternative for treating ML because of its oral administration and cure rate after long-term follow-up.

Treatment of American tegumentary leishmaniasis in special populations: a summary of evidence

We aimed to assess and synthesize the information available in the literature regarding the treatment of American tegumentary leishmaniasis in special populations. We searched MEDLINE (via PubMed), EMBASE, LILACS, SciELO, Scopus, Cochrane Library and mRCT databases to identify clinical trials and observational studies that assessed the pharmacological treatment of the following groups of patients: pregnant women, nursing mothers, children, the elderly, individuals with chronic diseases and individuals with suppressed immune systems. The quality of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. The available evidence suggests that the treatments of choice for each population or disease entity are as follows: nursing mothers and children (meglumine antimoniate or pentamidine), patients with renal disease (amphotericin B or miltefosine), patients with heart disease (amphotericin B, miltefosine or pentamidine), immunosuppressed patients (liposomal amphotericin), the elderly (meglumine antimoniate), pregnant women (amphotericin B) and patients with liver disease (no evidence available). The quality of evidence is low or very low for all groups. Accurate controlled studies are required to fill in the gaps in evidence for treatment in special populations. Post-marketing surveillance programs could also collect relevant information to guide treatment decision-making.

Relapse of kala-azar after use of multiple drugs: A case report and brief review of literature.

We present a case of kala-azar infection that recurred in a patient after completion of the standard treatment course of miltefosine, amphotericin B-deoxycholate (short course), and amphotericin B lipid formulations. The patient was cured after continuous amphotericin B-deoxycholate administration for 4 weeks. This is a unique case of relapse following the use of three important drugs. Although amphotericin B-deoxycholate is a second line drug in Nepal, it has shown a satisfactory clinical response with continuous treatment for 4 weeks. Therefore, an extended course of amphotericin B-deoxycholate may be beneficial in patients with resistance to the standard short course and other anti-leishmania drugs.

Estudo comparativo entre miltefosina oral e antimoniato de N-metil glucamina parenteral no tratamento da leishmaniose experimental causada por Leishmania (Leishmania) amazonensis / Comparative study between oral miltefosine and parenteral N-metil glucamine antimoniate for the treatment of experimental leishmaniasis caused Leishmania (Leishmania) amazonensis

Vinte e cinco camundongos infectados com Leishmania amazonensis foram tratados com antimoniato de N-metil glucamina e miltefosina oral. Critérios: medidas das patas, pesquisa de amastigotas e culturas após-tratamento. Miltefosina: 2,43mm e glucamina 3,46mm (p=0,05). Miltefosina: esfregaços e culturas negativos. Glucamina: 2 esfregaços positivos e culturas positivas (p<0,05). Concluímos que miltefosina foi semelhante à glucamina.

Twenty-five mice were infected with Leishmania amazonensis and treated with glucamine and oral miltefosine. The criteria used were pad measurements and investigations of amastigotes and cultures after treatment. Measurements: miltefosine 2.43 mm and glucamine 3.46 mm (p: 0.05). Miltefosine smears and cultures were negative. Glucamine produced two positive smears and the cultures were positive (p < 0.05). Miltefosine was similar to or better than glucamine.

Evaluation of miltefosine against Leishmania major [MRHO/IR/75/ER]: In vitro and vivo studies

Cutaneous leishmaniasis is endemic in 88 different countries. There are an estimated 1.5 million new cases each year, with over 90% occurring in Afghanistan, Algeria, Iran, Iraq, Saudi Arabia, Syria [Old World] and in Brazil and Peru [New World]. Miltefosine is effective in vitro and in vivo against Leishmania species and it was demonstrated efficacy in animals via the oral route. This study is the first one for evaluating the effect of miltefosine on cutaneous leishmaniasis of L. major [MRHO/IR/75/ER] by in vivo and in vitro studies in the BALB/c mouse model. As it was shown, miltefosine has a better effect on reduction of size of lesion compared to Glucantime[R], also it was not significant by statistical analysis. The results of this study show that miltefosine has a good activity against the proliferation of amastigotes of L. major. The results suggest that oral miltefosine might be a promising approach for developing new anti-Leishmanial drugs. [c] 2008 Tehran University of Medical Sciences. All rights reserved