Thermoterapy effective and safer than miltefosine in the treatment of cutaneous leishmaniasis in Colombia / Termoterapia efectiva y más segura que la miltefosina en el tratamiento de la leishmaniasis cutánea en Colombia

In Colombia, pentavalent antimonials and miltefosine are the drugs of choice for the treatment of cutaneous leishmaniasis; however, their toxicity, treatment duration, (treatment adherence problems), cost, and decreased parasite sensitivity make the search for alternative treatments of American cutaneous leishmaniasis necessary. Based on the results found in a controlled, open, randomized, phase III clinical trial, the efficacy and safety of miltefosine was compared to that of thermotherapy for the treatment of cutaneous leishmaniasis in Colombia. Adult patients from the Colombian army participated in the study; they received either 50 mg of miltefosine three times per day for 28 days by the oral route (n = 145) or a thermotherapy (Thermomed®) application of 50 °C for 30 seconds over the lesion and surrounding area (n = 149). Both groups were comparable with respect to their sociodemographic, clinical, and parasitological characteristics. The efficacy of miltefosine by protocol and by intention to treat was 70% (85/122 patients) and 69% (85/145 patients), respectively. The adverse effects were primarily gastrointestinal for miltefosine and pain at the lesion site after treatment for thermotherapy. No statistically significant difference was found in the efficacy analysis (intention to treat and protocol) between the two treatments. ClinicalTrials.gov: NCT00471705.

En Colombia antimoniales pentavalentes y miltefosina son los medicamentos de primera elección para el tratamiento de la leishmaniosis cutánea; sin embargo, su toxicidad, duración (que lleva a problemas de adherencia), costo y la disminución de la sensibilidad de los parásitos a los mismos, hacen necesaria la búsqueda de nuevas alternativas de tratamiento para la leishmaniosis cutánea americana. A partir de resultados derivados de un ensayo clínico controlado abierto, aleatorizado, fase III, se comparó la eficacia y seguridad de la miltefosina con la de la termoterapia, para el tratamiento de la leishmaniosis cutánea en Colombia. Adultos pertenecientes al Ejército de Colombia participaron el estudio. Miltefosina, una cápsula de 50 mg tres veces día durante 28 días, vía oral (n = 145). Termoterapia (Thermomed®) aplicación de 50 °C/30" sobre la lesión y el área circundante (n = 149). Ambos grupos fueron comparables en características sociodemográficas, clínicas y parasitológicas. Eficacia de la miltefosina por protocolo 70% (85/122 pacientes) y 69% (85/145 pacientes) por intención a tratar. Termoterapia eficacia por protocolo 64% (86/134 pacientes) y 58% (86/149 pacientes) por intención a tratar. En miltefosina los eventos adversos fueron principalmente de tipo gastrointestinal y en termoterapia se encontró dolor en el sitio de la lesión luego del tratamiento. En el análisis de eficacia (intención a tratar y protocolo) no se encontró diferencia estadísticamente significativa entre los tratamientos evaluados. ClinicalTrials.gov: NCT00471705.

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.

Oral miltefosine treatment in children with visceral leishmaniasis: a brief review

Visceral leishmaniasis (VL) or kala-azar is an infection disease caused by hemiflagellate protozoan parasites (Leishmania donovani) and transmitted to humans by the phlebotomine sandfly. Leishmaniasis is distributed worldwide and 13 million people are estimated to be infected, with about 1.8 million new cases each year. All antileishmanial drugs are toxic and most have to be used parenterally for prolonged period. The therapy has been further complicated by large number of infected children and declining effectiveness of pentavalent antimonial compounds. Although the lipid formulations of amphotericin B are an important advance in therapy, their high cost precludes their use. Miltefosine, a phosphocholine analogue originally developed as antimalignant drug, has been found to be highly active against Leishmania in vitro and in animal model. Based on these experiences this drug was tried against human visceral leishmaniasis and found to be highly effective in children. The aim of this review is to evidence the pharmacodymamic and pharmacokinetic characteristics and the safety, tolerance and efficacy of this drug for treatment of visceral leishmaniasis in children.

Pharmacovigilance in kala-azar patients with severe thrombocytopenia caused by sodium antimony gluconate & miltefosine.

Sodium antimony gluconate (SAG) and miltefosine used in the treatment of kala-azar are known to cause several side effects but severe thrombocytopenia has not been reported. Four cases of severe thrombocytopenia, two caused by SAG and two by miltefosine were promptly detected and treated by immediate withdrawal of the offending drugs, platelet and blood transfusions and dexamethasone. After improvement Leishman-Donovan (LD) bodies were demonstrated in splenic aspirates of both patients of SAG group and one of miltefosine and they were treated with 1 mg/kg body wt of amphotericin B for 20 days and cured. One patient of miltefosine group treated outside only on the basis of rK-39 positivity did not show LD bodies in splenic aspirates and improved without any antikala- azar drug. None of the patients relapsed within 6 months of follow up. Prompt detection of side effects under the concept of pharmacovigilance can save life of such patients.

Miltefosine in children with visceral leishmaniasis: a prospective, multicentric, cross-sectional study.

OBJECTIVE: Miltefosine, an alkyl phospholipid has been found effective against visceral leishmaniasis (VL) in adults in various studies. The authors safety, tolerance and efficacy of Miltefosine and compared with available gold standard anti-Ieishmanial drug, Amphotericin B, a parenteral formulation in children with VL. METHODS: All consecutive children aged 1 yr to 14 yr, presented with fever, splenomegaly and positive LD body in splenic smear examination, admitted in pediatric ward of Nalanda Medical college and Child care center between 1st July 03 to 30th June 05 were taken for study. Patients were randomized into four groups. Group-l and 2 patients were given Miltefosine in dose of 2.5 mg/Kg day o.d. or b.i.d. per orally to a maxiIpum of 100 mg and group 3 and 4 Amphotericin B at a dose of 1 mg/Kg/day (total: 15 mg/Kg). All patients were followed at completion of therapy, 3 months and 6 months for clinical response, splenic size and parasitologically. RESULTS: Out of 125 children, 44 were in group-I, 20 in group-2, 38 in group-3 and 23 in group- 4, 124 patients had parasitological cure with relapse in one patient of group 1 during follow up. One patient in-group II had no response with first course but became parasitologically negative with 2nd course of Miltefosine. In-group I, one patient had persistent splenomegaly and found to have associated portal hypertension. Final cure rate with Miltefosine and Amphotericin B was 93.2%, 95%, 92.1% and 91.3% in-group 1, 2, 3 and 4 respectively, which are statistically insignificant. Majority of patients had pancytopenia. Eievated". AL T (>3 times of normal) were seen in 28, 11, 19 and 13 patients of group 1, 2, 3 and group 4 respectively which returned to normal in subsequent follow up. Raised BUN was observed more in patients who got Amphotericin B i.e. 65.42% and 73.91 % in-group 3 and 4 respectively. GI side effects i.e. diarrhea and vomiting were observed in 26 and 23 patients in-group 1 and 2 respectively. CONCLUSION: Miltefosine is safe, well tolerable, and highly effective and has same efficacy as Amphotericin B in newly diagnosed and SAG resistant children with visceral leishmaniasis.