The effect of oral miltefosine in treatment of antimoniate resistant anthroponotic cutaneous leishmaniasis: An uncontrolled clinical trial

Author summary Leishmaniasis is endemic in 98 countries, mainly the Middle Eastern countries including Iran. More than 20 causative species of leishmania are known resulting in diverse disease manifestations, ranging from cutaneous localized ulcers to visceral leishmaniasis that can be fatal. Cutaneous leishmaniasis is usually a localized and self-limited disease, however, chronic non-healing lesions are one of challenging issues. Cutaneous leishmaniasis in Iran is mainly cause by two species: L. major-which causes anthroponotic cutaneous leishmaniasis (ACL)- and L.tropica-which causes zoonotic cutaneous leishmaniasis (ZCL)-. Conventionally, meglumine antimoniate (MA) is administered as standard treatment for ACL. However, resistant forms of ACL to MA are increasingly recognized in endemic areas. Antileishmanial drug miltefosine is capable of immunomodulation and evokes host immune responses. Therapeutic effects of oral miltefosine has been previously confirmed for treatment of visceral and muco-cutaneous leishmanisis. In the current study, oral miltefosine (similar to 2.5 mg/kg daily) was administered by 27 patients (42 lesions) with MA resistant ACL lesions. After 6-month follow-up, 68% of patients were definitely cured. Therefore, oral miltefosine could be an effective treatment choice for MA resistant ACL. Background Recent circumstantial evidence suggests increasing number of Iranian patients with cutaneous leishmaniasis (CL) who are unresponsive to meglumine antimoniate (MA), the first line of treatment in Iran. Oral meltifosine was previously reported to be effective in visceral leishmaniasis as well CL. The current study is designed to determine efficacy and safety of oral miltefosine for the treatment of anthroponotic cutaneous leishmaniasis (ACL) cases who were refractory to MA in Iran. Methodology/Principal findings Miltefosine was orally administered for 27 patients with MA resistant ACL with approved L.tropica infection, at a dosage of similar to 2.5 mg/kg daily for 28 days. Patients were evaluated on day 14 and 28, as well as 3, 6 and 12 month post treatment follow up sessions. Laboratory data were performed and repeated at each visit. Data were analyzed using SPSS version 17. Twenty-seven patients including 16 men (59.25%) and 11 women (40.74%) with mean age of 28.56 +/- 4.8 (range 3-54 years old) were enrolled. Total number of lesions were 42 (1-4 in each patient). Most of lesions were on face (76.19%). Mean lesions' induration size was 2.38 +/- 0.73 cm at the base-line which significantly decreased to1.31 +/- 0.58 cm and 0.61 +/- 0.49 cm after 14 and 28 days of therapy, respectively (p value <0.05). At 12-months follow-up post treatment, 22 patients had definite/partial cure (81.48%) including 17 definitely cured patients, corresponding to a cure rate of 68% on per protocol analysis, and 62.96% according to intention to treat analysis. Recurrence of lesion was only occurred in one patient (3.70%). Nausea was the most subjective complication during the therapy (33.33%). Conclusion Oral miltefosine could be an effective alternative for the treatment of MA-resistant ACL.

Automated summary

Leishmaniasis is a common disease in Iran, with cutaneous leishmaniasis being a major health concern. Some patients show resistance to traditional treatment methods like meglumine antimoniate. Oral miltefosine may serve as an effective alternative treatment.