Effectiveness of miltefosine in cutaneous leishmaniasis caused by Leishmania tropica in Pakistan after antimonial treatment failure or contraindications to first line therapy—A retrospective analysis

Background Cutaneous leishmaniasis (CL) is a neglected tropical skin disease, caused by Leishmania protozoa. In Pakistan, where CL caused by L . tropica is highly endemic, therapy with pentavalent antimonials is the standard of care, but has significant toxicity when used in systemic therapy, while are no evidence-based safer alternative treatment options for L . tropica . The efficacy of oral miltefosine has not been studied in CL caused by L . tropica . We evaluated effectiveness and tolerability of miltefosine in patients with previous treatment failure or with contraindications to systemic antimonial treatment. Methods A retrospective review was conducted of a cohort of CL patients who were treated with a 28-day course of miltefosine between December 2017 and August 2019, in urban Quetta, Pakistan, an area endemic for L . tropica . Descriptive analyses were performed, and effectiveness was assessed by initial response after treatment, and final cure at routine follow up visits, six weeks to three months post-treatment. Tolerability was assessed by routinely reported adverse events. Results Of the 76 CL patients in the cohort, 42 (55%) had contraindications to systemic antimonial treatment, and 34 (45%) had failure or relapse after antimonial treatment. Twelve patients defaulted during treatment and 12 patients were lost to follow up. In the remaining 52 patients, final cure rate was 77% (40/52). In those with contraindications to systemic antimonial treatment the final cure rate was 83% (24/29) and in the failure and relapse group 70% (16/23). Twenty-eight patients (40.0%) reported 39 mild to moderate adverse events with the main complaints being nausea (41.0%), general malaise (25.6%), and stomach pain (12.8%). Conclusion Results indicate that miltefosine is an effective second line treatment in CL in areas endemic for L . tropica . Prospective studies with systematic follow up are needed to obtain definitive evidence of effectiveness and tolerability, including identification of risk factors for miltefosine treatment failure.