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

Abstract

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.

Intralesional Metronidazole (5%) VS Intralesional Meglumine Antimonate in Cutaneous Leishmaniasis

“…In our study population, there were more males than female patients like many other comparable studies of 5,16,17 Pakistan . This difference may be because of multi-Cutaneous leishmaniasis is an endemic disease in many 18 areas of Pakistan including Multan.…”

“…Moreover, it is also postulated that metronidazole may locally interfere with the osm-13 otic pressure and harms the microorganism . Previously, intralesional Metronidazole efficacy in CL has been assessed by many studies but the results are 5,[13][14][15][16][17] conflicting .…”

Treatment outcome of imported cutaneous leishmaniasis among travelers and migrants infected with Leishmania major and Leishmania tropica: a retrospective study in European centers 2013 to 2019

“…The outcome has so far been found to be superior to treatment with antimony, with a high cure rate for complicated CL ( Mosimann et al, 2016 ). Evaluation of miltefosine as a treatment for CL caused by L. tropica in Pakistan showed a cure rate of 83% as first-line treatment and 70% as second-line treatment ( Kämink et al, 2021 ). These results, and our results with a 100% cure rate on immunocompetent patients, indicate that miltefosine is an effective treatment for CL caused by L. tropica when local treatment cannot be used.…”

Efficacy of Systemic Treatment for Leishmania tropica Cutaneous Leishmaniasis

“…Miltefosine is emerging as an attractive alternative as an oral medication that can be taken at home with good tolerance. The efficacy of miltefosine in paediatric patients with L. tropica CL has been shown recently (17,24). In the current retrospective study, data about miltefosine treatment was not included.…”

“…However, the intravenous (IV) L-AmB treatment is still used as a rescue treatment in resistant SSG cases. Miltefosine is a new emerging attractive alternative as an oral medication that can be taken at home with good tolerance ( 17 ). However, data regarding the efficacy and safety of L-AmB for the treatment of L. tropica CL are scarce and the 2 systemic treatments (L-AmB and SSG) have been compared in only a small group of patients ( 10 , 13 ).…”