Treatment of Cutaneous Leishmaniasis Caused by Leishmania aethiopica: A Systematic Review

Leishmania aethiopica is the etiological agent of cutaneous leishmaniasis (CL) in Ethiopia and can cause severe and complicated cases such as diffuse CL (DCL), mucocutaneous leishmaniasis or extensive CL, requiring systemic treatment. Despite the substantial burden, evidence-based treatment guidelines are lacking. We conducted a systematic review of clinical studies reporting on treatment outcomes of CL due to L aethiopica in order to help identify potentially efficacious medications on CL that can be taken forward for clinical trials. We identified a total of 24 records reporting on 506 treatment episodes of CL presumably due to L aethiopica. The most commonly used drugs were antimonials (n = 201), pentamidine (n = 150) and cryotherapy (n = 103). There were 20 case reports/series, with an overall poor study quality. We only identified two small and/or poor quality randomized controlled trials conducted a long time ago. There were two prospective non-randomized studies reporting on cryotherapy, antimonials and pentamidine. With cryotherapy, cure rates were 60–80%, and 69–85% with antimonials. Pentamidine appeared effective against complicated CL, also in cases non-responsive to antimonials. However, all studies suffered from methodological limitations. Data on miltefosine, paromomycin and liposomal amphotericin B are extremely scarce. Only a few studies are available on DCL. The only potentially effective treatment options for DCL seem to be antimonials with paromomycin in combination or pentamidine, but none have been properly evaluated. In conclusion, the evidence-base for treatment of complicated CL due to L aethiopica is extremely limited. While antimonials remain the most available CL treatment in Ethiopia, their efficacy and safety in CL should be better defined. Most importantly, alternative first line treatments (such as miltefosine or paromomycin) should be explored. High quality trials on CL due to L aethiopica are urgently needed, exploring group sequential methods to evaluate several options in parallel.Author Summary: Cutaneous leishmaniasis (CL) refers to skin ulcers caused by the Leishmania parasite, which is transmitted by the bite of sandflies. In Ethiopia, CL is caused by the Leishmania aethiopica parasite. CL in Ethiopia can be associated with severe and complicated disease such as diffuse CL (DCL), which presents with multiple skin lesions spread over the body. For such severe cases, topically applied treatment is not sufficient and systemic treatment (given in tablets or via injections) is required. Although the total number of patients that suffer from CL in Ethiopia is high, there are no evidence-based treatment guidelines. We conducted a systematic review of clinical studies reporting on treatment outcomes of CL due to L aethiopica. We identified a total of 24 records reporting on 506 treatment episodes of CL presumably due to L aethiopica. The most commonly used drugs were antimonials, pentamidine, and cryotherapy. Most studies were case reports or case series. There were two small clinical trials and two prospective non-randomized studies. However, all studies had some methodological limitations. With cryotherapy, cure rates were 60–80%, and 69–85% with antimonials. Pentamidine appeared effective against complicated CL, also in cases that did not improve on antimonials. Data on miltefosine, paromomycin and liposomal amphotericin B are extremely scarce. Only a few studies were available on DCL. The evidence-base for treatment of complicated CL due to L aethiopica is extremely limited. While antimonials remain the most available CL treatment in Ethiopia, more data on the efficacy and safety in CL are needed. High quality trials on CL due to L aethiopica are urgently needed, evaluating treatments beyond antimonials. Interesting options in the short term are drugs such as miltefosine, paromomycin and liposomal amphotericin B, as they are currently available in Ethiopia for treatment of visceral leishmaniasis.