Combination Therapy for Post-Kala-Azar Dermal Leishmaniasis: A Literature Review of Current Evidence.

Abstract

Post-kala-azar dermal leishmaniasis (PKDL) is a neglected skin disease that has tremendous epidemiological significance as a reservoir of Leishmania parasites. Relapse, drug resistance, non-compliance to prolonged treatment, poor health-seeking behaviour, along with limited therapeutic options pose a significant impact on the management of PKDL. In this study, we aimed to review the efficacy, safety and tolerability data of combination therapies for PKDL in the published literature. We have also described patients' compliance with treatment and associated co-infections in PKDL. A comprehensive literature search was conducted in PubMed, Scopus and Google Scholar to identify the relevant articles. A total of nine studies were eligible for inclusion in this review. Drug combinations used in India were miltefosine-liposomal amphotericin-B, miltefosine-paromomycin, miltefosine-amphotericin-B, sodium stibogluconate (SSG)-immunotherapy and SSG-rifampicin. However, in Sudan, except one, all studies have used SSG-based combinations viz. SSG-rifampicin, SSG-paromomycin and SSG-immunotherapy. The efficacy and safety of miltefosine in combination with liposomal amphotericin-B as well as conventional amphotericin-B were found to be excellent in a limited number of patients. These combinations are said to have better patient compliance and shorter treatment duration. Another combination of miltefosine and paromomycin was found to be satisfactory with a final cure rate of 83.3%. SSG in combination with paromomycin had a good clinical outcome among severe PKDL patients in Sudan, though pain at the injection site was experienced by all patients. There is a lack of data on combination therapies for PKDL through large-scale randomised controlled trials (RCTs). Therefore, multicentric randomized controlled trials with a sufficiently large sample size are urgently needed to verify the efficacy, safety, and other advantages of combination therapies for PKDL. With the availability of liposomal amphotericin-B, miltefosine and immunotherapy, clinical management of PKDL appears promising.