To evaluate efficacy and safety of amphotericin B in two different doses in the treatment of post kala-azar dermal leishmaniasis (PKDL)

Abstract

Background: Post kala-azar dermal leishmaniasis (PKDL) is a skin disorder that usually occurs among patients with a past history of visceral leishmaniasis (VL). Cases are also reported without a history of VL. There is no satisfactory treatment regimen available at present. We aimed to compare the efficacy and safety of amphotericin B in two different doses (0.5mg/kg vs 1mg/kg) in a prospective randomized trial in 50 PKDL patients.

Methods: In this open label study 50 patients with PKDL, aged between 5-60 years were randomized in two groups. Group A received amphotericin B in the dose of 0.5 mg/kg in 5% dextrose, daily for 20 infusions for 3 courses at an interval of 15 days between each course and Group B received amphotericin B in the dose of 1mg/kg in 5% dextrose on alternate days, 20 infusions for 3 courses an interval of 15 days between each course and followed up for one year.

Results: A total of 50 patients were enrolled, 25 in each of group A and group B. Two patients lost to follow up and three patients withdrew consent due to adverse events. The initial cure rate was 92% in group A and 88% in group B by intention to treat analysis and final cure rate by per protocol analysis was 95.65% and 95.45% in group A and group B respectively. Two patients each from either group relapsed. Nephrotoxicity was the most common adverse event occurring in both the groups.

Conclusion: The lower dose appears to have fewer adverse events however, nephrotoxicity remains a problem in both regimens. The 0.5mg/kg regimen may be considered instead of the higher dosage however safer treatments remain critical for PKDL treatment.

Fig 1. Patients flow diagram

Fig 2. Parasite load (parasites/μg tissue DNA) in tissue biopsy samples were determined by quantitative real-time PCR (Q-PCR) using standard curve with SYBR Green.

Extracted DNA from L. donovani were used for standard curve after 10-fold serial dilution. Ct- threshold cycle value; slope- 3.23; intercept- 25.08; R2- 0.991.

Fig 3. Parasitic load before treatment and at end of treatment shown by bar graph in which parasitic load is inversely proportional to Ct value.

Fig 4

Skin lesions in a male patient- (a) before treatment, (b) after treatment with amphotericin B 0.5mg/kg/day.

Fig 5

Skin lesions in a female patient- (a) before treatment, (b) after treatment with amphotericin B 0.5mg/kg/day.