Rapid Healing of Cutaneous Leishmaniasis by High-Frequency Electrocauterization and Hydrogel Wound Care with or without DAC N-055: A Randomized Controlled Phase IIa Trial in Kabul

Background Anthroponotic cutaneous leishmaniasis (CL) due to Leishmania (L.) tropica infection is a chronic, frequently disfiguring skin disease with limited therapeutic options. In endemic countries healing of ulcerative lesions is often delayed by bacterial and/or fungal infections. Here, we studied a novel therapeutic concept to prevent superinfections, accelerate wound closure, and improve the cosmetic outcome of ACL. Methodology/Principal Findings From 2004 to 2008 we performed a two-armed, randomized, double-blinded, phase IIa trial in Kabul, Afghanistan, with patients suffering from L. tropica CL. The skin lesions were treated with bipolar high-frequency electrocauterization (EC) followed by daily moist-wound-treatment (MWT) with polyacrylate hydrogel with (group I) or without (group II) pharmaceutical sodium chlorite (DAC N-055). Patients below age 5, with facial lesions, pregnancy, or serious comorbidities were excluded. The primary, photodocumented outcome was the time needed for complete lesion epithelialization. Biopsies for parasitological and (immuno)histopathological analyses were taken prior to EC (1(st)), after wound closure (2(nd)) and after 6 months (3(rd)). The mean duration for complete wound closure was short and indifferent in group I (59 patients, 43.1 d) and II (54 patients, 42 d; p=0.83). In patients with Leishmania-positive 2(nd) biopsies DAC N-055 caused a more rapid wound epithelialization (37.2 d vs. 58.3 d; p=0.08). Superinfections occurred in both groups at the same rate (8.8%). Except for one patient, reulcerations (10.2% in group I, 18.5% in group II; p=0.158) were confined to cases with persistent high parasite loads after healing. In vitro, DAC N-055 showed a leishmanicidal effect on pro- and amastigotes. Conclusions/Significance Compared to previous results with intralesional antimony injections, the EC plus MWT protocol led to more rapid wound closure. The tentatively lower rate of relapses and the acceleration of wound closure in a subgroup of patients with parasite persistence warrant future studies on the activity of DAC N-055. Trial Registration ClinicalTrails.gov NCT00947362 Author Summary In many countries of the Middle East such as Afghanistan, cutaneous leishmaniasis is a highly prevalent, chronic and stigmatizing skin disease. Poor hygiene conditions frequently aggravate the lesions due to bacterial and fungal superinfections. Classical treatments with injections of pentavalent antimony are hampered by costs, side effects, resistance development, supply and manufactural quality problems. In the present study on Afghan patients with Leishmania tropica-induced skin lesions we evaluated the clinical effect of an initial removal of lesion tissue by electrocoagulation using a bipolar high-frequency electrosurgery instrument, followed by daily moist wound treatment with or without a preparation of pharmaceutical sodium chlorite (DAC N-055). DAC N-055 is a compound with anti-infective, immunomodulatory and tissue repair-promoting effects. Our analysis revealed that the carefully performed moist wound treatment led to a rapid healing of the wounds within an average period of 6 weeks, even in the absence of the sodium chlorite preparation. This is considerably faster than the time spans previously reported for local or systemic antimony treatment. We believe that the current standard for local care of chronic wounds should also be applied to Leishmania skin lesions. If combined with an initial single high-frequency electrocoagulation, it is a highly effective, inexpensive and well-tolerated treatment option for cutaneous leishmaniasis.