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Studies of topical treatments for leishmaniasis were systematically reviewed, to evaluate the therapeutic efficacy, safety and any adverse effects of these treatments. The papers identified in the databases PubMed and Web of Knowledge involved eight studies with a total of 1744 patients. The majority of trials was from Iran (4/8), covered a period of 8 years (2003-2011), and included patients 4-85 years of age. The most frequent Leishmania species in the studies were L. tropica (4/8) and L. major (2/8). The treatments administered were thermotherapy, paromomycin and combinations, CO2 laser, 5-aminolevulinic acid hydrochloride (10%) plus visible red light (633 nm) and cryotherapy. Six articles reported cure rates over 80·0%. Six studies reported on failure rates, three of them reporting rates lower than 10%. Four studies did not report relapses or recurrences, while the other studies reported low rates (1·8-6·3%). The most common adverse effects of the topical treatments were redness/erythema, pain, pruritus burning, oedema, vesicles and hyper- or hypopigmentation. The results provide strong evidence that the treatments topical evaluated showed high cure rates, safety and effectiveness, with low side-effects, relapse and recurrence rates, except for cryotherapy, which showed a moderate cure rate.

Tetradenia riparia plant is used as a traditional medicine in Africa for the treatment of inflammatory and infectious diseases as like parasitic. Therapy for leishmaniasis caused by Leishmania (Leishmania) amazonensis specie often fails, and the conventional drugs are toxic, expensive, require a long period of treatment, and adverse effects are common. The alternative therapies using natural products are inexpensive and have few or any adverse reaction. These reasons are sufficient to investigate the new natural therapeutic for leishmaniasis. We evaluated the potential of the essential oil (TrEO) and 6,7-dehydroroyleanone (TrROY) isolated from T. riparia on L. (L.) amazonensis promastigote and amastigote forms, cytotoxicity on human erythrocytes and murine macrophages, nitric production and inducible nitric oxide synthase (iNOS) mRNA expression. TrEO was the most effective to promote the Leishmania promastigote death. After 72 h incubation, the lethal dose of TrEO and TrROY that promoted 50% Leishmania death (LD50) were 0.8 μg/mL and 3 μg/mL, respectively. TrEO and TrROY were not cytotoxic to human erythrocytes, but TrROY was toxic to murine macrophages resulting in a low selectivity index. The transmission electronic microscopy showed that TrEO (0.03 μg/mL) was able to modify the promastigote ultrastructures suggesting autophagy as chromatin condensation, blebbing, membranous profiles and nuclear fragmentation. Infected-macrophages treated with TrEO (0.03 μg/mL) or TrROY (10 μg/mL) had an infection index decreased in 65 and 48%. TrEO did not induce iNOS mRNA expression or nitrite production in macrophages infected with Leishmania. TrROY and mainly TrEO promoted the Leishmania death, and TrROY showed loss toxicity to erythrocytes cells. Other compounds derived from T. riparia and the essential oil could be explored to develop a new alternative treatment for leishmaniasis.

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