First-Line Therapy for Human Cutaneous Leishmaniasis in Peru Using the TLR7 Agonist Imiquimod in Combination with Pentavalent Antimony

Abstract

BackgroundCurrent therapies for cutaneous leishmaniasis are limited by poor efficacy, long-term course of treatment, and the development of resistance. We evaluated if pentavalent antimony (an anti-parasitic drug) combined with imiquimod (an immunomodulator) was more effective than pentavalent antimony alone in patients who had not previously been treated.MethodsA randomized double-blind clinical trial involving 80 cutaneous leishmaniasis patients was conducted in Peru. The study subjects were recruited in Lima and Cusco (20 experimental and 20 control subjects at each site). Experimental arm: Standard dose of pentavalent antimony plus 5% imiquimod cream applied to each lesion three times per week for 20 days. Control arm: Standard dose of pentavalent antimony plus placebo (vehicle cream) applied as above. The primary outcome was cure defined as complete re-epithelization with no inflammation assessed during the 12 months post-treatment period.ResultsOf the 80 subjects enrolled, 75 completed the study. The overall cure rate at the 12-month follow-up for the intention-to-treat analysis was 75% (30/40) in the experimental arm and 58% (23/40) in the control arm (p = 0.098). Subgroup analyses suggested that combination treatment benefits were most often observed at the Cusco site, where L. braziliensis is the prevalent species. Over the study period, only one adverse event (rash) was recorded, in the experimental arm.ConclusionThe combination treatment of imiquimod plus pentavalent antimony performed better than placebo plus pentavalent antimony, but the difference was not statistically significant.Trial RegistrationClinical Trials.gov NCT00257530

Intralesional Pentamidine: A Novel Therapy for Single Lesions of Bolivian Cutaneous Leishmaniasis

“…17 Sb-unresponsive CL is being seen clinically in the sense that recent cure rates of New World L. (Viannia) CL treated with systemic Sb are surprisingly low for a standard therapy, approximately 50-75%. [18][19][20][21][22] An undecided issue is whether there is a correlation between in vitro and clinical data, whether parasite resistance is the cause of clinical unresponsiveness. For Leishmania tropica from Iran, the mean effective dose (ED50) for parasites from 165 lesions that responded to systemic or ILSb was 4.6 μg/mL, whereas the mean ED50 for parasites from 16 lesions that did not respond was 19 μg/mL.…”

Toll-Like Receptors Participate in Macrophage Activation and Intracellular Control of Leishmania (Viannia) panamensis

“…L. major DNA has been shown to promote IFN-␥ production by CD4 ϩ T cells through TLR9-dependent activation of DCs (1). The potential therapeutic applicability of activation through endolysosomal TLRs has been demonstrated by the enhanced resolution of experimental L. donovani infection and human cutaneous leishmaniasis (12,36), using the TLR7/8 ligand imiquimod. Although our results support the participation of endolysosomal TLR signaling during L. panamensis infection, the specific TLR(s) involved remains to be identified.…”

Diagnostic Performance of Filter Paper Lesion Impression PCR for Secondarily Infected Ulcers and Nonulcerative Lesions Caused by Cutaneous Leishmaniasis

“…However, it has not been evaluated for secondarily infected ulcers, which account for 10 to 15% of ulcers in CL (14). As incising secondarily infected skin to obtain invasive specimens prior to a course of antibiotics is contraindicated, FPLI PCR may provide rapid diagnosis of CL in secondarily infected ulcers rather than waiting until clearance of bacterial infection to perform the diagnostic evaluation.…”