Interventions for American Cutaneous and Mucocutaneous Leishmaniasis: A Systematic Review Update

Introduction: Leishmaniasis is an important public health problem in the Americas. A Cochrane review published in 2009 analyzed 38 randomized controlled trials (RCT). We conducted a systematic review to evaluate the effects of therapeutic interventions for American cutaneous and mucocutaneous leishmaniasis. Methods: All studies were extracted from PubMed, Embase, Lilacs (2009 to July, 2012 respectively), the Cochrane Central Register of Controlled Trials (6-2012) and references of identified publications. RCTs' risk of bias was assessed. Results: We identified 1865 references of interest; we finally included 10 new RCTs. The risk of bias scored low or unclear for most domains. Miltefosine was not significantly different from meglumine antimoniate in the complete cure rate at 6 months (4 RCT; 584 participants; ITT; RR: 1.12; 95%CI: 0.85 to 1.47; I2 78%). However a significant difference in the rate of complete cure favoring miltefosine at 6 months was found in L. panamensis and L. guyanensis (2 RCTs, 206 participants; ITT; RR: 1.22; 95%CI: 1.02 to 1.46; I2 0%). One RCT found that meglumine antimoniate was superior to pentamidine in the rate of complete cure for L. braziliensis (80 participants, ITT; RR: 2.21; 95%CI: 1.41 to 3.49), while another RCT assessing L. guyanensis did not find any significant difference. Although meta-analysis of three studies found a significant difference in the rate of complete cure at 3 months favoring imiquimod versus placebo (134 participants; ITT; RR: 1.45; 95%CI: 1.12 to 1.88; I2 0%), no significant differences were found at 6 and 12 months. Thermotherapy and nitric oxide were not superior to meglumine antimoniate. Conclusion: Therapeutic interventions for American cutaneous and mucocutaneous leishmaniasis are varied and should be decided according to the context. Since mucosal disease is the more neglected form of leishmaniasis a multicentric trial should be urgently considered.