title: The Cure Rate after Placebo or No Therapy in American Cutaneous Leishmaniasis: A Systematic Review and Meta-Analysis.
abstract: BACKGROUND
  There are few drugs with proven efficacy in cutaneous leishmaniasis (CL), and pentavalent antimonial derivatives are still the main first-line therapeutic agents worldwide, despite their recognized high toxicities. Randomized controlled clinical trials assessing the efficacy and safety of new therapeutic modalities are of high priority, and the definition of the design of such trials raises debate about the use of placebo as a comparator. To support the use of placebo as a comparator, two main points need to be addressed: 1--the cure rate without any therapeutic intervention and 2--the damage caused by CL and its impact on patients.
  
  
  OBJECTIVE
  The aim of this study was to systematically assess the spontaneous cure rate for American CL and to broaden the discussion about placebo use in CL trials.
  
  
  METHODS
  The PRISMA guidelines for systematic reviews and the Cochrane manual were followed. The sources used were the PubMed and LILACS databases. Studies were included if they reported cure rates using placebo or no treatment in American CL.
  
  
  RESULTS
  Thirteen studies of a total of 352 patients were ultimately included in this review. The summarized global cure rates for all Leishmania species according to the intention-to-treat analyses performed at approximately three ("initial cure") and nine ("definitive cure") months after "no treatment" or placebo use were 26% (CI95%: 16 to 40%) and 26% (CI95%:16 to 38%), respectively. Notably, a significantly lower cure rate was observed for L. braziliensis infection (6.4%, CI95%:0.2 to 20%) than for L. mexicana infection (44%, CI95%:19 to 72%), p = 0.002. Of note, relapse occurred in 20% of patients with initial healing (CI95%:9.2 to 38.9%).
  
  
  CONCLUSIONS
  These results clearly demonstrate a low spontaneous cure rate following no-treatment or placebo use, confirming that this strategy for the control group in CL studies expose patients to greater morbidity, especially for CL caused by L. braziliensis. Therefore, from this point, the crucial question to consider regarding placebo use is the seriousness of the suffering caused by this disease.
authors.affiliation: Clinical Research and Public Policy in Infectious and Parasitic Diseases, Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz, Fiocruz, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Gláucia Fernandes
authors.initials: GF
authors.lastname: Cota
authors.affiliation: Post-Graduate Program in Adult Health Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Marcos Roberto
authors.initials: MR
authors.lastname: de Sousa
authors.affiliation: Hospital Eduardo de Menezes, Fundação Hospitalar do Estado de Minas Gerais-FHEMIG, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Tatiani Oliveira
authors.initials: TO
authors.lastname: Fereguetti
authors.affiliation: Hospital Eduardo de Menezes, Fundação Hospitalar do Estado de Minas Gerais-FHEMIG, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Priscila Said
authors.initials: PS
authors.lastname: Saleme
authors.affiliation: Hospital Eduardo de Menezes, Fundação Hospitalar do Estado de Minas Gerais-FHEMIG, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Thais Kawagoe
authors.initials: TK
authors.lastname: Alvarisa
authors.affiliation: Clinical Research and Public Policy in Infectious and Parasitic Diseases, Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz, Fiocruz, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Ana
authors.initials: A
authors.lastname: Rabello
mesh_terms: D000981:Antiprotozoal Agents / Q000627:therapeutic use*; D006801:Humans; D016773:Leishmaniasis, Cutaneous / Q000188:drug therapy*; D010919:Placebos / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
chemical_list: D000981:Antiprotozoal Agents; D010919:Placebos