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

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          Abstract

          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.

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          Most cited references79

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          Leishmaniases of the New World: current concepts and implications for future research.

          G. Grimaldi, R. Tesh (1993)
          Recent epidemiologic studies indicate that leishmaniasis in the Americas is far more abundant and of greater public health importance than was previously recognized. The disease in the New World is caused by a number of different parasite species that are capable of producing a wide variety of clinical manifestations. The outcome of leishmanial infection in humans is largely dependent on the immune responsiveness of the host and the virulence of the infecting parasite strain. This article reviews current concepts of the clinical forms, immunology, pathology, laboratory diagnosis, and treatment of the disease as well as aspects of its epidemiology and control. Recommendations for future research on the disease and its control are made.
          Article 0 comments Cited 73 times – based on 0 reviews     Review now
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            Miltefosine for new world cutaneous leishmaniasis.

            J Soto, Paula Luz, Carolina Toledo Piza … (2004)
            The oral agent miltefosine has demonstrated a >95% cure rate in Indian visceral leishmaniasis. We performed a large, placebo-controlled study of miltefosine therapy (2.5 mg/kg per day orally for 28 days) against cutaneous leishmaniasis in Colombia and Guatemala. In regions in Colombia where Leishmania vianna panamensis is common, the per-protocol cure rates for miltefosine and placebo were 91% (40 of 44 patients) and 38% (9 of 24). These values are similar to historic values for the antimony standard of care and placebo. In regions in Guatemala where L. v. braziliensis and L. mexicana mexicana are common, the per-protocol cure rates were 53% (20 of 38) for miltefosine and 21% (4 of 19) for placebo. The miltefosine rate was lower than historic antimony cure rates of >90%. Miltefosine was well tolerated. Miltefosine is a useful oral agent against cutaneous leishmaniasis due to L. v. panamensis in Colombia but not against leishmaniasis due to L. v. braziliensis in Guatemala.
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              Recruitment of CD8(+) T cells expressing granzyme A is associated with lesion progression in human cutaneous leishmaniasis.

              Humberto H. Carvalho, Walderez Dutra, Natalia P. Machado … (2009)
              Human infection with Leishmania braziliensis leads to the establishment of cutaneous leishmaniasis (CL), characterized by the appearance of skin lesions that progress from nonulcerated to ulcerated forms. Our goal was to characterize the immunological kinetics associated with this progression, comparing the cellular composition, cytokines and granzyme expression between lesions of patients with early (E-CL) and late stages (L-CL) of CL. Histopathological analysis showed that lesions from L-CL had more exuberant inflammatory infiltrate as compared to E-CL. Although E-CL and L-CL lesions were predominantly mononuclear, lesions from E-CL patients presented higher neutrophil and eosinophil counts than L-CL. While percentages of CD4(+) and of CD68(+) cells were slightly higher in L-CL, a fivefold increase of CD8(+) cells was observed in L-CL, as compared to E-CL. Moreover, CD8(+) T-cells from L-CL expressed significantly higher levels of granzyme A than E-CL. Interestingly, granzyme A expression was positively correlated with intensity of the inflammatory infiltrate in L-CL but not E-CL. Lastly, percentages of IFN-gamma(+) and IL-10(+) cells were higher in L-CL as compared to E-CL, with CD4(+) T-cells and CD68(+) monocytes as the main sources of these cytokines, respectively. These results suggest that recruitment of CD8(+) granzyme A(+) T cells is involved in lesion progression in human CL.
              Article 0 comments Cited 63 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Henk D. F. H. Schallig: Role: Editor
                Journal
                Journal ID (nlm-ta): PLoS One
                Journal ID (iso-abbrev): PLoS ONE
                Journal ID (publisher-id): plos
                Journal ID (pmc): plosone
                Title: PLoS ONE
                Publisher: Public Library of Science (San Francisco, USA )
                ISSN (Electronic): 1932-6203
                Publication date Collection: 2013
                Publication date (Electronic): 29 April 2013
                Volume: 8
                Issue: 4
                Electronic Location Identifier: e61843
                Affiliations
                [1 ]Health Systems Based on Primary Health Care, Pan American Health Organization (PAHO), Washington, D.C., United States of America
                [2 ]Health Surveillance Disease Prevention and Control, Communicable Diseases Project, Pan American Health Organization (PAHO), Duque de Caxias, Rio de Janeiro, Brazil
                [3 ]Center for Tropical Medicine, University of Brasilia and National Institute for Science and Technology for Health Technology Assessment (IATS/CNPq), Porto Alegre, Rio Grande do Sul, Brazil
                Royal Tropical Institute, The Netherlands
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: LR ANME. Performed the experiments: LR ANME. Analyzed the data: LR ANME RSN GASR ZEY. Wrote the paper: LR ANME RSN GASR ZEY.

                Article
                Publisher ID: PONE-D-13-00116
                DOI: 10.1371/journal.pone.0061843
                PMC ID: 3639260
                PubMed ID: 23637917
                SO-VID: acfe0f9f-b69b-40dd-8e8f-79f44b9bcb96
                Copyright statement: Copyright @ 2013
                License:

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                Date received : 21 December 2012
                Date accepted : 14 March 2013
                Page count
                Pages: 14
                Funding
                The authors have no support or funding to report.
                Categories
                Subject: Research Article
                Subject: Medicine
                Subject: Clinical Research Design
                Subject: Systematic Reviews
                Subject: Drugs and Devices
                Subject: Infectious Diseases
                Subject: Neglected Tropical Diseases
                Subject: Leishmaniasis
                Subject: Parasitic Diseases
                Subject: Leishmaniasis
                Subject: Veterinary Science
                Subject: Veterinary Diseases
                Subject: Zoonotic Diseases
                Subject: Leishmaniasis

                ScienceOpen disciplines: Uncategorized
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                ScienceOpen disciplines: Uncategorized

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