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      Favorable responses to treatment with 5 mg Sbv/kg/day meglumine antimoniate in patients with American tegumentary leishmaniasis acquired in different Brazilian regions

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          Abstract

          Abstract INTRODUCTION: Favorable responses in American tegumentary leishmaniasis (ATL) patients to treatment with 5 mg Sbv/kg/day meglumine antimoniate (MA) has been reported in Rio de Janeiro, but little is known regarding the therapeutic response to low doses in patients from other locations. METHODS: A retrospective review of medical records was conducted to compare the therapeutic response to 5 mg Sbv/kg/day MA treatment among 36 patients who acquired ATL in Brazilian states other than Rio de Janeiro (OS group) and 72 patients from Rio de Janeiro (RJ group). RESULTS: One course of 5 mg Sbv/kg/day MA cured 72.8% of 81 cutaneous (CL) and 66.6% of 27 mucosal (ML) leishmaniasis-infected patients: 70% in the CL/RJ group, 81% in the CL/OS group, 50% in the ML/RJ group, and 80% in the ML/OS group. After up to two additional treatment courses at the same dose, 88.9% and 85.2% of the CL and ML patients were cured, respectively. Adverse events were observed in 40% of patients in the CL/RJ group, 57% of the CL/OS group, 58% of the ML/RJ group, and 80% of the ML/OS group. No significant differences were observed in the cure rates or adverse effects between the RJ and OS groups. No patients required permanent discontinuation of treatment due to adverse events. CONCLUSIONS: Patients with ATL acquired in both RJ and OS may respond to low-dose MA. While high-dose MA should remain the standard treatment for ATL, low-dose MA might be preferred when toxicity is a primary concern.

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          A general classification of New World Leishmania using numerical zymotaxonomy.

          More than 250 strains of Leishmania isolated from different localities and hosts in the New World were analyzed by enzyme electrophoresis, and their electromorphic profiles were compared with 19 reference strains representing most of the described species of this parasite. The 18 enzymic loci analyzed were very polymorphic, and the strains were classified into 44 zymodemes, each grouping strains with the same enzyme profiles. Each zymodeme was considered as an elementary taxon and the phenetic and phylogenetic relationships were determined by agglomerative hierarchical, ordination, and cladistic techniques. The different classification methods produced very similar results. The 44 zymodemes could be clustered into two groups, corresponding to the subgenera Leishmania and Viannia, by the numerical methods. The subgenus Viannia was shown to be monophyletic and could be further divided into species complexes representing L. braziliensis, L. naiffi, and L. guyanensis/L. panamensis/L. shawi, as well as some isolated taxa including L. lainsoni. The subgenus Leishmania, on the other hand, was polyphyletic, with New World isolates related to L. major clustered separately from the L. mexicana species complex. Most of the other zymodemes in this group represented independent taxa. The results confirm Viannia as a valid taxon but suggest that the status of the subgenus Leishmania should be further investigated. Leishmania braziliensis and L. naiffi were shown to be the most polymorphic species, while L. guyanensis, in spite of being the most common species found in this study, was remarkably homogeneous. The only variants were found south of the Amazon river. North of this river, the species was monomorphic.
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            Genetic polymorphism and molecular epidemiology of Leishmania (Viannia) braziliensis from different hosts and geographic areas in Brazil.

            Numerical zymotaxonomy and variability of the internal transcribed spacers (ITS) between the small and large subunits of the rRNA genes were used to examine strain variation and relationships in natural populations of Leishmania (Viannia) braziliensis. A total of 101 strains from distinct hosts and Brazilian geographic regions were assigned to 15 zymodemes clustered in two major genetic groups. The great number of isolates (48.5%) placed in zymodeme IOC/Z-27 were collected on the Atlantic coast. The high molecular diversity found in populations in the Amazon Basin was related to the great number of sandfly vector(s) in that region. The results of the restriction fragment length polymorphism analysis of the ITS depicted considerable intraspecific variation. Genotypic groups A, B, and C contained 39, 40, and 22 isolates, which were divided into 16, 10, and 15 genotypes, respectively. The genetic polymorphism observed demonstrates the degree of diversity of L. (V.) braziliensis strains from different regions where they are endemic. The results reinforce the clonal theory for Leishmania parasites showing the genetic diversity of this pathogen and an association of L. (V.) braziliensis genotypes with specific transmission cycles, probably reflecting an adaptation of different clones to the vector species involved.
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              Comparison of cutaneous leishmaniasis due to Leishmania (Viannia) braziliensis and L. (V.) guyanensis in Brazil: therapeutic response to meglumine antimoniate.

              We conducted a quasi-experimental study to compare the response to meglumine antimoniate in patients with localized cutaneous leishmaniasis from two endemic areas of Brazil that were infected by two Leishmania species. Sixty-one were infected by Leishmania (Viannia) braziliensis (group B) and 57 by L. (V.) guyanensis (group G). All had a parasitologically proven diagnosis and were treated with 20 mg of pentavalent antimonial (SbV)/kg/day given intravenously or intramuscularly for 20 days. Main outcomes were diagnosed using clinical criteria three months after treatment and patients were followed for six months. Intention-to-treat analysis showed a higher failure rate in group G (relative risk [RR] = 1.5, 95% confidence interval [CI] = 1.1-2.0, chi2 = 7.44, P = 0.006). The analysis using an explanatory approach including 52 patients from group B and 49 from group G, who were regularly treated and followed for six months, showed a low cure rate (50.8% in group B and 26.3% in group G) with a greater risk of failure in the latter group (RR = 1.7, 95% CI = 1.2-2.5, chi2 = 8.56, P = 0.003). The effect of the etiologic agent remained significant after adjusting for age, disease duration, and site and number of lesions that were identified as predictors of failure in a logistic regression model. We concluded that Leishmania species constitute an important factor in predicting the outcome of cutaneous leishmaniasis treated with a pentavalent antimonial.
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                Author and article information

                Contributors
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                Journal
                rsbmt
                Revista da Sociedade Brasileira de Medicina Tropical
                Rev. Soc. Bras. Med. Trop.
                Sociedade Brasileira de Medicina Tropical - SBMT (Uberaba, MG, Brazil )
                0037-8682
                1678-9849
                December 2018
                : 51
                : 6
                : 769-780
                Affiliations
                [1] Rio de Janeiro orgnameFundação Oswaldo Cruz orgdiv1Instituto Nacional de Infectologia Evandro Chagas orgdiv2Laboratório de Pesquisa Clínica e Vigilância em Leishmanioses Brazil
                [3] Rio de Janeiro Rio de Janeiro orgnameUniversidade Federal do Rio de Janeiro orgdiv1Faculdade de Medicina orgdiv2Departamento de Otorrinolaringologia e Oftalmologia Brazil
                [4] Rio de Janeiro orgnameFundação Oswaldo Cruz orgdiv1Instituto Nacional de Infectologia Evandro Chagas orgdiv2Laboratório de Epidemiologia Clínica Brazil
                [2] Rio de Janeiro orgnameFundação Oswaldo Cruz orgdiv1Instituto Oswaldo Cruz orgdiv2Laboratório de Imunoparasitologia Brazil
                [5] Rio de Janeiro orgnameFundação Oswaldo Cruz orgdiv1Instituto Oswaldo Cruz orgdiv2Laboratório de Biologia de Tripanossomatídeos Brazil
                Article
                S0037-86822018000600769
                10.1590/0037-8682-0464-2017
                ad67ef73-8f6c-4c6e-828f-b025057556d0

                This work is licensed under a Creative Commons Attribution 4.0 International License.

                History
                : 12 December 2017
                : 08 October 2018
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 50, Pages: 12
                Product

                SciELO Brazil

                Categories
                Major Article

                American tegumentary leishmaniasis,Leishmania spp.,Leishmania (Viannia) braziliensis subpopulations,Therapy,Meglumine antimoniate,Low-dose

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