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      In Vitro Sensitivity of Paired Leishmania ( Viannia) braziliensis Samples Isolated before Meglumine Antimoniate Treatment and after Treatment Failure or Reactivation of Cutaneous Leishmaniasis

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          Abstract

          This study evaluated the in vitro sensitivity of paired Leishmania braziliensis samples isolated from the same patient before pentavalent antimonial treatment (Sample A) and after treatment failure or cutaneous leishmaniasis reactivation (Sample B) in patients undergoing intralesional administration or injections (5 mgSb V/kg/d) of meglumine antimoniate. Fourteen samples from 7 patients were studied. After 24 h of drug exposure, 50% lethal dose (LD 50) values for promastigotes ranged from 0.37 mg/mL to 5.86 mg/mL for samples obtained before treatment (A) and 0.89 mg/mL to 7.80 mg/mL for samples obtained after treatment (B). After 48 h, LD 50 values ranged from 0.37 mg/mL to 5.75 mg/mL and 0.70 mg/mL to 7.68 mg/mL for A and B samples, respectively. After 48 h, LD 50 values for amastigotes ranged from 11.7 to 44.3  μg/mL for A samples and 13.7 to 52.7  μg/mL for B samples. Of 7 patients, 1 discontinued treatment and 6 were cured after retreatment with amphotericin B (4 cases) or meglumine antimoniate (2 cases). Overall the B samples had higher LD 50 values than A samples; however the difference was not significant. These results do not support the hypothesis that low-dose and intralesional treatments induce selection of resistant parasites in vitro and suggest that other factors may influence therapeutic outcome in patients with poor response to initial treatment.

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          Control of the leishmaniases.

          (2010)
          This report makes recommendations on new therapeutic regimens for visceral and cutaneous leishmaniasis, on the use of rapid diagnostic tests, details on the management of Leishmania-HIV coinfection and consideration of social factors and climate change as risk factors for increased spread. Recommendations for research include the furtherance of epidemiological knowledge of the disease and clinical studies to address the lack of an evidence-based therapeutic regimen for cutaneous and mucocutaneous leishmaniasis and post-kala-azar dermal leishmaniasis (PKDL). This report not only provides clear guidance on implementation but should also raise awareness about the global burden of leishmaniasis and its neglect. It puts forward directions for formulation of national control programmes and elaborates the strategic approaches in the fight against the leishmaniases. The committee's work reflects the latest scientific and other relevant developments in the field of leishmaniasis that can be considered by member states when setting national programmes and making public health decisions.
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            In vitro susceptibilities of Leishmania donovani promastigote and amastigote stages to antileishmanial reference drugs: practical relevance of stage-specific differences.

            The in vitro susceptibilities of the reference strain Leishmania donovani MHOM/ET/67/L82 to sodium stibogluconate, amphotericin B, miltefosine, and the experimental compound PX-6518 were determined for extracellular log-phase promastigotes, established axenic amastigotes, fresh spleen-derived amastigotes, and intracellular amastigotes in primary mouse peritoneal macrophages. Susceptibility to amphotericin B did not differ across the various axenic models (50% inhibitory concentrations [IC50], 0.6 to 0.7 microM), and amphotericin B showed slightly higher potency against intracellular amastigotes (IC50, 0.1 to 0.4 microM). A similar trend was observed for miltefosine, with comparable efficacies against the extracellular (IC50, 0.4 to 3.8 microM) and intracellular (IC50, 0.9 to 4.3 microM) stages. Sodium stibogluconate, used either as Pentostam or as a crystalline substance, was inactive against all axenic stages (IC50, >64 microg SbV/ml) but showed good efficacy against intracellular amastigotes (IC50, 22 to 28 microg SbV/ml); the crystalline substance was about two to three times more potent (IC50, 9 to 11 microg SbV/ml). The activity profile of PX-6518 was comparable to that of sodium stibogluconate, but at a much higher potency (IC50, 0.1 microg/ml). In conclusion, the differential susceptibility determines which in vitro models are appropriate for either drug screening or resistance monitoring of clinical field isolates. Despite the more complex and labor-intensive protocol, the current results support the intracellular amastigote model as the gold standard for in vitro Leishmania drug discovery research and for evaluation of the resistance of field strains, since it also includes host cell-mediated effects. Axenic systems can be recommended only for compounds for which no cellular mechanisms are involved, for example, amphotericin B and miltefosine.
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              Tegumentary and visceral leishmaniases in Brazil: emerging anthropozoonosis and possibilities for their control

              The existence of a number of different species of Leishmania, the persistent increase in the infection rate of diseases caused by this parasite (tegumentary and visceral forms), the different epidemiological situations found in regions of both recent and older colonization, and the trend towards urbanization have led to the adoption of different strategies to control leishmaniases in Brazil. The control measures involve studies related to the parasite, vectors, sources of infection (animal and human), clinical aspects, geographical distribution, historical and socioeconomic factors, integration of health services, and adequate technologies for diagnosis, treatment, and immunoprophylaxis. Finally, successful control requires work with human communities, involving education, provision of information, health promotion, and participation of these communities in the planning, development, and maintenance of control programs.
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                Author and article information

                Journal
                Dis Markers
                Dis. Markers
                DM
                Disease Markers
                Hindawi Publishing Corporation
                0278-0240
                1875-8630
                2015
                31 January 2015
                : 2015
                : 943236
                Affiliations
                1Núcleo de Biossegurança, Bio-Manguinhos, Fundação Oswaldo Cruz, 21040-900 Rio de Janeiro, RJ, Brazil
                2Laboratório de Pesquisa Clínica e Vigilância em Leishmanioses, Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz, 21040-900 Rio de Janeiro, RJ, Brazil
                3Laboratório de Bioquímica de Tripanosomatídeos, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, 21040-360 Rio de Janeiro, RJ, Brazil
                4Laboratório de Imunoparasitologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, 21040-360 Rio de Janeiro, RJ, Brazil
                Author notes
                *Luciana de Freitas Campos Miranda: luciana.freitas@ 123456ini.fiocruz.br

                Academic Editor: Robert Pichler

                Article
                10.1155/2015/943236
                4329789
                25802480
                c665f232-da1b-48c3-b38d-7d242a3fbdd4
                Copyright © 2015 Cibele Baptista et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 12 December 2014
                : 9 January 2015
                Categories
                Research Article

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