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1.
Rev Soc Bras Med Trop ; 52: e20180292, 2019 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-30942258

RESUMO

INTRODUCTION: The treatment of mucosal leishmaniasis (ML) is difficult due to the toxicity and route of administration of standard drugs. Miltefosine is an oral agent used for leishmaniasis treatment; however, no data exist regarding its use for ML in Brazil. In this study, we aimed to evaluate the efficacy of miltefosine for ML treatment compared to that of pentavalent antimonial in a pilot study. METHODS: We performed a randomized clinical trial with two parallel groups. The tested intervention consisted of miltefosine 1.3-2 mg/kg/day (two capsules) for 28 days or intravenous 20 mg SbV/kg/day of meglumine antimoniate (N-MA) for 30 days. The final endpoint was defined as complete healing of the lesion four years after treatment. We also analyzed an early endpoint at 90 days after treatment. RESULTS: Forty patients were included in this study: each experimental group comprised 20 patients. Applying a multivariate model in an intention-to-treat analysis, we observed that patients treated with miltefosine had a cure probability 2.08 times greater (95% confidence interval [CI] = 1.03-4.18) than those treated with N-MA at 90 days after treatment. At the final endpoint, we observed no differences in cure probability between miltefosine and N-MA (relative risk = 0.66; 95% CI = 0.33-1.32). With respect to adverse reactions, significant differences between groups were related to gastrointestinal effects, which were more frequent in the miltefosine group. CONCLUSIONS: Miltefosine may be an interesting alternative for treating ML because of its oral administration and cure rate after long-term follow-up.


Assuntos
Antiprotozoários/administração & dosagem , Leishmaniose Mucocutânea/tratamento farmacológico , Antimoniato de Meglumina/administração & dosagem , Fosforilcolina/análogos & derivados , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fosforilcolina/administração & dosagem , Projetos Piloto , Fatores de Tempo , Resultado do Tratamento
2.
Parasite Immunol ; 41(5): e12623, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30870579

RESUMO

Phenotypic and functional aspects of monocytes from Localized Cutaneous Leishmaniasis (LCL) patients were evaluated. The frequencies of monocyte subsets and TLR2/TLR4 expression were evaluated in fresh peripheral blood whereas cytokine production was evaluated in whole blood cell cultures stimulated with TLR agonists or Leishmania braziliensis antigen (Ag). CD16+ monocytes frequency was increased in patients compared with controls. A TLR4 agonist (LPS) induced expression of TNF and IL-10 in monocyte subsets of patients and controls. The CD14+ CD16+ monocytes expressed higher levels of these cytokines than CD14+ CD16- cells. The levels of secreted TNF were higher in whole blood cell cultures from patients than controls after LPS/TLR4 or Ag stimulation. Whereas in controls there was a positive correlation between TNF and IL-10 levels, this was not observed in stimulated cell cultures from patients. The high levels of LPS-induced TNF were associated with the number of lesions and the percentages of CD14hi CD16+ monocytes. The levels of TLR2-induced TNF were also associated with number of lesions. All monocyte subsets from patients expressed higher levels of TLR2 and TLR4 than controls. Data suggest that systemically activated monocytes contribute for an imbalance in pro- and anti-inflammatory cytokine production during LCL, participating in the immunopathogenesis of the disease.


Assuntos
Leishmaniose Cutânea/imunologia , Adulto , Idoso , Citocinas/imunologia , Feminino , Humanos , Interleucina-10/imunologia , Leishmaniose Cutânea/parasitologia , Masculino , Pessoa de Meia-Idade , Monócitos/imunologia , Adulto Jovem
3.
Rev. Soc. Bras. Med. Trop ; 52: e20180292, 2019. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-990435

RESUMO

Abstract INTRODUCTION: The treatment of mucosal leishmaniasis (ML) is difficult due to the toxicity and route of administration of standard drugs. Miltefosine is an oral agent used for leishmaniasis treatment; however, no data exist regarding its use for ML in Brazil. In this study, we aimed to evaluate the efficacy of miltefosine for ML treatment compared to that of pentavalent antimonial in a pilot study. METHODS: We performed a randomized clinical trial with two parallel groups. The tested intervention consisted of miltefosine 1.3-2 mg/kg/day (two capsules) for 28 days or intravenous 20 mg SbV/kg/day of meglumine antimoniate (N-MA) for 30 days. The final endpoint was defined as complete healing of the lesion four years after treatment. We also analyzed an early endpoint at 90 days after treatment. RESULTS: Forty patients were included in this study: each experimental group comprised 20 patients. Applying a multivariate model in an intention-to-treat analysis, we observed that patients treated with miltefosine had a cure probability 2.08 times greater (95% confidence interval [CI] = 1.03-4.18) than those treated with N-MA at 90 days after treatment. At the final endpoint, we observed no differences in cure probability between miltefosine and N-MA (relative risk = 0.66; 95% CI = 0.33-1.32). With respect to adverse reactions, significant differences between groups were related to gastrointestinal effects, which were more frequent in the miltefosine group. CONCLUSIONS: Miltefosine may be an interesting alternative for treating ML because of its oral administration and cure rate after long-term follow-up.

4.
Am J Trop Med Hyg ; 99(5): 1165-1169, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30203744

RESUMO

The disseminated form of leishmaniasis is a serious and rare disease, being diagnosed in 2% of the cutaneous cases registered per year in Brazil. The main characteristic is the appearance of multiple pleomorphic lesions on the cutaneous surface. A 68-year-old male from the rural area of Tocantins, Brazil, presented atypical disseminated cutaneous leishmaniasis (ACL). The clinical course and histopathological and immunological findings presented a mixed pattern that hindered diagnosis and therapeutic management. Molecular typing revealed a mixed infection with Leishmania (V.) guyanensis and Leishmania (L.) amazonensis. Molecular identification of the agents responsible for ACL is important for adequate therapeutic planning, minimizing the possibility of sequellae that impact the quality of life of the patient.


Assuntos
Coinfecção/diagnóstico , Coinfecção/parasitologia , Leishmania guyanensis/genética , Leishmania mexicana/genética , Leishmaniose Cutânea/diagnóstico , Idoso , Anfotericina B/uso terapêutico , Antiprotozoários/uso terapêutico , Brasil , DNA de Protozoário/genética , Técnica Indireta de Fluorescência para Anticorpo , Humanos , Leishmania guyanensis/isolamento & purificação , Leishmania mexicana/isolamento & purificação , Leishmaniose Cutânea/tratamento farmacológico , Leishmaniose Cutânea/parasitologia , Masculino , Tipagem Molecular , População Rural , Pele/parasitologia , Pele/patologia
5.
Am J Trop Med Hyg ; 96(3): 656-659, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28070006

RESUMO

Leishmania (Viannia) braziliensis is the main causative species of tegumentary leishmaniasis in Brazil. In this study, we evaluated the susceptibility of 16 clinical isolates of L. (V.) braziliensis from different regions of Brazil to miltefosine in vitro. Half-maximal inhibitory concentrations of miltefosine varied from 22.9 to 144.2 µM against promastigotes and from 0.3 to 4.2 µM against intracellular amastigotes. No significant differences were found between isolates of different geographical origins. A clear correlation between the EC50 against promastigotes and amastigotes within each isolate was found. These findings contribute to the evaluation of miltefosine's potential and limitations for the treatment of tegumentary leishmaniasis in Brazil.


Assuntos
Resistência a Medicamentos , Leishmania braziliensis/efeitos dos fármacos , Leishmania braziliensis/isolamento & purificação , Fosforilcolina/análogos & derivados , Adolescente , Adulto , Idoso , Brasil , Pré-Escolar , Humanos , Concentração Inibidora 50 , Pessoa de Meia-Idade , Fosforilcolina/uso terapêutico , Adulto Jovem
6.
Biomed Res Int ; 2015: 350764, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26583102

RESUMO

The aim of this study was to characterize clinical field isolates of Leishmania spp. obtained from patients with American Tegumentary Leishmaniasis (ATL) who live in Goiás state, Brazil. The presumed areas of infection were in Goiás, Tocantins, and Pará states. Three isolates of parasites were identified as L. (Viannia) braziliensis and one as L. (V.) guyanensis. The in vitro growth profiles were found to be similar for all parasites. Nevertheless, in C57BL/6 mice, L. (V.) guyanensis infection was better controlled than L. (V.) braziliensis. Yet in C57BL/6 mice deficient in interferon gamma, L. (V.) guyanensis lesions developed faster than those caused by L. (V.) braziliensis isolates. In BALB/c mice, the development of lesions was similar for isolates from both species; however, on the 11th week of infection, amastigotes could not be observed in macrophages from L. (V.) guyanensis-infected mice. Thus, L. (V.) guyanensis can be circulating in Goiás, a state where autochthonous cases of this species had not yet been reported. Considering the difficulties to differentiate L. (V.) guyanensis from L. (V.) braziliensis at the molecular, morphological, and clinical (human and murine models) levels, the presence of L. (V.) guyanensis infections is possibly underestimated in several regions of Brazil.


Assuntos
Leishmania braziliensis/patogenicidade , Leishmania guyanensis/patogenicidade , Leishmaniose Cutânea/parasitologia , Animais , Brasil , Humanos , Leishmania braziliensis/isolamento & purificação , Leishmania guyanensis/isolamento & purificação , Leishmaniose Cutânea/patologia , Camundongos
7.
Biomed Res Int ; 2015: 393049, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25695070

RESUMO

This study was designed to assess in vitro metacyclogenesis of Leishmania (Viannia) braziliensis and Leishmania (Leishmania) amazonensis clinical field isolates obtained from patient lesions (L. braziliensis IMG3 and PPS6m; L. amazonensis MAB6). Metacyclogenesis was evaluated by different criteria, namely, promastigote size (morphometric analysis and flow cytometry), surface modifications (loss of lectin or monoclonal antibody (mAb) binding, complement resistance), and infectivity to human macrophages. Growth curves were similar for all parasites evaluated. The various features analyzed were expressed in a high percentage of promastigotes at 6th and 10th days of culture and a low percentage at the 2nd day. However, in most isolates, these features, considered as markers of metacyclogenesis, seemed to develop with different time courses, since the percentages of metacyclic forms detected with each technique were usually different. Parasites from 6th or 10th day and those negatively selected with lectin or mAb similarly infected human macrophages. From all isolates analyzed, L. amazonensis PH8 and MAB6 showed the highest and the lowest levels of susceptibility, respectively, to leishmanicidal activity of IFN-γ/LPS-activated macrophages. Our results showed that by using different techniques to evaluate different aspects of metacyclogenesis (morphological and biochemical modifications) different percentages of metacyclic promastigotes can be detected in each isolate culture.


Assuntos
Proteínas do Sistema Complemento/imunologia , Leishmania braziliensis/citologia , Leishmania braziliensis/imunologia , Estágios do Ciclo de Vida/imunologia , Macrófagos/imunologia , Macrófagos/parasitologia , Anticorpos Monoclonais/imunologia , Células Cultivadas , Humanos , Técnicas In Vitro , Interferon gama/imunologia , Lectinas/imunologia , Leishmania braziliensis/isolamento & purificação , Leishmaniose Cutânea/imunologia , Leishmaniose Cutânea/parasitologia , Lipopolissacarídeos/imunologia
8.
BMC Infect Dis ; 14: 249, 2014 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-24884781

RESUMO

BACKGROUND: The interleukin 32 (IL-32) is a proinflammatory cytokine produced by immune and non-immune cells. It can be induced during bacterial and viral infections, but its production was never investigated in protozoan infections. American Tegumentary Leishmaniasis (ATL) is caused by Leishmania protozoan leading to cutaneous, nasal or oral lesions. The aim of this study was to evaluate the expression of IL-32 in cutaneous and mucosal lesions as well as in peripheral blood mononuclear cells (PBMC) exposed to Leishmania (Viannia) braziliensis. METHODS: IL-32, tumour necrosis factor (TNF) and IL-10 protein expression was evaluated by immunohistochemistry in cutaneous, mucosal lesions and compared to healthy specimens. The isoforms of IL-32α, ß, δ, γ mRNA, TNF mRNA and IL-10 mRNA were assessed by qPCR in tissue biopsies of lesions and healthy skin and mucosa. In addition, PBMC from healthy donors were cultured with amastigotes of L. (V.) braziliensis. In lesions, the parasite subgenus was identified by PCR-RFLP. RESULTS: We showed that the mRNA expression of IL-32, in particular IL-32γ was similarly up-regulated in lesions of cutaneous (CL) or mucosal (ML) leishmaniasis patients. IL-32 protein was produced by epithelial, endothelial, mononuclear cells and giant cells. The IL-32 protein expression was associated with TNF in ML but not in CL. IL-32 was not associated with IL-10 in both CL and ML. Expression of TNF mRNA was higher in ML than in CL lesions, however levels of IL-10 mRNA were similar in both clinical forms. In all lesions in which the parasite was detected, L. (Viannia) subgenus was identified. Interestingly, L. (V.) braziliensis induced only IL-32γ mRNA expression in PBMC from healthy individuals. CONCLUSIONS: These data suggest that IL-32 plays a major role in the inflammatory process caused by L. (Viannia) sp or that IL-32 is crucial for controlling the L. (Viannia) sp infection.


Assuntos
Interleucina-10/biossíntese , Interleucinas/biossíntese , Leishmania braziliensis/imunologia , Leishmaniose Cutânea/metabolismo , Fator de Necrose Tumoral alfa/biossíntese , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Interleucinas/genética , Leishmaniose Cutânea/imunologia , Leucócitos Mononucleares/metabolismo , Masculino , Pessoa de Meia-Idade , Membrana Mucosa/metabolismo , Pele/metabolismo , Regulação para Cima , Adulto Jovem
9.
Rev Inst Med Trop Sao Paulo ; 52(2): 83-8, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20464128

RESUMO

Isolation of Leishmania parasite and species identification are important for confirmation and to help define the epidemiology of the leishmaniasis. Mice are often used to isolate pathogens, but the most common mouse strains are resistant to infection with parasites from the Leishmania (Viannia) subgenus. In this study we tested the inoculation of interferon gamma knockout (IFNgamma KO) mice with biopsy macerates from Leishmania-infected patients to increase the possibility of isolating parasites. Biopsies from twenty five patients with clinical signs of leishmaniasis were taken and tested for the presence of parasites. Immunohistochemical assay (IHC) and conventional histopathology detected the parasite in 88% and 83% of the patients, respectively. Leishmania sp. were isolated in biopsy macerates from 52% of the patients by culture in Grace's insect medium, but 13% of isolates were lost due to contamination. Inoculation of macerates in IFNgamma KO mice provides isolation of parasites in 31.8% of the biopsies. Most isolates belong to L. (Viannia) subgenus, as confirmed by PCR, except one that belongs to L. (Leishmania) subgenus. Our preliminary results support the use of IFNgamma KO mice to improve the possibility to isolate New World Leishmania species.


Assuntos
Leishmania/isolamento & purificação , Camundongos Knockout/parasitologia , Pele/parasitologia , Animais , Biópsia , Humanos , Interferon gama/genética , Interferon gama/imunologia , Leishmania/classificação , Camundongos , Camundongos Endogâmicos C57BL , Reação em Cadeia da Polimerase , Fatores de Tempo
10.
Rev. Inst. Med. Trop. Säo Paulo ; 52(2): 83-88, Mar.-Apr. 2010. ilus, tab
Artigo em Inglês | LILACS | ID: lil-545754

RESUMO

Isolation of Leishmania parasite and species identification are important for confirmation and to help define the epidemiology of the leishmaniasis. Mice are often used to isolate pathogens, but the most common mouse strains are resistant to infection with parasites from the Leishmania (Viannia) subgenus. In this study we tested the inoculation of interferon gamma knockout (IFNγ KO) mice with biopsy macerates from Leishmania-infected patients to increase the possibility of isolating parasites. Biopsies from twenty five patients with clinical signs of leishmaniasis were taken and tested for the presence of parasites. Immunohistochemical assay (IHC) and conventional histopathology detected the parasite in 88 percent and 83 percent of the patients, respectively. Leishmania sp. were isolated in biopsy macerates from 52 percent of the patients by culture in Grace's insect medium, but 13 percent of isolates were lost due to contamination. Inoculation of macerates in IFNγ KO mice provides isolation of parasites in 31.8 percent of the biopsies. Most isolates belong to L. (Viannia) subgenus, as confirmed by PCR, except one that belongs to L. (Leishmania) subgenus. Our preliminary results support the use of IFNγ KO mice to improve the possibility to isolate New World Leishmania species.


O isolamento e a identificação da espécie de parasito do gênero Leishmania são importantes para a confirmação e auxiliam na epidemiologia da leishmaniose. Os camundongos são freqüentemente utilizados para isolar patógenos, porém, as linhagens mais comuns de camundongos são resistentes à infecção por parasitos do subgênero Leishmania (Viannia). Neste estudo, avaliamos a inoculação de macerados de biópsias de pacientes infectados em camundongos deficientes do gene do interferon gama (IFNγ KO) como um método para aumentar a possibilidade de isolar Leishmania spp. Biópsias de 25 pacientes infectados com Leishmania sp. foram avaliadas para a presença de parasitos pelos métodos de imunohistoquímica (IHC) e histopatologia convencional. Os parasitos foram observados, respectivamente, em 88 por cento e 83 por cento das biópsias. Leishmania sp. foi isolada de macerados de biópsia de 52 por cento dos pacientes infectados, quando cultivados em meio Grace, porém, 13 por cento destes isolados foram perdidos devido a contaminações. Inoculação dos macerados em camundongos IFNγ KO proporcionou o isolamento de parasitos oriundos de 31,8 por cento dos pacientes. A maioria dos isolados pertence ao subgênero L. (Viannia), exceto um que pertence ao subgênero L. (Leishmania), como confirmado pela reação da polimerase em cadeia. Nossos resultados preliminares sugerem que o uso de camundongos IFNγ KO pode ser útil para aumentar a possibilidade de isolamento de leishmânias encontradas nas Américas.


Assuntos
Animais , Humanos , Camundongos , Leishmania/isolamento & purificação , Camundongos Knockout/parasitologia , Pele/parasitologia , Biópsia , Interferon gama/genética , Interferon gama/imunologia , Leishmania/classificação , Reação em Cadeia da Polimerase , Fatores de Tempo
12.
Rev. patol. trop ; 28(2): 139-64, jul.-dez. 1999. ilus
Artigo em Português | LILACS | ID: lil-280869

RESUMO

Neste trabalho sä revisadas as evidências sobre a interaçäo entre a infecçäo pelo HIV/aids e a hanseníase em consonância com os programas de controle e o desenvolvimento de pesquisas na duas últimas décadas. Säo apresentadas hipóteses e questöes suscitadas pelo possível efeito da co-infecçäo pelo HIV e Mycobacterium leprae alterar o curso de cada infecçäo/doença e desenvolver casos mais graves. Aspectos relacionados à interaçäo adversa entre as terapêuticas pdronizadas, quanto aplicadas simultaneamente para ambas infecçöes/doenças, e as implicaçöes na vacinaçäo BCG nos países em desenvolvimento säo também examinados. A interaçäo entre aids e tuberculose foi usada como exemplo de uma bem conhecida interaçäo biológica entre infecçäo pelo HIV e doenças infecciosas e para traçar um paralelo com outras micobactérias.


Assuntos
Humanos , Hanseníase/etiologia , Infecções por HIV/epidemiologia , Micobactérias não Tuberculosas , Mycobacterium leprae , Síndrome de Imunodeficiência Adquirida/complicações , Brasil/epidemiologia , Hanseníase/epidemiologia , Hanseníase/tratamento farmacológico , Síndrome de Imunodeficiência Adquirida/epidemiologia , Síndrome de Imunodeficiência Adquirida/tratamento farmacológico
14.
Rev. patol. trop ; 25(1): 1-4, jan.-jun. 1996.
Artigo em Português | LILACS | ID: lil-195526

RESUMO

O número de mulheres infectadas com o vírus da imunodeficiênicia humana vem aumentando nos últimos anos emconseqüência do uso de drogas injetáveis, múltiplos parceiros sexuais ou parceiros único HIV positivo ou em situaçöes de risco. A transmissäo materno-fetal varia de 14 a 30(pôr cento) e está relacionada com as características do vírus infecçäo primária durante a gravidez, doença materna avançada, estado imunológico da gestante, gestaçäo pré ou pós-termo e o tipo de parto. Revisamos os tipos de transmissäo mäe/filho, métodos diagnósticos e recomendaçÆes para prevençäo, incluindo o uso de Zidovudine


Assuntos
Feminino , Gravidez , Recém-Nascido , HIV , HIV-1/efeitos dos fármacos , HIV-1/fisiologia , Feto/patologia , HIV/genética
15.
Rev. goiana med ; 39(1/4): 7-12, jan. 1993-dez. 1994. tab
Artigo em Português | LILACS | ID: lil-176496

RESUMO

Desde 1985 o Hospital de Doenças Tropicais de Goiânia é o centro de treinamento, ligado ao Ministério da Saúde, responsável pela ccapacitaçåo profissional na área de controle de infecçåo hospitalar em Goiás. O objetivo deste trabalho é o de avaliar o programa de treinamento desenvolvido no período do 1985 a 1992. Nos últimos 8 anos foram treinados 913 profissionais de nível superior sendo 509 médicos, 286 enfermeiros, 78 farmacêuticos/bioquímicos e 40 de outras áreas da saúde; 84,6 pôr cento dos treinados trabalhavam em Goiânia e 15,4 pôr cento em cidades do interior de Goiás e Tocantins. Para que ema mudança efetiva no C.I.H. ocorra em nosso meio, såo necessários: seleçåo criteriosa da clientela dos cursos; inclusåo de estágios práticos complementares à parte teórica; desenvolvimento de programas de prevençåo; fiscalizaçåo efetiva pela Vigilância Sanitária Estadual


Assuntos
Humanos , Avaliação de Programas e Projetos de Saúde/estatística & dados numéricos , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/prevenção & controle
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