RESUMO
In Brazil, Leishmania amazonensis is the etiological agent of cutaneous and diffuse cutaneous leishmaniasis. The state of Maranhão in the Northeast of Brazil is prevalent for these clinical forms of the disease and also has high rates of HIV infection. Here, we characterized the drug susceptibility of a L. amazonensis clinical isolate from a 46-year-old man with diffuse cutaneous leishmaniasis coinfected with HIV from this endemic area. This patient underwent several therapeutic regimens with meglumine antimoniate, liposomal amphotericin B, and pentamidine, without success. In vitro susceptibility assays against promastigotes and intracellular amastigotes demonstrated that this isolate had low susceptibility to amphotericin B, when compared with the reference strain of this species that is considered susceptible to antileishmanial drugs. Additionally, we investigated whether the low in vitro susceptibility would affect the in vivo response to amphotericin B treatment. The drug was effective in reducing the lesion size and parasite burden in mice infected with the reference strain, whereas those infected with the clinical isolate and a resistant line (generated experimentally by stepwise selection) were refractory to amphotericin B treatment. To evaluate whether the isolate was intrinsically resistant to amphotericin B in animals, infected mice were treated with other drugs that had not been used in the treatment of the patient (miltefosine, paromomycin, and a combination of both). Our findings demonstrated that all drug schemes were able to reduce lesion size and parasite burden in animals infected with the clinical isolate, confirming the amphotericin B-resistance phenotype. These findings indicate that the treatment failure observed in the patient may be associated with amphotericin B resistance, and demonstrate the potential emergence of amphotericin B-resistant L. amazonensis isolates in an area of Brazil endemic for cutaneous leishmaniasis.
Assuntos
Anfotericina B , Antiprotozoários , Resistência a Medicamentos , Anfotericina B/farmacologia , Anfotericina B/uso terapêutico , Animais , Brasil , Pessoa de Meia-Idade , Antiprotozoários/farmacologia , Antiprotozoários/uso terapêutico , Humanos , Masculino , Camundongos , Leishmania/efeitos dos fármacos , Leishmania/isolamento & purificação , Leishmania/classificação , Leishmania mexicana/efeitos dos fármacos , Leishmania mexicana/isolamento & purificação , Leishmaniose Cutânea/tratamento farmacológico , Leishmaniose Cutânea/parasitologia , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Testes de Sensibilidade Parasitária , Camundongos Endogâmicos BALB C , Leishmaniose Tegumentar Difusa/parasitologia , Leishmaniose Tegumentar Difusa/tratamento farmacológicoRESUMO
Eosinophils are mainly associated with parasitic infections and allergic manifestations. They produce many biologically active substances that contribute to the destruction of pathogens through the degranulation of microbicidal components and inflammatory tissue effects. In leishmaniasis, eosinophils have been found within inflammatory infiltrate with protective immunity against the parasite. We analyzed the responses of eosinophils from patients with localized (LCL) and diffuse (DCL) cutaneous leishmaniasis, as well as from healthy subjects, when exposed to Leishmania mexicana. All DCL patients exhibited blood eosinophilia, along with elevated eosinophil counts in non-ulcerated nodules. In contrast, only LCL patients with prolonged disease progression showed eosinophils in their blood and cutaneous ulcers. Eosinophils from DCL patients secreted significantly higher levels of IL-6, IL-8, and IL-13, compared to eosinophils from LCL patients. Additionally, DCL patients displayed higher serum levels of anti-Leishmania IgG antibodies. We also demonstrated that eosinophils from both LCL and DCL patients responded to L. mexicana promastigotes with a robust oxidative burst, which was equally intense in both patient groups and significantly higher than in healthy subjects. Coincubation of eosinophils (from donors with eosinophilia) with L. mexicana promastigotes in vitro revealed various mechanisms of parasite damage associated with different patterns of granule exocytosis: 1) localized degranulation on the parasite surface, 2) the release of cytoplasmic membrane-bound "degranulation sacs" containing granules, 3) release of eosinophil extracellular traps containing DNA and granules with major basic protein. In conclusion, eosinophils damage L. mexicana parasites through the release of granules via diverse mechanisms. However, despite DCL patients having abundant eosinophils in their blood and tissues, their apparent inability to provide protection may be linked to the release of cytokines and chemokines that promote a Th2 immune response and disease progression in these patients.
Assuntos
Eosinofilia , Leishmania mexicana , Leishmaniose Cutânea , Leishmaniose Tegumentar Difusa , Parasitos , Animais , Humanos , Eosinófilos , Progressão da DoençaRESUMO
Background and Objectives: Elucidating the potential impact of COVID-19 on surveillance interventions and programs, such as the tegumentary leishmaniasis one, during the first year of the pandemic can help understand its consequences for notification systems, which can inform immediate public policy and health education actions, as well as highlight the need to implement new strategies to strengthen epidemiological surveillance services. The objective of the present study was to analyze the possible impact of the COVID-19 pandemic on the number of cases of tegumentary leishmaniasis in Maranhão, Brazil. Methods: Ecological study of confirmed cases of tegumentary leishmaniasis in the period from January 2015 to December 2020. Data were obtained from the Brazilian Information System for Notifiable Diseases. The P-score metrics were used to evaluate the possible underreporting of tegumentary leishmaniasis. Results: In the period from 2015 to 2020, 7,886 new cases of the disease were registered. For the year 2020, 1,346 cases were expected, but 1,158 were notified, which represented a decrease of 13.94%. The regional health centers of São Luís, São João dos Patos, and Presidente Dutra showed the greatest drops in possible expected new cases. Conclusion: The challenges in diagnosing tegumentary leishmaniasis cases seem to have intensified in the context of COVID-19 in Maranhão, which signals an important alert for health services and managers.(AU)
Justificativa e Objetivos: O potencial impacto da COVID-19 nas intervenções e nos programas de vigilância, como a leishmaniose tegumentar, durante o primeiro ano da pandemia, auxilia no entendimento das consequências da pandemia nos sistemas de notificação, com o intuito de subsidiar ações imediatas de políticas públicas e educação em saúde, além de evidenciar a necessidade de implementação de novas estratégias de fortalecimento dos serviços de vigilância epidemiológica. Este estudo teve como objetivo analisar o possível impacto da pandemia da COVID-19 no número de registros de casos de leishmaniose tegumentar no Maranhão, Brasil. Métodos: Trata-se de um estudo ecológico dos casos confirmados de leishmaniose tegumentar no período de janeiro de 2015 a dezembro de 2020. Os dados foram obtidos do Sistema de Informação de Agravos de Notificação. A métrica P-score foi utilizada para avaliar os possíveis subregistros de leishmaniose tegumentar. Resultados: No período de 2015 a 2020, foram registrados 7.886 casos novos da doença. Para o ano de 2020, eram esperados 1.346 casos, porém 1.158 foram notificados, o que representa uma diminuição de 13,94%. As regionais de saúde de São Luís, São João dos Patos e Presidente Dutra apresentam as maiores quedas de possíveis novos casos esperados. Conclusão: Os desafios no diagnóstico dos casos de leishmaniose tegumentar parecem ter se intensificado no contexto da COVID-19 no Maranhão, o que sinaliza um alerta importante para os serviços de saúde e gestores.(AU)
Justificación y Objetivos: El posible impacto de la COVID-19 en las intervenciones y programas de vigilancia, como el de la leishmaniasis tegumentaria, durante el primer año de la pandemia, ayuda a comprender las consecuencias de la pandemia en los sistemas de notificación, con el fin de subsidiar las acciones inmediatas de política pública y educación para la salud, además de resaltar la necesidad de implementar nuevas estrategias para fortalecer los servicios de vigilancia epidemiológica. Este estudio tuvo como objetivo analizar el posible impacto de la pandemia de COVID-19 en el número de registros de casos de leishmaniasis tegumentaria en Maranhão, Brasil. Métodos: Se trata de un estudio ecológico de los casos confirmados de leishmaniasis tegumentaria desde enero de 2015 hasta diciembre de 2020. Los datos se obtuvieron del Sistema de Información de Enfermedades de Declaración Obligatoria. Se utilizó la métrica P-score para evaluar los posibles subregistros de leishmaniasis tegumentaria. Resultados: Entre 2015 y 2020, se registraron 7.886 nuevos casos de la enfermedad. Para 2020 se esperaban 1.346 casos, pero se notificaron 1.158, lo que representa una disminución del 13,94%. Los centros regionales de salud de São Luís, São João dos Patos y Presidente Dutra presentaron las mayores caídas en los posibles nuevos casos esperados. Conclusión: Los desafíos en el diagnóstico de los casos de leishmaniasis tegumentaria parecen haberse intensificado en el contexto de la COVID-19 en Maranhão, lo que señala una alerta importante para los servicios y gestores de salud.(AU)
Assuntos
Humanos , Leishmaniose Tegumentar Difusa , Monitoramento Epidemiológico , COVID-19 , Coronavirus , Estudos Ecológicos , Doenças Negligenciadas , Sistemas de Informação em SaúdeRESUMO
Analisam os fatores biológicos, sociais e ambientais responsáveis pela ocorrência da doença na Amazônia mostrando os cientistas e sanitaristas que tiveram papel fundamental nas pesquisas sobre essa e outras endemias
Assuntos
Doenças Parasitárias , Leishmaniose/história , Leishmaniose Tegumentar Difusa/história , Leishmaniose Cutânea/história , Leishmaniose Visceral/história , BrasilRESUMO
Abstract Diffuse cutaneous leishmaniasis is a rare universal disease associated with an inadequate host cell immune response, caused by different species: infantum, aethiopica, major, mexicana, and others, which presents the challenge of a poor therapeutic response. In Brazil, it is caused by L. amazonensis. A case confirmed by histopathology with an abundance of vacuolated macrophages full of amastigotes and lymphocyte scarcity, identified by RFLP-ITS1PCR and in vitro decrease and exhaustion of the host cell immune response to L. amazonensis antigen, was treated early (3 months after the onset) with Glucantime (2 months) and allopurinol (29 months) with clinical cure, after a follow-up for 30 months after treatment.
Assuntos
Humanos , Leishmania mexicana , Leishmaniose Tegumentar Difusa/tratamento farmacológico , Leishmaniose Cutânea/tratamento farmacológico , Antiprotozoários/uso terapêutico , Brasil , Antimoniato de MegluminaRESUMO
The compound 3-bromopyruvate (3-BrPA) is well-known and studies from several researchers have demonstrated its involvement in tumorigenesis. It is an analogue of pyruvic acid that inhibits ATP synthesis by inhibiting enzymes from the glycolytic pathway and oxidative phosphorylation. In this work, we investigated the effect of 3-BrPA on energy metabolism of L. amazonensis. In order to verify the effect of 3-BrPA on L. amazonensis glycolysis, we measured the activity level of three glycolytic enzymes located at different points of the pathway: (i) glucose kinases, step 1, (ii) glyceraldehyde 3-phosphate dehydrogenase (GAPDH), step 6, and (iii) enolase, step 9. 3-BrPA, in a dose-dependent manner, significantly reduced the activity levels of all the enzymes. In addition, 3-BrPA treatment led to a reduction in the levels of phosphofruto-1-kinase (PFK) protein, suggesting that the mode of action of 3-BrPA involves the downregulation of some glycolytic enzymes. Measurement of ATP levels in promastigotes of L. amazonensis showed a significant reduction in ATP generation. The O2 consumption was also significantly inhibited in promastigotes, confirming the energy depletion effect of 3-BrPA. When 3-BrPA was added to the cells at the beginning of growth cycle, it significantly inhibited L. amazonensis proliferation in a dose-dependent manner. Furthermore, the ability to infect macrophages was reduced by approximately 50% when promastigotes were treated with 3-BrPA. Taken together, these studies corroborate with previous reports which suggest 3-BrPA as a potential drug against pathogenic microorganisms that are reliant on glucose catabolism for ATP supply.
Assuntos
Leishmania mexicana/efeitos dos fármacos , Leishmaniose Tegumentar Difusa/parasitologia , Piruvatos/farmacologia , Animais , Western Blotting , Brasil , Cricetinae , Humanos , Leishmania mexicana/enzimologia , Leishmania mexicana/crescimento & desenvolvimento , Leishmania mexicana/metabolismo , Macrófagos/parasitologia , Camundongos , Consumo de Oxigênio/efeitos dos fármacos , Fosfopiruvato Hidratase/metabolismo , Células RAW 264.7RESUMO
Diffuse cutaneous leishmaniasis is a rare universal disease associated with an inadequate host cell immune response, caused by different species: infantum, aethiopica, major, mexicana, and others, which presents the challenge of a poor therapeutic response. In Brazil, it is caused by L. amazonensis. A case confirmed by histopathology with an abundance of vacuolated macrophages full of amastigotes and lymphocyte scarcity, identified by RFLP-ITS1PCR and in vitro decrease and exhaustion of the host cell immune response to L. amazonensis antigen, was treated early (3 months after the onset) with Glucantime (2 months) and allopurinol (29 months) with clinical cure, after a follow-up for 30 months after treatment.
Assuntos
Antiprotozoários , Leishmania mexicana , Leishmaniose Cutânea , Leishmaniose Tegumentar Difusa , Antiprotozoários/uso terapêutico , Brasil , Humanos , Leishmaniose Cutânea/tratamento farmacológico , Leishmaniose Tegumentar Difusa/tratamento farmacológico , Antimoniato de MegluminaRESUMO
Immunological tests may represent valuable tools for the diagnosis of human tegumentary leishmaniasis (TL) due to their simple execution, less invasive nature and potential use as a point-of-care test. Indeed, several antigenic targets have been used with the aim of improving the restricted scenario for TL-diagnosis. We performed a worldwide systematic review to identify antigenic targets that have been evaluated for the main clinical forms of TL, such as cutaneous (CL) and mucosal (ML) leishmaniasis. Included were original studies evaluating the sensitivity and specificity of immunological tests for human-TL, CL and/or ML diagnosis using purified or recombinant proteins, synthetic peptides or polyclonal or monoclonal antibodies to detect Leishmania-specific antibodies or antigens. The review methodology followed PRISMA guidelines and all selected studies were evaluated in accordance with QUADAS-2. Thirty-eight original studies from four databases fulfilled the selection criteria. A total of 79 antigens were evaluated for the detection of antibodies as a diagnostic for TL, CL and/or ML by ELISA. Furthermore, three antibodies were evaluated for the detection of antigen by immunochromatographic test (ICT) and immunohistochemistry (IHC) for CL-diagnosis. Several antigenic targets showed 100% of sensitivity and specificity, suggesting potential use for TL-diagnosis in its different clinical manifestations. However, a high number of proof-of-concept studies reinforce the need for further analysis aimed at verifying true diagnostic accuracy in clinical practice.
Assuntos
Anticorpos Antiprotozoários/sangue , Antígenos de Protozoários/sangue , Leishmania/imunologia , Leishmaniose Tegumentar Difusa/diagnóstico , Leishmaniose Mucocutânea/diagnóstico , Antígenos de Protozoários/classificação , Antígenos de Protozoários/imunologia , Cromatografia de Afinidade/normas , Ensaio de Imunoadsorção Enzimática/normas , Humanos , Imuno-Histoquímica/normas , Leishmaniose Tegumentar Difusa/imunologia , Leishmaniose Tegumentar Difusa/parasitologia , Leishmaniose Mucocutânea/imunologia , Leishmaniose Mucocutânea/parasitologia , Testes Imediatos/normas , Guias de Prática Clínica como Assunto , Sensibilidade e EspecificidadeRESUMO
Durante vários anos de transmissão de Leishmaniose tegumentar na região de Campinas-SP, alguns municípios apresentaram elevado número de casos em relação a esta região. Os principais municípios foram estudados, considerando os limites espaciais das Sub-bacias Hidrográficas dos Rios Principais e a concentração de casos avaliada pelo estimador de Kernel no contexto das relações ecológicas do modelo mancha-corredormatriz como relevantes para estabelecer o cenário para Vigilância Entomológica da doença nesta região. Os resultados demonstraram que 86% (6/7) dos principais "pontos quentes" de casos e 77,6% (38/49) das Sub-bacias Hidrográficas com ocorrência de casos, os Rios Principais estavam presentes. Os resultados observados neste estudo sugeriram maior permeabilidade da matriz para ocorrência da doença em mosaicos com a presença dos Rios Principais e reforça a necessidade de considerar os limites espaciais das Sub-bacias Hidrográficas dos Rios Principais para elaboração dos cenários da Vigilância Entomológica da doença nesta Região.
Assuntos
Características de Residência , Leishmaniose Tegumentar Difusa , Monitoramento EpidemiológicoRESUMO
La leishmaniasis cutánea o mucocutánea presenta variedad de formas clínicas, siendo la más frecuente la úlcera moldurada. Una forma poco frecuente es la llamada leishmaniasis cutánea difusa caracterizada por presentar pápulas, tubérculos, nódulos, placas e infiltración. Inicialmente localizadas, pero con tendencia a la progresión, pudiendo llegar a ser diseminadas. Es una forma aún no comunicada en Paraguay. Presentamos el caso de una mujer adulta mayor, con placas y nódulos en ambos miembros inferiores, y cuyo frotis y anatomía patológica confirmaron el diagnóstico de leishmaniasis. Clínicamente clasificada como leishmaniasis cutánea difusa, la PCR y HRM demostraron ser producida por Leishmania (Viannia) brasiliensis.
Cutaneous or mucocutaneous leishmaniasis presents a variety of clinical forms, the most common being a molded ulcer. A rare form is the so-called diffuse cutaneous leishmaniasis characterized by presenting papules, tubers, nodules, plaques and infiltration; initially located but with a tendency to progression, and may become widespread. It is a form not reported in Paraguay. We present the case of an older adult woman, with plaques and nodules on both lower limbs, and whose smear and pathological anatomy confirmed the diagnosis of leishmaniasis. Clinically classified as diffuse cutaneous leishmaniasis, PCR and HRM were shown to be produced by Leishmania (Viannia) brasiliensis.
Assuntos
Leishmania braziliensis , Leishmaniose Tegumentar Difusa , Leishmaniose Tegumentar Difusa/epidemiologiaRESUMO
Tegumentary leishmaniasis (TL) is a parasitic disease that can result in wide spectrum clinical manifestations. It is necessary to understand host and parasite determinants of clinical outcomes to identify novel therapeutic targets. Previous studies have indicated that the polyamine biosynthetic pathway is critical for Leishmania growth and survival. Despite its importance, expression of the such pathway has not been previously investigated in TL patients. We performed an exploratory analysis employing Systems Biology tools to compare circulating polyamines and amino acid concentration as well as polyamine pathway gene expression in cutaneous lesions patients presenting with distinct TL disease presentations. Diffuse cutaneous leishmaniasis (DCL) was associated with higher concentrations of amino acids, polyamines and its substrate transporters than mucosal cutaneous leishmaniasis or localized cutaneous leishmaniasis. In addition, the RNA expression of polyamine-related genes of patients lesions from two separate cohorts demonstrated that differential activation of this pathway is associated with parasite loads and able to discriminate the clinical spectrum of TL. Taken together, our findings highlight a new aspect of DCL immunopathogenesis indicating that the polyamine pathway may be explored as a novel therapeutic target to control disease burden.
Assuntos
Aminoácidos/metabolismo , Vias Biossintéticas/fisiologia , Leishmaniose Tegumentar Difusa/metabolismo , Poliaminas/metabolismo , Pele/metabolismo , Adulto , Aminoácidos/sangue , Estudos Transversais , Feminino , Humanos , Masculino , Mucosa/metabolismo , Poliaminas/sangueRESUMO
Leishmaniasis is a disease that can affect visceral organs (visceral leishmaniasis; VL) or mucous membranes and skin, causing lesions of different forms and levels of severities (tegumentary leishmaniasis; TL). Like several others, leishmaniasis is a neglected disease, as the pharmaceutical industry seems to show little to no interest in developing new drugs targeting the disease. This study aims to trace the epidemiological profile of leishmaniasis in the Municipality of Patrocínio, State of Minas Gerais, over a period of time. Secondary data of reported cases from 2000 to 2017 were analyzed as provided by the Patrocinio Health Department. As no literature was found on the status of such a disease in Patrocinio, it is important to trace the epidemiological profile of leishmaniasis in the area. The findings pointed out that the disease affected predominantly male in the economically active population, mainly from the urban area, and that it had no relationship with professional activity. Twenty-two cases of leishmaniasis (15 of TL and 7 of VL) were reported, all of which were treated and cured. Five cases of TL and 1 case of VL were autochthonous, and confirmed cases of canine infection took place in 2011, 2016 and 2017.KEYWORDS: Alto Paranaíba. Autochthonous. Human leishmaniasis. Triângulo Mineiro. INTRODUCTION Leishmaniasis is a parasitic disease caused by protozoa of the Leishmania genus, which are transmitted from one host to another by phlebotomine sandflies (NAGLE et al., 2014). It may affect both visceral organs and skin surfaces (HANDLER et al., 2015) and lead to four major clinical syndromes: cutaneous leishmaniasis (CL), mucocutaneous leishmaniasis (MCL), visceral leishmaniasis or kala-azar (VL) and post-kala-azar dermal leishmaniasis (PKDL) (ANVERSA et al., 2018). Leishmaniasis is treated as a public health problem due to its high incidence and the disorders it can cause to the affected individuals. TL is characterized by ulcers on the face and/or extremities and nasal/oral/pharyngeal mucous (HANDLER et al, 2015), which can cause deformities such as disfiguring and permanent scars with partial or total mutilation of the nasopharyngeal mucosa, with further social, economic and psychological implications (ANVERSA et al., 2018, SUNYOTO; BOELAERT; MEHEUS, 2019). The mortality rate for VL, a more severe form, is 10%, making it the second most deadly tropical parasitic infection in the world after malaria (HANDLER et al., 2015). Updated regional information on the disease is important for epidemiological surveillance. However, the actual number of leishmaniasis cases is unknown due to underreporting, lack of epidemiological surveillance system or adequate diagnostic methods. Most data on incidence rates are based on estimates (PACE, 2014). Around 1.5 to 2 million new cases of leishmaniasis are estimated to occur annually worldwide: 500,000 are VL; 1 to 1.5 million cases are related to cutaneous or mucocutaneous leishmaniasis. Both forms commonly occur in Brazil (ANVERSA et al., 2018; WHO, 2020). Silva (2017) reported that the highest incidence rates of VL in the State of Minas Gerais, Brazil, from 2002 to 2013 were concentrated in the mesoregions in the North (Noroeste de Minas, Norte de Minas, and Jequitinhonha), in the East (Vale do Rio Doce) and in the center of the state (Central Mineira and Metropolitana de Belo Horizonte). The other mesoregions (Campo das Verentes, Oeste de Minas, Sul/Sudoeste de Minas, Triângulo Received: 08/04/19 Accepted: 20/12/19
A leishmaniose é uma doença que pode afetar órgãos viscerais (leishmaniose visceral; LV) ou as mucosas e a pele, provocando lesões de diferentes formas e gravidades (leishmaniose tegumentar; LT). Como várias outras moléstias, a leishmaniose é uma doença negligenciada, já que a indústria farmacêutica parece mostrar pouco ou nenhum interesse em desenvolver novos medicamentos direcionados à enfermidade. O estudo teve como objetivo traçar o perfil epidemiológico da leishmaniose no município de Patrocínio, estado de Minas Gerais, ao longo de um período de tempo. Dados secundários de casos registrados no período de 2000 a 2017 foram analisados, conforme fornecido pelo Departamento de Saúde de Patrocínio. Como não foi encontrada literatura sobre a situação dessa doença em Patrocínio, é importante traçar o perfil epidemiológico da leishmaniose na região. Os achados apontaram que a doença afetou predominantemente o sexo masculino da população economicamente ativa, principalmente da área urbana, e que não tinha relação com a atividade profissional. Foram notificados 22 casos de leishmaniose (15 de LT e 7 de LV), todos tratados e curados. Cinco casos de LT e 1 de LV foram considerados autóctones, e houve casos confirmados de infecção canina nos anos de 2011, 2016 e 2017.
Assuntos
Leishmaniose Tegumentar Difusa , Leishmaniose VisceralRESUMO
Diffuse cutaneous leishmaniasis (DCL) is a rare type of leishmaniasis characterized by diffuse skin lesions. In Brazil, Leishmania (L.) amazonensis is the main etiological agent of this clinical form. The state of Maranhão has the highest prevalence of this disease in the country, as well as a high rate of HIV infection. Here, we report the first case of DCL/HIV of Brazil. A 46-year-old man from the Amazonian area of Maranhão state presented atypical lesion in the left upper limb and dissemination of diffuse erythematous nodules over his entire body. Histopathological examination confirmed the presence of intracellular amastigotes of Leishmania, and a polymerase chain reaction and molecular identification by restriction fragment profile identified L. (L.) amazonensis as the causative agent of the disease. The patient was also diagnosed with HIV virus after the leishmaniasis diagnosis. The initial treatments for leishmaniasis were liposomal amphotericin B (AmB-L) (4 mg/kg) for 10 days and prophylactic use of Glucantime® (10 mg/Sb+5/kg) for 2 months. After unsuccessful initial treatments, he was treated with a combination of AmB-L (4 mg/kg) alternated with pentamidine (4 mg/kg) for 10 days but failed in the first therapeutic cycle. Subsequently, he had a good response to treatment with pentamidine (4 mg/kg).
Assuntos
Antiprotozoários/administração & dosagem , Coinfecção , Infecções por HIV/diagnóstico , Leishmania/isolamento & purificação , Leishmaniose Tegumentar Difusa/diagnóstico , Antimoniato de Meglumina/administração & dosagem , Pentamidina/administração & dosagem , Anfotericina B/administração & dosagem , Infecções por HIV/virologia , Humanos , Leishmaniose Tegumentar Difusa/tratamento farmacológico , Leishmaniose Tegumentar Difusa/microbiologia , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
l-Arginine metabolism through arginase 1 (Arg-1) and inducible nitric oxide synthase (NOS2) constitutes a fundamental axis for the resolution or progression of leishmaniasis. Infection with Leishmania mexicana can cause two distinct clinical manifestations: localized cutaneous leishmaniasis (LCL) and diffuse cutaneous leishmaniasis (DCL). In this work, we analyzed in an in vivo model the capacity of two L. mexicana isolates, one obtained from a patient with LCL and the other from a patient with DCL, to regulate the metabolism of l-arginine through Arg-1 and NOS2. Susceptible BALB/c mice were infected with L. mexicana isolates from both clinical manifestations, and the evolution of the infection as well as protein presence and activity of Arg-1 and NOS2 were evaluated. The lesions of mice infected with the DCL isolate were bigger, had higher parasite loads, and showed greater protein presence and enzymatic activity of Arg-1 than the lesions of mice infected with the LCL isolate. In contrast, NOS2 protein synthesis was poorly or not induced in the lesions of mice infected with the LCL or DCL isolate. The immunochemistry analysis of the lesions allowed the identification of highly parasitized macrophages positive for Arg-1, while no staining for NOS2 was found. In addition, we observed in lesions of patients with DCL macrophages with higher parasite loads and stronger Arg-1 staining than those in lesions of patients with LCL. Our results suggest that L. mexicana isolates obtained from patients with LCL or DCL exhibit different virulence or pathogenicity degrees and differentially regulate l-arginine metabolism through Arg-1.
Assuntos
Arginase/metabolismo , Arginina/metabolismo , Interações Hospedeiro-Patógeno , Leishmania mexicana/fisiologia , Leishmaniose Tegumentar Difusa/metabolismo , Leishmaniose Tegumentar Difusa/parasitologia , Animais , Modelos Animais de Doenças , Suscetibilidade a Doenças , Humanos , Leishmania mexicana/isolamento & purificação , Macrófagos/imunologia , Macrófagos/metabolismo , Macrófagos/parasitologia , Camundongos , Óxido Nítrico Sintase Tipo II/metabolismo , Fatores de TempoRESUMO
PURPOSE: Dendritic cells (DCs) are the most potent antigen-presenting cells (APCs), and their capacity to activate the immune response has been widely used in immunotherapies against different diseases, predominantly cancer. However, they have not been so widely used in immunotherapies against infectious diseases. Leishmania mexicana is the causative agent of cutaneous leishmaniasis in Mexico, which can result in localized cutaneous leishmaniasis (LCL) and diffuse cutaneous leishmaniasis (DCL). DCL is characterized by the incapability of the immune response to control the parasite, which thus disseminates to all teguments. Treatments against DCL have shown low efficacy, which is a reason why alternative therapies such as immunotherapies are promising. One adjuvant that has proven its effectiveness in immunotherapies against some cancers and infections is GK1, a component of the SPVac vaccine against porcine cysticercosis. GK1 has the capacity to elicit proinflammatory cytokines and chemokines from DCs and macrophages. METHODS: We pulsed bone marrow-derived dendritic cells (BMDCs) with GK1 and a lysate obtained from L. mexicana promastigotes and tested the efficacy of this combination against the infection of susceptible mice with L. mexicana. RESULTS: We found that BMDCs stimulated with GK1 and a lysate of L. mexicana promastigotes secreted IFN-γ and IL-12, and when they were adoptively transferred to BALB/c mice which were then infected with L. mexicana promastigotes, there was a reduction in the size of the lesion and in the parasite load. CONCLUSIONS: The adjuvant properties of GK1 along with parasite antigens may have a protective effect against the infection of BALB/c mice with L. mexicana.
Assuntos
Células Dendríticas/efeitos dos fármacos , Células Dendríticas/imunologia , Peptídeos Cíclicos/imunologia , Peptídeos Cíclicos/farmacologia , Proteínas de Protozoários/imunologia , Adjuvantes Imunológicos/farmacologia , Transferência Adotiva , Animais , Interferon gama/imunologia , Interleucina-12/imunologia , Leishmania mexicana , Leishmaniose Cutânea/imunologia , Leishmaniose Tegumentar Difusa/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Carga Parasitária , Proteínas de Protozoários/farmacologiaRESUMO
Apanhado dos estudos sobre as leishmanioses no Brasil englobando a descoberta dos seus agentes etiológicos, diversas espécies associadas às diferentes formas clínicas da doença, seus hospedeiros reservatórios e os flebotomíneos vetores, bem como aspectos da epidemiologia e ações de controle implementadas em contextos sociopolíticos e momentos diversos
Assuntos
Leishmaniose/história , Leishmaniose Cutânea/história , Leishmaniose Visceral/história , Leishmaniose Tegumentar Difusa , Doenças Parasitárias , Brasil , História do Século XIX , História do Século XXRESUMO
Diffuse cutaneous leishmaniasis is a rare chronic infectious disease, associated with Leishmania mexicana and L. amazonensis, presenting as multiple non-ulcerative painless nodules, with a tendency to relapse soon after treatment. We report a case of a 56-year-old Mexican woman exhibiting nodular lesions, plaques, crusts and scars involving the whole body. A solitary nodule was present at the junction between hard and soft palates. Diffuse cutaneous leishmaniasis is a disfiguring disease resulting in severe scarring if untreated.
Assuntos
Leishmania mexicana/fisiologia , Leishmaniose Tegumentar Difusa/complicações , Leishmaniose Tegumentar Difusa/diagnóstico , Doenças da Boca/etiologia , Doenças da Boca/parasitologia , Palato/patologia , Feminino , Humanos , Leishmaniose Tegumentar Difusa/parasitologia , Leishmaniose Tegumentar Difusa/patologia , México , Pessoa de Meia-Idade , Palato/parasitologia , RecidivaAssuntos
Infecções por HIV/complicações , Leishmaniose Tegumentar Difusa/patologia , Adulto , Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Ácido Desoxicólico/uso terapêutico , Combinação de Medicamentos , Humanos , Leishmaniose Tegumentar Difusa/complicações , Leishmaniose Tegumentar Difusa/diagnóstico , MasculinoRESUMO
La leishmaniasis cutánea es una enfermedad parasitaria granulomatosa crónica que se transmite por la picadura de flebótomos infectados, esta patología afecta a todos los grupos etarios y los menores de 12 años constituyen únicamente el 10%, las manifestaciones clínicas dependerán de factores como el estado inmune y la especie de Leishmania, la forma clínica de leishmaniasis cutánea representa el 99% en los pacientes pediátricos siendo así la más frecuente, el diagnóstico se basa en criterios clínicos, epidemiológicos y de laboratorio. El tratamiento en la edad pediátrica puede hacerse con antimoniato de meglumina con buena respuesta como en los casos que presentamos a continuación
Cutaneous leishmaniasis is a chronic granulomatous parasitic disease that is transmitted by the bite of infected sandflies, this pathology affects all age groups and those under 12 years constitute only 10%, the clinical manifestations depend on factors such as the immune status and the species of leishmania, the clinical form of cutaneous leishmaniasis represents 99% in pediatric patients being the most frequent, the diagnosis is based on clinical, epidemiological and laboratory criteria. Treatment in the pediatric age can be done with meglumineantimonate with good response as in the cases presented below.
Assuntos
Humanos , Leishmaniose Cutânea , Leishmaniose Mucocutânea , Leishmaniose Tegumentar DifusaRESUMO
CONTEXTO: A leishmaniose tegumentar (LT) é uma doença infecciosa e não contagiosa, que acomete pele e mucosas, e é causada por protozoários do gênero Leshmania. A doença apresenta baixa letalidade, mas pode causar graves deformidades que impactam na autoestima dos pacientes. É considerada uma doença negligenciada por acometer principalmente populações de baixa renda e permanece como relevante problema de saúde pública, com consideráveis taxas de incidência e prevalência no País. Os medicamentos atualmente preconizados pelo Ministério da Saúde para o tratamento da LT são todos de uso sistêmico e apresentam um potencial hepato, cardio e nefrotóxico, sendo o antimoniato de meglumina, o tratamento de primeira escolha. A maior parte dos casos de LT ocorre em áreas de difícil acesso, o que dificulta tanto a aplicação parenteral da droga, como o monitoramento de seus efeitos colaterais. A miltefosina é um medicamento de uso oral e eficaz no tratamento da LT, mas ainda não é disponibilizada no SUS. A disponibilização de um medicamento de uso oral e efetivo contra a leishmaniose aumentaria a adesão ao tratamento nas áreas mais pobres e remotas do Brasil. TECNOLOGIA: Miltefosina. PERGUNTA: O uso da miltefosina é eficaz e seguro no tratamento da leishmaniose tegumentar quando comparado ao uso do medicamento recomendado como primeira linha de tratamento pelo Ministério da Saúde, o antimoniato de meglumina? EVIDÊNCIAS CIENTÍFICAS: O Parecer Técnico Científico (PTC) da Fiocruz "Miltefosina para tratamento de leishmaniose tegumentar americana: Evidências de eficácia e segurança" foi utilizado como base das evidências científicas. Na busca realizada nesse PTC, foram selecionados 6 ensaios clínicos randomizados comparando a miltefosina via oral com o antimoniato de meglumina via parenteral. Os estudos mostraram taxas similares de cura em 6 meses com os 2 medicamentos e eventos adversos de menor gravidade com a miltefosina. AVALIAÇÃO DE IMPACTO ORÇAMENTÁRIO: Estima-se que impacto orçamentário anual com a incorporação da miltefoseina varie de R$ 561.863,89 a R$ 2.809.319,45, no primeiro ano, e de R$ 8.427.958,35 a R$ 19.665.236,16, ao longo dos próximos cinco anos. O cálculo do impacto orçamentário não levou em conta os custos que seriam economizados com a incorporação da miltefosina: custos diretos, relacionados à administração parenteral dos medicamentos, e os indiretos, relacionados ao deslocamento diário do paciente, sozinho ou acompanhado de cuidadores ou outros membros da família, de sua residência até uma unidade de saúde para receber a administração parenteral dos medicamentos. Como a maioria desses pacientes residem em áreas rurais com difícil acesso aos serviços de saúde, esse deslocamento resulta em perda de trabalho. RECOMENDAÇÃO PRELIMINAR: A CONITEC, em 10/11/2016 recomendou a incorporação no SUS de miltefosina para o tratamento de pacientes com leishmaniose tegumentar. CONSULTA PÚBLICA: O tema foi colocado em consulta pública nº 40, realizada entre os dias 30/11/16 a 19/12/2016. Foram recebidas 06 contribuições de cunho técnico-científico e 3 contribuições de experiência ou opinião. Foram feitas alterações de texto e nenhuma argumentação foi considerada suficiente para alterar a recomendação preliminar. RECOMENDAÇÃO FINAL: Os membros da CONITEC em 09/05/2018 deliberaram, por unanimidade, por recomendar a incorporação no SUS de miltefosina para o tratamento de leishmaniose tegumentar em primeira linha de tratamento. DECISÃO: Incorporar a miltefosina para o tratamento da leishmaniose tegumentar em primeira linha de tratamento, no âmbito do Sistema Único de Saúde - SUS. Dada pela Portaria nº 60 de 31 de outubro de 2018, publicada no Diário Oficial da União nº 210, de 31 de outubro de 2018, seção 1, página 40.