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1.
PLoS Negl Trop Dis ; 15(3): e0009214, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33690671

RESUMEN

BACKGROUND: Leprosy continues to be a public health problem in Brazil. Furthermore, detection rates in elderly people have increased, particularly those of multibacillary (L-Lep) patients, who are responsible for transmitting M. leprae. Part of the decline in physiological function during aging is due to increased oxidative damage and change in T cell subpopulations, which are critical in defense against the disease. It is not still clear how age-related changes like those related to oxidation affect elderly people with leprosy. The aim of this work was to verify whether the elderly leprosy patients have higher ROS production and how it can impact the evolution of leprosy. METHODOLOGY/PRINCIPAL FINDINGS: 87 leprosy patients, grouped according to age range and clinical form of leprosy, and 25 healthy volunteers were analyzed. Gene expression analysis of antioxidant and oxidative burst enzymes were performed in whole blood using Biomark's microfluidic-based qPCR. The same genes were evaluated in skin lesion samples by RT-qPCR. The presence of oxidative damage markers (carbonylated proteins and 4-hydroxynonenal) was analyzed by a DNPH colorimetric assay and immunofluorescence. Carbonylated protein content was significantly higher in elderly compared to young patients. One year after multidrug therapy (MDT) discharge and M. leprae clearance, oxidative damage increased in young L-Lep patients but not in elderly ones. Both elderly T and L-Lep patients present higher 4-HNE in cutaneous lesions than the young, mainly surrounding memory CD8+ T cells. Furthermore, young L-Lep demonstrated greater ability to neutralize ROS compared to elderly L-Lep patients, who presented lower gene expression of antioxidant enzymes, mainly glutathione peroxidase. CONCLUSIONS/SIGNIFICANCE: We conclude that elderly patients present exacerbated oxidative damage both in blood and in skin lesions and that age-related changes can be an important factor in leprosy immunopathogenesis. Ultimately, elderly patients could benefit from co-supplementation of antioxidants concomitant to MDT, to avoid worsening of the disease.

2.
Front Immunol ; 12: 647385, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33777045

RESUMEN

Leprosy is an infectious disease that remains endemic in approximately 100 developing countries, where about 200,000 new cases are diagnosed each year. Moreover, multibacillary leprosy, the most contagious form of the disease, has been detected at continuously higher rates among Brazilian elderly people. Due to the so-called immunosenescence, characterized by several alterations in the quality of the immune response during aging, this group is more susceptible to infectious diseases. In view of such data, the purpose of our work was to investigate if age-related alterations in the immune response could influence the pathogenesis of leprosy. As such, we studied 87 individuals, 62 newly diagnosed and untreated leprosy patients distributed according to the age range and to the clinical forms of the disease and 25 healthy volunteers, who were studied as controls. The frequency of senescent and memory CD8+ leukocytes was assessed by immunofluorescence of biopsies from cutaneous lesions, while the serum levels of IgG anti-CMV antibodies were analyzed by chemiluminescence and the gene expression of T cell receptors' inhibitors by RT-qPCR. We noted an accumulation of memory CD8+ T lymphocytes, as well as reduced CD8+CD28+ cell expression in skin lesions from elderly patients, when compared to younger people. Alterations in LAG3 and PDCD1 gene expression in cutaneous lesions of young MB patients were also observed, when compared to elderly patients. Such data suggest that the age-related alterations of T lymphocyte subsets can facilitate the onset of leprosy in elderly patients, not to mention other chronic inflammatory diseases.

3.
Front Immunol ; 11: 1493, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32849508

RESUMEN

In HIV-infected individuals, a paradoxical clinical deterioration may occur in preexisting leprosy when highly active antiretroviral therapy (HAART)-associated reversal reaction (RR) develops. Leprosy-HIV co-infected patients during HAART may present a more severe form of the disease (RR/HIV), but the immune mechanisms related to the pathogenesis of leprosy-HIV co-infection remain unknown. Although the adaptive immune responses have been extensively studied in leprosy-HIV co-infected individuals, recent studies have described that innate immune cells may drive the overall immune responses to mycobacterial antigens. Monocytes are critical to the innate immune system and play an important role in several inflammatory conditions associated with chronic infections. In leprosy, different tissue macrophage phenotypes have been associated with the different clinical forms of the disease, but it is not clear how HIV infection modulates the phenotype of innate immune cells (monocytes or macrophages) during leprosy. In the present study, we investigated the phenotype of monocytes and macrophages in leprosy-HIV co-infected individuals, with or without RR. We did not observe differences between the monocyte profiles in the studied groups; however, analysis of gene expression within the skin lesion cells revealed that the RR/HIV group presents a higher expression of macrophage scavenger receptor 1 (MRS1), CD209 molecule (CD209), vascular endothelial growth factor (VEGF), arginase 2 (ARG2), and peroxisome proliferator-activated receptor gamma (PPARG) when compared with the RR group. Our data suggest that different phenotypes of tissue macrophages found in the skin from RR and RR/HIV patients could differentially contribute to the progression of leprosy.

4.
Immunohorizons ; 4(2): 47-56, 2020 02 07.
Artículo en Inglés | MEDLINE | ID: mdl-32034084

RESUMEN

Erythema nodosum leprosum (ENL) is an inflammatory complication in leprosy. Yet, the involvement of ENL neutrophils in the inflammatory response against Mycobacterium leprae remains poorly explored. Our primary aim was to investigate the utility of the surface expression of neutrophil IL-10R1 as an ENL biomarker and, secondarily, to evaluate whether leprosy or healthy M. leprae-stimulated neutrophils produce cytokines and are able to respond to IL-10. We, in this study, describe a subpopulation of circulating neutrophils of ENL patients that exclusively expressed IL-10R1, providing evidence that IL-10R1+ neutrophils are present in ENL lesions. It was also found that ENL neutrophils, but not those of nonreactional leprosy controls, were able to secret detectable levels of TNF ex vivo and the addition of IL-10 blocked TNF release. It was likewise observed that M. leprae-stimulated, healthy neutrophils expressed IL-10R1 in vitro, and ENL-linked cytokines were released by M. leprae-cultured neutrophils in vitro. Moreover, consistent with the presence of a fully functional IL-10R, the addition of IL-10 prevented the release of M. leprae-induced cytokines. Most importantly, dead M. leprae revealed its superior capacity to induce CCL4 and IL-8 in primary neutrophils over live Mycobacterium, suggesting that M. leprae may hamper the inflammatory machinery as an immune escape mechanism.


Asunto(s)
Eritema Nudoso/inmunología , Subunidad alfa del Receptor de Interleucina-10/metabolismo , Interleucina-10/farmacología , Lepra Lepromatosa/inmunología , Neutrófilos/metabolismo , Piel/inmunología , Adulto , Células Cultivadas , Citocinas/metabolismo , Eritema Nudoso/tratamiento farmacológico , Femenino , Humanos , Mediadores de Inflamación/metabolismo , Lepra Lepromatosa/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Mycobacterium leprae/inmunología , Infiltración Neutrófila/efectos de los fármacos , Neutrófilos/efectos de los fármacos , Neutrófilos/microbiología , Talidomida/uso terapéutico , Adulto Joven
5.
Mem Inst Oswaldo Cruz ; 114: e190056, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31389520

RESUMEN

BACKGROUND: Fibrosis in the peripheral nerve is the end stage of leprous neuropathy and the cause of the resulting permanent neural function impairments. Preventive measures to avoid this irreversible pathological state are a relief strategy for leprosy sufferers. OBJECTIVES: The present study describes the frequency of fibrosis along with its characterisation and pathogenic development. METHODS: Six-hundred-and-thirteen nerve samples were sorted from 278 neural leprosy (NL) and 335 non-leprosy neuropathy patients (ON). The total number of samples was histologically examined by routine staining methods (haematoxylin-eosin, Wade staining and Gomori's trichrome) and fibrosis was evaluated via semi-quantitative estimation. FINDINGS: Fibrosis was most frequent in the NL group (33% against 0.4% in ON) while fibrosis in association with endoneurial microfasciculation was found in 38 (41.3%) of the NL samples in the examination of semithin sections. Pericytic activation in the perivascular environment was confirmed to be the source of the fibroblasts and perineurial cells delimiting microfascicles. End-stage fibrosis in leprosy displays an arrangement of microfascicles devoid of neural components (i.e., Schwann cells and axons) lined by an intermediate phenotype of fibroblastic-perineurial cells filled with bundles of collagen fibres. MAIN CONCLUSIONS: The present study underscores that fibrosis is frequently the severe end stage of neural leprosy NL pathogeny after analysing the notably distinct development of fibrosis within the neural environment.


Asunto(s)
Fibrosis/patología , Lepra Tuberculoide/patología , Nervios Periféricos/patología , Biopsia , Humanos , Inmunohistoquímica , Enfermedades del Sistema Nervioso Periférico/patología , Células de Schwann/patología
6.
Mem. Inst. Oswaldo Cruz ; 114: e190056, 2019. tab, graf
Artículo en Inglés | LILACS | ID: biblio-1012667

RESUMEN

BACKGROUND Fibrosis in the peripheral nerve is the end stage of leprous neuropathy and the cause of the resulting permanent neural function impairments. Preventive measures to avoid this irreversible pathological state are a relief strategy for leprosy sufferers. OBJECTIVES The present study describes the frequency of fibrosis along with its characterisation and pathogenic development. METHODS Six-hundred-and-thirteen nerve samples were sorted from 278 neural leprosy (NL) and 335 non-leprosy neuropathy patients (ON). The total number of samples was histologically examined by routine staining methods (haematoxylin-eosin, Wade staining and Gomori's trichrome) and fibrosis was evaluated via semi-quantitative estimation. FINDINGS Fibrosis was most frequent in the NL group (33% against 0.4% in ON) while fibrosis in association with endoneurial microfasciculation was found in 38 (41.3%) of the NL samples in the examination of semithin sections. Pericytic activation in the perivascular environment was confirmed to be the source of the fibroblasts and perineurial cells delimiting microfascicles. End-stage fibrosis in leprosy displays an arrangement of microfascicles devoid of neural components (i.e., Schwann cells and axons) lined by an intermediate phenotype of fibroblastic-perineurial cells filled with bundles of collagen fibres. MAIN CONCLUSIONS The present study underscores that fibrosis is frequently the severe end stage of neural leprosy NL pathogeny after analysing the notably distinct development of fibrosis within the neural environment.


Asunto(s)
Humanos , Fibrosis/diagnóstico , Fibrosis/terapia , Lepra Tuberculoide/diagnóstico , Lepra Tuberculoide/prevención & control
7.
Am J Trop Med Hyg ; 98(6): 1609-1613, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29611495

RESUMEN

Neural pain is a frequent symptom in leprosy disease. There is a paucity of data regarding neural pain diagnostics resulting in common prescriptive errors when neuritis is confused with neuropathic or mixed nociceptive-neuropathic pain. The present study identified important demographic, clinical, and neurophysiological features of 42 leprosy neuropathy patients presenting neuropathic pain (NP). During routine evaluations, patients were selected asking if they had ever experienced neural pain. Data analyses of their pain characteristics, clinical examination results, and both the Douleur Neuropathique 4 Questionnaire and Hamilton Depression Scale scores were used to classify these patients. The most common word they used to describe the sensation of pain for 25 (60%) of these patients was "burning." In the early stages of the disease and before leprosy diagnosis, 19 (45%) had already complained about NP and leprosy treatment was unable to prevent its occurrence in 15 (36%). Leprosy reactions, considered NP risk factors, occurred in 32 (76%) cases. Knowledge of typical NP characteristics could be used to develop more effective therapeutic approaches for a notoriously difficult-to-treat pain condition.


Asunto(s)
Lepra/complicaciones , Neuralgia/fisiopatología , Adulto , Anciano , Femenino , Humanos , Lepra/epidemiología , Lepra/fisiopatología , Lepra Multibacilar/complicaciones , Lepra Multibacilar/epidemiología , Lepra Multibacilar/fisiopatología , Masculino , Persona de Mediana Edad , Trastornos Motores/epidemiología , Trastornos Motores/etiología , Conducción Nerviosa/fisiología , Neuralgia/epidemiología , Neuralgia/etiología , Dolor , Dimensión del Dolor , Trastornos de la Sensación/epidemiología , Trastornos de la Sensación/etiología , Adulto Joven
8.
Trials ; 19(1): 244, 2018 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-29685164

RESUMEN

BACKGROUND: The annual new-case detection rate for leprosy, while generally stable over the last decade, shows that transmission rates have remained stagnant despite the successful worldwide administration of multidrug therapy since the 1980s. As such, novel control strategies are urgently needed. Focusing on managing leprosy patient contacts, the most susceptible to contracting the disease, has been seen as a potential strategy in limiting the spread of leprosy as shown by a number of recent epidemiological studies. Immunoprophylaxis with Bacillus Calmette-Guérin (BCG) has been seen as an effective preventive measure due to its ability to stimulate the development of cellular immunity which is essential in controlling the disease, especially in its multibacillary (MB) forms. The association of immunoprophylaxis with chemoprophylaxis in a single dose of rifampicin has been shown to be a promising preventive strategy, although a variety of studies have found instances of early case detection just a few months after BCG vaccination. METHODS/DESIGN: The present study is a phase IV chemoprophylactic clinical trial consisting of administration of a single dose of rifampicin in MB leprosy patient contacts under care at the Souza Araújo Outpatient Clinic/FIOCRUZ as part of a randomized (2:1), double-blind, placebo-controlled study. It is comprised of two groups: 1) rifampicin + BCG; and 2) placebo + BCG. DISCUSSION: The aim is to evaluate whether the use of chemoprophylaxis with a single dose of rifampicin in MB leprosy patient contacts prior to the BCG vaccine would be able to prevent the onset of leprosy in those cases that may occur just a few months after vaccination. Contact subclinical infections (polymerase chain reaction) and the immunological parameters (anti-PGL-1, anti-LID-1, and IFN-γ) will be evaluated and the results will be compared after 12 months of follow-up. TRIAL REGISTRATION: The Brazilian Registry of Clinical Trials (ReBEC), RBR-69QK5P . Retrospectively registered on 1 June 2017.


Asunto(s)
Vacuna BCG/administración & dosificación , Trazado de Contacto , Leprostáticos/administración & dosificación , Lepra Multibacilar/prevención & control , Rifampin/administración & dosificación , Adolescente , Adulto , Anciano , Vacuna BCG/efectos adversos , Brasil , Niño , Preescolar , Ensayos Clínicos Fase IV como Asunto , Método Doble Ciego , Esquema de Medicación , Femenino , Humanos , Lactante , Leprostáticos/efectos adversos , Lepra Multibacilar/inmunología , Lepra Multibacilar/microbiología , Lepra Multibacilar/transmisión , Masculino , Persona de Mediana Edad , Ensayos Clínicos Controlados Aleatorios como Asunto , Rifampin/efectos adversos , Factores de Tiempo , Resultado del Tratamiento , Vacunación , Adulto Joven
9.
An Bras Dermatol ; 93(1): 145-147, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29641721

RESUMEN

Leprosy is a chronic infectious disease caused by Mycobacterium leprae, which affects peripheral nerves, skin and mucous membranes. The impairment of neural function as well as sensory or sensory-motor disabilities in leprosy continue to be a problem that requires careful attention in the management of patients with the aim to avoid or minimize their progression to prevent sequelae. One of the most common characteristics of these ulcers is the tendency to chronicity, with variable therapeutic response. In this article, we shall discuss the therapeutic management of thirteen trophic leprosy ulcers in eight patients using polyhexanide 0.2% products.


Asunto(s)
Biguanidas/uso terapéutico , Desinfectantes/uso terapéutico , Úlcera del Pie/tratamiento farmacológico , Úlcera del Pie/complicaciones , Humanos , Lepra/complicaciones , Datos Preliminares , Resultado del Tratamiento
10.
PLoS Negl Trop Dis ; 12(3): e0006214, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-29565968

RESUMEN

BACKGROUND: Leprosy is a chronic dermato-neurological disease caused by Mycobacterium leprae infection. In 2016, more than 200,000 new cases of leprosy were detected around the world, representing the most frequent cause of infectious irreversible deformities and disabilities. PRINCIPAL FINDINGS: In the present work, we demonstrate a consistent procoagulant profile on 40 reactional and non-reactional multibacillary leprosy patients. A retrospective analysis in search of signs of coagulation abnormalities among 638 leprosy patients identified 35 leprosy patients (5.48%) which displayed a characteristic lipid-like clot formed between blood clot and serum during serum harvesting, herein named 'leprosum clot'. Most of these patients (n = 16, 45.7%) belonged to the lepromatous leprosy pole of the disease. In addition, formation of the leprosum clot was directly correlated with increased plasma levels of soluble tissue factor and von Willebrand factor. High performance thin layer chromatography demonstrated a high content of neutral lipids in the leprosum clot, and proteomic analysis demonstrated that the leprosum clot presented in these patients is highly enriched in fibrin. Remarkably, differential 2D-proteomics analysis between leprosum clots and control clots identified two proteins present only in leprosy patients clots: complement component 3 and 4 and inter-alpha-trypsin inhibitor family heavy chain-related protein (IHRP). In agreement with those observations we demonstrated that M. leprae induces hepatocytes release of IHRP in vitro. CONCLUSIONS: We demonstrated that leprosy MB patients develop a procoagulant status due to high levels of plasmatic fibrinogen, anti-cardiolipin antibodies, von Willebrand factor and soluble tissue factor. We propose that some of these components, fibrinogen for example, presents potential as predictive biomarkers of leprosy reactions, generating tools for earlier diagnosis and treatment of these events.


Asunto(s)
Trastornos de la Coagulación Sanguínea/microbiología , Eritema Nudoso/sangre , Lepra Lepromatosa/sangre , Piel/microbiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Brasil , Niño , Electroforesis en Gel Bidimensional , Electroforesis en Gel de Poliacrilamida , Eritema Nudoso/complicaciones , Femenino , Humanos , Lepra Lepromatosa/complicaciones , Modelos Lineales , Masculino , Espectrometría de Masas , Persona de Mediana Edad , Mycobacterium leprae/aislamiento & purificación , Estudios Prospectivos , Proteómica/métodos , Estudios Retrospectivos , Adulto Joven
11.
An. bras. dermatol ; 93(1): 145-147, Jan.-Feb. 2018. graf
Artículo en Inglés | LILACS | ID: biblio-1038263

RESUMEN

Abstract: Leprosy is a chronic infectious disease caused by Mycobacterium leprae, which affects peripheral nerves, skin and mucous membranes. The impairment of neural function as well as sensory or sensory-motor disabilities in leprosy continue to be a problem that requires careful attention in the management of patients with the aim to avoid or minimize their progression to prevent sequelae. One of the most common characteristics of these ulcers is the tendency to chronicity, with variable therapeutic response. In this article, we shall discuss the therapeutic management of thirteen trophic leprosy ulcers in eight patients using polyhexanide 0.2% products.


Asunto(s)
Humanos , Biguanidas/uso terapéutico , Úlcera del Pie/tratamiento farmacológico , Desinfectantes/uso terapéutico , Resultado del Tratamiento , Úlcera del Pie/complicaciones , Datos Preliminares , Lepra/complicaciones
12.
Rev. méd. Minas Gerais ; 28: [1-4], jan.-dez. 2018.
Artículo en Portugués | LILACS | ID: biblio-970215

RESUMEN

INTRODUÇÃO: A Hanseníase é uma dermatose infectocontagiosa crônica, causada pelo Mycobacterium leprae, caracterizada por apresentar formas clínicas contrastantes, que são dependentes da interação do bacilo com a resposta imune do hospedeiro. Apesar de curável, ela ainda é um problema de saúde pública relevante, pois persiste como endemia em muitos países, dentre eles o Brasil. DESCRIÇÃO DO CASO: Paciente, 58 anos, após tratamento quimioterápico para Carcinoma Ductal Invasivo da Mama, desenvolveu manchas com perda de sensibilidade que após exame clinico e anatomopatológico evidenciou se tratar de uma Reação Reversa Hansênica. DISCUSSÃO: O diagnóstico precoce da hanseníase permanece um importante desafio de saúde pública, principalmente devido à heterogeneidade das suas manifestações clínicas. No caso apresentado, a recuperação imunológica, após tratamento quimioterápico desencadeou a reação reversa hansênica, permitindo o reconhecimento da doença e a sua confirmação diagnóstica. CONCLUSÃO: O diagnóstico precoce da Hanseníase requer o conhecimento não apenas das suas formas clínicas, como também de seus episódios reacionais, já que são durante esses episódios, que ocorre piora das lesões neurológicas e aumento das incapacidades físicas. (AU)


Introduction: Leprosy is a chronic infectious contagious dermatosis caused by Mycobacterium leprae, characterized by presenting contrasting clinical forms, which are dependent on the interaction of the bacillus with a host immune response. Although curable, it is still a relevant public health problem, as it persists as an endemic disease in many countries, including Brazil. Case Description: Patient, 58 years old, after chemotherapy treatment for Invasive Ductal Breast Carcinoma of the Mama, developed spots with loss of sensitivity by clinical and anatomopathological examination evidenced whether it is a Reverse Hansen Reaction. Discussion: The prior diagnosis of leprosy remains an important public health challenge, mainly due to the heterogeneity of its clinical manifestations. In the case, an immunological recovery, a chemotherapeutic treatment triggered the leprosy reverse reaction, allowing the recognition of the disease and its diagnostic confirmation. Conclusion: The previous diagnosis of the applicant leprosy is not only in its clinical forms, but also in its reactional episodes, since it is during these episodes that worsening of the neurological lesions and increase of the physical incapacities occur. (AU)


Asunto(s)
Humanos , Femenino , Persona de Mediana Edad , Lepra , Diagnóstico Precoz , Lepra/diagnóstico , Lepra/prevención & control , Carcinoma Ductal de Mama , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos
13.
s.l; s.n; 2018. 20 p. ilus, tab, graf.
No convencional en Inglés | Sec. Est. Saúde SP, HANSEN, SESSP-ILSLPROD, Sec. Est. Saúde SP, SESSP-ILSLACERVO, Sec. Est. Saúde SP | ID: biblio-1023805

RESUMEN

Hemostatic illnesses are frequently associated with acute and chronic infections. In the present work we demonstrated that leprosy patients developed hemostatic abnormalities, like the formation of an atypical lipid clot mass during sera harvesting, a phenomenon previously observed and never unraveled. We characterize the nature of the "leprosum clot", formed during a protrombotic state developed by some patients. During the proteomic analysis of the leprosum clot we discovered a set of potential serum biomarkers to leprosy reactional episodes diagnosis, which at this moment is based only in clinical features. Taking together, our data suggest that leprosy patients are suffering from a procoagulant status, being beneficiated by the introduction of routine coagulation tests during their treatment, which will aloud physicians to prevent some of the acute clinical symptoms related with superficial vein thrombosis such as cyanosis and tissue necrosis observed during severe cases of leprosy reactional episodes. (AU)


Asunto(s)
Humanos , Masculino , Femenino , Niño , Adolescente , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Adulto Joven , Piel/microbiología , Espectrometría de Masas , Trastornos de la Coagulación Sanguínea/microbiología , Biomarcadores/sangre , Electroforesis en Gel Bidimensional , Lepra Lepromatosa/complicaciones , Lepra Lepromatosa/sangre , Modelos Lineales , Proteómica/métodos , Electroforesis en Gel de Poliacrilamida , Eritema Nudoso/complicaciones , Eritema Nudoso/sangre , Mycobacterium leprae/aislamiento & purificación , Estudios Prospectivos , Estudios Retrospectivos
14.
Rev Saude Publica ; 51: 80, 2017 Sep 04.
Artículo en Inglés, Portugués | MEDLINE | ID: mdl-28876410

RESUMEN

OBJECTIVE: Describe the process of cross-cultural adaptation of the "Explanatory Model Interview Catalog - Stigma Scale" for people affected by leprosy in Brazil. METHODS: After being authorized by the author of the scale to use it in the national context, we initiated the five steps process of cross-cultural adaptation: (1) translation, (2) synthesis meeting, (3) back-translation, (4) committee of experts and (5) pre-test. The internal consistency of the scale was evaluated using Cronbach's alpha coefficient. RESULTS: The 15 items of the scale's original version were translated into Brazilian Portuguese. The adapted scale showed evidence of a good understanding of its content, attested both by experts and members of the target population. Its internal consistency was 0.64. CONCLUSIONS: The adapted instrument shows satisfactory internal consistency. It may be useful in future studies that intend to provide broad situational analysis that supports solid public health programs with a focus on effective stigma reduction. In a later study, the construct's validity, criterion, and reproducibility will be evaluated. OBJETIVO: Descrever o processo de adaptação transcultural da "Explanatory Model Interview Catalogue - Stigma Scale" para pessoas afetadas por hanseníase no Brasil. MÉTODOS: Após a autorização do autor da escala para seu uso no contexto nacional, deu-se início aos cinco passos do processo de adaptação transcultural: (1) tradução, (2) reunião de síntese, (3) retrotradução, (4) comitê de peritos e (5) pré-teste. A consistência interna da escala foi avaliada utilizando o coeficiente alfa de Cronbach. RESULTADOS: Os 15 itens da versão original da escala foram traduzidos para a língua portuguesa do Brasil. A escala adaptada apresentou evidência de boa compreensão de seu conteúdo, atestada tanto por peritos como por membros da população alvo. Sua consistência interna foi de 0,64. CONCLUSÕES: O instrumento adaptado apresenta consistência interna satisfatória. Pode ser útil em estudos futuros que intencionem viabilizar ampla análise situacional que sustente programas sólidos de saúde pública com enfoque na efetiva redução de estigma. Em estudo ulterior será avaliada a validade de constructo, critério e reprodutibilidade.


Asunto(s)
Comparación Transcultural , Lepra/psicología , Estigma Social , Encuestas y Cuestionarios , Adulto , Anciano , Brasil , Femenino , Humanos , Lenguaje , Masculino , Persona de Mediana Edad , Traducciones
15.
An Bras Dermatol ; 92(4): 575-577, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28954119

RESUMEN

One of the biggest challenges in treating leprosy is the control of reaction events. Patients with lepromatous leprosy may present reaction type II, or erythema nodosum leprosum, during treatment, and this reaction can remain in a recurrent form after being released from the hospital, requiring the use of thalidomide and/or prednisone for long periods of time, in turn increasing the risk of side effects. Two reports of the use of antiTNF to treat erythema nodosum leprosum were found in the literature. A good response was found after an assay with infliximab and etanercept. This study reports on a patient with lepromatous leprosy and recurrent reaction, controlled by using etanercept and a 10-month follow-up, with the interruption of thalidomide and the maintenance of prednisone at 10 mg/day.


Asunto(s)
Antiinflamatorios no Esteroideos/uso terapéutico , Eritema Nudoso/tratamiento farmacológico , Etanercept/uso terapéutico , Lepra Lepromatosa/tratamiento farmacológico , Adulto , Humanos , Inmunosupresores/uso terapéutico , Masculino , Prednisona/uso terapéutico , Talidomida/uso terapéutico
16.
An. bras. dermatol ; 92(4): 575-577, July-Aug. 2017. graf
Artículo en Inglés | LILACS | ID: biblio-1038255

RESUMEN

Abstract: One of the biggest challenges in treating leprosy is the control of reaction events. Patients with lepromatous leprosy may present reaction type II, or erythema nodosum leprosum, during treatment, and this reaction can remain in a recurrent form after being released from the hospital, requiring the use of thalidomide and/or prednisone for long periods of time, in turn increasing the risk of side effects. Two reports of the use of antiTNF to treat erythema nodosum leprosum were found in the literature. A good response was found after an assay with infliximab and etanercept. This study reports on a patient with lepromatous leprosy and recurrent reaction, controlled by using etanercept and a 10-month follow-up, with the interruption of thalidomide and the maintenance of prednisone at 10 mg/day.


Asunto(s)
Humanos , Masculino , Adulto , Lepra Lepromatosa/tratamiento farmacológico , Antiinflamatorios no Esteroideos/uso terapéutico , Eritema Nudoso/tratamiento farmacológico , Etanercept/uso terapéutico , Talidomida/uso terapéutico , Prednisona/uso terapéutico , Inmunosupresores/uso terapéutico
17.
PLoS Negl Trop Dis ; 11(7): e0005754, 2017 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-28715406

RESUMEN

The pathways that trigger exacerbated immune reactions in leprosy could be determined by genetic variations. Here, in a prospective approach, both genetic and non-genetic variables influencing the amount of time before the development of reactional episodes were studied using Kaplan-Meier survival curves, and the genetic effect was estimated by the Cox proportional-hazards regression model. In a sample including 447 leprosy patients, we confirmed that gender (male), and high bacillary clinical forms are risk factors for leprosy reactions. From the 15 single nucleotide polymorphisms (SNPs) at the 8 candidate genes genotyped (TNF/LTA, IFNG, IL10, TLR1, NOD2, SOD2, and IL6) we observed statistically different survival curves for rs751271 at the NOD2 and rs2069845 at the IL6 genes (log-rank p-values = 0.002 and 0.023, respectively), suggesting an influence on the amount of time before developing leprosy reactions. Cox models showed associations between the SNPs rs751271 at NOD2 and rs2069845 at IL6 with leprosy reactions (HRGT = 0.45, p = 0.002; HRAG = 1.88, p = 0.0008, respectively). Finally, IL-6 and IFN-γ levels were confirmed as high, while IL-10 titers were low in the sera of reactional patients. Rs751271-GT genotype-bearing individuals correlated (p = 0.05) with lower levels of IL-6 in sera samples, corroborating the genetic results. Although the experimental size may be considered a limitation of the study, the findings confirm the association of classical variables such as sex and clinical forms with leprosy, demonstrating the consistency of the results. From the results, we conclude that SNPs at the NOD2 and IL6 genes are associated with leprosy reactions as an outcome. NOD2 also has a clear functional pro-inflammatory link that is coherent with the exacerbated responses observed in these patients.


Asunto(s)
Predisposición Genética a la Enfermedad , Inflamación/patología , Interleucina-6/genética , Lepra/patología , Proteína Adaptadora de Señalización NOD2/genética , Polimorfismo de Nucleótido Simple , Adulto , Estudios de Cohortes , Femenino , Humanos , Inflamación/genética , Lepra/genética , Masculino , Persona de Mediana Edad , Factores de Riesgo
18.
Fontilles, Rev. leprol ; 31(1): 21-32, ene.-abr. 2017. graf, tab
Artículo en Español | IBECS | ID: ibc-163766

RESUMEN

Antecedentes: El Mycobacterium leprae y el VIH causan enfermedades de tipo infecciosas muy preocupantes para la sanidad mundial. Son especial motivo de preocupación cuando los pacientes se coinfectan con ambos agentes patógenos. El objetivo de este estudio es evaluar los episodios de reacción de reversión (RR) y el efecto del uso de corticosteroides sobre el tratamiento de pacientes de lepra borderline tuberculoide co-infectados con el virus de inmunodeficiencia humana (VIH). Métodos: Este trabajo es un estudio retrospectivo de cohortes en el que se observan las respuestas a la terapia con corticoides y sus manifestaciones clínicas. Se analizan variables durante y después de la multiterapia farmacológica de la Organización Mundial de la Salud (OMS) entre el primer y último día de la toma de prednisona, con un máximo de hasta 6 meses posteriores a haber iniciado la terapia corticosteroidea. Resultados: Se incluye un total de 22 casos VIH-positivos y 28 VIH-negativos. La pérdida de sensibilidad y el engrosamiento neural eran estadísticamente significativos mientras que las lesiones ulceradas sólo se detectaron en el grupo coinfectado. La mayoría de pacientes fueron diagnosticados de lepra en fase de leprorreacción RR y seis pacientes manifestaron RR como un síndrome inflamatorio de restitución inmunológica. De promedio, ambos grupos recibieron dosis similares de corticosteroides (diferencia de 0·1 mg/kg/día). Conclusiones: Las manifestaciones clínicas de ambos grupos fueron similares y la mejoría general fue debida a la administración de corticoides. Registro del ensayo: Este trabajo fue presentado y aprobado por el Ethics Committee on Research of the Oswaldo Cruz Institute el 8 de agosto de 2011 (registro 616/11)


Background: Mycobacterium leprae and HIV cause infectious diseases of great concern for the public health care sector worldwide. Both are especially worrisome diseases when patients become co-infected and exhibit the expected clinical exuberance. The objective of this study was to evaluate episodes of reversal reaction (RR) and the effect of the use of corticosteroids on the treatment of borderline tuberculoid leprosy patients co-infected with the human immunodeficiency virus (HIV). Methods: This is a retrospective cohort study in which the clinical manifestations of the patients and their responses to corticosteroid therapy were observed. Variables were analysed during and after multidrug therapy between the first and last days of prednisone, which occurred up to a maximum of 6 months after initiating corticosteroid therapy. Results: A total of 22 HIV-positive and 28 HIV-negative cases were included. Loss of sensitivity and neural thickening were statistically significant while clinically ulcerated lesions were only observed in the co-infected group. Most patients were diagnosed with leprosy in the presence of RR and six patients manifested RR as an immune reconstitution inflammatory syndrome. On average, both groups received similar doses of corticosteroids (difference of 0·1 mg/kg/day).Conclusions: It is of special interest that the clinical manifestations in both groups were found to be similar and that overall improvement occurred as a result of corticosteroid therapy.Trial registration This work was submitted to and approved by the Ethics Committee on Research of the Oswaldo Cruz Institute on August 8, 2011 (registration 616/11)


Asunto(s)
Humanos , Femenino , Masculino , Adolescente , Corticoesteroides/uso terapéutico , Lepra Tuberculoide/tratamiento farmacológico , Infecciones por VIH/complicaciones , Coinfección/tratamiento farmacológico , Lepra Tuberculoide/complicaciones , Estudios Retrospectivos , Mycobacterium leprae/patogenicidad , Terapia Antirretroviral Altamente Activa
19.
PLoS Negl Trop Dis ; 11(2): e0005364, 2017 02.
Artículo en Inglés | MEDLINE | ID: mdl-28192426

RESUMEN

BACKGROUND: Leprosy remains an important public health problem in Brazil where 28,761 new cases were diagnosed in 2015, the second highest number of new cases detected globally. The disease is caused by Mycobacterium leprae, a pathogen spread by patients with multibacillary (MB) leprosy. This study was designed to identify population groups most at risk for MB disease in Brazil, contributing to new ideas for early diagnosis and leprosy control. METHODS: A national databank of cases reported in Brazil (2001-2013) was used to evaluate epidemiological characteristics of MB leprosy. Additionally, the databank of a leprosy reference center was used to determine factors associated with higher bacillary loads. RESULTS: A total of 541,090 cases were analyzed. New case detection rates (NCDRs) increased with age, especially for men with MB leprosy, reaching 44.8 new cases/100,000 population in 65-69 year olds. Males and subjects older than 59 years had twice the odds of MB leprosy than females and younger cases (OR = 2.36, CI95% = 2.33-2.38; OR = 1.99, CI95% = 1.96-2.02, respectively). Bacillary load was higher in male and in patients aged 20-39 and 40-59 years compared to females and other age groups. From 2003 to 2013, there was a progressive reduction in annual NCDRs and an increase in the percentage of MB cases and of elderly patients in Brazil. These data suggest reduction of leprosy transmission in the country. CONCLUSION: Public health policies for leprosy control in endemic areas in Brazil should include activities especially addressed to men and to the elderly in order to further reduce M. leprae transmission.


Asunto(s)
Lepra Multibacilar/epidemiología , Grupos de Población , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Brasil/epidemiología , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Medición de Riesgo , Factores de Riesgo , Adulto Joven
20.
PLoS Pathog ; 13(1): e1006103, 2017 01.
Artículo en Inglés | MEDLINE | ID: mdl-28056107

RESUMEN

Leprosy is a chronic infectious disease that may present different clinical forms according to the immune response of the host. Levels of IFN-γ are significantly raised in paucibacillary tuberculoid (T-lep) when compared with multibacillary lepromatous (L-lep) patients. IFN-γ primes macrophages for inflammatory activation and induces the autophagy antimicrobial mechanism. The involvement of autophagy in the immune response against Mycobacterium leprae remains unexplored. Here, we demonstrated by different autophagic assays that LC3-positive autophagosomes were predominantly observed in T-lep when compared with L-lep lesions and skin-derived macrophages. Accumulation of the autophagic receptors SQSTM1/p62 and NBR1, expression of lysosomal antimicrobial peptides and colocalization analysis of autolysosomes revealed an impairment of the autophagic flux in L-lep cells, which was restored by IFN-γ or rapamycin treatment. Autophagy PCR array gene-expression analysis revealed a significantly upregulation of autophagy genes (BECN1, GPSM3, ATG14, APOL1, and TPR) in T-lep cells. Furthermore, an upregulation of autophagy genes (TPR, GFI1B and GNAI3) as well as LC3 levels was observed in cells of L-lep patients that developed type 1 reaction (T1R) episodes, an acute inflammatory condition associated with increased IFN-γ levels. Finally, we observed increased BCL2 expression in L-lep cells that could be responsible for the blockage of BECN1-mediated autophagy. In addition, in vitro studies demonstrated that dead, but not live M. leprae can induce autophagy in primary and lineage human monocytes, and that live mycobacteria can reduce the autophagy activation triggered by dead mycobacteria, suggesting that M. leprae may hamper the autophagic machinery as an immune escape mechanism. Together, these results indicate that autophagy is an important innate mechanism associated with the M. leprae control in skin macrophages.


Asunto(s)
Autofagia/fisiología , Lepra/inmunología , Piel/microbiología , Adulto , Anciano , Western Blotting , Ensayo de Inmunoadsorción Enzimática , Femenino , Técnica del Anticuerpo Fluorescente , Humanos , Inmunohistoquímica , Interferón gamma/inmunología , Lepra/patología , Macrófagos/inmunología , Masculino , Microscopía Electrónica de Transmisión , Persona de Mediana Edad , Mycobacterium leprae/inmunología , Reacción en Cadena de la Polimerasa , Piel/inmunología , Piel/patología , Transcriptoma , Adulto Joven
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