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1.
Artigo em Português | PAHOIRIS | ID: phr-55176

RESUMO

[RESUMO]. Objetivo. Avaliar o uso combinado de marcadores sorológicos e análise espacial para ampliar a sensibilidade da vigilância epidemiológica da hanseníase. Método. Este estudo transversal foi realizado com vizinhos de casos de hanseníase e familiares e vizinhos de escolares com sorologia positiva anti-glicolipídeo fenólico I (PGL-I) em Diamantina, Minas Gerais, Brasil. Definiram- se como vizinhos as pessoas que residiam em um raio de até 100 metros de escolares e de casos de hanseníase. Para a coleta de dados, foram realizados entrevista semiestruturada, exame dermatoneurológico e teste sorológico rápido ML Flow. Todos os endereços foram georreferenciados. Foram realizadas regressão multivariada e análise espacial, tendo a sororreatividade anti-PGL-I como variável dependente. Resultados. Foram estudadas 1 491 pessoas: 1 009 (67,7%) familiares e vizinhos dos escolares com sorologia positiva e 482 (32,3%) vizinhos dos casos de hanseníase. Do total, 421 (28,2%) apresentaram soropositividade anti-PGL-I. A chance de soropositividade foi maior entre familiares e vizinhos dos escolares soropositivos (P < 0,001), entre pessoas com renda familiar de 1 salário-mínimo (P < 0,001), entre os mais jovens (P < 0,001) e entre os que residiam em domicílios com um a cinco cômodos (P = 0,007). A taxa de soropositividade foi maior em área geográfica correspondente aos escolares soropositivos (P < 0,001), ou seja, houve divergência entre o foco de maior concentração de casos e o de maior soropositividade. Conclusões. O uso combinado de marcadores sorológicos e análise espacial possibilitou identificar fragilidades operacionais dos serviços e uma possível endemia oculta de hanseníase nos setores censitários urbanos do município. Atividades de rastreamento de contatos sociais e vizinhos, busca ativa, campanhas educativas, inquéritos escolares e análise do território facilitam o diagnóstico precoce da hanseníase.


ABSTRACT Objective. To evaluate the combined use of serologic markers and spatial analysis to increase the sensitivity of leprosy epidemiological surveillance. Method. This cross-sectional study was performed with neighbors of leprosy cases and neighbors and family members of schoolchildren with a positive anti-phenolic glycolipid I (PGL-I) test in Diamantina, state of Minas Gerais, Brazil. Neighbors were those living within a 100-m radius of schoolchildren or leprosy cases. Data collection included a semi-structured interview, dermatologic examination, and rapid ML Flow test. All residential addresses were georeferenced. Multivariate regression and spatial analysis were performed with anti-PGL-I seropositivity as the dependent variable. Results. The study included 1 491 individuals: 1 009 (67.7%) family members and neighbors of schoolchildren with positive serology test and 482 (32.3%) neighbors of leprosy cases. Of the total, 421 (28.2%) were positive for anti-PGL-I. Seropositivity was higher among family members and neighbors of seropositive schoolers (P < 0.001), among people with family income of 1 minimum wage (P < 0.001), among the youngest participants (P < 0.001), and among those living in homes with one to five rooms (P = 0.007). The seropositivity rate was higher in the geographic area corresponding to seropositive schoolchildren (P < 0.001), that is, the spot with the highest number of cases was different from the spot with the highest rate of seropositivity. Conclusions. The combined use of serologic markers and spatial analysis allowed us to easily identify operational weaknesses of services and a possible occult leprosy endemism in the municipality’s urban census tracts. Tracing of social contact and neighbors, active search, educational campaigns, school surveys, and territorial analyses facilitate the early diagnosis of leprosy.


[RESUMEN]. Objetivo. Evaluar el uso conjunto de los marcadores serológicos y del análisis espacial para ampliar la sensibilidad de la vigilancia epidemiológica de la lepra. Método. Este estudio transversal se realizó con vecinos de personas con casos de lepra y con familiares y vecinos de escolares con resultados positivos en las pruebas serológicas del antígeno glicolípido fenólico I (PGL-I) en Diamantina (Minas Gerais, Brasil). Se definieron como vecinos las personas residentes en un radio de hasta 100 metros de distancia de los escolares y de las personas con casos de lepra. Para la recopilación de datos se realizaron entrevistas semiestructuradas, exámenes dermatoneurológicos y pruebas serológicas rápidas ML Flow. Todas las direcciones se ubicaron por georreferencia. Se realizó una regresión multivariante y un análisis espacial, y se empleó la reactividad serológica anti-PGL-I como variable dependiente. Resultados. Se estudiaron 1 491 personas: 1 009 (67,7%) familiares y vecinos de escolares con resultados positivos en las pruebas serológicas y 482 (32,3%) vecinos de las personas con casos de lepra. Del total, 421 (28,2%) presentaron seropositividad anti-PGL-I. La posibilidad de presentar seropositividad fue mayor en los familiares y vecinos de los escolares seropositivos (P < 0,001), en las personas con ingresos familiares de un salario mínimo (P < 0,001), en las personas más jóvenes (P < 0,001) y en los residentes en domicilios con una a cinco habitaciones (P = 0,007). La tasa de seropositividad fue mayor en la zona geográfica correspondiente a los escolares seropositivos (P < 0,001), por lo que hubo divergencia entre el foco de mayor concentración de casos y el de mayor seropositividad. Conclusiones. El uso conjunto de los marcadores serológicos y del análisis espacial permitió determinar las fragilidades operativas de los servicios y una posible endemia oculta de lepra en los sectores urbanos del municipio incluidos en el censo correspondiente. Las actividades de rastreo de contactos sociales y cercanos, la búsqueda activa de casos, las campañas educativas, las encuestas escolares y el análisis del territorio facilitan el diagnóstico temprano de la lepra.


Assuntos
Hanseníase , Mycobacterium leprae , Monitoramento Epidemiológico , Sorologia , Análise Espacial , Brasil , Hanseníase , Monitoramento Epidemiológico , Sorologia , Análise Espacial , Brasil , Hanseníase , Monitoramento Epidemiológico , Sorologia , Análise Espacial
2.
Braz J Infect Dis ; 25(5): 101634, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34648742

RESUMO

Leprosy can be considered a dissimulated disease, mainly when presented as atypical cases leading to mistaken diagnosis at the emergency setting. Herein we report six patients referred to the emergence room with hypotheses of acute myocardial infarction and arterial and venous thrombosis, although with chronic neurological symptoms; the seventh patient was referred with a wrong suspicion of infected skin ulcer. Positive findings included hypo-anesthetic skin lesions and thickened nerves; 100% were negative for IgM anti-phenolic glycolipid-I, while 71.4%, 100% and 42.8% were positive for IgA, IgM and IgG Mce1A. RLEP-PCR was positive in all patients. Ultrasound of peripheral nerves showed asymmetric and focal multiple mononeuropathy for all patients. Unfortunately, in many patients leprosy is often misdiagnosed as other medical conditions for long periods thus delaying initiation of specific treatment. This paper is intended to increase physicians' awareness to recognize leprosy cases presented as both classical and unusual forms, including in emergency department.


Assuntos
Hanseníase , Serviço Hospitalar de Emergência , Glicolipídeos , Humanos , Mycobacterium leprae
3.
BMC Infect Dis ; 21(1): 1050, 2021 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-34627197

RESUMO

BACKGROUND: Leprosy is a chronic infectious disease caused by Mycobacterium leprae. Patients have distinct clinical forms, and the host´s immunological response regulate those manifestations. In this work, the presence of the myeloid-derived suppressor cell and the regulatory protein annexin A1 is described in patients with multibacillary leprosy and with type 1 and 2 reactions. METHODS: Patients were submitted to skin biopsy for histopathological analysis to obtain a bacilloscopic index. Immunofluorescence was used to detect myeloid-derived suppressor cells and annexin A1. RESULTS: The data demonstrated that the presence of granulocytic and monocytic myeloid-derived suppressor cells in leprosy patients. A high number of monocytic myeloid-derived suppressor cells were observed in lepromatous leprosy and type 2 reactional patients. The presence of annexin A1 was observed in all myeloid-derived suppressor cells. In particular, the monocytic myeloid-derived suppressor cell in the lepromatous patients has higher levels of this protein when compared to the reactional patients. This data suggest that the higher expression of this protein may be related to regulatory response against a severe infection, contributing to anergic response. In type 1 reactional patients, the expression of annexin A1 was reduced. CONCLUSIONS: Myeloid-derived suppressor cell are present in leprosy patients and annexin A1 might be regulated the host response against Mycobacterium leprae.


Assuntos
Anexina A1 , Hanseníase Virchowiana , Hanseníase , Células Supressoras Mieloides , Anexina A1/genética , Humanos , Mycobacterium leprae
4.
Adv Exp Med Biol ; 1313: 155-177, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34661895

RESUMO

Leprosy is an ancient insidious disease caused by Mycobacterium leprae, where the skin and peripheral nerves undergo chronic granulomatous infections, leading to sensory and motor impairment with characteristic deformities. Susceptibility to leprosy and its disease state are determined by the manifestation of innate immune resistance mediated by cells of monocyte lineage. Due to insufficient innate resistance, granulomatous infection is established, influencing the specific cellular immunity. The clinical presentation of leprosy ranges between two stable polar forms (tuberculoid to lepromatous) and three unstable borderline forms. The tuberculoid form involves Th1 response, characterized by a well demarcated granuloma, infiltrated by CD4+ T lymphocytes, containing epitheloid and multinucleated giant cells. In the lepromatous leprosy, there is no characteristic granuloma but only unstructured accumulation of ineffective macrophages containing engulfed pathogens. Th1 response, characterised by IFN-γ and IL-2 production, activates macrophages in order to kill intracellular pathogens. Conversely, a Th2 response, characterized by the production of IL-4, IL-5 and IL-10, helps in antibody production and consequently downregulates the cell-mediated immunity induced by the Th1 response. M. lepare has a long generation time and its inability to grow in culture under laboratory conditions makes its study challenging. The nine-banded armadillo still remains the best clinical and immunological model to study host-pathogen interaction in leprosy. In this chapter, we present cellular morphology and the genomic uniqueness of M. leprae, and how the pathogen shows tropism for Schwann cells, macrophages and dendritic cells.


Assuntos
Hanseníase , Humanos , Imunidade Celular , Mycobacterium leprae , Pele , Linfócitos T
5.
Int J Mycobacteriol ; 10(2): 155-161, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34558467

RESUMO

Background: Mycobacterium leprae was considered the only causal agent of leprosy until Mycobacterium lepromatosis was identified' which it has been suggested has greater pathogenicity and is linked to diffuse lepromatous leprosy (DLL) and Lucio's phenomenon (LPh). Our objective is to identify Mycobacterium spp. in an endemic area of leprosy in Colombia. Methods: The study included cases with a diagnosis of leprosy by clinical and histopathological analysis. DNA extraction and two specific rounds of semi-nested polymerase chain reaction (PCR) were performed in paraffin biopsies skin to identify M. leprae and M. lepromatosis. Demographic, clinical, and histopathological data were extracted and tabulated for analysis. Results: Forty-one cases of leprosy were analyzed. The most frequent clinical diagnosis was lepromatous leprosy (36.6%); there was one case with DLL and two with LPh. The most common histopathological finding was tuberculoid leprosy (36.59%); three cases had negative histopathology. M. lepromatosis was not detected; all cases corresponded to M. leprae including cases with negative histopathology' DLL, and LPh. Conclusion: In this study, M. leprae was the causative agent of leprosy, encompassing even its most severe phenotypic forms. It is appropriate to consider PCR as an indispensable tool for the diagnosis of leprosy and to continue to carry out the active search for M. lepromatosis.


Assuntos
Hanseníase Virchowiana , Hanseníase , Mycobacterium , Região do Caribe , Colômbia/epidemiologia , Humanos , Hanseníase/diagnóstico , Hanseníase/epidemiologia , Hanseníase Virchowiana/diagnóstico , Hanseníase Virchowiana/epidemiologia , Mycobacterium leprae/genética
6.
Cells ; 10(9)2021 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-34571865

RESUMO

Leprosy reactional episodes are acute inflammatory events that may occur during the clinical course of the disease. Type 1 reaction (T1R) is associated with an increase in neural damage, and the understanding of the molecular pathways related to T1R onset is pivotal for the development of strategies that may effectively control the reaction. Interferon-gamma (IFN-γ) is a key cytokine associated with T1R onset and is also associated with autophagy induction. Here, we evaluated the modulation of the autophagy pathway in Mycobacterium leprae-stimulated cells in the presence or absence of IFN-γ. We observed that IFN-γ treatment promoted autophagy activation and increased the expression of genes related to the formation of phagosomes, autophagy regulation and function, or lysosomal pathways in M. leprae-stimulated cells. IFN-γ increased interleukin (IL)-15 secretion in M. leprae-stimulated THP-1 cells in a process associated with autophagy activation. We also observed higher IL15 gene expression in multibacillary (MB) patients who later developed T1R during clinical follow-up when compared to MB patients who did not develop the episode. By overlapping gene expression patterns, we observed 13 common elements shared between T1R skin lesion cells and THP-1 cells stimulated with both M. leprae and IFN-γ. Among these genes, the autophagy regulator Translocated Promoter Region, Nuclear Basket Protein (TPR) was significantly increased in T1R cells when compared with non-reactional MB cells. Overall, our results indicate that IFN-γ may induce a TPR-mediated autophagy transcriptional program in M. leprae-stimulated cells similar to that observed in skin cells during T1R by a pathway that involves IL-15 production, suggesting the involvement of this cytokine in the pathogenesis of T1R.


Assuntos
Autofagia/genética , Interleucina-15/genética , Hanseníase/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Células Cultivadas , Criança , Citocinas/genética , Feminino , Expressão Gênica/genética , Humanos , Interferon gama/genética , Hanseníase/microbiologia , Masculino , Pessoa de Meia-Idade , Mycobacterium leprae/patogenicidade , Pele/metabolismo , Pele/microbiologia , Células THP-1/metabolismo , Adulto Jovem
7.
PLoS Negl Trop Dis ; 15(8): e0009716, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34415916

RESUMO

BACKGROUND: Regarding the leprosy transmission through the upper airways, overcrowded locations such as prisons can become a risk to get sick. Like the leprosy hidden endemic demonstrated in male prison population, being interesting to assess the leprosy scene also among confined women. METHODS: A prospective descriptive study conducted at Female Penitentiary, Brazil. Leprosy Suspicion Questionnaire (LSQ) were applied to the participants, and submitted to specialized dermatoneurological exam, peripheral nerve ultrasonography, and anti-PGL-I serology. FINDINGS: 404 female inmates were evaluated, 14 new cases were diagnosed (LG-leprosy group), a new case detection rate (NCDR) of 3.4%, 13 multibacillary, while another 390 constituted the Non-Leprosy group (NLG). Leprosy cases were followed up during multidrug therapy with clinical improvement. The confinement time median was 31 months in LG, similar to NLG, less than the time of leprosy incubation. Regarding LSQ, the neurological symptoms reached the highest x2 values as Q1-numbness (5.6), Q3-anesthetizes areas in the skin (7.5), Q5-Stinging sensation (5.8), and Q7-pain in the nerves (34.7), while Q4-spots on the skin was 4.94. When more than one question were marked in the LSQ means a 12.8-fold higher to have the disease than a subject who marked only one or none. The high 34% rate of anti-PGL-I seropositivity in the penitentiary, higher levels in LG than NLG. Three additional leprosy cases each were diagnosed on the second (n = 66) and third (n = 14) reevaluations 18 and 36 months after the initial one. Semmes-Weinstein monofilaments demonstrated lower limbs (32.2%) more affected than the upper limbs (25%) with improvement during the follow-up. INTERPRETATION: The NCDR in this population showed an hidden endemic of leprosy as well as the efficacy of a search action on the part of a specialized team with the aid of the LSQ and anti-PGL-I serology as an auxiliary tracking tools.


Assuntos
Hanseníase/diagnóstico , Prisões/estatística & dados numéricos , Adulto , Brasil/epidemiologia , Feminino , Seguimentos , Humanos , Hansenostáticos/efeitos adversos , Hansenostáticos/uso terapêutico , Hanseníase/tratamento farmacológico , Hanseníase/epidemiologia , Hanseníase/microbiologia , Pessoa de Meia-Idade , Mycobacterium leprae/efeitos dos fármacos , Mycobacterium leprae/fisiologia , Estudos Prospectivos , Adulto Jovem
8.
Front Immunol ; 12: 662307, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34354699

RESUMO

The treatment of multibacillary cases of leprosy with multidrug therapy (MDT) comprises 12 doses of a combination of rifampicin, dapsone and clofazimine. Previous studies have described the immunological phenotypic pattern in skin lesions in multibacillary patients. Here, we evaluated the effect of MDT on skin cell phenotype and on the Mycobacterium leprae-specific immune response. An analysis of skin cell phenotype demonstrated a significant decrease in MRS1 (SR-A), CXCL10 (IP-10) and IFNG (IFN-γ) gene and protein expression after MDT release. Patients were randomized according to whether they experienced a reduction in bacillary load after MDT. A reduction in CXCL10 (IP-10) in sera was associated with the absence of a reduction in the bacillary load at release. Although IFN-γ production in response to M. leprae was not affected by MDT, CXCL10 (IP-10) levels in response to M. leprae increased in cells from patients who experienced a reduction in bacillary load after treatment. Together, our results suggest that CXCL10 (IP-10) may be a good marker for monitoring treatment efficacy in multibacillary patients.


Assuntos
Quimiocina CXCL10/sangue , Hansenostáticos/uso terapêutico , Hanseníase/tratamento farmacológico , Pele/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carga Bacteriana/efeitos dos fármacos , Biomarcadores/sangue , Quimiocina CXCL10/imunologia , Quimioterapia Combinada , Feminino , Humanos , Hansenostáticos/administração & dosagem , Hanseníase/imunologia , Masculino , Pessoa de Meia-Idade , Mycobacterium leprae/imunologia , Pele/microbiologia , Pele/patologia , Resultado do Tratamento , Adulto Jovem
9.
Front Immunol ; 12: 657449, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34456901

RESUMO

The respiratory tract is considered the main port of entry of Mycobacterium leprae, the causative agent of leprosy. However, the great majority of individuals exposed to the leprosy bacillus will never manifest the disease due to their capacity to develop protective immunity. Besides acting as a physical barrier, airway epithelium cells are recognized as key players by initiating a local innate immune response that orchestrates subsequent adaptive immunity to control airborne infections. However, to date, studies exploring the interaction of M. leprae with the respiratory epithelium have been scarce. In this work, the capacity of M. leprae to immune activate human alveolar epithelial cells was investigated, demonstrating that M. leprae-infected A549 cells secrete significantly increased IL-8 that is dependent on NF-κB activation. M. leprae was also able to induce IL-8 production in human primary nasal epithelial cells. M. leprae-treated A549 cells also showed higher expression levels of human ß-defensin-2 (hßD-2), MCP-1, MHC-II and the co-stimulatory molecule CD80. Furthermore, the TLR-9 antagonist inhibited both the secretion of IL-8 and NF-κB activation in response to M. leprae, indicating that bacterial DNA sensing by this Toll-like receptor constitutes an important innate immune pathway activated by the pathogen. Finally, evidence is presented suggesting that extracellular DNA molecules anchored to Hlp, a histone-like protein present on the M. leprae surface, constitute major TLR-9 ligands triggering this pathway. The ability of M. leprae to immune activate respiratory epithelial cells herein demonstrated may represent a very early event during infection that could possibly be essential to the generation of a protective response.


Assuntos
Células Epiteliais Alveolares/imunologia , Células Epiteliais Alveolares/metabolismo , Imunidade Inata , Hanseníase/imunologia , Hanseníase/metabolismo , Mycobacterium leprae/imunologia , Receptor Toll-Like 9/metabolismo , Células A549 , Biomarcadores , Células Cultivadas , Histonas/metabolismo , Interações Hospedeiro-Patógeno/imunologia , Humanos , Imunomodulação , Hanseníase/microbiologia , NF-kappa B/metabolismo
10.
Mol Immunol ; 138: 48-57, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34343723

RESUMO

Knowledge of immunodominant B-cell epitopes is essential to design powerful diagnostic strategies aiming for antibody detection. Outstanding progress in computational prediction has achieved a significant contribution to the biomedical fields, including immunodiagnosis. In silico analysis may have an even more important role when information concerning antigens from etiologic agents of neglected diseases, such as leprosy, is scarce. The aim of this study was to provide mapping of B-cell epitopes from two Mycobacterium leprae-derived antigens (Ag85B and ML2055), confirm their antigenicity, and to assess the ability of in silico immunoinformatics tools to accurately predict them. Linear B-cell epitopes predicted by ABCpred and SVMTrip servers were compared to antigenic regions of synthetic overlapping peptides that exhibited reactivity to antibodies from patients with leprosy. Our in vitro results identified several immunodominant regions that had also been indicated by in silico prediction, providing agreement between experimental and simulated data. After chemical synthesis, we used enzyme-linked immunosorbent assays to determine the effectiveness of the first identified sequence (GTNVPAEFLENFVHG) which had 72 % sensitivity and 78 % specificity (AUC = 0.79) while the second one (PVSSEAQPGDPNAPS) had 72 % sensitivity and 93.8 % specificity (AUC = 0.85). Using dot blotting, an easy-to-read visual test, both peptides could distinguish sera from patients with leprosy from those with tuberculosis and from sera of healthy volunteers. Our findings suggest that these synthetic peptides, with some refinement, may be useful as serological diagnostic antigens for leprosy. In addition, it was displayed that immunoinformatics provides reliable information for mapping potential B-cell epitopes for development of peptide-based diagnostic assays for neglected diseases.


Assuntos
Antígenos de Bactérias/imunologia , Mapeamento de Epitopos/métodos , Epitopos de Linfócito B/imunologia , Hanseníase/diagnóstico , Testes Sorológicos/métodos , Adulto , Anticorpos Antibacterianos/imunologia , Feminino , Humanos , Hanseníase/sangue , Hanseníase/imunologia , Masculino , Pessoa de Meia-Idade , Mycobacterium leprae
11.
Front Cell Infect Microbiol ; 11: 709972, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34395315

RESUMO

Upon infection, Mycobacterium leprae, an obligate intracellular bacillus, induces accumulation of cholesterol-enriched lipid droplets (LDs) in Schwann cells (SCs). LDs are promptly recruited to M. leprae-containing phagosomes, and inhibition of this process decreases bacterial survival, suggesting that LD recruitment constitutes a mechanism by which host-derived lipids are delivered to intracellular M. leprae. We previously demonstrated that M. leprae has preserved only the capacity to oxidize cholesterol to cholestenone, the first step of the normal cholesterol catabolic pathway. In this study we investigated the biochemical relevance of cholesterol oxidation on bacterial pathogenesis in SCs. Firstly, we showed that M. leprae increases the uptake of LDL-cholesterol by infected SCs. Moreover, fluorescence microscopy analysis revealed a close association between M. leprae and the internalized LDL-cholesterol within the host cell. By using Mycobacterium smegmatis mutant strains complemented with M. leprae genes, we demonstrated that ml1942 coding for 3ß-hydroxysteroid dehydrogenase (3ß-HSD), but not ml0389 originally annotated as cholesterol oxidase (ChoD), was responsible for the cholesterol oxidation activity detected in M. leprae. The 3ß-HSD activity generates the electron donors NADH and NADPH that, respectively, fuel the M. leprae respiratory chain and provide reductive power for the biosynthesis of the dominant bacterial cell wall lipids phthiocerol dimycocerosate (PDIM) and phenolic glycolipid (PGL)-I. Inhibition of M. leprae 3ß-HSD activity with the 17ß-[N-(2,5-di-t-butylphenyl)carbamoyl]-6-azaandrost-4-en-3one (compound 1), decreased bacterial intracellular survival in SCs. In conclusion, our findings confirm the accumulation of cholesterol in infected SCs and its potential delivery to the intracellular bacterium. Furthermore, we provide strong evidence that cholesterol oxidation is an essential catabolic pathway for M. leprae pathogenicity and point to 3ß-HSD as a prime drug target that may be used in combination with current multidrug regimens to shorten leprosy treatment and ameliorate nerve damage.


Assuntos
Hanseníase , Mycobacterium leprae , Trifosfato de Adenosina , Colesterol , Humanos , Lipídeos
12.
PLoS Negl Trop Dis ; 15(8): e0009667, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34449763

RESUMO

BACKGROUND: Leprosy elimination primarily targets transmission of Mycobacterium leprae which is not restricted to patients' households. As interruption of transmission is imminent in many countries, a test to detect infected asymptomatic individuals who can perpetuate transmission is required. Antibodies directed against M. leprae antigens are indicative of M. leprae infection but cannot discriminate between active and past infection. Seroprevalence in young children, however, reflects recent M. leprae infection and may thus be used to monitor transmission in an area. Therefore, this literature review aimed to evaluate what has been reported on serological tests measuring anti-M. leprae antibodies in children without leprosy below the age of 15 in leprosy-endemic areas. METHODS AND FINDINGS: A literature search was performed in the databases Pubmed, Infolep, Web of Science and The Virtual Health Library. From the 724 articles identified through the search criteria, 28 full-text articles fulfilled all inclusion criteria. Two additional papers were identified through snowballing, resulting in a total of 30 articles reporting data from ten countries. All serological tests measured antibodies against phenolic glycolipid-I or synthetic derivatives thereof, either quantitatively (ELISA or UCP-LFA) or qualitatively (ML-flow or NDO-LID rapid test). The median seroprevalence in children in endemic areas was 14.9% and was stable over time if disease incidence remained unchanged. Importantly, seroprevalence decreased with age, indicating that children are a suitable group for sensitive assessment of recent M. leprae infection. However, direct comparison between areas, solely based on the data reported in these studies, was impeded by the use of different tests and variable cut-off levels. CONCLUSIONS: Quantitative anti-PGL-I serology in young children holds promise as a screening test to assess M. leprae infection and may be applied as a proxy for transmission and thereby as a means to monitor the effect of (prophylactic) interventions on the route to leprosy elimination.


Assuntos
Anticorpos Antibacterianos/sangue , Hanseníase/epidemiologia , Mycobacterium leprae/isolamento & purificação , Antígenos de Bactérias/imunologia , Criança , Pré-Escolar , Busca de Comunicante , Doenças Endêmicas , Características da Família , Humanos , Hanseníase/sangue , Hanseníase/transmissão , Mycobacterium leprae/imunologia
14.
Medicine (Baltimore) ; 100(31): e26744, 2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34397815

RESUMO

ABSTRACT: Cured leprosy patients have special physical conditions, which could pose challenges for safety and immunogenicity after immunization. We performed an observational clinical study aimed to identify the safety and immunogenicity of influenza vaccine in cured leprosy patients. A total of 65 participants from a leprosarium were recruited into leprosy cured group or control group, and received a 0.5 ml dose of the inactivated split-virion trivalent influenza vaccine and a follow-up 28 days proactive observation of any adverse events. Hemagglutination and hemagglutination inhibition test was performed to evaluate serum antibody titer, flow cytometry was conducted to screen of cytokines level. The total rate of reactogenicity was 0.0% [0/41] in leprosy cured group and 37.5% [9/24] in control group. The seroconversion rate for H1N1 was difference between leprosy cured group and control group (41.83% vs 79.17%, P = .0082), but not for H3N2 (34.25% vs 50.00%, P = .4468). At day 0, leprosy cured group have relatively high concentration of interleukin-6, interleukin-10, tumor necrosis factor, interferon-γ, and interleukin-17 compared to control group. The interleukin-2 concentration increased 2 weeks after vaccination compared to pre-vaccination in leprosy cured group, but declined in control group (0.92 pg/ml vs -0.02 pg/ml, P = .0147). Leprosy cured group showed a more rapid down-regulation of interleukin-6 when influenza virus was challenged compared to control group (-144.38 pg/ml vs -11.52 pg/ml, P < .0001). Subgroup analysis revealed that the immunization administration declined interleukin-17 concentration in Tuberculoid type subgroup, but not in Lepromatous type subgroup or control group. Clinically cured leprosy patients are relatively safe for influenza vaccine. Leprosy cured patient have immune deficit in producing antibody. Interleukin-6 and interleukin-17 were 2 sensitive indicators in immune response for leprosy affected patients. The identification of indicators might be help management of leprosy and used as predictive markers in leprosy early symptom monitoring.


Assuntos
Imunidade/efeitos dos fármacos , Imunogenicidade da Vacina , Vacinas contra Influenza/normas , Hanseníase/tratamento farmacológico , Formação de Anticorpos/efeitos dos fármacos , Humanos , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Vírus da Influenza A Subtipo H1N1/imunologia , Vírus da Influenza A Subtipo H3N2/efeitos dos fármacos , Vírus da Influenza A Subtipo H3N2/imunologia , Vacinas contra Influenza/efeitos adversos , Vacinas contra Influenza/uso terapêutico , Hanseníase/imunologia , Mycobacterium/efeitos dos fármacos , Mycobacterium/patogenicidade , Mycobacterium leprae/efeitos dos fármacos , Mycobacterium leprae/patogenicidade
15.
An Bras Dermatol ; 96(5): 598-601, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34325921

RESUMO

Histoid leprosy is considered a rare form of lepromatous leprosy. Its peculiar clinical picture makes its diagnosis a challenging one, which can delay starting treatment and perpetuate the disease as endemic. In addition to representing a reservoir of bacilli, and being an important means of contamination, these patients have greater resistance to standard treatment. This is a report of a typical case of this rare presentation, aiming to share the knowledge and favor earlier diagnosis of the disease.


Assuntos
Hanseníase Virchowiana , Hanseníase , Humanos , Hanseníase Virchowiana/diagnóstico , Hanseníase Virchowiana/tratamento farmacológico , Mycobacterium leprae
16.
Am J Trop Med Hyg ; 105(1): 31-36, 2021 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-34232909

RESUMO

Leprosy is an infectious disease caused by Mycobacterium leprae. China was once one of the countries with severe leprosy epidemics, but its incidence has remained low in recent years. Despite this, there has been no decrease in its incidence more recently, and it is still a public health problem which needs to be controlled. In this study, we analyzed the epidemiological characteristics and trends in the detection rate of new cases of leprosy in China between 2004 and 2016. There were 4,519 cases of leprosy in 28 provinces, municipalities, and autonomous regions between 2004 and 2016, and the total incidence was 0.02815 (per 100,000 individuals) and 21 deaths. The overall incidence of leprosy showed an inverted "V" distribution (i.e., an increase followed by a decrease). Yunnan, Sichuan, Guangdong, Guizhou, and Guangxi were the top five regions with the highest incidence rates, and they accounted for 68.7% of the total cases. There were more male patients than female patients, and peasants accounted for 71.7% of the leprosy cases. The patients with leprosy in China were mainly concentrated in the age-group 15-44 years, as this group accounted for 57.2% of the total cases. The purpose of this study is to explore the epidemiology of leprosy in China. This analysis will be useful for future monitoring of leprosy and establishment of public health measures in China, in keeping with the "Programme for the Elimination of Leprosy in China 2011-2020."


Assuntos
Hanseníase/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , China/epidemiologia , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Mycobacterium leprae/isolamento & purificação , Estudos Retrospectivos , Adulto Jovem
17.
Front Immunol ; 12: 647987, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34248935

RESUMO

Cutaneous leishmaniasis caused by L. braziliensis induces a pronounced Th1 inflammatory response characterized by IFN-γ production. Even in the absence of parasites, lesions result from a severe inflammatory response in which inflammatory cytokines play an important role. Different approaches have been used to evaluate the therapeutic potential of orally administrated heat shock proteins (Hsp). These proteins are evolutionarily preserved from bacteria to humans, highly expressed under inflammatory conditions and described as immunodominant antigens. Tolerance induced by the oral administration of Hsp65 is capable of suppressing inflammation and inducing differentiation in regulatory cells, and has been successfully demonstrated in several experimental models of autoimmune and inflammatory diseases. We initially administered recombinant Lactococcus lactis (L. lactis) prior to infection as a proof of concept, in order to verify its immunomodulatory potential in the inflammatory response arising from L. braziliensis. Using this experimental approach, we demonstrated that the oral administration of a recombinant L. lactis strain, which produces and secretes Hsp65 from Mycobacterium leprae directly into the gut, mitigated the effects of inflammation caused by L. braziliensis infection in association or not with PAM 3CSK4 (N-α-Palmitoyl-S-[2,3-bis(palmitoyloxy)-(2RS)-propyl]-L-cysteine, a TLR2 agonist). This was evidenced by the production of anti-inflammatory cytokines and the expansion of regulatory T cells in the draining lymph nodes of BALB/c mice. Our in vitro experimental results suggest that IL-10, TLR-2 and LAP are important immunomodulators in L. braziliensis infection. In addition, recombinant L. lactis administered 4 weeks after infection was observed to decrease lesion size, as well as the number of parasites, and produced a higher IL-10 production and decrease IFN-γ secretion. Together, these results indicate that Hsp65-producing L. lactis can be considered as an alternative candidate for treatment in both autoimmune diseases, as well as in chronic infections that cause inflammatory disease.


Assuntos
Proteínas de Bactérias/administração & dosagem , Proteínas de Bactérias/metabolismo , Chaperonina 60/administração & dosagem , Chaperonina 60/metabolismo , Tolerância Imunológica/efeitos dos fármacos , Lactococcus lactis/metabolismo , Leishmania braziliensis/efeitos dos fármacos , Leishmaniose Cutânea/tratamento farmacológico , Mycobacterium leprae/enzimologia , Administração Oral , Animais , Proteínas de Bactérias/genética , Chaperonina 60/genética , Citocinas/metabolismo , Feminino , Inflamação/tratamento farmacológico , Inflamação/imunologia , Lactococcus lactis/genética , Leishmaniose Cutânea/imunologia , Leishmaniose Cutânea/parasitologia , Camundongos , Camundongos Endogâmicos BALB C , Organismos Geneticamente Modificados/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/imunologia , Linfócitos T Reguladores/imunologia
18.
Lancet Infect Dis ; 21(11): 1590-1597, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34237262

RESUMO

BACKGROUND: Trials of BCG vaccination to prevent or reduce severity of COVID-19 are taking place in adults, some of whom have been previously vaccinated, but evidence of the beneficial, non-specific effects of BCG come largely from data on mortality in infants and young children, and from in-vitro and animal studies, after a first BCG vaccination. We assess all-cause mortality following a large BCG revaccination trial in Malawi. METHODS: The Karonga Prevention trial was a population-based, double-blind, randomised controlled in Karonga District, northern Malawi, that enrolled participants between January, 1986, and November, 1989. The trial compared BCG (Glaxo-strain) revaccination versus placebo to prevent tuberculosis and leprosy. 46 889 individuals aged 3 months to 75 years were randomly assigned to receive BCG revaccination (n=23 528) or placebo (n=23 361). Here we report mortality since vaccination as recorded during active follow-up in northern areas of the district in 1991-94, and in a demographic surveillance follow-up in the southern area in 2002-18. 7389 individuals who received BCG (n=3746) or placebo (n=3643) lived in the northern follow-up areas, and 5616 individuals who received BCG (n=2798) or placebo (n=2818) lived in the southern area. Year of death or leaving the area were recorded for those not found. We used survival analysis to estimate all-cause mortality. FINDINGS: Follow-up information was available for 3709 (99·0%) BCG recipients and 3612 (99·1%) placebo recipients in the northern areas, and 2449 (87·5%) BCG recipients and 2413 (85·6%) placebo recipients in the southern area. There was no difference in mortality between the BCG and placebo groups in either area, overall or by age group or sex. In the northern area, there were 129 deaths per 19 694 person-years at risk in the BCG group (6·6 deaths per 1000 person-years at risk [95% CI 5·5-7·8]) versus 133 deaths per 19 111 person-years at risk in the placebo group (7·0 deaths per 1000 person-years at risk [95% CI 5·9-8·2]; HR 0·94 [95% CI 0·74-1·20]; p=0·62). In the southern area, there were 241 deaths per 38 399 person-years at risk in the BCG group (6·3 deaths per 1000 person-years at risk [95% CI 5·5-7·1]) versus 230 deaths per 38 676 person-years at risk in the placebo group (5·9 deaths per 1000 person-years at risk [95% CI 5·2-6·8]; HR 1·06 [95% CI 0·88-1·27]; p=0·54). INTERPRETATION: We found little evidence of any beneficial effect of BCG revaccination on all-cause mortality. The high proportion of deaths attributable to non-infectious causes beyond infancy, and the long time interval since BCG for most deaths, might obscure any benefits. FUNDING: British Leprosy Relief Association (LEPRA); Wellcome Trust.


Assuntos
Vacina BCG/administração & dosagem , Imunização Secundária/estatística & dados numéricos , Mortalidade , Vacinação/métodos , Adolescente , Adulto , Idoso , Vacina BCG/imunologia , COVID-19/epidemiologia , COVID-19/imunologia , COVID-19/prevenção & controle , Criança , Pré-Escolar , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Imunogenicidade da Vacina , Hanseníase/imunologia , Hanseníase/mortalidade , Hanseníase/prevenção & controle , Malaui/epidemiologia , Masculino , Pessoa de Meia-Idade , Mycobacterium leprae/imunologia , SARS-CoV-2/imunologia , Resultado do Tratamento , Tuberculose/imunologia , Tuberculose/mortalidade , Tuberculose/prevenção & controle , Vacinação/estatística & dados numéricos , Adulto Jovem
19.
Rev Bras Epidemiol ; 24: e210039, 2021.
Artigo em Português, Inglês | MEDLINE | ID: mdl-34231829

RESUMO

OBJECTIVE: To investigate the risk factors associated with leprosy in contacts of patients. METHOD: We carried out a systematic review and meta-analysis by searching the databases MEDLINE, Embase, Cochrane Library, CINAHL, LILACS, Scopus, and Web of Science until September 2019. Four reviewers carried out the selection, analysis, and evaluation of quality of studies. The random effects model was used to calculate the pooled relative risk (RR) and 95% confidence intervals (95% CI) when heterogeneity was greater than 50%. RESULTS: The search resulted in 2,148 references and included 24 reports. Most of the studies had been conducted in Brazil and India, had a cohort design and included household, neighbors, and social contacts. The risk factors associated with illness due to leprosy in contacts were: illiteracy (RR = 1,48; 95%CI 1,22 - 1,79), living in the same house (RR = 2,41; 95%CI 1,87 - 3,10) of a case of leprosy with high bacillary load (RR = 2.40; 95%CI 1.69 - 3.41), seropositivity to the Mycobacterium leprae PGL-1 (phenolic glycolipid-1) antigen (RR = 3.54; 95%CI 2.21 - 5.67), presence of the bacillus in the bloodstream (RR = 10.61; 95%CI 4.74 - 23.77) and negative Mitsuda reaction (RR = 2,68; 95%CI 1,76 - 4,07). Immunization with BCG (bacillus Calmette-Guérin) vaccine had a protective effect against leprosy. CONCLUSION: Leprosy in contacts of patients involves social determination, individual susceptibility, and difficulties in access to disease control actions, but modifiable risk factors are the main determinants of illness in this population.


Assuntos
Antígenos de Bactérias , Hanseníase , Brasil/epidemiologia , Glicolipídeos , Humanos , Hanseníase/epidemiologia , Mycobacterium leprae
20.
Methods Mol Biol ; 2314: 1-58, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34235647

RESUMO

Building upon the foundational research of Robert Koch, who demonstrated the ability to grow Mycobacterium tuberculosis for the first time in 1882 using media made of coagulated bovine serum, microbiologists have continued to develop new and more efficient ways to grow mycobacteria. Presently, all known mycobacterial species can be grown in the laboratory using either axenic culture techniques or in vivo passage in laboratory animals. This chapter provides conventional protocols to grow mycobacteria for diagnostic purposes directly from clinical specimens, as well as in research laboratories for scientific purposes. Detailed protocols used for production of M. tuberculosis in large scale (under normoxic and hypoxic conditions) in bioreactors and for production of obligate intracellular pathogens such as Mycobacterium leprae and "Mycobacterium lepromatosis" using athymic nude mice and armadillos are provided.


Assuntos
Técnicas Bacteriológicas , Infecções por Mycobacterium/microbiologia , Mycobacterium/crescimento & desenvolvimento , Animais , Tatus , Técnicas Bacteriológicas/instrumentação , Reatores Biológicos , Modelos Animais de Doenças , Humanos , Camundongos Nus , Viabilidade Microbiana , Mycobacterium/isolamento & purificação , Mycobacterium leprae/crescimento & desenvolvimento , Mycobacterium leprae/isolamento & purificação , Fatores de Tempo
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