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1.
Front Immunol ; 12: 727580, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34621273

RESUMO

Despite being treatable, leprosy still represents a major public health problem, and many mechanisms that drive leprosy immunopathogenesis still need to be elucidated. B cells play important roles in immune defense, being classified in different subgroups that present distinct roles in the immune response. Here, the profile of B cell subpopulations in peripheral blood of patients with paucibacillary (TT/BT), multibacillary (LL/BL) and erythema nodosum leprosum was analyzed. B cell subpopulations (memory, transition, plasmablasts, and mature B cells) and levels of IgG were analyzed by flow cytometry and ELISA, respectively. It was observed that Mycobacterium leprae infection can alter the proportions of B cell subpopulations (increase of mature and decrease of memory B cells) in patients affected by leprosy. This modulation is associated with an increase in total IgG and the patient's clinical condition. Circulating B cells may be acting in the modulation of the immune response in patients with various forms of leprosy, which may reflect the patient's ability to respond to M. leprae.


Assuntos
Linfócitos B/imunologia , Hanseníase Multibacilar/imunologia , Adulto , Feminino , Humanos , Imunoglobulina G/sangue , Memória Imunológica , Hanseníase Multibacilar/sangue , Masculino , Pessoa de Meia-Idade , Fenótipo
2.
J Med Case Rep ; 15(1): 488, 2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34602094

RESUMO

BACKGROUND: Melkersson-Rosenthal syndrome is a rare disease characterized by the triad of recurrent orofacial swelling with facial paralysis and fissured dorsal tongue. Histologically, noncaseating granulomatous inflammation occurs that confirms the diagnosis. Overlaps between granulomatous diseases such as sarcoidosis and Crohn's disease are described. Systemic corticosteroid therapy is the treatment of choice for acute attacks. CASE PRESENTATION: We here present a case of a 59-year-old White woman suffering from Melkersson-Rosenthal syndrome with a past history of sarcoidosis on therapy with leflunomide in combination with low-dose tacrolimus successfully treated with the anti-leprosy drug clofazimine after failure of systemic steroid therapy. CONCLUSIONS: We propose clofazimine as an alternative treatment in steroid-refractory cases.


Assuntos
Doença de Crohn , Paralisia Facial , Síndrome de Melkersson-Rosenthal , Sarcoidose , Terapia Comportamental , Feminino , Humanos , Síndrome de Melkersson-Rosenthal/complicações , Síndrome de Melkersson-Rosenthal/diagnóstico , Síndrome de Melkersson-Rosenthal/tratamento farmacológico , Pessoa de Meia-Idade , Sarcoidose/complicações , Sarcoidose/diagnóstico , Sarcoidose/tratamento farmacológico
3.
Rev Chilena Infectol ; 38(4): 532-539, 2021 Aug.
Artigo em Espanhol | MEDLINE | ID: mdl-34652399

RESUMO

BACKGROUND: Leprosy, a chronic infectious disease, is one of the major causes of preventable disability. Early treatment prevents neurological damage and disability. AIM: To identify prognostic factors of disability in individuals with multibacillary and paucibacillary leprosy who completed a drug treatment between 2011 and 2017 in Paraguay. METHODS: A case-control study was carried out on 34 patients, of them 9 were cases and 25 controls. Cases were those patients with Grade 1, presented lack of sensation in lower or upper limbs, and those of Grade 2 lagophthalmos, rigidity, visible deformity ulcerations, passive claw, active claw. Controls had no disabilities. RESULTS: Mean age of the patients was 53 ± 15.2 years, 55.9% were male, and 58.9% had primary education or no formal education. Multibacillary leprosy was found in 58.8% of patients; and 64.7% were diagnosed after consulting with two or more physicians. Diagnosis delay of more than one year was significantly (p = 0.047) greater in the cases than in the controls (77.8% vs 12%; OR: 7.44; 95% CI: 1.02-67.86). CONCLUSION: In this study, a diagnosis delay of more than one year is a prognostic factor for disability.


Assuntos
Hanseníase , Adulto , Idoso , Estudos de Casos e Controles , Humanos , Hanseníase/diagnóstico , Hanseníase/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Paraguai/epidemiologia , Prognóstico
4.
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
5.
Cien Saude Colet ; 26(9): 4233-4242, 2021 Sep.
Artigo em Português, Inglês | MEDLINE | ID: mdl-34586274

RESUMO

Drug utilization research to describe the control of thalidomide in Brazil and its use in Minas Gerais state. An online questionnaire was sent to the Brazilian federative units to collect data concerning distribution, dispensation, user registration, and thalidomide adverse events. Distribution (2011-2018) and dispensing (2015-2018) data in Minas Gerais were obtained through the pharmaceutical care management system. Analysis of variance and Tukey test were used for data comparisons. Of the 16 participating federative units, 100% and 50% used electronic distribution and dispensing systems, respectively, and about 43% registered users. Adverse event reporting systems were scarce. A 44% reduction was observed in the distribution in Minas Gerais for the period. Dispensing remained constant (mean 0.0004 DDD/1,000 inhabitants/day) and occurred mainly for erythema nodosum leprosum and multiple myeloma. Off-label use (2.2%) was increasing. Most users were male (mean age 56 years) and thirty percent of women were of childbearing age. Thalidomide surveillance is a public health challenge. Despite the increased use and mandatory control, there is no national standardization, and adverse event reporting is incipient.


Assuntos
Uso de Medicamentos , Talidomida , Brasil , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Talidomida/efeitos adversos
6.
PLoS Negl Trop Dis ; 15(8): e0009434, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34449765

RESUMO

Pyruvate kinase (PK), encoded by the PKLR gene, is a key player in glycolysis controlling the integrity of erythrocytes. Due to Plasmodium selection, mutations for PK deficiency, which leads to hemolytic anemia, are associated with resistance to malaria in sub-Saharan Africa and with susceptibility to intracellular pathogens in experimental models. In this case-control study, we enrolled 4,555 individuals and investigated whether PKLR single nucleotide polymorphisms (SNPs) putatively selected for malaria resistance are associated with susceptibility to leprosy across Brazil (Manaus-North; Salvador-Northeast; Rondonópolis-Midwest and Rio de Janeiro-Southeast) and with tuberculosis in Mozambique. Haplotype T/G/G (rs1052176/rs4971072/rs11264359) was associated with leprosy susceptibility in Rio de Janeiro (OR = 2.46, p = 0.00001) and Salvador (OR = 1.57, p = 0.04), and with tuberculosis in Mozambique (OR = 1.52, p = 0.07). This haplotype downregulates PKLR expression in nerve and skin, accordingly to GTEx, and might subtly modulate ferritin and haptoglobin levels in serum. Furthermore, we observed genetic signatures of positive selection in the HCN3 gene (xpEHH>2 -recent selection) in Europe but not in Africa, involving 6 SNPs which are PKLR/HCN3 eQTLs. However, this evidence was not corroborated by the other tests (FST, Tajima's D and iHS). Altogether, we provide evidence that a common PKLR locus in Africans contribute to mycobacterial susceptibility in African descent populations and also highlight, for first, PKLR as a susceptibility gene for leprosy and TB.


Assuntos
Malária/genética , Polimorfismo de Nucleotídeo Único , Piruvato Quinase/genética , Adulto , Brasil , Estudos de Casos e Controles , Feminino , Frequência do Gene , Predisposição Genética para Doença , Haplótipos , Humanos , Desequilíbrio de Ligação , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Moçambique , Piruvato Quinase/deficiência , Adulto Jovem
7.
PLoS Negl Trop Dis ; 15(8): e0009654, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34424909

RESUMO

INTRODUCTION: Since ancient times leprosy has had a negative perception, resulting in stigmatization. To improve the lives of persons affected by leprosy, these negative perceptions need to change. The aim of this study is to evaluate interventions to change perceptions and improve knowledge of leprosy. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a pre-post intervention study in Fatehpur and Chandauli districts, Uttar Pradesh, India. Based on six steps of quality intervention development (6SQuID) two interventions were designed: (1) posters that provided information about leprosy and challenged misconceptions, and (2) meetings with persons affected by leprosy, community members and influential people in the community. The effect of the interventions was evaluated in a mixed-methods design; in-depth interviews, focus group discussions, and questionnaires containing a knowledge measure (KAP), two perception measures (EMIC-CSS, SDS) and an intervention evaluation tool. 1067 participants were included in Survey 1 and 843 in Survey 2. The interventions were effective in increasing knowledge of all participant groups, and in changing community and personal attitudes of close contacts and community members (changes of 19%, 24% and 13% on the maximum KAP, EMIC-CSS and SDS scores respectively, p<0.05). In Survey 1, 13% of participants had adequate knowledge of leprosy versus 53% in Survey 2. Responses showed stigmatizing community attitudes in 86% (Survey 1) and 61% (Survey 2) of participants and negative personal attitudes in 37% (Survey 1) and 19% (Survey 2). The number of posters seen was associated with KAP, EMIC-CSS and SDS scores in Survey 2 (p<0.001). In addition, during eight post-intervention focus group discussions and 48 interviews many participants indicated that the perception of leprosy in the community had changed. CONCLUSIONS/SIGNIFICANCE: Contextualized posters and community meetings were effective in changing the perception of leprosy and in increasing leprosy-related knowledge. We recommend studying the long-term effect of the interventions, also on behavior.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Hanseníase/epidemiologia , Hanseníase/psicologia , Percepção Social , Adulto , Feminino , Grupos Focais , Humanos , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Análise de Regressão , Estigma Social , Inquéritos e Questionários , 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.
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
10.
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
12.
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
13.
Front Immunol ; 12: 632482, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34276644

RESUMO

Recent evidence suggests that inflammation was participated in the pathogenesis of PD, thus, to understand the potential mechanism of gut microbiota in the pathogenesis of Parkinson's disease (PD), we performed a metagenomic analysis of fecal samples from PD patient and controls. Using a two-stage metagenome-wide association strategy, fecal DNA samples from 69 PD patients and 244 controls in three groups (comprising 66 spouses, 97 age-matched, and 81 normal samples, respectively) were analyzed, and differences between candidate gut microbiota and microbiota-associated epitopes (MEs) were compared. In the study, 27 candidate bacterial biomarkers and twenty-eight candidate epitope peptides were significantly different between the PD patients and control groups. Further, enriched 4 and 13 MEs in PD were positively associated with abnormal inflammatory indicators [neutrophil percentage (NEUT.1), monocyte count/percentage (MONO/MONO.1), white blood cell count (WBC)] and five candidate bacterial biomarkers (c_Actinobacteria, f_Bifidobacteriaceae, g_Bifidobacterium, o_Bifidobacteriales, p_Actinobacteria) from Actinobacteria phylum, and they were also positively associated with histidine degradation and proline biosynthesis pathways, respectively. Additionally, enriched 2 MEs and 1 ME in PD were positively associated with above inflammatory indicators and two bacteria (f_Lactobacillaceae, g_Lactobacillus) from Firmicutes phylum, and they were also positively associated with pyruvate fermentation to propanoate I and negatively associated with isopropanol biosynthesis, respectively. Of these MEs, two MEs from GROEL2, RPSC were derived from Mycobacterium tuberculosis, triggered the T cell immune response, as previously reported. Additionally, other candidate epitope peptides derived from Mycobacterium tuberculosis and Mycobacterium leprae may also have potential immune effects in PD. In all, the altered MEs in PD may relate to abnormalities in immunity and glutamate and propionate metabolism, which furthers our understanding of the pathogenesis of PD.


Assuntos
Actinobacteria/imunologia , Epitopos/imunologia , Firmicutes/imunologia , Doença de Parkinson/microbiologia , Actinobacteria/classificação , Actinobacteria/genética , Actinobacteria/metabolismo , Idoso , Biomarcadores , Vias Biossintéticas , Citocinas/sangue , Fezes/microbiologia , Feminino , Firmicutes/classificação , Firmicutes/genética , Firmicutes/metabolismo , Microbioma Gastrointestinal/genética , Microbioma Gastrointestinal/imunologia , Humanos , Inflamação , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/imunologia
14.
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
15.
PLoS Negl Trop Dis ; 15(6): e0009495, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34125854

RESUMO

BACKGROUND: This study evaluates implementation strategies for leprosy diagnosis based on responses to a Leprosy Suspicion Questionnaire (LSQ), and analyzes immunoepidemiological aspects and follow-up of individuals living in a presumptively nonendemic area in Brazil. METHODOLOGY/PRINCIPAL FINDINGS: Quasi-experimental study based on LSQ throughout Jardinópolis town by community health agents, theoretical-practical trainings for primary care teams, dermatoneurological examination, anti-PGL-I serology, RLEP-PCR, and spatial epidemiology. A Leprosy Group (LG, n = 64) and Non-Leprosy Group (NLG, n = 415) were established. Overall, 3,241 LSQs were distributed; 1,054 (32.5%) LSQ were positive for signs/symptoms (LSQ+). Among LSQ+ respondents, Q2-Tingling (pricking)? (11.8%); Q4-Spots on the skin? (11.7%); Q7-Pain in the nerves? (11.6%); Q1-Numbness in your hands and/or feet? (10.7%) and Q8-Swelling of hands and feet? (8.5%) were most frequently reported symptoms. We evaluated 479 (14.8%) individuals and diagnosed 64 new cases, a general new case detection rate (NCDR) of 13.4%; 60 were among 300 LSQ+ (NCDR-20%), while 4 were among 179 LSQ negative (NCDR-2.23%). In LG, Q7(65%), Q2(60%), Q1(45%), Q4(40%) and Q8(25%) were most frequent. All 2x2 crossings of these 5 questions showed a relative risk for leprosy ranging from 3 to 5.8 compared with NLG. All patients were multibacillary and presented hypochromatic macules with loss of sensation. LG anti-PGL-I titers were higher than NLG, while 8.9% were positive for RLEP-PCR. The leprosy cases and anti-PGL-I spatial mappings demonstrated the disease spread across the town. CONCLUSIONS/SIGNIFICANCE: Implementation actions, primarily LSQ administration focused on neurological symptoms, indicate hidden endemic leprosy in a nonendemic Brazilian state.


Assuntos
Agentes Comunitários de Saúde/educação , Hanseníase/diagnóstico , Hanseníase/epidemiologia , Mycobacterium leprae/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mycobacterium leprae/genética , Mycobacterium leprae/isolamento & purificação , Prevalência , Inquéritos e Questionários
16.
Nat Immunol ; 22(7): 839-850, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34168371

RESUMO

Granulomas are complex cellular structures composed predominantly of macrophages and lymphocytes that function to contain and kill invading pathogens. Here, we investigated the single-cell phenotypes associated with antimicrobial responses in human leprosy granulomas by applying single-cell and spatial sequencing to leprosy biopsy specimens. We focused on reversal reactions (RRs), a dynamic process whereby some patients with disseminated lepromatous leprosy (L-lep) transition toward self-limiting tuberculoid leprosy (T-lep), mounting effective antimicrobial responses. We identified a set of genes encoding proteins involved in antimicrobial responses that are differentially expressed in RR versus L-lep lesions and regulated by interferon-γ and interleukin-1ß. By integrating the spatial coordinates of the key cell types and antimicrobial gene expression in RR and T-lep lesions, we constructed a map revealing the organized architecture of granulomas depicting compositional and functional layers by which macrophages, T cells, keratinocytes and fibroblasts can each contribute to the antimicrobial response.


Assuntos
Hanseníase Virchowiana/imunologia , Hanseníase Tuberculoide/imunologia , Mycobacterium leprae/imunologia , Pele/imunologia , Adolescente , Adulto , Idoso , Feminino , Fibroblastos/imunologia , Fibroblastos/microbiologia , Fibroblastos/patologia , Perfilação da Expressão Gênica , Interações Hospedeiro-Patógeno , Humanos , Queratinócitos/imunologia , Queratinócitos/microbiologia , Queratinócitos/patologia , Hanseníase Virchowiana/genética , Hanseníase Virchowiana/microbiologia , Hanseníase Virchowiana/patologia , Hanseníase Tuberculoide/genética , Hanseníase Tuberculoide/microbiologia , Hanseníase Tuberculoide/patologia , Macrófagos/imunologia , Macrófagos/microbiologia , Macrófagos/patologia , Masculino , Pessoa de Meia-Idade , Mycobacterium leprae/patogenicidade , RNA-Seq , Análise de Célula Única , Pele/microbiologia , Pele/patologia , Linfócitos T/imunologia , Linfócitos T/microbiologia , Linfócitos T/patologia , Transcriptoma
17.
Cien Saude Colet ; 26(5): 1805-1816, 2021 May.
Artigo em Português, Inglês | MEDLINE | ID: mdl-34076121

RESUMO

This study aimed to describe the prevalence of leprosy and verify the factors associated with multibacillary clinical types in a Family Health Strategy priority setting to control and monitor the disease in northeastern Brazil. This cross-sectional study used data from the Notifiable Diseases Information System related to leprosy cases notified in Imperatriz, Maranhão, between 2008 and 2017. The prevalence was determined yearly and for the period. Poisson regression models with a significance level of 5% were employed to associate the variables and the multibacillary clinical types. Most of the 2,476 leprosy cases analyzed referred to multibacillary clinical types. The prevalence ranged from 7.8 and 15.6/10,000 inhabitants, with high and very high endemicity levels. The variables male, age groups between 30 and 59 years and ≥60 years, schooling <8 years, level 2 physical disability, types 1 and 2 reactive episodes, and urban residence area showed significant associations (p≤0.05) with multibacillary clinical types. Such findings can serve as a basis for elaborating and implementing leprosy control and surveillance measures, gearing actions to the most vulnerable groups, and becoming more effective.


Assuntos
Saúde da Família , Hanseníase , Adulto , Brasil/epidemiologia , Estudos Transversais , Humanos , Hanseníase/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência
18.
Artigo em Inglês | MEDLINE | ID: mdl-34161550

RESUMO

Leprosy may present kidney and endothelial abnormalities, being a risk factor for complications. However, the involvement of renal and vascular endothelia has been poorly investigated. We aimed to investigate if the levels of systemic endothelial biomarkers are associated with kidney abnormalities and the clinical forms of leprosy. This is a cross-sectional study with leprosy patients enrolled in January 2017 to December 2018, before the initiation of the multidrug therapy. Leprosy-associated clinical and epidemiological data were collected. Two groups were investigated: Paucibacillary (PB) and Multibacillary (MB) infections, for the comparisons. Serum and urine samples were obtained for laboratory analysis. In serum samples, were evaluated the endothelial biomarkers VCAM-1 and ICAM-1. In total, 101 leprosy patients were included, the mean age was 48±Ù¡Ù¥ years and 71 (70%) were male. The multibacillary form occurred in 81 cases (80%), among which 22 had the Virchowian form. Serum creatinine was more elevated in the MB group than in PB patients. In addition, VCAM-1 was elevated in the MB group and was correlated with the bacteriological index (rho = 0.372, p <0.01), the duration of disease symptoms (rho = 0.234, p = 0.04), and the number of skin lesions (rho = 0.468, p <0.001). Moreover, in MB patients who presented albuminuria >15 mg/g of creatinine, VCAM-1 showed a significant correlation with increased albuminuria and improved the correlation with the number of skin lesions (rho= 0.563, p=0.010). In conclusion, higher systemic VCAM-1 levels were associated with the multibacillary clinical form of leprosy and with increased albuminuria. Prospective studies are necessary to establish a cause-effect and evaluate the preventive role of these biomarkers to improve the clinical care.


Assuntos
Albuminúria , Hanseníase Multibacilar , Albuminúria/tratamento farmacológico , Estudos Transversais , Quimioterapia Combinada , Humanos , Hansenostáticos/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
19.
PLoS Negl Trop Dis ; 15(6): e0009456, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34166403

RESUMO

BACKGROUND: Ethiopia has over 3,200 new cases of leprosy diagnosed every year. Prevention remains a challenge as transmission pathways are poorly understood. Susceptibility and disease manifestations are highly dependent on individual host-immune response. Nutritional deficiencies, such as protein-energy malnutrition, have been linked to reduced cell-mediated immunity, which in the case of leprosy, could lead to a higher chance of active leprosy and thus an increased reservoir of transmissible infection. METHODOLOGY/PRINCIPAL FINDINGS: Between June and August 2018, recently diagnosed patients with leprosy and individuals without known contact with cases were enrolled as controls in North Gondar regional health centers. Participants answered survey questions on biometric data, demographics, socioeconomic situation, and dietary habits. Descriptive statistics, univariate, and multivariate logisitic regression examined associations between undernutrition, specifically body mass index (BMI), middle upper arm circumference (MUAC), and leprosy. Eighty-one participants (40 cases of leprosy, 41 controls) were enrolled (75% male) with an average age of 38.6 years (SD 18.3). The majority of cases were multibacillary (MB) (90%). There was a high prevalence of undernutrition with 24 (29.6%) participants underweight (BMI <18.5) and 17 (21%) having a low MUAC. On multivariate analysis, underweight was significantly associated with leprosy (aOR = 9.25, 95% CI 2.77, 30.81). Also found to be associated with leprosy was cutting the size of meals/skipping meals (OR = 2.9, 95% CI 1.0, 8.32) or not having enough money for food (OR = 10, 95% CI 3.44 29.06). CONCLUSIONS/SIGNIFICANCE: The results suggest a strong association between leprosy and undernutrition, while also supporting the framework that food insecurity may lead to undernutrition that then could increase susceptibility to leprosy. In conclusion, this study highlights the need to study the interplay of undernutrition, food insecurity, and the manifestations of leprosy.


Assuntos
Insegurança Alimentar/economia , Hanseníase/epidemiologia , Hanseníase/etiologia , Desnutrição/complicações , Desnutrição/epidemiologia , Pobreza , Adulto , Estudos de Casos e Controles , Etiópia/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Adulto Jovem
20.
Rev Assoc Med Bras (1992) ; 67(1): 19-25, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34161488

RESUMO

OBJECTIVE: To describe the epidemiological and neurofunctional profile, as well as the prevalence of factors associated with the occurrence of physical disabilities due to leprosy in a reference center in Northeast Brasil. METHODS: A cross-sectional study including 50 leprosy patients diagnosed in Juazeiro-Bahia. Variables analyzed: sex, age, history of leprosy in the family, time to diagnosis, clinical form, operational classification, degree of disability, eyes-hand-foot score, peripheral nerve function, muscle strength and sensitivity. Descriptive statistics and inferential statistics (χ² test or Fisher's exact, Poisson regression with robust estimation and prevalence reason were used. Significance of 5%). RESULTS: An equal distribution was found between men and women of economically active age and low education; multibacillary forms in men (64%) and paucibacillary forms in women (60%). 78% of individuals had some degree of disability and 64% had a compromised ulnar nerve. Plantar sensitivity was decreased in 66% of patients. The predictors of disability were: age ≥45 years (PR 1.44; p=0.005), no education (PR 1.21; p=0.013) and OMP score ≥6 (PR 1.29; p<0.001). CONCLUSION: The findings show the importance of monitoring neural functions and developing measures that allow early diagnosis, the opportune method and the prevention of disabilities, especially in the male population.


Assuntos
Pessoas com Deficiência , Hanseníase , Brasil/epidemiologia , Estudos Transversais , Feminino , Humanos , Hanseníase/complicações , Hanseníase/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência
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