High-Resolution Plasma Metabolomics Identifies Alterations in Fatty Acid, Energy, and Micronutrient Metabolism in Adults Across the Leprosy Spectrum.

BACKGROUND: High-resolution metabolomics (HRM) is an innovative tool to study challenging infectious diseases like leprosy, where the pathogen cannot be grown with standard methods. Here, we use HRM to better understand associations between disease manifestations, nutrition, and host metabolism. METHODS: From 2018 to 2019, adults with leprosy and controls were recruited in Minas Gerais, Brazil. Plasma metabolites were detected using an established HRM workflow and characterized by accurate mass, mass to charge ratio m/z and retention time. The mummichog informatics package compared metabolic pathways between cases and controls and between multibacillary (MB) and paucibacillary (PB) leprosy. Additionally, select individual metabolites were quantified and compared. RESULTS: Thirty-nine cases (62% MB and 38% PB) and 25 controls were enrolled. We found differences (P < .05) in several metabolic pathways, including fatty acid metabolism, carnitine shuttle, retinol, vitamin D3, and C-21 steroid metabolism, between cases and controls with lower retinol and associated metabolites in cases. Between MB and PB, leukotrienes, prostaglandins, tryptophan, and cortisol were all found to be lower in MB (P < .05). DISCUSSION: Metabolites associated with several nutrient-related metabolic pathways appeared differentially regulated in leprosy, especially MB versus PB. This pilot study demonstrates the metabolic interdependency of these pathways, which may play a role in the pathophysiology of disease.

Evolução do grau de incapacidade física e do escore olhos, mãos e pés em casos novos de hanseníase: do diagnóstico à alta medicamentosa / Evolution of the degree of physical disability and the eye, hand and foot score in new cases of leprosy: from diagnosis to medication discharge

Este estudo tem por objetivo avaliar a evolução do grau de incapacidade física e do escore olhos, mãos e pés, do diagnóstico à alta medicamentosa, segundo as variáveis sociodemográficas e clínicas, em pacientes diagnosticados com hanseníase. Trata-se de estudo transversal, baseado na análise de 71 pacientes com diagnóstico de hanseníase, acompanhados no Hospital Eduardo de Menezes, centro de referência em Belo Horizonte, Minas Gerais, Brasil, entre janeiro de 2017 a dezembro de 2020. Foi observado predomínio do sexo feminino (53,5%), média de idade de 46 anos, sendo a maioria procedente de outros municípios do interior de Minas Gerais (54,9%). A forma clínica mais frequente foi a dimorfa (64,8%), classificação operacional multibacilar (84,5%). O grau de incapacidade física 0 foi o mais prevalente no diagnóstico (56,5%) e na alta (53,1%), e em relação ao escore olhos, mãos e pés, houve variação entre 0 e 10 no diagnóstico e entre 0 e 8 na alta. Pelo teste de McNemar foi observado que dentre os pacientes que apresentavam algum grau de incapacidade física no momento do diagnóstico, 30,8% apresentaram ausência de incapacidade na alta. Ao comparar a evolução do grau de incapacidade física de paucibacilares e multibacilares no momento do diagnóstico e da alta, houve manutenção em 59,3% e melhora em 17,2% dos pacientes. Os dados apresentados indicam que muitos pacientes foram tratados tardiamente já apresentando as formas graves e com sequelas, já que o estudo foi desenvolvido em um centro de referência, que atende casos mais complexos e com complicações já instaladas. Os dados sugerem que pacientes assistidos que realizam o tratamento com poliquimioterapia podem ter melhora das incapacidades já instaladas. O mesmo ocorreu com o escore olhos, mãos e pés, que ao final do tratamento instituído houve melhora se comparado com a admissão.(AU)

This study aims to evaluate the evolution of the degree of physical disability and the eye, hand and foot score, from diagnosis to medication discharge, according to sociodemographic and clinical variables, in patients diagnosed with leprosy. This is a cross-sectional study, based on the analysis of 71 patients diagnosed with leprosy, followed by Hospital Eduardo de Menezes, a reference center in Belo Horizonte, Minas Gerais, Brazil, between January 2017 and December 2020. There was a predominance of females (53.5%), average age of 46 years old, the majority coming from other municipalities in the interior of Minas Gerais (54.9%). The most frequent clinical form was borderline (64.8%), multibacillary operational classification (84.5%). Degree of physical disability 0 was the most prevalent at diagnosis (56.5%) and at discharge (53.1%); in relation to the eye, hand and foot score, there was variation between 0 and 10 at diagnosis and between 0 and 8 at discharge. By the McNemar test, it was observed that of the patients who had degree of physical disability at the time of diagnosis, 30.8% had no disability at discharge. When comparing the evolution of the GIF in paucibacillary and multibacillary patients at the time of diagnosis and discharge, there was maintenance in 59.3% and improvement in 17.2% of the patients. The presented data indicates that many patients were treated late, already presenting severe forms and with sequelae, since the study was carried out in a reference center, which treats cases with complications already installed and more complex cases. The data suggest that assisted patients undergoing treatment with multidrug therapy may experience improvement in disabilities already established. The same occurred with eye, hand and foot score, at the end of the established treatment there was an improvement compared to admission.(AU)

Factors associated with the development of leprosy in Brazilian contacts: a systematic review.

People who interact with leprosy patients in their environment, neighborhood, family, or social relationships are at risk to develop the disease. This systematic review investigated the risk and protective factors associated with the development of leprosy in Brazilian contacts. The studies were found in Cochrane Library, PubMed (MEDLINE), Embase, Virtual Health Library, grey literature and hand search until July 2021. The study selection, data extraction and quality assessment were independently performed by two investigators. The quality assessment was performed using the Newcastle-Ottawa Scale (NOS). This review was registered in PROSPERO (CRD42020160680). Seventeen articles fulfilled the inclusion criteria (n=544). The immunological and molecular factors, such as Anti-phenolic Glycolipid Antibodies (Anti-PGL-1) seropositivity, negative Mitsuda test, absence of Bacillus Calmette-Guérin (BCG) scar, positive Polymerase Chain Reaction (PCR) in blood; age and race; conviviality, education, contact time and type of contact, as well as elements related to the index case (bacilloscopic index; genetic conditions, family relationships), and some combined factors were shown to be relevant risk factors associated with the development of the disease in Brazilian leprosy contacts. The protective factors reported were the presence of one or more BCG scars, positive Mitsuda test, and education level. All selected studies were considered of high quality according to NOS. The knowledge of disease-related risk and protective factors provides the scientific basis for decision-making in the management of the disease in leprosy contacts.

Reduced vitamin D receptor (VDR) and cathelicidin antimicrobial peptide (CAMP) gene expression contribute to the maintenance of inflammatory immune response in leprosy patients.

Leprosy is an infectious disease influenced by genetic, immunological, and environmental factors. Reduced gene expressions may be associated with the immunological response pattern and leprosy susceptibility. We investigated the direct and indirect effects of Vitamin D Receptor (VDR) and Cathelicidin Antimicrobial Peptide (CAMP) gene expressions on the serum levels of vitamin D, Cathelicidin, and cytokines in newly-diagnosed leprosy patients and post-six-months of multidrug therapy (MDT). Thirty-four leprosy patients were assessed, paucibacillary (PB; n = 14) and multibacillary (MB; n = 20) cases, untreated or having received six months of MDT, 18 healthy controls, and 25 household contacts. VDR and CAMP gene expression levels were strongly correlated to some important cytokines in both, untreated leprosy patients (PB, r = 0.9319; MB, r = 0.9569) and patients who had undergone MDT (PB, r = 0.9667; MB, r = 0.9569). We observed that both gene expressions directly influenced IL-2, IFN-γ, and IL-17F serum levels in leprosy patients compared to the household contacts and healthy individuals. VDR and CAMP gene expressions induced a persistent inflammatory response in PB and MB leprosy patients, even after six months of MDT, to fight the Mycobacterium leprae infection. Due to the persistent inflammatory profile, multidrug therapy is suggested to be maintained for more than six months, especially for MB patients. Vitamin D supplementation is recommended from the onset as a transcription factor to improve VDR and CAMP gene expression in leprosy patients.

Associations between occupation, leprosy disability and other sociodemographic factors in an endemic area of Brazil.

BACKGROUND: In Brazil, new leprosy cases with grade-2 disability (G2D) have been increasing. Physical disability has been associated with experienced stigmatization, psychological distress, and social restriction. OBJECTIVES: To identify factors associated with leprosy disability in an endemic area of Brazil focusing on occupational and other sociodemographic factors. METHODS: Between July and December 2015, adult patients with multibacillary leprosy who attended a clinic in Belo Horizonte, Brazil were enrolled. Social, clinical, and demographic factors were collected from an administered questionnaire and medical charts. Occupations were categorized as manual vs non-manual. Descriptive statistics and multivariable logistic regression were performed to study associated factors with disability (Grade 1 disability (G1D) and G2D combined). FINDINGS: Seventy-three patients were enrolled with 48 (65.8%) presenting with either G1D or G2D at the time of enrollment. Twenty-nine (39.7%) had G2D. About half of the patients (n = 36, 49%) reported a manual labor occupation and reactions were common (n = 53, 73%). On univariate analyses, older age (p = 0.048) and low education (p = 0.007) were associated with disability. On multivariable analyses, only low education (primary or less) was associated with disability (OR = 6.34, 95% CI 1.37, 29.26). Greater distance from clinic, income, smoking, marital status, and occupation were not associated. MAIN CONCLUSIONS: Low education was associated with leprosy disability, consistent with prior studies, and therefore should be a focus for disability reduction programs. While the sample size of this study may have limited detection of associations between disability and social determinants tested, half of the patients reported a manual job, highlighting the need for more extensive studies on associations between occupation, disability, and related injuries.

Factors associated with the development of leprosy in Brazilian contacts: a systematic review

ABSTRACT People who interact with leprosy patients in their environment, neighborhood, family, or social relationships are at risk to develop the disease. This systematic review investigated the risk and protective factors associated with the development of leprosy in Brazilian contacts. The studies were found in Cochrane Library, PubMed (MEDLINE), Embase, Virtual Health Library, grey literature and hand search until July 2021. The study selection, data extraction and quality assessment were independently performed by two investigators. The quality assessment was performed using the Newcastle-Ottawa Scale (NOS). This review was registered in PROSPERO (CRD42020160680). Seventeen articles fulfilled the inclusion criteria (n=544). The immunological and molecular factors, such as Anti-phenolic Glycolipid Antibodies (Anti-PGL-1) seropositivity, negative Mitsuda test, absence of Bacillus Calmette-Guérin (BCG) scar, positive Polymerase Chain Reaction (PCR) in blood; age and race; conviviality, education, contact time and type of contact, as well as elements related to the index case (bacilloscopic index; genetic conditions, family relationships), and some combined factors were shown to be relevant risk factors associated with the development of the disease in Brazilian leprosy contacts. The protective factors reported were the presence of one or more BCG scars, positive Mitsuda test, and education level. All selected studies were considered of high quality according to NOS. The knowledge of disease-related risk and protective factors provides the scientific basis for decision-making in the management of the disease in leprosy contacts.

Hypovitaminosis D and reduced cathelicidin are strongly correlated during the multidrug therapy against leprosy.

Mycobacterium leprae infection depends on the competence of the host immune defense to induce effective protection against this intracellular pathogen. The present study investigated the serum levels of vitamin D and the antimicrobial peptide cathelicidin, to determine the statistical correlation between them in leprosy patients before and post-six months of multidrug therapy (MDT), household contacts, and healthy individuals. Previous studies associated these molecules with high risks to develop mycobacterial diseases, such as tuberculosis and leprosy. A total of 34 leprosy patients [paucibacillary (n = 14), multibacillary (n = 20)], and 25 household contacts were recruited. Eighteen healthy adults were selected as a control group. Serum concentrations of vitamin D (25(OH)VD3) and cathelicidin were measured using high-performance liquid chromatography (HPLC), and an enzyme-linked immunosorbent assay (ELISA) kit, respectively. There were no significant differences in serum levels of 25(OH)VD3 between all groups, and the overall prevalence rate of vitamin D deficiency was 67.1%. Cathelicidin levels were significantly lower in both untreated and treated patients when compared to controls and household contacts (p < 0.05). Strong correlations between hypovitaminosis D and reduced cathelicidin in untreated (r = 0.86) and post-six months of MDT (r = 0.79) leprosy patients were observed. These results suggest that vitamin D status and cathelicidin levels are strongly correlated during multidrug therapy for leprosy and nutritional supplementation from the beginning of treatment could strengthen the immune response against leprosy.

The Burden of Helminth Coinfections and Micronutrient Deficiencies in Patients with and without Leprosy Reactions: A Pilot Study in Minas Gerais, Brazil.

Leprosy reactions are immune-mediated complications occurring in up to 50% of patients. The immune consequences of helminth infections and micronutrient deficiencies suggest a potential role in type 1 reactions (T1R) or type 2 reactions (T2R). We conducted a case-control study in Minas Gerais, Brazil, to evaluate whether comorbidities and other factors are associated with reactions in patients with multibacillary leprosy. Stool and serum were tested for helminth infections. Deficiencies of vitamin A, D, and iron were measured using serum retinol, 25-hydroxyvitamin D, and ferritin, respectively. Logistic regression models identified associations between reactions and helminth infections, micronutrient deficiencies, and other variables. Seventy-three patients were enrolled, 24 (33%) with T1R, 21 (29%) with T2R, 8 (15%) with mixed T1R/T2R, and 20 (27%) without reactions. Evidence of helminth infections were found in 11 participants (15%) and included IgG4 reactivity against Schistosoma mansoni, Strongyloides, and Ascaris antigens. Thirty-eight (52%) had vitamin D deficiency, eight (11%) had vitamin A insufficiency, 21 (29%) had anemia, and one (1.4%) had iron deficiency. Multivariable logistic regression showed no statistically significant associations between helminth coinfections and total reactions (adjusted odds ratios [aOR]: 1.36, 95% CI: 0.22, 8.33), T1R (aOR: 0.85, 95% CI: 0.17, 4.17), or T2R (aOR: 2.41, 95% CI: 0.29, 20.0). Vitamin D deficiency and vitamin A insufficiency were also not statistically associated with reactions. However, vitamin deficiencies and helminth infections were prevalent in these patients, suggesting a potential role for additional treatment interventions. Studying reactions prospectively may further clarify the role of comorbidities in the clinical presentation of leprosy.

Deep Venous Thrombosis in Patients with Erythema Nodosum Leprosum in the Use of Thalidomide and Systemic Corticosteroid in Reference Service in Belo Horizonte, Minas Gerais.

INTRODUCTION: Erythema nodosum leprosum (ENL) is a type of lepra reaction treated with corticosteroids and thalidomide, but this association increases the risk of deep venous thrombosis (DVT). OBJECTIVE: To report cases of ENL with DVT in the use of thalidomide/corticosteroid associated. METHODOLOGY: The study was conducted between December 2015 and December 2016 at the Eduardo de Menezes Hospital (HEM-FHEMIG). RESULTS: A clinical case series of 16 patients, eight from HEM-FHEMIG and eight from the literature. DVT occurred on 4 continents, mainly in adults and men. All patients were multibacillary; four people had pulmonary embolism (PE); there were 11 unilateral and five bilateral DVT cases; 12 cases were proximal, two distal, and two unspecified. Pharmacological thromboprophylaxis was used on two individuals. Outcome after DVT, 14 patients improved, one had sequelae, and one died. DISCUSSION: DVT increased in association with thalidomide/corticosteroid in multiple myeloma, but this complication is poorly described in ENL. In proximal DVT, there was a greater risk of PE and sequelae venous insufficiency. After DVT, start anticoagulation. ASA 100mg/day as prophylaxis for DVT in case of this drug association in ENL is recommended. CONCLUSION: The article illustrates the incidence increase of DVT because of the thalidomide/corticosteroid combination in ENL. When this association is necessary, use ASA 100mg/day as prophylaxis.

Fatores de risco para a ocorrência das úlceras plantares decorrente da hanseníase de acordo com a árvore de decisão / Risk factors for plantar ulcers from leprosy according to the decision tree

Objective:To identify the risk factors for plantar ulcers in patients with leprosy.Methods:This is an epidemiological, observational, cross-sectional and analytical study. The population was composed of leprosy cases reported from 2005 to 2016. Pearson's Chi-square test or Fisher's exact test andMann-Whitney test were used for the univariate analysis, with a statistical significance of 5% (p < 0.05). In the multivariate analysis, a decision tree was elaborated using the CHAID algorithm. Results:Clinical form, degree of physical incapacity at discharge, affected nerve and the lack of insoles or adapted footwear before appearing to ulcer are risk factors for plantar ulcer. Conclusion:the need for an early diagnosis of leprosy was highlighted, as well as the efficient association of non-drug interventions with disability prevention techniques and the use of accommodating insoles and/or special shoes.

Objetivo:Identificar os fatores de risco para a ocorrência das úlceras plantares em pacientes com hanseníase. Métodos:Trata-se de um estudo epidemiológico, do tipo observacional, transversal e analítico. A população foi composta pelos casos de hanseníase notificados no período de 2005 a 2016. Para a análise univariada foram utilizados os testes Qui-quadrado de Pearson ou teste exato de Fisher e teste de Mann-Whitney, com significância estatística de 5% (p < 0,05). Na análise multivariada, foi elaborada árvore de decisão utilizando o algoritmo CHAID. Resultados: A forma clínica, grau de incapacidade física na alta, nervo acometido e o não uso de palmilhas ou calçado adaptado antes de surgir a úlcera são fatores de risco para a ocorrência de úlcera plantar. Conclusão:evidenciou a necessidade do diagnóstico precoce da hanseníase, como também da eficiente associação das intervenções medicamentosas e não medicamentosas por meio das técnicas de prevenção de incapacidade e uso de palmilhas acomodativas e/ou calçados especiais

Reading of the Mitsuda test: comparison between diameter and total area by means of a computerized method.

The Mitsuda test is a skin test based on the individual's immune response through late and highly specific hypersensitivity reaction to the Mycobacterium leprae bacillus. A negative reaction identifies individuals who present a higher risk of becoming ill if exposed to M. leprae and, if they become ill, to develop the virchowian form of disease. The Mitsuda test reading is performed by means of a millimeter ruler. The dermatoscopy is a method that has not been used in the evaluation of cutaneous tests, although its use has increased in several areas. The study aimed to compare the results between the standardized reading and the total area of the Mitsuda test obtained by a computerized method which was structured by the association of digital dermatoscopy, the Dermatology Web system and the Image Tool 3.0 software. Data collection was performed at the Dermatology Outpatient Clinic of the Eduardo de Menezes Hospital, in Belo Horizonte, from November 2015 to August 2016. The sample consisted of 100 leprosy domiciliary contacts. There was an excellent agreement between the Mitsuda test (diameter and area), with a coefficient greater than 80%, and an excellent correlation with the Spearman's correlation coefficient (0.936). The intraclass correlation coefficient indicated a low (0.219) but significant agreement between the two measurements. In conclusion, there is a significant correlation between the standardized reading and the total area of the Mitsuda test. Digital dermoscopy can be an alternative instrument of evaluation, allowing the computerization and recording of the Mitsuda test.

Risk factors for physical disability upon release from multidrug therapy in new cases of leprosy at a referral center in Brazil.

The present study sought to investigate the risk factors for physical disability upon release from multidrug therapy (MDT) in new cases of leprosy, registered at a referral center in Brazil. This is a longitudinal and retrospective study that evaluated 260 patients. Multivariate analyses, using both the ordinal logistic regression, as well as the classification and regression tree (CART) algorithm were performed to determine the factors associated with physical disability upon release from treatment. The prevalence of disability did not differ significantly between diagnosis and release from treatment. Number of affected nerves and sensory impairment upon diagnosis were risk factors for disability at the end of MDT. The analysis using the CART algorithm resulted in the development of a clinical score to predict the risk of disability upon release from MDT. The decision tree may have a direct applicability in clinical practice for professionals dealing with leprosy, as it allows them to identify patients with a higher risk of physical disability through the use of simple and widely available clinical tests. This study also shows that the disability grade upon admission is the main risk factor for disability upon release from MDT. This result draws attention to the importance of early diagnosis in disability prevention.

Regulatory T cells: Friends or foe in human Mycobacterium leprae infection?

Regulatory T cells (Tregs) are known to control immune responses by suppressing the antigen-presenting and effector T cells. Some mechanisms adopted by Tregs in combating Mycobacterium infections have been proposed. Nevertheless, in M. leprae infection, also known as leprosy or Hansen's disease, the role of Tregs has not been completely elucidated. Using multicolor flow cytometry, we evaluated the expression of different cell surface and intracellular molecules present in Tregs from peripheral blood samples of leprosy patients. Before initiating treatment, thirteen new cases of leprosy were grouped according to the Ridley-Jopling classification in to the paucibacilary (PB) or multibacilary (MB) group. Fifteen non-infected individuals (NI) were included as control subjects. Tregs were higher in the MB group than in the NI group. Tregs also co-expressed high amounts of PD1 and PDL-1, indicating that these cells could induce apoptosis of effector cells and simultaneously prevent their own apoptosis. Our data showed that compared to the NI group, Tregs from the PB group expressed higher levels of CD95L, which may be associated with other apoptotic pathways that may decrease Tregs in these patients. Correlation analysis reinforced that PD1 and CD95L are efficient apoptosis' pathway that decreased levels of Tregs in the NI and PB groups. We also observed significant differences in cytokine expression of Tregs from the PB and MB groups. Compared to the NI group, Tregs from the MB group showed higher IL-17 expression; however, compared to the PB group, the expression of IL-10 in Tregs from the MB group was lower, suggesting inefficient control of inflammation. Therefore, we concluded that different pathways were involved in Treg-induced suppression of leprosy. Moreover, Treg-mediated regulation of inflammation via IL-10 and IL-17 expression in leprosy patients was inefficient. Thus, we propose that during M. leprae infection, Tregs may impair the immune responses elicited against this bacillus, favor bacterial replication, and aid in persistence of a disseminated multibacillary disease.

A Case of Subcutaneous Phaeohyphomycosis Associated with Leprosy.

BACKGROUND: Subcutaneous phaeohyphomycosis is an infection caused by melanized fungi and is increasingly reported among immunosuppressive patients. The most commonly cited etiologic agent is Exophiala jeanselmei, followed by Alternaria spp. We present a case of subcutaneous phaeohyphomycosis in a 48-yearold woman, with a history of lepromatous leprosy, using corticosteroid in immunosuppressive doses due to a type 2 repetitive reaction leprosy outbreak. RESULT AND DISCUSSION: The diagnosis was confirmed by fine-needle aspiration of the secretion, with subsequent direct mycological observations, culture and molecular analysis. The species agent was identified by culture and nucleotide sequences of ribosomal DNA as Exophiala dermatitidis.

Cytokines as biomarkers to monitoring the impact of multidrug therapy in immune response of leprosy patients.

Leprosy or Hansen's disease is a chronic infectious disease of the skin and nerves, caused by the intracellular bacilli Mycobacterium leprae. It is characterized by a spectrum of clinical forms depending on the host's immune response to M. leprae. Patients with tuberculoid (TT) leprosy have strong cell-mediated immunity (CMI) with elimination of the bacilli, whereas patients with lepromatous (LL) leprosy exhibit defective CMI to M. leprae. Despite advances in the understanding of the pathogenesis of leprosy and the development of new therapeutic strategies, there is a need for the identification of biomarkers which be used for early diagnosis and to discrimination between different forms of the disease, as prognostic markers. Here, we analyzed the serum levels of IL-1ß, IL-6, IL-8, IL-10, IL-12p70, IL-13, IL-17A, IFN-γ and TNF in order to address the contribution of these cytokines in late phase of M. leprae infection, and the impact of multidrug therapy (MDT). Our results demonstrated that patients of LL group presented higher expression of serum levels of inflammatory cytokines before MDT, while TT patients presented a balance between inflammatory and regulatory cytokines. MDT changes the profile of serum cytokines in M. leprae infected patients, as evidenced by the cytokine network, especially in TT patients. LL patients displayed a multifaceted cytokine system characterized by strong connecting axes involving inflammatory/regulatory molecules, while TT patients showed low involvement of regulatory cytokines in network overall. Cytokines can be identified as good biomarkers of the impact of MDT on the immune system and the effectiveness of treatment.

Leprosy classification methods: a comparative study in a referral center in Brazil.

OBJECTIVES: Different methods for the classification of leprosy have been proposed since the 1930s. The aim of this study was to compare the current methods at a referral center in Brazil. METHODS: The World Health Organization (WHO) operational classification was compared to the Ridley and Jopling classification, the Madrid classification, and a classification based on the number of body areas affected by skin and/or neural lesions (NBAA). The correlation between the clinical and histopathological components of the Ridley and Jopling classification was assessed. RESULTS: The agreement between the WHO operational classification and the Ridley and Jopling classification was 77.6% (kappa = 0.53). The WHO operational classification tended to overestimate the number of multibacillary patients. The WHO operational classification showed its best agreement with the NBAA. There was perfect agreement between the clinical and histopathological Ridley and Jopling classification in 46.9% of the patients. CONCLUSIONS: The agreement between the WHO operational classification and the Ridley and Jopling classification was better than any other purely clinical classification, reinforcing the importance and simplicity of the operational method. Although major disagreement between the clinical and histopathological Ridley and Jopling classification was uncommon, perfect agreement occurred in less than half of the cases, and was even lower for the borderline lepromatous and tuberculoid forms. Possible reasons for the differences are discussed; these showed that there may be room for improvement in the Ridley and Jopling classification histopathological criteria.

Qualidade de registros de hanseníase em centro de referência no estado deMinas Gerais, no período de 2006 a 2010 / Quality of data on leprosy at a refernce center in the Minas Gerais state from 2006 to 2010

Introdução: a hanseníase é uma doença de impacto mundial. No Brasil, o Sistema de Informação de Agravos Notificáveis (SINAN) registra dados referentes ao controle da hanseníase. Poucos trabalhos analisaram a qualidade dos registros desse sistema em relação à hanseníase. Neste estudo, avaliou-se a qualidade do preenchimento das fichas de notificação da hanseníase. Material e método: trata-se de estudo de banco de dados de variáveis de fichas do SINAN para hanseníase e registros de prontuários médicos. Analisaram-se 147 fichas de notificação de pacientes diagnosticados com hanseníase no Centro de Referência de Minas Gerais, de janeiro de 2006 a dezembro de 2010. Construiu-se questionário com dados relativos ao prontuário e à ficha do SINAN com dupla coleta e entrada de dados no banco de dados. Para avaliar a qualidade dos registros, verificaram-se a completitude e consistência dos registros e aplicou-se o coeficiente Kappa para confiabilidade. Resultados: foram avaliados o grau de completitude de 12 variáveis em 147 fichas; 74 (50,3%) apresentaram pelo menos um campo em branco; oito entre 12 variáveis (66,7%) apresentaram percentual superior a 90% de preenchimento. Para a análise da concordância, foram consideradas sete variáveis categóricas, com coeficiente Kappa variando de 0,86 a 1,0. Conclusão: a análise de completitude foi similar à de outros trabalhos, porém a confiabilidade dos registros foi diferente de estudos anteriores, que encontraram graus de concordância inferiores ao estudo atual. Mais estudos são necessários para confirmar a qualidade de registros em outros centros e em etapas diferentes do fluxo de informações do SINAN.

Introduction: Leprosy is a disease of worldwide impact. In Brazil, the Information System of Notifiable Diseases (SINAN) records data relating to leprosy control. Few studies have analyzed data quality of the records of this system in relation to leprosy. In this study, we evaluated the quality of the information reporting forms on leprosy. Methods: This is a study of Database variables evaluating data quality from SINAN forms on leprosy and medical records. We analyzed 147 forms with records of patients diagnosed with leprosy at the Reference Center of Minas Gerais from January 2006 to December 2010. We developed a questionnaire based on selected variables extracted from the SINAN form. Data collection and data entry into the database was performed twice. To assess the quality of the records, we evaluated the completeness and consistency of records and applied kappa statistics for data reliability. Results: We evaluated the completeness of twelve variables in 147 forms; half of the records showed at least one not filled in. Eight out of twelve variables (66.7%) showed more than 90 % coverage. The kappa statistics ranged from 0.86 to 1.0 (almost perfect to perfect agreement). Conclusion: Analysis of completeness was similar to other studies, but the reliability of the records was different from previous studies that found lower degrees of agreement than the current study. More studies are needed to confirm the quality of records in other centers and in different stages of the SINAN information flow.

Serial measurement of the circulating levels of tumour necrosis factor and its soluble receptors 1 and 2 for monitoring leprosy patients during multidrug treatment

Leprosy is an infectious and contagious spectral disease accompanied by a series of immunological events triggered by the host response to the aetiologic agent, Mycobacterium leprae . The induction and maintenance of the immune/inflammatory response in leprosy are linked to multiple cell interactions and soluble factors, primarily through the action of cytokines. The purpose of the present study was to evaluate the serum levels of tumour necrosis factor (TNF)-α and its soluble receptors (sTNF-R1 and sTNF-R2) in leprosy patients at different stages of multidrug treatment (MDT) in comparison with non-infected individuals and to determine their role as putative biomarkers of the severity of leprosy or the treatment response. ELISA was used to measure the levels of these molecules in 30 healthy controls and 37 leprosy patients at the time of diagnosis and during and after MDT. Our results showed increases in the serum levels of TNF-α and sTNF-R2 in infected individuals in comparison with controls. The levels of TNF-α, but not sTNF-R2, decreased with treatment. The current results corroborate previous reports of elevated serum levels of TNF-α in leprosy and suggest a role for sTNF-R2 in the control of this cytokine during MDT.

Serial measurement of the circulating levels of tumour necrosis factor and its soluble receptors 1 and 2 for monitoring leprosy patients during multidrug treatment.

Leprosy is an infectious and contagious spectral disease accompanied by a series of immunological events triggered by the host response to the aetiologic agent, Mycobacterium leprae . The induction and maintenance of the immune/inflammatory response in leprosy are linked to multiple cell interactions and soluble factors, primarily through the action of cytokines. The purpose of the present study was to evaluate the serum levels of tumour necrosis factor (TNF)-α and its soluble receptors (sTNF-R1 and sTNF-R2) in leprosy patients at different stages of multidrug treatment (MDT) in comparison with non-infected individuals and to determine their role as putative biomarkers of the severity of leprosy or the treatment response. ELISA was used to measure the levels of these molecules in 30 healthy controls and 37 leprosy patients at the time of diagnosis and during and after MDT. Our results showed increases in the serum levels of TNF-α and sTNF-R2 in infected individuals in comparison with controls. The levels of TNF-α, but not sTNF-R2, decreased with treatment. The current results corroborate previous reports of elevated serum levels of TNF-α in leprosy and suggest a role for sTNF-R2 in the control of this cytokine during MDT.

Degree of skin denervation and its correlation to objective thermal sensory test in leprosy patients.

BACKGROUND: Leprosy is an infectious disease affecting skin and peripheral nerves resulting in increased morbidity and physical deformities. Early diagnosis provides opportune treatment and reduces its complications, relying fundamentally on the demonstration of impaired sensation in suggestive cutaneous lesions. The loss of tactile sensitivity in the lesions is preceded by the loss of thermal sensitivity, stressing the importance of the thermal test in the suspicious lesions approach. The gold-standard method for the assessment of thermal sensitivity is the quantitative sensory test (QST). Morphological study may be an alternative approach to access the thin nerve fibers responsible for thermal sensitivity transduction. The few studies reported in leprosy patients pointed out a rarefaction of thin dermo-epidermal fibers in lesions, but used semi-quantitative evaluation methods. METHODOLOGY/PRINCIPAL FINDINGS: This work aimed to study the correlation between the degree of thermal sensitivity impairment measured by QST and the degree of denervation in leprosy skin lesions, evaluated by immunohistochemistry anti-PGP 9.5 and morphometry. Twenty-two patients were included. There were significant differences in skin thermal thresholds among lesions and contralateral skin (cold, warm, cold induced pain and heat induced pain). The mean reduction in the density of intraepidermal and subepidermal fibers in lesions was 79.5% (SD = 19.6) and 80.8% (SD = 24.9), respectively. CONCLUSIONS/SIGNIFICANCE: We observed a good correlation between intraepidermal and subepidermal fibers deficit, but no correlation between these variables and those accounting for the degree of impairment in thermal thresholds, since the thin fibers rarefaction was homogeneously intense in all patients, regardless of the degree of sensory deficit. We believe that the homogeneously intense denervation in leprosy lesions should be objective of further investigations focused on its diagnostic applicability, particularly in selected cases with only discrete sensory impairment, patients unable to perform the sensory test and especially those with nonspecific histopathological finds.