Utility of immunoglobulin isotypes against LID-1 and NDO-LID for, particularly IgG1, confirming the diagnosis of multibacillary leprosy.

BACKGROUND Leprosy remains a health problem in many countries, with difficulties in diagnosis resulting in delayed treatment and more severe disabilities. Antibodies against several Mycobacterium leprae antigens have, however, shown value as diagnostic and/or prognostic markers. OBJECTIVES The objective of this study was to evaluate serum immunoglobulin (Ig) IgM and IgG subclass reactivity against three M. leprae specific antigens: NDO-HSA, a conjugate formed by natural octyl disaccharide bound to human serum albumin; LID-1, the fusion protein product of the ml0405 and ml2331 genes; and NDO-LID, a combination of LID-1 and NDO. METHODS Sera from healthy controls, paucibacillary (PB) and multibacillary (MB) leprosy patients, and their respective household contacts, were evaluated for the presence of antigen-specific IgM, IgG, and IgG subclass antibodies by enzyme-linked immunosorbent assay (ELISA). The sensitivity and specificity of each ELISA were evaluated by receiver operating characteristic (ROC) curve analysis. FINDINGS Our data confirm that serum IgM antibodies against NDO-HSA and IgG antibodies against LID-1, as well as IgG/M antibodies against NDO-LID, are markedly increased in MB patients. For the first time, our data reveal a selective increase in IgG1 and IgG3 antibodies against LID-1 and NDO-LID in MB patients, demonstrating that these antibody isotypes are suitable for differentiation between MB and PB patients. ROC curve analysis indicates an improved capacity for diagnosing MB leprosy patients using the detection of IgG antibodies, particularly the IgG1 isotype, specific to LID-1 and NDO-LID over the performance levels attained with NDO-HSA. CONCLUSIONS Our findings indicate that serological tests based on the detection of antigen-specific IgG1 antibodies are a useful tool to differentiate MB from PB patients, and indicate the enhanced performance of the LID-1 and NDO-LID antigens in the serodiagnosis of leprosy.

The role of oxidative and nitrosative bursts caused by azoles and amphotericin B against the fungal pathogen Cryptococcus gattii.

OBJECTIVES: Although the most accepted mechanisms of action of amphotericin B and azoles are related to ergosterol, it is possible that these drugs have other effects on the fungal cell. In the present study, the role of endogenous reactive oxygen species (ROS) and peroxynitrite produced by azoles and amphotericin B in the fungus Cryptococcus gattii were examined. METHODS: We studied distinct parameters to evaluate the effect of oxidative and nitrosative stresses induced by these drugs in C. gattii cells: lipid peroxidation, ergosterol content, ROS and peroxynitrite production, enzymatic activity of the antioxidant system and the in vitro interaction of antifungal drugs with a peroxidase inhibitor, a superoxide dismutase inhibitor and a peroxynitrite scavenger. RESULTS: The data demonstrated that itraconazole led to ROS formation and lipid peroxidation in C. gattii cells in the early stages of the treatment; this did not occur with fluconazole. This phenomenon strongly increased the activities of enzymes of the antioxidant system. These results were confirmed by synergism observed between the catalase inhibitor and itraconazole. Amphotericin B caused lipid peroxidation in C. gattii cells through a greatly enhanced production of oxidative and nitrosative radicals with increased peroxidase activity. These data were confirmed by the synergism between the catalase/superoxide dismutase inhibitors and amphotericin B. In addition, the effect of this antifungal was antagonized by the peroxynitrite scavenger. CONCLUSIONS: Oxidative and nitrosative bursts play an important role in the antifungal activity of itraconazole and amphotericin B against C. gattii.

Interplay among differential exposure to Mycobacterium leprae and TLR4 polymorphism impacts the immune response in household contacts of leprosy patients.

Introduction: The aim of the present study was to investigate the association between the single nucleotide polymorphism (SNP) rs1927914 A/G in TLR4 gene and the immunological profile of household contacts (HHC) of leprosy patients. Leprosy classification is usually complex and requires the assessment of several clinical and laboratorial features. Methods: Herein, we have applied distinct models of descriptive analysis to explore qualitative/quantitative changes in chemokine and cytokine production in HHC further categorized according to operational classification [HHC(PB) and HHC(MB)] and according to TLR4SNP. Results and discussion: Our results showed that M. leprae stimuli induced an outstanding production of chemokines (CXCL8;CCL2; CXCL9; CXCL10) by HHC(PB), while increase levels of pro-inflammatory cytokines (IL-6; TNF; IFN-γ; IL-17) were observed for HHC(MB). Moreover, the analysis of chemokine and cytokine signatures demonstrated that A allele was associated with a prominent soluble mediator secretion (CXCL8; CXCL9; IL-6; TNF; IFN-γ). Data analysis according to TLR4 SNP genotypes further demonstrated that AA and AG were associated with a more prominent secretion of soluble mediators as compared to GG, supporting the clustering of AA and AG genotypes into dominant genetic model. CXCL8, IL-6, TNF and IL-17 displayed distinct profiles in HHC(PB) vs HHC(MB) or AA+AG vs GG genotype. In general, chemokine/cytokine networks analysis showed an overall profile of AA+GA-selective (CXCL9-CXCL10) and GG-selective (CXCL10-IL-6) axis regardless of the operational classification. However, mirrored inverted CCL2-IL-10 axis and a (IFN-γ-IL-2)-selective axis were identified in HHC(MB). CXCL8 presented outstanding performance to classify AA+AG from GG genotypes and HHC(PB) from HHC(MB). TNF and IL-17 presented elevated accuracy to classify AA+AG from GG genotypes and HHC(PB) (low levels) from HHC(MB) (high levels), respectively. Our results highlighted that both factors: i) differential exposure to M. leprae and ii) TLR4 rs1927914 genetic background impact the immune response of HHC. Our main results reinforce the relevance of integrated studies of immunological and genetic biomarkers that may have implications to improve the classification and monitoring of HHC in future studies.

Distinct cytokine profiles of circulating mononuclear cells stimulated with Staphylococcus aureus enterotoxin A in vitro during early and late episodes of chronic osteomyelitis.

We investigated the cytokine profile of peripheral mononuclear cells from chronic osteomyelitis (OST) patients following in vitro stimulation with staphylococcal enterotoxin A (SEA). We demonstrate that stimulation with SEA induced prominent lymphocyte proliferation and high levels of tumour necrosis factor (TNF)-α, interleukin (IL)-4 and IL-10 secretion in both OST and non-infected individuals (NI). Even though stimulation with SEA had no impact on IL-6 production in either patient group, the baseline level of IL-6 production by cells from OST patients was always significantly less than that produced by cells from NI. After classifying the osteomyelitic episodes based on the time after the last reactivation event as "early" (1-4 months) or "late" osteomyelitis (5-12 months), we found that increased levels of TNF-α and IL-4 in combination with decreased levels of IL-6 were observed in the early episodes. By contrast, increased levels of IL-10, IL-2 and IL-6 were hallmarks of late episodes. Our data demonstrate that early osteomyelitic episodes are accompanied by an increased frequency of "high producers" of TNF-α and IL-4, whereas late events are characterised by increased frequencies of "high producers" of IL-10, IL-6 and IL-2. These findings demonstrate the distinct cytokine profiles in chronic osteomyelitis, with a distinct regulation of IL-6 production during early and late episodes.

Leprosy Screening Based on Artificial Intelligence: Development of a Cross-Platform App.

BACKGROUND: According to the World Health Organization, achieving targets for control of leprosy by 2030 will require disease elimination and interruption of transmission at the national or regional level. India and Brazil have reported the highest leprosy burden in the last few decades, revealing the need for strategies and tools to help health professionals correctly manage and control the disease. OBJECTIVE: The main objective of this study was to develop a cross-platform app for leprosy screening based on artificial intelligence (AI) with the goal of increasing accessibility of an accurate method of classifying leprosy treatment for health professionals, especially for communities further away from major diagnostic centers. Toward this end, we analyzed the quality of leprosy data in Brazil on the National Notifiable Diseases Information System (SINAN). METHODS: Leprosy data were extracted from the SINAN database, carefully cleaned, and used to build AI decision models based on the random forest algorithm to predict operational classification in paucibacillary or multibacillary leprosy. We used Python programming language to extract and clean the data, and R programming language to train and test the AI model via cross-validation. To allow broad access, we deployed the final random forest classification model in a web app via shinyApp using data available from the Brazilian Institute of Geography and Statistics and the Department of Informatics of the Unified Health System. RESULTS: We mapped the dispersion of leprosy incidence in Brazil from 2014 to 2018, and found a particularly high number of cases in central Brazil in 2014 that further increased in 2018 in the state of Mato Grosso. For some municipalities, up to 80% of cases showed some data discrepancy. Of a total of 21,047 discrepancies detected, the most common was "operational classification does not match the clinical form." After data processing, we identified a total of 77,628 cases with missing data. The sensitivity and specificity of the AI model applied for the operational classification of leprosy was 93.97% and 87.09%, respectively. CONCLUSIONS: The proposed app was able to recognize patterns in leprosy cases registered in the SINAN database and to classify new patients with paucibacillary or multibacillary leprosy, thereby reducing the probability of incorrect assignment by health centers. The collection and notification of data on leprosy in Brazil seem to lack specific validation to increase the quality of the data for implementations via AI. The AI models implemented in this work had satisfactory accuracy across Brazilian states and could be a complementary diagnosis tool, especially in remote areas with few specialist physicians.

Prospects for new leprosy diagnostic tools, a narrative review considering ELISA and PCR assays.

Slit skin smear and histopathological examinations are currently the main laboratory tools used to aid the diagnosis of leprosy. However, their sensitivity is low, and many cases are not detected. New methodologies have been studied to develop more accurate tests. This narrative review aims to raise attention to the results of molecular (polymerase chain reaction) and serological (Enzyme-Linked Immunosorbent Assay) tests applied to the diagnosis of leprosy, and to summarize the available information about the former. Original scientific articles published in indexed international journals, whose study involved aspects of the diagnosis and classification of leprosy cases or home contacts, were selected. The data were extracted independently using a standardized method that dictated the inclusion of the following information: diagnosis in Paucibacillary and Multibacillary cases and in household contacts; sample number; sample type; study design; studied variables; statistical analysis employed; main results; and limitations identified. In clinical practice, the results from molecular and serological tests are assessed separately, with moderate sensitivity and specificity. However, an integrated study of these methodologies has been suggested for greater accuracy in diagnosis.

A novel integrated molecular and serological analysis method to predict new cases of leprosy amongst household contacts.

BACKGROUND: Early detection of Mycobacterium leprae is a key strategy for disrupting the transmission chain of leprosy and preventing the potential onset of physical disabilities. Clinical diagnosis is essential, but some of the presented symptoms may go unnoticed, even by specialists. In areas of greater endemicity, serological and molecular tests have been performed and analyzed separately for the follow-up of household contacts, who are at high risk of developing the disease. The accuracy of these tests is still debated, and it is necessary to make them more reliable, especially for the identification of cases of leprosy between contacts. We proposed an integrated analysis of molecular and serological methods using artificial intelligence by the random forest (RF) algorithm to better diagnose and predict new cases of leprosy. METHODS: The study was developed in Governador Valadares, Brazil, a hyperendemic region for leprosy. A longitudinal study was performed, including new cases diagnosed in 2011 and their respective household contacts, who were followed in 2011, 2012, and 2016. All contacts were diligently evaluated by clinicians from Reference Center for Endemic Diseases (CREDEN-PES) before being classified as asymptomatic. Samples of slit skin smears (SSS) from the earlobe of the patients and household contacts were collected for quantitative polymerase chain reaction (qPCR) of 16S rRNA, and peripheral blood samples were collected for ELISA assays to detect LID-1 and ND-O-LID. RESULTS: The statistical analysis of the tests revealed sensitivity for anti-LID-1 (63.2%), anti-ND-O-LID (57.9%), qPCR SSS (36.8%), and smear microscopy (30.2%). However, the use of RF allowed for an expressive increase in sensitivity in the diagnosis of multibacillary leprosy (90.5%) and especially paucibacillary leprosy (70.6%). It is important to report that the specificity was 92.5%. CONCLUSION: The proposed model using RF allows for the diagnosis of leprosy with high sensitivity and specificity and the early identification of new cases among household contacts.

Identificação de um paciente com hanseníase multibacilar por meio do teste sorológico (LID) em ações de busca ativa: um relato de caso / Identification of a patient with multibacillary leprosy using the serological test (LID) in active search actions: a case report

A hanseníase é uma doença crônica e infectocontagiosa causada pelo Mycobacterium leprae (M. leprae). Apresenta alta infectividade e baixa patogenicidade. O estudo teve como objetivo relatar a identificação de um paciente com hanseníase multibacilar através do teste sorológico (LID) em ação de busca ativa. Paciente do sexo masculino, 54 anos, residente em Governador Valadares, Minas Gerais, Brasil, proveniente da busca ativa do Núcleo de Pesquisa em Hansenologia (NuPqHans/UFJF-GV), apresentou teste sorológico positivo para proteínas recombinantes do bacilo (ML0405/ML2331). Encaminhado ao Centro de Referência de Doenças Endêmicas e Programas Especiais (CREDENPES), queixando-se de lesões na pele e nódulos pelo corpo, relatou histórico de traumas na cabeça, tonturas ocasionais, dormência nos pés e sangramento nasal. O paciente apresentou resultados de baciloscopia e biopsia positivos, concluindo o diagnóstico de hanseníase multibacilar, recebendo poliquimioterapia indicada. Após três meses de tratamento observou-se redução na área/diâmetro das lesões do abdômen, indicando a eficácia do tratamento. O resultado positivo do teste sorológico, permitiu a identificação de um paciente multibacilar, até então sem diagnóstico de hanseníase. Ademais, a utilização do teste sorológico LID nas atividades de busca ativa em áreas endêmicas para realização do diagnóstico precoce pode contribuir para o conceito zero hanseníase estipulado pela Organização Mundial da Saúde. (AU).

Leprosy is a chronic and infectious disease caused by Mycobacterium leprae (M. leprae). It has high infectivity and low pathogenicity. The aim of this study was to report the identification of a patient with multibacillary leprosy using the serological test (LID) during an active search. A 54-year-old male patient, living in Governador Valadares, Minas Gerais, Brazil, from the active search of the Leprosy Research Center (NuPqHans/UFJF-GV), presented a positive serological test for recombinant bacillus proteins (ML0405/ML2331). He was referred to the Reference Center for Endemic Diseases and Special Programs (CREDENPES), complaining of skin lesions and nodules all over his body, and reported a history of head trauma, occasional dizziness, numbness in his feet, and nosebleeds. The patient presented positive bacilloscopy and biopsy results, concluding the diagnosis of multibacillary leprosy and receiving the indicated multidrug therapy. After three months of treatment, there was a reduction in the area/diameter of the lesions on the abdomen, indicating the effectiveness of the treatment. The positive result of the serological test (LID) allowed the identification of a multibacillary patient, who until then had not been diagnosed with leprosy. In addition, the use of the LID serological test in active search activities in endemic areas for early diagnosis can contribute to the zero-leprosy concept stipulated by the World Health Organization. (AU)

Evaluation of the CCA Immuno-Chromatographic Test to Diagnose Schistosoma mansoni in Minas Gerais State, Brazil.

BACKGROUND: The Kato-Katz (KK) stool smear is the standard test for the diagnosis of Schistosoma mansoni infection, but suffers from low sensitivity when infections intensities are moderate to low. Thus, misdiagnosed individuals remain untreated and contribute to the disease transmission, thereby forestalling public health efforts to move from a modality of disease control to one of elimination. As an alternative, the urine-based diagnosis of schistosomiasis mansoni via the circulating cathodic antigen immuno-chromatographic test (CCA-ICT) has been extensively evaluated in Africa with the conclusion that it may replace the KK test in areas where prevalences are moderate or high. METHODS AND FINDINGS: The objective was to measure the performance of the CCA-ICT in a sample study population composed of residents from non-endemic and endemic areas for schistosomiasis mansoni in two municipalities of Minas Gerais state, Brazil. Volunteers (130) were classified into three infection status groups based on duplicate Kato-Katz thick smears from one stool sample (2KK test): 41 negative individuals from non-endemic areas, 41 negative individuals from endemic areas and 48 infected individuals from endemic areas. Infection status was also determined by the CCA-ICT and infection exposure by antibody ELISA (enzyme-linked immunosorbent assay) to S. mansoni soluble egg antigen (SEA) and soluble (adult) worm antigen preparation (SWAP). Sensitivity and specificity were influenced by whether the trace score visually adjudicated in the CCA-ICT was characterized as positive or negative for S. mansoni infection. An analysis of a two-graph receiver operating characteristic was performed to change the cutoff point. When the trace score was interpreted as a positive rather than as a negative result, the specificity decreased from 97.6% to 78.0% whereas sensitivity increased from 68.7% to 85.4%. A significantly positive correlation between the CCA-ICT scores and egg counts was identified (r = 0.6252, p = 0.0001). However, the CCA-ICT misdiagnosed as negative 14.6% of 2KK positive individuals, predominantly those with light infections (fewer than 100 eggs/g feces). Considering 2KK as reference test, the discriminating power of the CCA-ICT (the area under the curve [AUC] = 0.817) was greater than the SEA-ELISA (AUC = 0.744) and SWAP-ELISA (AUC = 0.704). CONCLUSION: Our data for the performance of the CCA-ICT in the Brazilian communities endemic for schistosomiasis mansoni support those from Africa, i.e., in areas with greater infection prevalence and intensities, the CCA-ICT may be useful as a tool to indicate community-based preventative chemotherapy without individual diagnosis. However, because of the Brazilian Ministry of Health's recommendation for individual diagnosis in areas where prevalence is less than 15%, i.e., those areas in which infection intensities are likely to be lowest, the CCA-ICT lacks the sensitivity to be used as standalone diagnostic tool.

Prospects for new leprosy diagnostic tools, a narrative review considering ELISA and PCR assays

Abstract Slit skin smear and histopathological examinations are currently the main laboratory tools used to aid the diagnosis of leprosy. However, their sensitivity is low, and many cases are not detected. New methodologies have been studied to develop more accurate tests. This narrative review aims to raise attention to the results of molecular (polymerase chain reaction) and serological (Enzyme-Linked Immunosorbent Assay) tests applied to the diagnosis of leprosy, and to summarize the available information about the former. Original scientific articles published in indexed international journals, whose study involved aspects of the diagnosis and classification of leprosy cases or home contacts, were selected. The data were extracted independently using a standardized method that dictated the inclusion of the following information: diagnosis in Paucibacillary and Multibacillary cases and in household contacts; sample number; sample type; study design; studied variables; statistical analysis employed; main results; and limitations identified. In clinical practice, the results from molecular and serological tests are assessed separately, with moderate sensitivity and specificity. However, an integrated study of these methodologies has been suggested for greater accuracy in diagnosis.

High levels of IgG4 to Schistosoma mansoni egg antigens in individuals with periportal fibrosis.

Specific IgG4 and IgE responses to adult worm antigen and soluble egg antigen (SEA) were examined in 267 individuals from an area in which schistosomiasis mansoni is endemic. Based on information obtained from clinical and sonographic examinations of this sample, the individuals were divided in three groups: 1) 204 individuals without periportal fibrosis, and liver and spleen enlargements; 2) 41 individuals without periportal fibrosis, but presenting with organopathy, with or without organomegaly; and 3) 22 individuals with periportal fibrosis, regardless of their status as having hepatomegaly and/or splenomegaly. Levels of IgG4 to SEA were significantly higher in sera from patients with fibrosis compared with the patients from the other two groups. We also found significantly higher levels of IgG4 against SEA in egg-negative patients with fibrosis compared with egg-negative patients from the other two groups. This report demonstrates a specific humoral response in patients presenting with initial fibrosis, a form of schistosomiasis transient between intestinal and severe hepatosplenic.

Utility of immunoglobulin isotypes against LID-1 and NDO-LID for, particularly IgG1, confirming the diagnosis of multibacillary leprosy

BACKGROUND Leprosy remains a health problem in many countries, with difficulties in diagnosis resulting in delayed treatment and more severe disabilities. Antibodies against several Mycobacterium leprae antigens have, however, shown value as diagnostic and/or prognostic markers. OBJECTIVES The objective of this study was to evaluate serum immunoglobulin (Ig) IgM and IgG subclass reactivity against three M. leprae specific antigens: NDO-HSA, a conjugate formed by natural octyl disaccharide bound to human serum albumin; LID-1, the fusion protein product of the ml0405 and ml2331 genes; and NDO-LID, a combination of LID-1 and NDO. METHODS Sera from healthy controls, paucibacillary (PB) and multibacillary (MB) leprosy patients, and their respective household contacts, were evaluated for the presence of antigen-specific IgM, IgG, and IgG subclass antibodies by enzyme-linked immunosorbent assay (ELISA). The sensitivity and specificity of each ELISA were evaluated by receiver operating characteristic (ROC) curve analysis. FINDINGS Our data confirm that serum IgM antibodies against NDO-HSA and IgG antibodies against LID-1, as well as IgG/M antibodies against NDO-LID, are markedly increased in MB patients. For the first time, our data reveal a selective increase in IgG1 and IgG3 antibodies against LID-1 and NDO-LID in MB patients, demonstrating that these antibody isotypes are suitable for differentiation between MB and PB patients. ROC curve analysis indicates an improved capacity for diagnosing MB leprosy patients using the detection of IgG antibodies, particularly the IgG1 isotype, specific to LID-1 and NDO-LID over the performance levels attained with NDO-HSA. CONCLUSIONS Our findings indicate that serological tests based on the detection of antigen-specific IgG1 antibodies are a useful tool to differentiate MB from PB patients, and indicate the enhanced performance of the LID-1 and NDO-LID antigens in the serodiagnosis of leprosy.

A importância da busca ativa como estratégia de controle da hanseníase em territórios endêmicos / The importance of active surveillance as a strategy to control leprosy in endemic areas

De acordo com a literatura, contatos de casos de hanseníase apresentam maior risco de adoecimento e, nesse sentido, é primordial fortalecer e ampliar as ações de busca ativa de casos no âmbito da atenção primária de saúde, potencializando a ampliação do diagnóstico precoce, tratamento oportuno e demais medidas de vigilância, controle e reabilitação necessárias. Neste cenário, objetivou-se realizar a busca ativa de novos casos de hanseníase em um distrito rural do município de Mantena, MG, e caracterizar a situação socioeconômica e epidemiológica da doença na região. Foram realizadas visitas aos residentes do distrito e palestras informativas sobre a doença, sendo os moradores convidados a participar da pesquisa. Um total de 292 indivíduos foi examinado no período de julho de 2016 a fevereiro de 2017. Foram diagnosticados 27 casos novos, 22 dos quais eram multibacilares. Os graus de incapacidade 1 e 2 foram identificados em 74% da amostra. Sobre as variáveis socioeconômicas, a maioria dos casos possui baixa escolaridade e baixa renda familiar, além de todos os casos terem tido contato com a doença em algum momento. A busca ativa foi eficiente para a detecção de casos novos de hanseníase na população estudada e contribuiu para o controle da doença que é endêmica na região. Ademais, a busca ativa foi relevante, especialmente considerando a baixa instrução dos indivíduos e, portanto, menor acesso à informação.

Contacts of leprosy cases present a higher risk of illness and, therefore it is essential to strengthen and expand actions to actively search for cases in primary health care, thus intensifying early diagnosis, timely treatment and other surveillance measures, and improve control and rehabilitation. In this setting, we aimed to perform the active search of new cases of leprosy in the rural area of Mantena, MG, and to characterize the socioeconomic and epidemiological situation related to the disease in the region. For this purpose, visits were made to the residents of the region with informative talks about the disease, and subsequently inhabitants were invited to participate in the research. A total of 292 individuals were examined from July 2016 to February 2017. Twenty-seven new cases were diagnosed, 22 of which were multibacillary. Grade 1 and 2 physical disabilities were identified in 74% of the new cases. Regarding socioeconomic variables, the majority of the cases had little schooling and low family income. In addition, all cases had had contact with the illness, at some point. We conclude that the active search was efficient to detect new leprosy cases in the population, and it contributed to the control of the disease, which is endemic in the region. In addition, active search is an important methodology, especially when the population involved has little schooling and thus less access to information.

Perfil epidemiológico da hanseníase num município superendêmico do interior do sudeste brasileiro / Epidemiological profile of leprosy in the hyperendemic municipality in the inner of brazilian southeastern

A hanseníase é uma doença infecto-contagiosa de evolução crônica que se manifesta principalmente através de sinais e sintomas dermatoneurológicos. O objetivo deste trabalho foi avaliar a situação epidemiológica da hanseníase no município de Teófilo Otoni (TO)-MG, no período de 2001 a 2010 de forma descritiva e retrospectiva.Os altos coeficientes de detecção geral e em menores de 15 anos encontrados, mantêm o município como hiperendêmico para hanseníase, sinalizando a necessidade de intensificar as ações de vigilância epidemiológica.O percentual médio de grau 2 de incapacidade,entre os casos novos estudados no momento do diagnóstico foi considerado alto (10,1%) segundo Ministério da Saúde (MS). O percentual médio de casos novos avaliados, no momento da alta por cura, apresentando grau 2 de incapacidade física foi de 4,3%. O coeficiente de prevalência no município de TO foi considerado médio (1- 4,9/10.000hab) no período de 2001 a 2010 com exceção dos anos de 2003, 2004 e 2005 quando foi considerado muito alto (12,7; 14,1 e 12,6/10.000 habitantes)respectivamente. Com relação a variável prevalência oculta, verificou-se que 526 casos de hanseníase não foram diagnosticados no município, significando que 40,3% dos doentes permaneceram sem diagnóstico naquele período, podendo atuar como fontes de contágio contribuindo para a cadeia de transmissão da doença.É necessário que o município promova e intensifique a descentralização das ações de controle da doença,desenvolva programas de capacitação para as equipes multiprofissionais da Estratégia de Saúde da Família(ESF) e estimule a busca ativa de novos casos.

Leprosy is an infectious disease manifested primarily bysigns and symptoms dermato-neurological. The objectiveof this study was to evaluate the epidemiological situation of leprosy in the city of Teofilo Otoni (TO), MGstate in the period 2001-2010 as a descriptive and retrospective study. The high detection rates in general and in children under 15 years found in TO, keep this municipality as hyper-endemic for leprosy, signaling the need to strengthen the epidemiological surveillance. The average percentage of grade 2 disability among new cases studied at diagnosis was considered high (10.1 %) according to the Ministry of Health in Brazil. The average percentage of new cases assessed at the time of discharge after cure, with grade 2 disability was 4.3 %. The prevalence rate in the city of TO was considered medium (1 to 4.9 /10.000 hab ) in the period from 2001 to 2010 except for the years 2003 , 2004 and 2005 when it was considered very high ( 12.7 , 14.1 and 12.6 / 10.000 hab) respectively. Regarding the prevalence hidden variable, it was found that 526 cases of leprosy were not diagnosed in the city,meaning that 40.3 % of patients remained undiagnosed at that time and may act as sources of infection contributing to the chain of disease transmission. It is necessary for the municipality to promote and intensify the decentralization of control of the disease, and also develop training programs for the multidisciplinary teams at family health strategy (ESF) and encourage active search for new cases.

Distinct cytokine profiles of circulating mononuclear cells stimulated with Staphylococcus aureus enterotoxin A in vitro during early and late episodes of chronic osteomyelitis

We investigated the cytokine profile of peripheral mononuclear cells from chronic osteomyelitis (OST) patients following in vitro stimulation with staphylococcal enterotoxin A (SEA). We demonstrate that stimulation with SEA induced prominent lymphocyte proliferation and high levels of tumour necrosis factor (TNF)-α, interleukin (IL)-4 and IL-10 secretion in both OST and non-infected individuals (NI). Even though stimulation with SEA had no impact on IL-6 production in either patient group, the baseline level of IL-6 production by cells from OST patients was always significantly less than that produced by cells from NI. After classifying the osteomyelitic episodes based on the time after the last reactivation event as "early" (1-4 months) or "late" osteomyelitis (5-12 months), we found that increased levels of TNF-α and IL-4 in combination with decreased levels of IL-6 were observed in the early episodes. By contrast, increased levels of IL-10, IL-2 and IL-6 were hallmarks of late episodes. Our data demonstrate that early osteomyelitic episodes are accompanied by an increased frequency of "high producers" of TNF-α and IL-4, whereas late events are characterised by increased frequencies of "high producers" of IL-10, IL-6 and IL-2. These findings demonstrate the distinct cytokine profiles in chronic osteomyelitis, with a distinct regulation of IL-6 production during early and late episodes.