Abstract INTRODUCTION: Immunological control of Mycobacterium tuberculosis infection is dependent on the cellular immune response, mediated predominantly by Th1 type CD4+ T cells. Polarization of the immune response to Th2 can inhibit the host immune protection against pathogens. Patients with tuberculosis coinfected with helminths demonstrate more severe pulmonary symptoms, a deficiency in the immune response against tuberculosis, and an impaired response to anti-tuberculosis therapy. METHODS: We evaluated the cellular immune response and the impact of the presence of Ascaris lumbricoides on the immune and clinical response in pulmonary tuberculosis patients. Ninety-one individuals were included in the study: 38 tuberculosis patients, 11 tuberculosis patients coinfected with Ascaris lumbricoides and other helminths, 10 Ascaris lumbricoides patients, and 34 non-infected control individuals. Clinical evolution of pulmonary tuberculosis was studied on 0, 30, 60, and 90 days post-diagnosis of Mycobacterium tuberculosis and Ascaris lumbricoides. Furthermore, immune cells and plasma cytokine profiles were examined in mono/coinfection by Mycobacterium tuberculosis and Ascaris lumbricoides using flow cytometry. RESULTS: There were no statistical differences in any of the evaluated parameters and the results indicated that Ascaris lumbricoides infection does not lead to significant clinical repercussions in the presentation and evolution of pulmonary tuberculosis. CONCLUSIONS: The association with Ascaris lumbricoides did not influence the Th1, Th2, and Th17 type responses, or the proportions of T lymphocyte subpopulations. However, higher serum levels of IL-6 in tuberculosis patients may explain the pulmonary parenchymal damage.

Abstract: BACKGROUND: The Clinical Trial for Uniform Multidrug Therapy for Leprosy Patients in Brazil (U-MDT/CT-BR), designed to evaluate the effectiveness of a six-months regimen, assessed the adverse effects caused by the drugs. OBJECTIVE: Describe adverse effects due to MDT in U-MDT/CT-BR, comparing the uniform regimen (U-MDT) to the current WHO regimen (R-MDT). Patients and methods: After operational classification, patients were randomly allocated to the study groups. U-MDT PB and U-MDT MB groups, received the U-MDT regimen, six doses of MB-MDT (rifampicin, dapsone and clofazimine). R-MDT PB and R-MDT MB groups, received the WHO regimens: six doses (rifampicin and dapsone) for PB and 12 doses (rifampicin, dapsone and clofazimine) for MB. During treatment, patients returned monthly for clinical and laboratorial evaluation. Patients with single lesion were not included in this trial. RESULTS: Skin pigmentation (21.7%) and xerosis (16.9%) were the most frequent complaints among 753 patients. Laboratory exams showed hemoglobin concentration lower than 10g/dL in 23.3% of the patients, glutamic oxaloacetic transaminase (GOT) above 40U/L in 29.5% and glutamic pyruvic transaminase (GPT) above 40U/L in 28.5%. Twenty-four patients (3.2%) stopped dapsone intake due to adverse effects, of whom 16.6% due to severe anemia. One case of sulfone syndrome was reported. STUDY LIMITATIONS: Loss of some monthly laboratory sample collection. CONCLUSIONS: There was no statistical difference regarding adverse effects in the R-MDT and U-MDT groups but anemia was greater in patients from R-MDT/MB group, therefore adverse effects do not represent a constraint to recommend the six-month uniform regimen of treatment for all leprosy patients.

Abstract: In this review, the most relevant and current epidemiological data, the main clinical, laboratory and therapeutical aspects of leprosy are presented. Detailed discussion of the main drugs used for leprosy treatment, their most relevant adverse effects, evolution of the therapeutic regimen, from dapsone as a monotherapy to the proposed polychemotherapy by World Health Organization (WHO) can be found in this CME. We specifically highlight the drug acceptability, reduction in treatment duration and the most recent proposal of a single therapeutic regimen, with a fixed six months duration, for all clinical presentations, regardless of their classification.

A tuberculose (TB) em pessoas vivendo com HIV (PVHIV) é a maior causa infecciosa de morte relacionada à AIDS. O objetivo deste trabalho foi estimar a prevalência da coinfecção TB/HIV, avaliar a notificação dos dois agravos de maneira temporal, por meio de relacionamento de bases de dados, e buscar fatores associados às notificações de AIDS e TB. A prevalência de coinfecção TB/HIV foi de 7,7%. O grupo de PVHIV com posterior diagnóstico de TB foi o mais representativo, apesar de medidas preventivas disponíveis. A subnotificação de TB entre os casos de AIDS foi de 35%, e 19,6% dos casos de TB poderiam ser notificados como AIDS. Para os casos de AIDS com menção de TB, residir na capital apresentou uma chance 75% maior de ser notificado no Sistema de Informação de Agravos de Notificação/Tuberculose (SINAN TB), e ter falecido aumentou em 40% a chance de registro. Dos casos de TB com menção de HIV, ser de cor parda, ter entre 25 e 39 anos, residir na capital e ter evoluído para o óbito estiveram associados à maior chance de notificação na AIDS. O linkage periódico dessas bases pode ser uma ferramenta programática poderosa para diminuir a subnotificação.

Tuberculosis (TB) in persons living with HIV (PLHIV) is the leading infectious cause of AIDS-related death. The aim of this study was to estimate the prevalence of TB/HIV coinfection, evaluate notification of the two diseases over time by probabilistic database linkage, and identify factors associated with AIDS and TB notifications. Prevalence of TB/HIV coinfection was 7.7%. The group of PLHIV with subsequent TB diagnosis was the most representative, despite available preventive measures. Underreporting of TB among AIDS cases was 35%, and 19.6% of TB cases could have been reported as AIDS. For AIDS cases with mention of TB, living in the state capital showed 75% greater odds of being reported to the Tuberculosis Notification System (SINAN-TB), and having died increased the odds of reporting by 40%. Of TB cases with mention of HIV, brown skin color, age 25 to 39 years, living in the state capital, and having evolved to death were associated with higher odds of reporting to the AIDS Notification System. Periodic linkage of these databases can be a powerful tool for programs to decrease underreporting.

La tuberculosis (TB) en personas viviendo con VIH (PVVIH) es la mayor causa infecciosa de muerte relacionada con el SIDA. El objetivo de este trabajo fue estimar la prevalencia de la coinfección TB/VIH, evaluar la notificación de las dos enfermedades de manera temporal, relación de bases de datos, y buscar factores asociados a las notificaciones de SIDA y TB. La prevalencia de coinfección TB/VIH fue de un 7,7%. El grupo de PVVIH, con posterior diagnóstico de TB, fue el más representativo, a pesar de las medidas preventivas disponibles. La subnotificación de TB entre los casos de SIDA fue de un 35%, y un 19,6% de los casos de TB podrían ser notificados como SIDA. Para los casos de SIDA con mención de TB, residir en la capital presentó una oportunidad un 75% mayor de ser notificada en el Sistema de Notificación de Tuberculosis (SINAN TB), y haber fallecido aumentó en un 40% la oportunidad de registro. De los casos de TB con mención de VIH, ser mestizo, tener entre 25 y 39 años, residir en la capital y haber evolucionado hacia el óbito estuvieron asociados a una mayor oportunidad de notificación en el SIDA. La vinculación periódica de estas bases puede ser una herramienta programática poderosa para disminuir la subnotificación.

A tuberculose (TB) em pessoas vivendo com HIV (PVHIV) é a maior causa infecciosa de morte relacionada à AIDS. O objetivo deste trabalho foi estimar a prevalência da coinfecção TB/HIV, avaliar a notificação dos dois agravos de maneira temporal, por meio de relacionamento de bases de dados, e buscar fatores associados às notificações de AIDS e TB. A prevalência de coinfecção TB/HIV foi de 7,7%. O grupo de PVHIV com posterior diagnóstico de TB foi o mais representativo, apesar de medidas preventivas disponíveis. A subnotificação de TB entre os casos de AIDS foi de 35%, e 19,6% dos casos de TB poderiam ser notificados como AIDS. Para os casos de AIDS com menção de TB, residir na capital apresentou uma chance 75% maior de ser notificado no Sistema de Informação de Agravos de Notificação/Tuberculose (SINAN TB), e ter falecido aumentou em 40% a chance de registro. Dos casos de TB com menção de HIV, ser de cor parda, ter entre 25 e 39 anos, residir na capital e ter evoluído para o óbito estiveram associados à maior chance de notificação na AIDS. O linkage periódico dessas bases pode ser uma ferramenta programática poderosa para diminuir a subnotificação.

Tuberculosis (TB) in persons living with HIV (PLHIV) is the leading infectious cause of AIDS-related death. The aim of this study was to estimate the prevalence of TB/HIV coinfection, evaluate notification of the two diseases over time by probabilistic database linkage, and identify factors associated with AIDS and TB notifications. Prevalence of TB/HIV coinfection was 7.7%. The group of PLHIV with subsequent TB diagnosis was the most representative, despite available preventive measures. Underreporting of TB among AIDS cases was 35%, and 19.6% of TB cases could have been reported as AIDS. For AIDS cases with mention of TB, living in the state capital showed 75% greater odds of being reported to the Tuberculosis Notification System (SINAN-TB), and having died increased the odds of reporting by 40%. Of TB cases with mention of HIV, brown skin color, age 25 to 39 years, living in the state capital, and having evolved to death were associated with higher odds of reporting to the AIDS Notification System. Periodic linkage of these databases can be a powerful tool for programs to decrease underreporting.

La tuberculosis (TB) en personas viviendo con VIH (PVVIH) es la mayor causa infecciosa de muerte relacionada con el SIDA. El objetivo de este trabajo fue estimar la prevalencia de la coinfección TB/VIH, evaluar la notificación de las dos enfermedades de manera temporal, relación de bases de datos, y buscar factores asociados a las notificaciones de SIDA y TB. La prevalencia de coinfección TB/VIH fue de un 7,7%. El grupo de PVVIH, con posterior diagnóstico de TB, fue el más representativo, a pesar de las medidas preventivas disponibles. La subnotificación de TB entre los casos de SIDA fue de un 35%, y un 19,6% de los casos de TB podrían ser notificados como SIDA. Para los casos de SIDA con mención de TB, residir en la capital presentó una oportunidad un 75% mayor de ser notificada en el Sistema de Notificación de Tuberculosis (SINAN TB), y haber fallecido aumentó en un 40% la oportunidad de registro. De los casos de TB con mención de VIH, ser mestizo, tener entre 25 y 39 años, residir en la capital y haber evolucionado hacia el óbito estuvieron asociados a una mayor oportunidad de notificación en el SIDA. La vinculación periódica de estas bases puede ser una herramienta programática poderosa para disminuir la subnotificación.

Tuberculosis (TB) is one of the infectious diseases that contributes most to the morbidity and mortality of millions of people worldwide. Brazil is one of 22 countries that accounts for 80% of the tuberculosis global burden. The highest incidence rates in Brazil occur in the States of Amazonas and Rio de Janeiro. The aim of this study was to describe the temporal distribution of TB in the State of Amazonas. Between 2001 and 2011, 28,198 cases of tuberculosis were reported in Amazonas, distributed among 62 municipalities, with the capital Manaus reporting the highest (68.7%) concentration of cases. Tuberculosis was more prevalent among males (59.3%) aged 15 to 34 years old (45.5%), whose race/color was predominantly pardo (64.7%) and who had pulmonary TB (84.3%). During this period, 81 cases of multidrug-resistant TB were registered, of which the highest concentration was reported from 2008 onward (p = 0.002). The municipalities with the largest numbers of indigenous individuals affected were São Gabriel da Cachoeira (93%), Itamarati (78.1%), and Santa Isabel do Rio Negro (70.1%). The future outlook for this region includes strengthening the TB control at the primary care level, by expanding diagnostic capabilities, access to treatment, research projects developed in collaboration with the Dr. Heitor Vieira Dourado Tropical Medicine Foundation .;Fundação de Medicina Tropical Dr. Heitor Vieira Dourado (FMT-HVD).; and financing institutions, such as the project for the expansion of the Clinical Research Center and the creation of a hospital ward for individuals with transmissible respiratory diseases, including TB.

FUNDAMENTOS: Em países altamente endêmicos a transmissão e infecção sub-clínica da hanseníase provavelmente ocorrem e a doença se manifesta em indivíduos sem qualquer contato próximo conhecido com paciente com hanseníase. Os trabalhadores de saúde são contatos sociais que pertencem à mesma rede (Sistema de Saúde) e alguns deles compartilham o mesmo ambiente social (auxiliares de enfermagem) com pacientes conhecidos e/ou portadores. OBJETIVO: Conhecer a soropositividade ao ML Flow entre os profissionais de saúde. MÉTODOS: Foi realizado um estudo transversal através de inquérito sorológico com o teste ML Flow em 450 profissionais de saúde (médicos, enfermeiros e auxiliares de enfermagem) visando conhecer a soropositividade em áreas de alta e baixa endemicidade em municípios de três estados brasileiros (RS, MS e RJ). RESULTADOS: Os resultados mostraram 16% de soropositividade em geral, mais elevada na área de baixa endemicidade, independente da assistência direta a pacientes com hanseníase. Paradoxalmente foi observada associação estatística entre a área estudada e soropositividade, apontando o lugar de mais baixa endemicidade (CA) com o maior valor (p=0,033). CONCLUSÃO: os autores sugerem a presença de ligação inespecífica a soroalbumina bovina (BSA), carreadora do antígeno PGL-1 no teste ML Flow para explicar os resultados inesperados e recomendam testagem ampliada utilizando testes com albumina humana e bovina.

BACKGROUND: In highly endemic countries, transmission and sub-clinical infection of leprosy are likely and the disease manifests itself in individuals without any known close contact with a leprosy patient. Health workers are social contacts belonging to the same network (the Health System) and some of them share the same social environment (nursing assistants) as patients with known patients and / or carriers. OBJECTIVE: To identify ML Flow seropositivity among health professionals. METHODS: We conducted a cross-sectional study using a serological survey with the ML Flow test in 450 health professionals (doctors, nurses and nursing assistants), in order to detect seropositivity in areas of high and low endemicity in municipalities from three Brazilian states (RJ, MS and RS). RESULTS: The results showed general 16% seropositivity, higher in low endemic areas, regardless of whether there was direct care for leprosy patients. Paradoxically, a statistical association was observed between the area studied and seropositivity, as the place with the lowest endemicity (CA) had the highest seropositivity rate (p = 0.033). CONCLUSION: The authors suggest these results are associated with a presence of an unspecified link to bovine serum albumin (BSA), carrier of PGL-1 in the ML Flow test, and recommend expanded seroepidemiological research utilizing tests with human and bovine albumin.

IntroductionYellow fever is a non-contagious infectious disease, highly lethal, transmitted by the Aedes, Haemagogus and Sabethes.MethodsDescriptive retrospective study of the yellow fever cases in Amazonas, between 1996 and 2009.ResultsForty two cases of yellow fever were confirmed, with 30 deaths, 10% of which were foreigners.ConclusionsThe presence of Aedes aegypti and Aedes albopictus in both rural Amazonas and its capital demonstrates the dispersion of these vectors and underscores the need for better and continuous epidemiological and entomological control.

The diagnosis of leprosy continues to be based on clinical symptoms and early diagnosis and treatment are critical to preventing disability and transmission. Sensitive and specific laboratory tests are not available for diagnosing leprosy. Despite the limited applicability of anti-phenolic glycolipid-I (PGL-I) serology for diagnosis, it has been suggested as an additional tool to classify leprosy patients (LPs) for treatment purposes. Two formats of rapid tests to detect anti-PGL-I antibodies [ML immunochromatography assay (ICA) and ML Flow] were compared in different groups, multibacillary patients, paucibacillary patients, household contacts and healthy controls in Brazil and Nepal. High ML Flow intra-test concordance was observed and low to moderate agreement between the results of ML ICA and ML Flow tests on the serum of LPs was observed. LPs were "seroclassified" according to the results of these tests and the seroclassification was compared to other currently used classification systems: the World Health Organization operational classification, the bacilloscopic index and the Ridley-Jopling classification. When analysing the usefulness of these tests in the operational classification of PB and MB leprosy for treatment and follow-up purposes, the ML Flow test was the best point-of-care test for subjects in Nepal and despite the need for sample dilution, the ML ICA test yielded better performance among Brazilian subjects. Our results identified possible ways to improve the performance of both tests.

New Mycobacterium leprae protein antigens can contribute to improved serologic tests for leprosy diagnosis/classification and multidrug therapy (MDT) monitoring. This study describes seroreactivity to M. leprae proteins among participants from three highly endemic leprosy areas in Brazil: central-western Goiânia/Goiás (GO) (n = 225), Rondonópolis/Mato Grosso (MT) (n = 764) and northern Prata Village/Pará (PA) (n = 93). ELISA was performed to detect IgG to proteins (92f, 46f, leprosy IDRI diagnostic-1, ML0405, ML1213) and IgM to phenolic glycolipid-I (PGL-I). Multibacillary (MB) leprosy had positive rates for PGL-I that were similar to those for proteins; however, some anti-PGL-I-negative subjects were positive for proteins, suggesting that adding protein antigen to PGL-I can enhance the sensitivity of MB leprosy detection. In MT, different degrees of seroreactivity were observed and ranked for MB, former patients after MDT, paucibacillary (PB) leprosy, household contact (HHC) and endemic control (EC) groups. The seroreactivity of PB patients was low in GO and MT. HHCs from different endemic sites had similar IgG antibody responses to proteins. 46f and 92f were not recognised by most tuberculosis patients, ECs or HHCs within GO, an area with high BCG vaccination coverage. Low positivity in EC and HHC was observed in PA and MT. Our results provide evidence for the development of an improved serologic test that could be widely applicable for MB leprosy testing in Brazil.

This study sought to verify the correlation between leprosy types and the adverse effects of treatment drugs. This quantitative, prospective, nested study was developed at the Dona Libânia Dermatology Centre in Fortaleza, Brazil. Data were collected from November 2007-November 2008. During this period, 818 leprosy patients were diagnosed and began treatment. Forty patients with tuberculoid leprosy (TT) were selected. Twenty patients followed a standard therapy of dapsone and rifampicin and 20 were administered dapsone, rifampicin and clofazimine (U-MDT). Twenty patients with borderline lepromatous (BL) and lepromatous leprosy (LL) were also selected and treated with U-MDT. All of the subjects received six doses. With the exception of haemolytic anaemia, there was a low incidence of adverse effects in all the groups. We did not observe any differences in the incidence of haemolytic anaemia or other side effects across groups of patients with TT, BL or LL treated with U-MDT.

Leprosy will continue to be a public health problem for several decades. The World Health Organization (WHO) recommends that, for treatment purposes, leprosy cases be classified as either paucibacillary or multibacillary (MB). A uniform leprosy treatment regimen would simplify treatment and halve the treatment duration for MB patients. The clinical trial for uniform multidrug therapy (U-MDT) for leprosy patients (LPs) in Brazil is a randomised, open-label clinical trial to evaluate if the effectiveness of U-MDT for leprosy equals the regular regimen, to determine the acceptability of the U-MDT regimen and to identify the prognostic factors. This paper details the clinical trial methodology and patient enrolment data. The study enrolled 858 patients at two centres and 78.4% of participants were classified as MB according to the WHO criteria. The main difficulty in evaluating a new leprosy treatment regimen is that no reliable data are available for the current treatment regimen. Relapse, reaction and impaired nerve function rates have never been systematically determined, although reaction and impaired nerve function are the two major causes of nerve damage that lead to impairments and disabilities in LPs. Our study was designed to overcome the need for reliable data about the current treatment and to compare its efficacy with that of a uniform regimen.

O surgimento de resistência múltipla às drogas de primeira linha implica na utilização de fármacos de maior custo, com duração mais longa, maior complexidade e mais efeitos colaterais. Relatamos os casos de três pacientes com multirresistência primária aos tuberculostáticos. O portador de HIV evoluiu para óbito antes do resultado do teste de sensibilidade. Portanto, o diagnóstico precoce de tuberculose multirresistente e o tratamento adequado devem ser prioridades do Programa Nacional do Controle da Tuberculose, visando interromper a cadeia de transmissão. Além disto, é urgente que seja avaliada a substituição do método das proporções por técnicas mais modernas e mais rápidas.

The occurrence of tuberculosis with first-line multidrug resistance leads to the use of alternative medications, often at higher costs, longer treatment periods, and greater clinical complexity. Here, we report 3 patients with multidrug-resistant tuberculosis. One patient with human immunodeficiency virus died before the sensitivity test was performed. The early diagnosis of multidrug-resistant tuberculosis and appropriate treatment should be priorities of the National Tuberculosis Control Program in order to break the chain of transmission. In addition, the possibility of substituting the proportion method with more modern and faster techniques should be urgently evaluated.

A hanseníase é uma doença infecciosa de evolução crônica causada pelo Mycobacterium leprae que acomete com maior frequência a mucosa nasal. Esse acometimento independe da forma clínica da doença e pode ocorrer mesmo antes do aparecimento de lesões na pele ou em outras partes do corpo. Faz-se necessário a vigilância epidemiológica dos contatos de casos novos de hanseníase para o diagnóstico precoce da doença. OBJETIVOS: Identificar lesões específicas e precoces de hanseníase por meio de exame endoscópico, baciloscópico, histopatológico e da reação em cadeia da polimerase em Tempo Real da mucosa das cavidades nasais dos contatos domiciliares e peridomiciliares com sorologia positiva para o antígeno glicolipídio fenólico. MATERIAL E MÉTODOS: Estudo prospectivo transversal em 31 contatos de pacientes de hanseníase com sorologia positiva (PGL-1), 05 controles negativos e 01 positivo no período de 2003 a 2006. RESULTADOS: Entre os contatos soropositivos a PCR-RT foi positiva para a presença de DNA de M. leprae em 06 (19,35%) destes e o maior número de cópias do genoma do bacilo foi encontrado no contato que adoeceu. CONCLUSÃO: Isoladamente os exames da mucosa nasal não permitiram o diagnóstico precoce da hanseníase, mas com a combinação de vários métodos, o exame dos contatos pôde ajudar na identificação da infecção subclínica e monitoramento daqueles que poderiam ter papel importante na transmissão da doença.

Leprosy is a chronic infectious disease caused by Mycobacterium leprae. The disease more frequently affects the nasal mucosa and can occur independently of its clinical form or even before lesions on the skin or on other parts of the body. It is necessary to employ epidemiological surveillance of household contacts with new leprosy cases for early disease diagnosis. AIM: identify specific and early leprosy lesions through endoscopic, baciloscopy, histopathology exams, and real time polymerase chain reaction of the nasal cavity mucosa on household and peridomiciliary contacts with positive serology for the phenolic glycolipid 1 antigen. METHODOLOGY: Between 2003 at 2006 there was a prospective cross-sectional clinical study with 31 contacts with patients with leprosy with positive serology against PGL-1, 05 negative controls and 01 positive control. RESULTS: Between seropositive contacts, real-time PCR was positive for M. leprae DNA in 06 (19.35%) of them and the higher number of genome copies were found in contacts who became sick. CONCLUSION: Nasal mucosa tests alone did not enable the early diagnosis of Leprosy. However, through the combination of various methods, tests on the contacts can help identify subclinical infection and monitor the contacts that could be responsible for spreading the disease.