Brazilian Thoracic Association recommendations for the management of post-tuberculosis lung disease.

Historically, all efforts against tuberculosis were focused on rapid diagnosis and effective treatment to break the chain of transmission of Mycobacterium tuberculosis. However, in the last few years, more and more evidence has been found on the dramatic consequences of the condition defined as post-tuberculosis lung disease (PTLD). Approximately one third of patients surviving pulmonary tuberculosis face considerable ongoing morbidities, including respiratory impairment, psychosocial challenges, and reduced health-related quality of life after treatment completion. Given the important global and local burden of tuberculosis, as well as the estimated burden of PTLD, the development of a consensus document by a Brazilian scientific society-Sociedade Brasileira de Pneumologia e Tisiologia (SBPT)-was considered urgent for the prevention and management of this condition in order to allocate resources to and within tuberculosis services appropriately and serve as a guide for health care professionals. A team of eleven pulmonologists and one methodologist was created by the SBPT to review the current evidence on PTLD and develop recommendations adapted to the Brazilian context. The expert panel selected the topics on the basis of current evidence and international guidelines. During the first phase, three panel members drafted the recommendations, which were divided into three sections: definition and prevalence of PTLD, assessment of PTLD, and management of PTLD. In the second phase, all panel members reviewed, discussed, and revised the recommendations until a consensus was reached. The document was formally approved by the SBPT in a special session organized during the 2023 SBPT Annual Conference.

Diversity of pulsed-field gel electrophoresis patterns of Mycobacterium abscessus type 2 clinical isolates.

An epidemic of infections by rapidly growing mycobacteria related to surgical procedures between 2004 and 2008 in Brazil was caused by a unique strain showing the Mycobacterium abscessus type 2 pattern when it was analyzed by the molecular method of PCR-restriction enzyme analysis of the hsp65 gene (PRA-hsp65). In order to investigate the diversity of M. abscessus type 2 clinical isolates and to assess whether this epidemic strain was present in specimens from nonsurgical patients, we studied 52 isolates from 38 patients showing this characteristic PRA-hsp65 pattern obtained between 2005 and 2009. All isolates were identified by sequencing of region V of the rpoB gene and typed by pulsed-field gel electrophoresis (PFGE) using two restriction enzymes, DraI and AseI. Seven isolates obtained from sputum, bronchoalveolar lavage fluid, and urine in three different Brazilian states showed rpoB sequences 100% similar to the rpoB sequence of epidemic strain INCQS 594 and PFGE patterns highly related to the patterns of isolates, evidencing the presence of the epidemic strain in isolates from patients not associated with the surgical epidemic. The remaining isolates showed diverse rpoB sequences, with the highest similarities being to the corresponding sequences of M. massiliense(T) CIP 108297 (21 isolates), M. bolletii(T) CIP 108541 (19 isolates), or M. abscessus(T) ATCC 19977 (5 isolates). Two additional clusters could be detected by PFGE. PFGE showed 100% typeability and reproducibility and discriminatory powers, calculated by Simpson's index of diversity, of 0.978 (DraI) and 0.986 (AseI), confirming its suitability for the discrimination of M. abscessus type 2 isolates.

Diagnosis of tuberculosis: a consensus statement from the Brazilian Thoracic Association.

Early, accurate diagnosis of tuberculosis is one of the major pillars of the control of the disease. The purpose of this consensus statement is to provide health professionals with the most current, useful evidence for the diagnosis of tuberculosis in Brazil. To that end, the Tuberculosis Committee of the Brazilian Thoracic Association brought together 14 members of the Association with recognized expertise in tuberculosis in Brazil to compose the statement. A nonsystematic review of the following topics was carried out: clinical diagnosis, bacteriological diagnosis, radiological diagnosis, histopathological diagnosis, diagnosis of tuberculosis in children, and diagnosis of latent tuberculosis infection.

Long-term survival and cause-specific mortality of patients newly diagnosed with tuberculosis in São Paulo state, Brazil, 2010-15: a population-based, longitudinal study.

BACKGROUND: Long-term survival and cause-specific mortality of patients who start tuberculosis treatment is rarely described. We aimed to assess the long-term survival of these patients and evaluate the association between vulnerable conditions (social, health behaviours, and comorbidities) and cause-specific mortality in a country with a high burden of tuberculosis. METHODS: In this population-based, longitudinal study in São Paulo state, Brazil, we described the 5-year survival of patients who were newly diagnosed with tuberculosis in 2010. We included patients with newly-diagnosed tuberculosis, aged 15 years or older, and notified to the São Paulo State Tuberculosis Program in 2010. We excluded patients whose diagnosis had changed during follow-up (ie, they did not have tuberculosis) and patients who had multidrug-resistant (MDR) tuberculosis. We selected our population with tuberculosis from the dedicated electronic system TBweb. Our primary objective was to estimate the excess mortality over 5 years and within the group who survived the first year, compared with the general São Paulo state population. We also estimated the association between social vulnerability (imprisonment and homelessness), health behaviours (alcohol and drug use), and comorbidities (diabetes and mental disorders) with all-cause and cause-specific mortality. We used the competing risk analysis framework, estimating cause-specific hazard ratios (HRs) adjusted for potential confounding factors. FINDINGS: In 2010, there were 19 252 notifications of tuberculosis cases. We excluded 550 cases as patients were younger than 15 years, 556 cases that were not tuberculosis, 2597 retreatments, and 48 cases of MDR tuberculosis, resulting in a final cohort of 15 501 patients with tuberculosis. Over a period of 5 years from tuberculosis diagnosis, 2660 (17%) of 15 501 patients died. Compared with the source population, matched by age, sex, and calendar year, the standardised mortality ratio was 6·47 (95% CI 6·22-6·73) over 5 years and 3·93 (3·71-4·17) among those who survived the first year. 1197 (45%) of 2660 deaths were due to infection. Homelessness and alcohol and drug use were associated with death from infection (adjusted cause-specific HR 1·60, 95% CI 1·39-1·85), cardiovascular (1·43, 1·06-1·95), and external or ill-defined causes of death (1·80, 1·37-2·36). Diabetes was associated with deaths from cardiovascular causes (1·70, 1·23-2·35). INTERPRETATION: Patients newly diagnosed with tuberculosis were at a higher risk of death than were the source population, even after tuberculosis treatment. Post-tuberculosis sequelae and vulnerability are associated with excess mortality and must be addressed to mitigate the tuberculosis burden worldwide. FUNDING: Wellcome Trust.

Predictive model of unfavorable outcomes for multidrug-resistant tuberculosis.

OBJECTIVE: to analyze the temporal trend, identify the factors related and elaborate a predictive model for unfavorable treatment outcomes for multidrug-resistant tuberculosis (MDR-TB). METHODS: Retrospective cohort study with all cases diagnosed with MDR-TB between the years 2006 and 2015 in the state of São Paulo. The data were collected from the state system of TB cases notifications (TB-WEB). The temporal trend analyzes of treatment outcomes was performed through the Prais-Winsten analysis. In order to verify the factors related to the unfavorable outcomes, abandonment, death with basic cause TB and treatment failure, the binary logistic regression was used. Pictorial representations of the factors related to treatment outcome and their prognostic capacity through the nomogram were elaborated. RESULTS: Both abandonment and death have a constant temporal tendency, whereas the failure showed it as decreasing. Regarding the risk factors for such outcomes, using illicit drugs doubled the odds for abandonment and death. Besides that, being diagnosed in emergency units or during hospitalizations was a risk factor for death. On the contrary, having previous multidrug-resistant treatments reduced the odds for the analyzed outcomes by 33%. The nomogram presented a predictive model with 65% accuracy for dropouts, 70% for deaths and 80% for failure. CONCLUSIONS: The modification of the current model of care is an essential factor for the prevention of unfavorable outcomes. Through predictive models, as presented in this study, it is possible to develop patient-centered actions, considering their risk factors and increasing the chances for cure.

Brazilian Thoracic Association recommendations for the management of post-tuberculosis lung disease / Recomendações da Sociedade Brasileira de Pneumologia e Tisiologia para o manejo da doença pulmonar pós-tuberculose

ABSTRACT Historically, all efforts against tuberculosis were focused on rapid diagnosis and effective treatment to break the chain of transmission of Mycobacterium tuberculosis. However, in the last few years, more and more evidence has been found on the dramatic consequences of the condition defined as post-tuberculosis lung disease (PTLD). Approximately one third of patients surviving pulmonary tuberculosis face considerable ongoing morbidities, including respiratory impairment, psychosocial challenges, and reduced health-related quality of life after treatment completion. Given the important global and local burden of tuberculosis, as well as the estimated burden of PTLD, the development of a consensus document by a Brazilian scientific society-Sociedade Brasileira de Pneumologia e Tisiologia (SBPT)-was considered urgent for the prevention and management of this condition in order to allocate resources to and within tuberculosis services appropriately and serve as a guide for health care professionals. A team of eleven pulmonologists and one methodologist was created by the SBPT to review the current evidence on PTLD and develop recommendations adapted to the Brazilian context. The expert panel selected the topics on the basis of current evidence and international guidelines. During the first phase, three panel members drafted the recommendations, which were divided into three sections: definition and prevalence of PTLD, assessment of PTLD, and management of PTLD. In the second phase, all panel members reviewed, discussed, and revised the recommendations until a consensus was reached. The document was formally approved by the SBPT in a special session organized during the 2023 SBPT Annual Conference.

RESUMO Historicamente, todos os esforços contra a tuberculose concentraram-se no diagnóstico rápido e no tratamento efetivo para quebrar a cadeia de transmissão do Mycobacterium tuberculosis. No entanto, nos últimos anos, têm sido encontradas mais e mais evidências sobre as dramáticas consequências da condição definida como doença pulmonar pós-tuberculose (DPPT). Aproximadamente um terço dos pacientes que sobrevivem à tuberculose pulmonar enfrenta morbidades consideráveis e persistentes, incluindo comprometimento respiratório, desafios psicossociais e redução da qualidade de vida relacionada à saúde após o término do tratamento. Diante da importante carga global e local da tuberculose, bem como da carga estimada da DPPT, considerou-se urgente o desenvolvimento de um documento de consenso por uma sociedade científica brasileira - a Sociedade Brasileira de Pneumologia e Tisiologia (SBPT) - para a prevenção e manejo dessa condição, a fim de alocar recursos de forma adequada para e nos serviços de tuberculose e servir de guia para os profissionais de saúde. Uma equipe de onze pneumologistas e um metodologista foi criada pela SBPT para revisar as evidências atuais sobre a DPPT e desenvolver recomendações adaptadas ao contexto brasileiro. O painel de especialistas selecionou os temas com base nas evidências atuais e diretrizes internacionais. Durante a primeira fase, três membros do painel redigiram as recomendações, que foram divididas em três seções: definição e prevalência de DPPT, avaliação da DPPT e manejo da DPPT. Na segunda fase, todos os membros do painel analisaram, discutiram e revisaram as recomendações até chegar a um consenso. O documento foi aprovado formalmente pela SBPT em sessão especial organizada durante o Congresso Anual da SBPT de 2023.

Clinical and laboratory parameters in the differential diagnosis of pleural effusion secondary to tuberculosis or cancer.

PURPOSE: To evaluate the clinical and laboratory characteristics of pleural effusions secondary to tuberculosis (TB) or cancer (CA). METHODS: A total of 326 patients with pleural effusion due to TB (n=182) or CA (n=144) were studied. The following parameters were analyzed: patient gender, age and pleural effusion characteristics (size, location, macroscopic fluid aspect, protein concentration, lactate dehydrogenase (DHL) and adenosine deaminase activity (ADA) and nucleated cell counts). RESULTS: Young male patients predominated in the tuberculosis group. The effusions were generally moderate in size and unilateral in both groups. Yellow-citrine fluid with higher protein (p < 0.001) levels predominated in effusions from the tuberculosis group (5.3 + 0.8 g/dL) when compared to the CA group (4.2 +/- 1.0 g/dL), whereas DHL levels were more elevated in CA (1,177 +/- 675 x 1,030 +/- 788 IU; p = 0.003) than in TB. As expected, ADA activity was higher in the TB group (107.6 +/- 44.2 x 30.6 +/- 57.5 U/L; p < 0.001). Both types of effusions presented with high nucleated cell counts, which were more pronounced in the malignant group (p < 0.001). TB effusion was characterized by a larger percentage of leukocytes and lymphocytes (p < 0.001) and a smaller number of mesothelial cells (p = 0.005). Lymphocytes and macrophages were the predominant nucleated cell in neoplastic effusions. CONCLUSION: Our results demonstrate that in lymphocytic pleural exudate obtained from patients with clinical and radiological evidence of tuberculosis, protein and ADA were the parameters that better characterize these effusions. In the same way, when the clinical suspicion is malignancy, serous-hemorrhagic lymphocytic fluid should be submitted to oncotic cytology once this easy and inexpensive exam reaches a high diagnostic performance (approximately equal 80%). In this context, we suggest thoracocentesis with fluid biochemical and cytological examination as the first diagnostic approach for these patients.

Diagnosis of tuberculosis: a consensus statement from the Brazilian Thoracic Association / Consenso sobre o diagnóstico da tuberculose da Sociedade Brasileira de Pneumologia e Tisiologia

ABSTRACT Early, accurate diagnosis of tuberculosis is one of the major pillars of the control of the disease. The purpose of this consensus statement is to provide health professionals with the most current, useful evidence for the diagnosis of tuberculosis in Brazil. To that end, the Tuberculosis Committee of the Brazilian Thoracic Association brought together 14 members of the Association with recognized expertise in tuberculosis in Brazil to compose the statement. A nonsystematic review of the following topics was carried out: clinical diagnosis, bacteriological diagnosis, radiological diagnosis, histopathological diagnosis, diagnosis of tuberculosis in children, and diagnosis of latent tuberculosis infection.

RESUMO O diagnóstico precoce e adequado da tuberculose é um dos pilares mais importantes no controle da doença. A proposta deste consenso brasileiro é apresentar aos profissionais da área de saúde um documento com as evidências mais atuais e úteis para o diagnóstico da tuberculose. Para tanto, a Comissão de Tuberculose da Sociedade Brasileira de Pneumologia e Tisiologia reuniu 14 membros da Sociedade com reconhecida experiência em tuberculose no Brasil. Foi realizada uma revisão não sistemática dos seguintes tópicos: diagnóstico clínico, diagnóstico bacteriológico, diagnóstico radiológico, diagnóstico histopatológico, diagnóstico da tuberculose na criança e diagnóstico da tuberculose latente.

Pulmonary tuberculosis: tomographic evaluation in the active and post-treatment phases.

CONTEXT: Adequate knowledge of images consistent with tuberculosis activity is an important resource for tuberculosis diagnosis and treatment. OBJECTIVE: To evaluate the structural alterations caused by tuberculosis in the pulmonary parenchyma, both during the active phase of the disease and after the end of the treatment, through computerized tomography of the thorax. TYPE OF STUDY: Prospective study. SETTING: Pulmonary Division, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo. PARTICIPANTS: 20 patients, carriers of pulmonary tuberculosis, confirmed by Mycobacterium tuberculosis culture. PROCEDURES: Conventional tomography scans of the patients were obtained at two times: upon diagnosis and after the end of the treatment. The following were considered suggestive signs of tuberculosis activity: centrilobular nodules with segmented distribution, confluent micronodules, consolidations, thick-walled cavities, nodules, masses, thickening of the bronchial walls, tree-in-bud appearance and cylindrical bronchiectasis. MAIN MEASUREMENTS: The presence of suggestive signs of tuberculosis activity was compared between the start and the end of treatment by means of the signs test (z). RESULTS: All patients (20/20) presented suggestive signs of tuberculosis activity at the start of treatment. After the end of treatment, 13 patients (13/20) still presented some suggestive signs consistent with activity. A reduction in the extent of lung attack was seen post-treatment, in relation to its start (z = 10.10). This change was statistically significant (p < 0.001). CONCLUSION: Signs suggestive of tuberculosis activity are present in the active disease and are seen via computed tomography. The extent of parenchymal attack significantly decreases following treatment. Such signs may be useful in the diagnosis of pulmonary tuberculosis.

Differentiation between Nocardia spp. and Mycobacterium spp.: Critical aspects for bacteriological diagnosis.

New methodologies were developed for the identification of Nocardia but the initial diagnosis still requires a fast and accurate method, mainly due to the similarity to Mycobacterium, both clinical and bacteriologically. Growth on Löwenstein-Jensen (LJ) medium, presence of acid-fast bacilli through Ziehl-Neelsen staining, and colony morphology can be confusing aspects between Nocardia and Mycobacterium. This study describes the occurrence of Nocardia spp. in a mycobacterial-reference laboratory, observing the main difficulties in differentiating Nocardia spp. from Mycobacterium spp., and correlating isolates with nocardiosis cases. Laboratory records for the period between 2008 and 2012 were analyzed, and the isolates identified as Nocardia sp. or as non-acid-fast filamentous bacilli were selected. Epidemiological and bacteriological data were analyzed as well. Thirty-three isolates identified as Nocardia sp. and 22 as non-acid-fast bacilli were selected for this study, and represented 0.12% of isolates during the study period. The presumptive identification was based on macroscopic and microscopic morphology, resistance to lysozyme and restriction profiles using the PRA-hsp65 method. Nocardia spp. can grow on media for mycobacteria isolation (LJ and BBL MGIT™) and microscopy and colony morphology are very similar to some mycobacteria species. Seventeen patients (54.8%) were reported and treated for tuberculosis, but presented signs and symptoms of nocardiosis. It was concluded that the occurrence of Nocardia sp. during the study period was 0.12%. Isolates with characteristics of filamentous bacilli, forming aerial hyphae, with colonies that may be pigmented, rough and without the BstEII digestion pattern in PRA-hsp65 method are suggestive of Nocardia spp. For a mycobacterial routine laboratory, a flow for the presumptive identification of Nocardia is essential, allowing the use of more accurate techniques for the correct identification, proper treatment and better quality of life for patients.

Long-term survival and cause-specific mortality of patients newly diagnosed with tuberculosis in São Paulo state, Brazil, 2010­15: a population-based, longitudinal study

Background Long-term survival and cause-specific mortality of patients who start tuberculosis treatment is rarely described. We aimed to assess the long-term survival of these patients and evaluate the association between vulnerable conditions (social, health behaviours, and comorbidities) and cause-specific mortality in a country with a high burden of tuberculosis. Methods In this population-based, longitudinal study in São Paulo state, Brazil, we described the 5-year survival of patients who were newly diagnosed with tuberculosis in 2010. We included patients with newly-diagnosed tuberculosis, aged 15 years or older, and notified to the São Paulo State Tuberculosis Program in 2010. We excluded patients whose diagnosis had changed during follow-up (ie, they did not have tuberculosis) and patients who had multidrug-resistant (MDR) tuberculosis. We selected our population with tuberculosis from the dedicated electronic system TBweb. Our primary objective was to estimate the excess mortality over 5 years and within the group who survived the first year, compared with the general São Paulo state population. We also estimated the association between social vulnerability (imprisonment and homelessness), health behaviours (alcohol and drug use), and comorbidities (diabetes and mental disorders) with all-cause and cause-specific mortality. We used the competing risk analysis framework, estimating cause-specific hazard ratios (HRs) adjusted for potential confounding factors. Findings In 2010, there were 19 252 notifications of tuberculosis cases. We excluded 550 cases as patients were younger than 15 years, 556 cases that were not tuberculosis, 2597 retreatments, and 48 cases of MDR tuberculosis, resulting in a final cohort of 15 501 patients with tuberculosis. Over a period of 5 years from tuberculosis diagnosis, 2660 (17%) of 15 501 patients died. Compared with the source population, matched by age, sex, and calendar year, the standardised mortality ratio was 6·47 (95% CI 6·22­6·73) over 5 years and 3·93 (3·71­4·17) among those who survived the first year. 1197 (45%) of 2660 deaths were due to infection. Homelessness and alcohol and drug use were associated with death from infection (adjusted cause-specific HR 1·60, 95% CI 1·39­1·85), cardiovascular (1·43, 1·06­1·95), and external or ill-defined causes of death (1·80, 1·37­2·36). Diabetes was associated with deaths from cardiovascular causes (1·70, 1·23­2·35). Interpretation Patients newly diagnosed with tuberculosis were at a higher risk of death than were the source population, even after tuberculosis treatment. Post-tuberculosis sequelae and vulnerability are associated with excess mortality and must be addressed to mitigate the tuberculosis burden worldwide.

Predictive model of unfavorable outcomes for multidrug-resistant tuberculosis / Modelo preditivo dos desfechos desfavoráveis da tuberculose multidroga-resistente

ABSTRACT OBJECTIVE to analyze the temporal trend, identify the factors related and elaborate a predictive model for unfavorable treatment outcomes for multidrug-resistant tuberculosis (MDR-TB). METHODS Retrospective cohort study with all cases diagnosed with MDR-TB between the years 2006 and 2015 in the state of São Paulo. The data were collected from the state system of TB cases notifications (TB-WEB). The temporal trend analyzes of treatment outcomes was performed through the Prais-Winsten analysis. In order to verify the factors related to the unfavorable outcomes, abandonment, death with basic cause TB and treatment failure, the binary logistic regression was used. Pictorial representations of the factors related to treatment outcome and their prognostic capacity through the nomogram were elaborated. RESULTS Both abandonment and death have a constant temporal tendency, whereas the failure showed it as decreasing. Regarding the risk factors for such outcomes, using illicit drugs doubled the odds for abandonment and death. Besides that, being diagnosed in emergency units or during hospitalizations was a risk factor for death. On the contrary, having previous multidrug-resistant treatments reduced the odds for the analyzed outcomes by 33%. The nomogram presented a predictive model with 65% accuracy for dropouts, 70% for deaths and 80% for failure. CONCLUSIONS The modification of the current model of care is an essential factor for the prevention of unfavorable outcomes. Through predictive models, as presented in this study, it is possible to develop patient-centered actions, considering their risk factors and increasing the chances for cure.

RESUMO OBJETIVO Analisar a tendência temporal, identificar os fatores relacionados e elaborar um modelo preditivo para os desfechos desfavoráveis do tratamento da tuberculose multidroga-resistente. MÉTODOS Estudo de coorte retrospectiva com todos os casos diagnosticados com tuberculose multidroga-resistente entre os anos de 2006 e 2015 no estado de São Paulo. Os dados secundários foram provenientes do sistema estadual de notificações de casos de tuberculose, o TBWeb. Foi realizada a análise de tendência temporal dos desfechos de tratamento por meio da regressão de Prais-Winsten. Para verificar os fatores relacionados com os desfechos desfavoráveis (óbito com tuberculose como causa básica, abandono e falência do tratamento), foi empregada a regressão logística binária. Representações pictóricas dos fatores relacionados ao desfecho do tratamento e sua capacidade prognóstica foram elaboradas por meio de nomogramas. RESULTADOS Tanto o abandono como o óbito tiveram tendência temporal estacionária, enquanto a falência apresentou tendência decrescente. Em relação aos fatores de risco para tais desfechos, utilizar drogas ilícitas dobrou as chances de abandono e óbito. Além disso, ser diagnosticado em unidades de urgência ou emergência ou durante internações hospitalares foi um fator de risco para o óbito. Ao contrário, ter feito tratamentos prévios da multidroga-resistência reduziu as chances dos desfechos analisados. O nomograma apresentou um modelo preditivo com precisão de 65% para os abandonos, 70% para os óbitos e 80% para a falência. CONCLUSÕES A prevenção de desfechos desfavoráveis no tratamento da tuberculose multidroga-resistente implica a modificação do modelo de atenção vigente. Utilizando modelos preditivos, como o apresentado neste estudo, torna-se possível elaborar ações centradas nos pacientes, considerando seus fatores de risco e aumentando as chances de cura.

Pulmonary involvement in pleural tuberculosis: how often does it mean disease activity?

OBJECTIVE: To evaluate in chest X-rays and high-resolution computed tomographies of patients with pleural tuberculosis, the incidence of parenchymal and mediastinal lung lesions suggestive of active disease. METHODS: Prospective study (2008-2009) evaluating the radiographic and tomographic abnormalities of 88 HIV-negative patients with pleural tuberculosis (unilateral effusion). The images were reviewed by 3 independent specialists, and the observed changes were classified according to previously established criteria: presence or absence of signs suggestive of disease activity, and nonspecific findings. RESULTS: Abnormal changes were observed in chest X-rays of 22 (25%) patients and in the computed tomography of 55 (63%). Images compatible with active pulmonary tuberculosis were detected by radiography in 9 (10%) patients and by tomography in 38 (43%). Only 4 (4.5%) patients had tomography images suggestive of residual disease. CONCLUSION: The present study demonstrates that pulmonary involvement is quite common in pleural tuberculosis. This finding is mainly observed in high-resolution computed tomography and has important epidemiological implications, since patients with pleural tuberculosis are significant sources of infection and disease dissemination.

Epidemiological aspects of pleural tuberculosis in the state of São Paulo, Brazil (1998-2005).

OBJECTIVE: To analyze the epidemiological characteristics of and trends regarding the incidence of pleural TB. METHODS: This was a retrospective descriptive study of TB cases reported between 1998 and 2005 and compiled from the Epidemiological Surveillance Tuberculosis System (Epi-TB database). RESULTS: A total of 144,347 new cases of TB were reported during the period studied. Pulmonary TB was the predominant form (118,575 cases; 82.2%). Among the extrapulmonary forms (25,773 cases; 17.8%), pleural TB was the form most often reported (12,545 cases; 48.7%). For all forms, the incidence (per 100,000 population) decreased (from 49.7 in 1998 to 44.6 in 2005; R(2) = 0.898; p < 0.001), whereas the incidence of pleural TB remained stable (4.1 in 1998 and 3.8 in 2005; R(2) = 0.433; p = 0.076). The highest incidence of pleural TB was found among males (2:1) aged from 30 to 59 years. Of the 12,545 patients with pleural TB, 4,018 (32.0%) presented comorbidities: alcoholism (9.5%); HIV (8.0%); diabetes (3.3%); and mental illness (1.2%). The diagnosis was based on bacteriological (14.2%) and histological (30.2%) methods, as well as on unspecified methods (55.6%). CONCLUSIONS: Pleural TB was the predominant extrapulmonary form of TB in the state of São Paulo, with a stable incidence between 1998 and 2005, although there was a trend toward a decrease in the incidence of the pulmonary forms. The diagnosis of pleural TB was confirmed through histology and bacteriology in 44.4% of the cases.

DIFFERENTIATION BETWEEN Nocardia spp. AND Mycobacterium spp.: CRITICAL ASPECTS FOR BACTERIOLOGICAL DIAGNOSIS / Diferenciação de Nocardia spp. e Mycobacterium spp.: aspectos críticos para o diagnóstico bacteriológico

New methodologies were developed for the identification of Nocardia but the initial diagnosis still requires a fast and accurate method, mainly due to the similarity to Mycobacterium, both clinical and bacteriologically. Growth on Löwenstein-Jensen (LJ) medium, presence of acid-fast bacilli through Ziehl-Neelsen staining, and colony morphology can be confusing aspects between Nocardia and Mycobacterium. This study describes the occurrence of Nocardia spp. in a mycobacterial-reference laboratory, observing the main difficulties in differentiating Nocardia spp. from Mycobacterium spp., and correlating isolates with nocardiosis cases. Laboratory records for the period between 2008 and 2012 were analyzed, and the isolates identified as Nocardia sp. or as non-acid-fast filamentous bacilli were selected. Epidemiological and bacteriological data were analyzed as well. Thirty-three isolates identified as Nocardia sp. and 22 as non-acid-fast bacilli were selected for this study, and represented 0.12% of isolates during the study period. The presumptive identification was based on macroscopic and microscopic morphology, resistance to lysozyme and restriction profiles using the PRA-hsp65 method. Nocardia spp. can grow on media for mycobacteria isolation (LJ and BBL MGIT™) and microscopy and colony morphology are very similar to some mycobacteria species. Seventeen patients (54.8%) were reported and treated for tuberculosis, but presented signs and symptoms of nocardiosis. It was concluded that the occurrence of Nocardia sp. during the study period was 0.12%. Isolates with characteristics of filamentous bacilli, forming aerial hyphae, with colonies that may be pigmented, rough and without the BstEII digestion pattern in PRA-hsp65 method are suggestive of Nocardia spp. For a mycobacterial routine laboratory, a flow for the presumptive identification of Nocardia is essential, allowing the use of more accurate techniques for the correct identification, proper treatment and better quality of life for patients.

Novas metodologias têm sido desenvolvidas para a identificação de Nocardia spp. mas o diagnóstico inicial ainda necessita de método rápido e preciso, principalmente devido à similaridade com o gênero Mycobacterium, clínica e bacteriologicamente. O crescimento em meio de Löwenstein Jensen (LJ), a presença de bacilos corados pela coloração de Ziehl Neelsen e colônias com características diferentes podem ser fatores de confusão entre nocardias e micobactérias. Este estudo descreve a ocorrência de Nocardia spp. em laboratório de referência em micobacteriologia, observando-se as principais dificuldades em diferenciar Nocardia spp. e Mycobacterium spp., correlacionando isolados com casos de nocardiose. Os registros laboratoriais dos anos 2008 a 2012 foram analisados e os isolados identificados como Nocardia sp. ou como bacilos não álcool - ácido resistentes (NBAAR) foram selecionados. Os dados epidemiológicos e bacteriológicos foram analisados. Trinta e três isolados identificados como Nocardia sp. e 22 como NBAAR foram selecionados para este estudo, perfazendo 0,12% do total de isolados identificados no período estudado. A identificação presuntiva foi baseada na morfologia macroscópica e microscópica, resistência à lisozima e perfis de restrição pelo método PRA-hsp65. Nocardia spp. pode crescer em meios de isolamento para micobactérias (LJ e BBL MGIT™) e microscopia de morfologia e as colônias são muito semelhantes a algumas espécies de micobactérias. Dezessete pacientes (54,8%) foram notificados e tratados para tuberculose, mas apresentaram sinais e sintomas para nocardiose. Concluimos que a ocorrência de Nocardia sp. no período estudado foi de 0,12%. Os isolados com características de bacilos filamentosos, formadores de hifas aéreas, com colônias que podem ter pigmento, rugosas e que não possuem padrão de digestão para BstEII no método PRA-hsp65 são sugestivos de Nocardia spp. Para um laboratório de rotina de Micobactérias, um fluxo de identificação presuntiva para Nocardia spp. é essencial para permitir que esses isolados sejam identificados com técnicas mais precisas, para que seja oferecido o tratamento adequado e qualidade de vida aos pacientes.

Transforming growth factor beta-1 as a predictor of fibrosis in tuberculous pleurisy.

BACKGROUND AND OBJECTIVE: To clarify the influence of transforming growth factor beta-1 (TGF-beta(1)) in the development of pleural thickening in tuberculosis (TB), the levels of TGF-beta(1) in pleural fluid and in serum of patients with pleural TB and transudative effusions were determined. METHODS: TGF-beta(1) was quantified in 58 pleural fluid and serum samples of patients with TB (n = 50) or transudative effusions (n = 8). Pleural thickening evaluated by high-resolution CT was scored as 0 (<3 mm); 1 (>or=3 and <10 mm) or 2 (>or=10 mm). RESULTS: The highest pleural fluid TGF-beta(1) levels before treatment for TB were observed in patients with a pleural thickness score of 2. Of the 14 patients with score 1, five regressed to 0, five progressed to 2, and four maintained 1. All 17 patients with score 2 maintained this evaluation. Patients who presented score 1 and progressed to 2 had higher TGF-beta(1) levels than those who maintained the same score or regressed (score 1 or 0). Patients with score 2 (before or after treatment) had higher TGF-beta(1) levels than those with score 0 or 1. CONCLUSION: Pleural fluid and serum TGF-beta(1) levels were higher in patients with TB, with a correlation between pleural fluid TGF-beta(1) levels before treatment and the degree of pleural thickening. This finding suggests that TGF-beta(1) might be considered as a predictor of pleural thickening in pleural tuberculosis.

Aspectos tomográficos da tuberculose pulmonar em pacientes adultos com AIDS / Computed tomography findings of pulmonary tuberculosis in adult AIDS patients

OBJETIVO: Este trabalho tem como finalidade descrever os achados tomográficos da tuberculose pulmonar em pacientes adultos com AIDS atendidos no serviço de radiologia de um hospital de referência em doenças infecciosas, procurar associações desses achados e a contagem de CD4. MATERIAIS E MÉTODOS: Foram estudados 45 pacientes por meio de tomografia computadorizada de tórax durante quatro anos. RESULTADOS: Foram encontrados linfonodomegalia mediastinal e/ou hilar em 31 (68,8 por cento) dos casos, derrame pleural em 29 (64,4 por cento), nódulos centrolobulares de distribuição segmentar em 26 (57,7 por cento), consolidação em 24 (53,3 por cento), confluência de micronódulos em 17 (37,7 por cento), nódulos mal definidos com distribuição centrolobular em 16 (35,5 por cento), padrão de "árvore em brotamento" em 13 (28,9 por cento), espessamento de parede brônquica em 12 (26,6 por cento), cavidade de parede espessa em 10 (22,2 por cento), nódulos miliares em 9 (20 por cento) e bronquiectasias cilíndricas em 6 (13,3 por cento). Dos 45 pacientes, 35 (77,8 por cento) apresentaram CD4 < 200 cel/mm³ e 10 (22,2 por cento) apresentaram CD4 > 200 cel/mm³. CONCLUSÃO: Concluímos que neste estudo, diversamente do descrito na literatura, linfonodomegalia mediastinal e/ou hilar e consolidação foram significativamente mais frequentes em pacientes com CD4 > 200 cel/mm³. No entanto, linfonodos com centro hipodenso foram mais frequentemente observados em pacientes com severa imunodepressão, ou seja, CD4 < 200 cel/mm³.

OBJECTIVE: The present study is aimed at describing computed tomography findings pulmonary tuberculosis in adult AIDS patients assisted at a radiology unit of a reference infectious diseases hospital, in an attempt to establish the association between such findings and CD4 count. MATERIALS AND METHODS: Forty-five patients were evaluated by chest computed tomography over a four-year period. RESULTS: Mediastinal and/or hilar lymph node enlargement was found in 31 (68.8 percent) cases, pleural effusion in 29 (64.4 percent), centrilobular nodules with segmental distribution in 26 (57.7 percent), consolidation in 24 (53.3 percent), confluent micronodules in 17 (37.7 percent), poorly defined nodules with centrilobular distribution in 16 (35.5 percent), tree-in-bud pattern in 13 (28.9 percent), bronchial wall thickening in 12 (26.6 percent), thick-walled cavity in 10 (22.2 percent), miliary nodules in 9 (20 percent), and cylindrical bronchiectasis in 6 (13.3 percent). Among the 45 patients, 35 (77.8 percent) presented CD4 count < 200 cel/mm³ and 10 (22.2 percent) presented CD4 count > 200 cel/mm³. CONCLUSION: Differently from reports in the literature, the authors conclude that mediastinal and/or hilar lymph node enlargement and consolidation were significantly most frequent in patients with CD4 count > 200 cel/mm³. However, lymph nodes with hypodense center were most often observed in severely immunosuppressed patients with CD4 count < 200 cel/mm³.

Aspectos epidemiológicos da tuberculose pleural no estado de São Paulo (1998-2005) / Epidemiological aspects of pleural tuberculosis in the state of São Paulo, Brazil (1998-2005)

OBJETIVO: Analisar as características epidemiológicas e tendências quanto à incidência de TB pleural. MÉTODOS: Estudo descritivo, retrospectivo dos casos de TB reportados entre 1998 e 2005 e coletados do banco de dados do Sistema de Notificação de Tuberculose (Epi-TB) da Secretaria de Saúde do Estado de São Paulo. RESULTADOS: Foram notificados 144.347 casos novos de TB durante o período estudado. A forma pulmonar foi predominante (118.575 casos; 82,2 por cento). Das formas extrapulmonares (25.773 casos; 17,8 por cento), a pleural foi a mais referida (12.545 casos; 48,7 por cento). A incidência (por 100.000 habitantes) de todas as formas diminuiu, (49,7 em 1998 e 44,6 em 2005; R² = 0,898; p < 0,001), enquanto a incidência de TB pleural permaneceu estável (4,1 em 1998 e 3,8 em 2005; R² = 0,433; p = 0,076). A maior incidência de TB pleural ocorreu em pacientes do sexo masculino (2:1) entre 30 e 59 anos de idade. Dos 12.545 pacientes com TB pleural, 4.018 (32,0 por cento) apresentaram comorbidades: alcoolismo (9,5 por cento); HIV (8,0 por cento); diabetes (3,3 por cento); e doença mental (1,2 por cento). O diagnóstico referido fundamentou-se em métodos bacteriológicos (14,2 por cento) e histológicos (30,2 por cento), assim como outros não especificados (55,6 por cento). CONCLUSÕES: No estado de São Paulo, a TB pleural foi a forma extrapulmonar predominante, apresentando incidência estável no período entre 1998 e 2005, apesar da tendência de diminuição das formas pulmonares. A histologia e a bacteriologia definiram o diagnóstico em 44,4 por cento dos casos.

OBJECTIVE: To analyze the epidemiological characteristics of and trends regarding the incidence of pleural TB. METHODS: This was a retrospective descriptive study of TB cases reported between 1998 and 2005 and compiled from the Epidemiological Surveillance Tuberculosis System (Epi-TB database). RESULTS: A total of 144,347 new cases of TB were reported during the period studied. Pulmonary TB was the predominant form (118,575 cases; 82.2 percent). Among the extrapulmonary forms (25,773 cases; 17.8 percent), pleural TB was the form most often reported (12,545 cases; 48.7 percent). For all forms, the incidence (per 100,000 population) decreased (from 49.7 in 1998 to 44.6 in 2005; R² = 0.898; p < 0.001), whereas the incidence of pleural TB remained stable (4.1 in 1998 and 3.8 in 2005; R² = 0.433; p = 0.076). The highest incidence of pleural TB was found among males (2:1) aged from 30 to 59 years. Of the 12,545 patients with pleural TB, 4,018 (32.0 percent) presented comorbidities: alcoholism (9.5 percent); HIV (8.0 percent); diabetes (3.3 percent); and mental illness (1.2 percent). The diagnosis was based on bacteriological (14.2 percent) and histological (30.2 percent) methods, as well as on unspecified methods (55.6 percent). CONCLUSIONS: Pleural TB was the predominant extrapulmonary form of TB in the state of São Paulo, with a stable incidence between 1998 and 2005, although there was a trend toward a decrease in the incidence of the pulmonary forms. The diagnosis of pleural TB was confirmed through histology and bacteriology in 44.4 percent of the cases.

Clinical and laboratory parameters in the differential diagnosis of pleural effusion secondary to tuberculosis or cancer

PURPOSE: To evaluate the clinical and laboratory characteristics of pleural effusions secondary to tuberculosis (TB) or cancer (CA). METHODS: A total of 326 patients with pleural effusion due to TB (n=182) or CA (n=144) were studied. The following parameters were analyzed: patient gender, age and pleural effusion characteristics (size, location, macroscopic fluid aspect, protein concentration, lactate dehydrogenase (DHL) and adenosine deaminase activity (ADA) and nucleated cell counts). RESULTS: Young male patients predominated in the tuberculosis group. The effusions were generally moderate in size and unilateral in both groups. Yellow-citrine fluid with higher protein (p < 0.001) levels predominated in effusions from the tuberculosis group (5.3 + 0.8 g/dL) when compared to the CA group (4.2 ± 1.0 g/dL), whereas DHL levels were more elevated in CA (1,177 ± 675 x 1,030 ± 788 IU; p = 0.003) than in TB. As expected, ADA activity was higher in the TB group (107.6 ± 44.2 x 30.6 ± 57.5 U/L; p < 0.001). Both types of effusions presented with high nucleated cell counts, which were more pronounced in the malignant group (p < 0.001). TB effusion was characterized by a larger percentage of leukocytes and lymphocytes (p < 0.001) and a smaller number of mesothelial cells (p = 0.005). Lymphocytes and macrophages were the predominant nucleated cell in neoplastic effusions. CONCLUSION: Our results demonstrate that in lymphocytic pleural exudate obtained from patients with clinical and radiological evidence of tuberculosis, protein and ADA were the parameters that better characterize these effusions. In the same way, when the clinical suspicion is malignancy, serous-hemorrhagic lymphocytic fluid should be submitted to oncotic cytology once this easy and inexpensive exam reaches a high diagnostic performance (approximately 80 percent). In this context, we suggest thoracocentesis with fluid biochemical...

OBJETIVO: Avaliar as características clínicas e laboratoriais de derrames pleurais secundários à tuberculose ou câncer. MÉTODOS: Um total de 326 pacientes com derrame pleural por tuberculose (n=182) ou câncer (n=144) foi avaliado. Os seguintes parâmetros foram analisados: sexo e idade dos pacientes e características do líquido pleural (tamanho, localização, aspecto macroscópico, concentração de proteínas, atividade da desidrogenase lática (DHL) e da adenosina deaminase (ADA) e contagem de células nucleadas). RESULTADOS: A tuberculose pleural predominou nos pacientes mais jovens e do sexo masculino. Em ambos os grupos, os derrames pleurais foram de tamanho moderado e unilaterais. Derrames com aspecto amarelo-citrino com níveis mais elevados de proteínas predominaram na tuberculose (5,3 ± 0,8 g/dL), quando comparados aos neoplásicos (4,2 ± 1,0 g/dL), enquanto que níveis mais elevados de DHL foram observados nos derrames neoplásicos (1.177 ± 675 x 1.030 ± 788 UI; p = 0,003). Conforme esperado, a atividade da ADA foi maior na tuberculose que no câncer (107,6 ± 44,2 x 30,6 ± 57,5 U/L; p < 0,001). Ambos os derrames apresentaram alta celularidade, embora mais pronunciada no grupo neoplásico (p < 0,001). Os derrames de etiologia tuberculosa se caracterizaram por apresentar uma maior percentagem de leucócitos e de linfócitos (p < 0,001) e um pequeno número de células mesoteliais (p = 0,005). Linfócitos e macrófagos foram as células nucleadas que predominaram nos derrames pleurais malignos. CONCLUSÃO: Nossos resultados demonstram que em exsudatos pleurais linfocíticos de pacientes com evidências clínicas e radiológicas de tuberculose, os níveis de proteína e de ADA foram os parâmetros que melhor caracterizaram esses derrames. Da mesma maneira, quando a suspeita clínica é câncer, um líquido serohemorrágico e linfocítico deve ser submetido à citologia oncótica, uma vez que este exame laboratorial de fácil...

Derrame pleural por micobactéria não tuberculosa / Pleural effusion caused by nontuberculous mycobacteria

O Mycobacterium kansasii, micobactéria não tuberculosa, pode causar doença pulmonar com manifestação clínico-radiológica semelhante à tuberculose. Estão associados fatores de risco: bronquiectasias, doença pulmonar obstrutiva crônica, seqüela de tuberculose, pneumoconiose e imunossupressão. Relata-se um caso de derrame pleural, em paciente de 67 anos, com doença pulmonar obstrutiva crônica e antecedente de tuberculose. O diagnóstico de tuberculose pleuropulmonar foi sugerido pelo exame anatomopatológico de pleura, que demonstrou processo crônico granulomatoso e presença de bacilo álcool-ácido resistente. Nas culturas de líquido e tecido pleurais foi detectado Mycobacterium kansasii. Discute-se o diagnóstico diferencial com outros agentes infecciosos na doença granulomatosa pleural e tratamento.