Diferenciação de Nocardia spp. e Mycobacterium spp.: aspectos críticos para o diagnóstico bacteriológico

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.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, 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

Tuberculose em trabalhadores de serviços de saúde: um problema a ser enfrentado

Since the beginning of the seventies of the last century, several authors have pointed to tuberculosis as a health risk to health service workers. Studies show that these professionals are four times more likely to get sick from TB than the general population and that health professionals in hospitals have a positive tuberculin test rate of 63.1% and conversion to 8.7% (10.7% Per 1,000 people per month). The risk factors associated with conversion to the tuberculin test are: (1) nosocomial exposure to a patient with pulmonary TB; (2) professional category of nurse; and (3) absence of biosafety measures implemented at the hospital. Several authors point out: (1) a very high rate of infection among health professionals, which is an object of concern both for the health infection control team and for occupational safety professionals; (2) a positive tuberculin test rate of 26.7% in health professionals, with the majority of these workers having direct contact with patients with smear-positive tuberculosis; and (3) that professionals with less than four years of exposure to the bacillus had higher test positive rates. According to data of the Division of Tuberculosis (DVTBC) of the Center for Epidemiological Surveillance - SES / SP considering the years 2006 to 2016, an average of 210 new cases of the disease are reported in health care workers. Given this scenario and the urgency of implementing specific preventive actions for all workers potentially exposed to Mycobacterium tuberculosis (Bacillus de Koch or BK). In this sense, DVST and CVE of the State Department of Health of São Paulo formed a Working Group (WG) for the construction of a Protocol for the Prevention of Occupational Tuberculosis (PPOT). The objective of this article is to present a model, form and content of this instrument for the prevention of a serious occupational disease and for the health promotion of potentially exposed workers.Desde o início dos anos setenta do século passado vários autores apontam a tuberculose (TB) como risco à saúde dos trabalhadores de serviços de saúde. Estudos evidenciam que estes profissionais têm quatro vezes mais chance de adoecer por TB que a população em geral e que profissionais de saúde em atividade em hospitais têm taxa de teste tuberculínico positivo de 63,1% e conversão em 8,7% (10,7 por 1.000 pessoas/mês). São apontados como fatores de risco associados à conversão ao teste tuberculínico: (1) exposição nosocomial a paciente com TB pulmonar; (2) categoria profissional de enfermeiro; e (3) ausência de medidas de biossegurança implantadas no hospital. Vários autores apontam: (1) taxa de infecção muito elevada entre profissionais da saúde, o que se torna em objeto de preocupação tanto para a equipe de controle de infecção do ambiente de saúde quanto para os profissionais de segurança do trabalho; (2) uma taxa de positividade ao teste tuberculínico de 26,7% nos profissionais de saúde, tendo a maioria desses trabalhadores contato direto com paciente com tuberculose bacilífera; e (3) que os profissionais com menos de quatro anos de exposição ao bacilo apresentam taxas maiores de positividade ao teste. De acordo com os dados da Divisão de Tuberculose do Centro de Vigilância Epidemiológica da Secretaria da Saúde do Estado de São Paulo, considerando os anos de 2006 a 2016, são notificados em média 210 casos novos da doença em trabalhadores de serviços de saúde. Diante deste cenário e da urgência de implantação de ações preventivas específicas para o conjunto dos trabalhadores potencialmente expostos ao Mycobacterium tuberculosis (Bacilo de Koch ou BK) constituiu-se um Grupo de Trabalho (GT) para construção de um Protocolo de Prevenção de Tuberculose Ocupacional (PPTO). O objetivo deste artigo é fundamentar a elaboração deste instrumento de prevenção de uma doença ocupacional grave e de promoção da saúde dos trabalhadores potencialmente expostos

Modelo preditivo dos desfechos desfavoráveis da tuberculose multidroga-resistente

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.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

Consenso sobre o diagnóstico da tuberculose da Sociedade Brasileira de Pneumologia e Tisiologia

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.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

Parâmetros clínicos e laboratoriais no diagnóstico diferencial de efusões pleurais secundárias à tuberculose ou ao 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 &plusmn; 1.0 g/dL), whereas DHL levels were more elevated in CA (1,177 &plusmn; 675 x 1,030 &plusmn; 788 IU; p = 0.003) than in TB. As expected, ADA activity was higher in the TB group (107.6 &plusmn; 44.2 x 30.6 &plusmn; 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 (;@; 80%). In this context, we suggest thoracocentesis with fluid biochemical and cytological examination as the first diagnostic approach for these patients.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 &plusmn; 0,8 g/dL), quando comparados aos neoplásicos (4,2 &plusmn; 1,0 g/dL), enquanto que níveis mais elevados de DHL foram observados nos derrames neoplásicos (1.177 &plusmn; 675 x 1.030 &plusmn; 788 UI; p = 0,003). Conforme esperado, a atividade da ADA foi maior na tuberculose que no câncer (107,6 &plusmn; 44,2 x 30,6 &plusmn; 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 realização e baixo custo apresenta alto desempenho diagnóstico (;@; 80%). Neste contexto, sugerimos que a toracocentese, com exames bioquímicos e citológicos do líquido pleural, seja a primeira abordagem diagnóstica do paciente

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