Objective: To propose a methodology for characterizing proficiency in sputum smear microscopy for acid-fast bacilli (AFB) in the diagnosis of tuberculosis and to determine the number of microscopies necessary to establish this proficiency, as well as the quality of the transcription of results, the causes of the discrepancies in the readings (rater or microscope used), and the criterion for classification of microscopy results that poses the most difficulty in characterizing proficiency. Methods: Four hundred sputum smear microscopies for the diagnosis of tuberculosis were analyzed through double-blind readings by six professionals who usually read/supervise microscopies performed in public health care facilities. The sample was stratified to obtain, at least, a reliability of 90% in the double-blind readings, an α error of 5%, and a precision of 3%. The results were analyzed using observed reliability and the kappa index. Results: Thirteen errors (0.27%) were found in the transcription of results. Reliability increased when the three distinct categories of positive results (AFB+, AFB++, and AFB+++) were grouped or when inconclusive results were excluded from the analysis. The quantification of the bacterial load was the classification criterion that posed the most difficulty in establishing proficiency. Using higher quality microscopes increased reliability. Reliability values stabilized only from the reading of 75 microscopies onward. Conclusions: Double-blind sputum smear microscopy readings using a panel containing 75 slides (36 negative, 4 inconclusive, and 35 positive) proved to be appropriate for characterizing proficiency in sputum smear microscopy for the diagnosis of tuberculosis when such proficiency is intended to reproduce laboratory routine.

Keywords: Tuberculosis; Microscopy; Reproducibility of results.

Objective: To evaluate the diagnostic accuracy of bronchoscopy in patients with clinical or radiological suspicion of tuberculosis who were unable to produce sputum or with negative sputum smear microscopy results. Methods: A prospective cross-sectional study involving 286 patients under clinical or radiological suspicion of having pulmonary tuberculosis and submitted to bronchoscopy-BAL and transbronchial biopsy (TBB). The BAL specimens were submitted to direct testing and culture for AFB and fungi, whereas the TBB specimens were submitted to histopathological examination. Results: Of the 286 patients studied, 225 (79%) were diagnosed on the basis of bronchoscopic findings, as follows: pulmonary tuberculosis, in 127 (44%); nonspecific chronic inflammation, in 51 (18%); pneumocystis, fungal infections, or nocardiosis, in 20 (7%); bronchiolitis obliterans organizing pneumonia, alveolites, or pneumoconiosis, in 14 (5%); lung or metastatic neoplasms, in 7 (2%); and nontuberculous mycobacterium infections, in 6 (2%). For the diagnosis of tuberculosis, BAL showed a sensitivity and a specificity of 60% and 100%, respectively. Adding the TBB findings significantly increased this sensitivity (to 84%), as did adding the post-bronchoscopy sputum smear microscopy results (total sensitivity, 94%). Minor post-procedure complications occurred in 5.6% of the cases. Conclusions: Bronchoscopy is a reliable method for the diagnosis of pulmonary tuberculosis, with low complication rates. The combination of TBB and BAL increases the sensitivity of the method and facilitates the differential diagnosis with other diseases.

Keywords: Bronchoscopy; Tuberculosis, pulmonary; Sputum; Bronchoalveolar lavage; Biopsy.

Objective: To determine the proportion of negative preoperative sputum smear results among patients presenting active TB, as identified through the evaluation of surgical samples. Methods: A retrospective study of patients undergoing surgery between 2003 and 2006 at a university hospital and receiving a histopathological diagnosis of active or latent TB. We reviewed patient histories, TB-related clinical aspects, acid-fast bacilli (AFB) test results, type of surgery performed and histopathological findings in surgical samples. Results: We included 43 patients, 27 of whom were male. The mean age was 44 ± 19 years. Twenty-eight patients had a history of TB (treated appropriately), and 15 reported no history of the disease. The main reason for seeking treatment was recurrent infection, followed by alterations seen in imaging studies. Of the 43 patients, 35 underwent preoperative AFB testing: 32 tested negative, and 3 tested positive. Among those 35 patients, the histopathological diagnosis was active TB in 26 and latent TB in 9. The 8 patients not submitted to preoperative AFB testing were also diagnosed with latent TB. The proportion of active TB in patients with negative sputum smear results was 72% (23/32), whereas that of negative sputum smear results in patients with active TB was 88% (23/26). Only 11.5% (3/26) of the patients had tested positive for AFB. Conclusions: Direct sputum smear microscopy has a very low yield. Many previously treated patients can present negative sputum smear results and yet have active TB. Active TB can be mistaken for secondary infections or for cancer.

Keywords: Tuberculosis; Diagnosis, differential; Sputum; Thoracic surgery; Thoracic surgery, video-assisted.

Objective: To determine the diagnostic sensitivity of bacteriological analyses in induced sputum (IS) for the diagnosis of pulmonary tuberculosis (TB) and to identify the clinical characteristics associated with the confirmed diagnosis, as well as to determine the diagnostic yield of bronchoscopy carried out when IS tests negative for AFB in smear microscopy. Methods: A retrospective, cross-sectional study of patients suspected of having active pulmonary TB and referred to our clinic for sputum induction. We consecutively reviewed the laboratory data of all patients submitted to sputum induction between June of 2003 and January of 2006, as well as their electronic medical records. In addition, the results of the bacteriological analysis of bronchoscopic specimens collected from the patients whose AFB tests were negative in IS were reviewed. Results: Of the 417 patients included in the study, 83 (19.9%) presented IS samples that tested positive for TB (smear microscopy or culture). In the logistic regression analysis, radiological findings of cavitation (OR = 3.8; 95% CI: 1.9-7.6) and of miliary infiltrate (OR = 3.7; 95% CI: 1.6-8.6) showed the strongest association with the diagnosis of pulmonary TB. In 134 patients, bronchoscopy was carried out after negative AFB results in IS and added 25 (64.1%) confirmed diagnoses of pulmonary TB. Conclusions: In our clinical practice, the frequency of confirmed diagnosis of pulmonary TB using IS (19.9%) was lower than that previously reported in controlled trials. Cavitation and miliary infiltrate increase the diagnostic probability of pulmonary TB using IS. The use of bronchoscopy when IS tests negative for AFB significantly increases sensitivity in the diagnosis of pulmonary TB.

Keywords: Tuberculosis, pulmonary; Diagnosis; Sputum.

Background: Tuberculosis continues to be a global health problem. Objective: To evaluate an automated system designed to diagnose tuberculosis, comparing it to sputum microscopy and culture in Löwenstein-Jensen medium. Method: A comparative study using 844 sputum samples, collected between September and December of 1999 at a reference center for tuberculosis in São Paulo, Brazil, to draw distinctions between the results obtained through the use of the automated system and those obtained through sputum microscopy and culture in Löwenstein-Jensen medium. Results: Of the 844 samples evaluated, 27.1% tested positive for acid-fast bacilli, and 72.9% tested negative. In Löwenstein-Jensen culture, 34.7% were positive and 63% were negative, compared with 37.1% positivity and 56.9% negativity using the automated system. Sensitivity was 98.1% for the automated system and 91.9% for Löwenstein-Jensen culture. Specificity and positive predictive value were 100% for both methods. Negative predictive value was 98.9% for the automated system and 95.5% for Löwenstein-Jensen culture. The degree of accuracy was 99.3% for the automated system and 97% for Löwenstein-Jensen culture, and the Kappa was 0.99 for the automated system and 0.94 for Löwenstein-Jensen culture. The difference between the mean time to detection of mycobacteria using the automated system (10.5 days) and that found using Löwenstein-Jensen culture (34.7 days) was statistically significant. Conclusion: The difference between the culture yield obtained using the automated system and that achieved with Löwenstein-Jensen culture was statistically significant. Mean time to detection of mycobacteria was significantly shorter with the automated system. The higher yield provided by this new system justifies its use in a reference center for tuberculosis in São Paulo

Keywords: Mycobacterium tuberculosis. Diagnostic. Automated systems.

Objective: To establish reproducible electron microscopic criteria for identifying the four major types of neuroendocrine tumors of the lung: carcinoid; atypical carcinoid; large cell neuroendocrine carcinoma; and small cell carcinoma. Methods: Measurements were made on electron micrographs using a digital image analyzer. Sixteen morphometric variables related to tumor cell differentiation were assessed in 27 tumors. The examination under electron microscopy revealed that all of the tumors could be classified as belonging to one of the four categories listed above. Cluster analysis of the morphometry variables was used to group the tumors into three clusters, and Kaplan-Meier survival function curves were employed in order to draw correlations between each cluster and survival. Results: All three clusters of neuroendocrine carcinomas were found to be associated with survival curves, demonstrating the prognostic significance of electron microscopic features. The tumors fell into three well-defined clusters, which represent the spectrum of neuroendocrine differentiation: typical carcinoid (cluster 1); atypical carcinoid and large cell neuroendocrine carcinoma (cluster 2); and small cell carcinoma (cluster 3). Cluster 2 represents an intermediate step in neuroendocrine carcinogenesis, between typical carcinoid tumors and small cell carcinomas. Conclusions: Our findings confirm that electron microscopy is useful in making the diagnosis and prognosis in cases of lung tumor.

Keywords: Neuroendocrine tumors/lung; Microscopy, electron; Cluster analysis; Survival analysis.

A comparative study to evaluate contamination in cultures of morning sputum samples, comparing those collected at home under currently recommended conditions and those collected under supervision after patient orientation and education. The home and supervised collection groups produced 43 and 76 sputum samples, respectively. The contamination rate was nearly 3-times higher among samples collected at home than among those collected under supervision (37% vs. 13%, p < 0.05; OR = 0.25). The simple educational and hygiene measures described can decrease the contamination rate among sputum samples collected for diagnostic culture.

Keywords: Tuberculosis/diagnosis; Sputum/microbiology; Culture techniques.

Background: Induced sputum is widely used in assessing airway inflammation. However, its utility as a diagnostic tool in the diagnosis of lung disease in immunosuppressed patients merits further investigation. Objectives: To determinate the diagnostic yield of sputum induction in the diagnosis of lung diseases in HIV-positive patients. Method: Subjects were selected from among HIV-positive patients older than 14 years who were evaluated at a reference hospital between January 2001 and September 2002. Those with respiratory symptoms for 7 days or longer with normal or abnormal chest X-rays, as well as those without respiratory symptoms but with abnormal chest X-rays, were included. All subjects were submitted to clinical examination, radiologic evaluation, sputum induction and laboratory testing. Subsequently, flexible fiberoptic bronchoscopy, bronchoalveolar lavage and transbronchial lung biopsy were performed. Samples were processed for Gram and Ziehl-Neelsen staining, quantitative culture for pyogenic bacteria, direct staining for fungi, culture for mycobacteria and fungi, silver stain for Pneumocystis jiroveci, as well as for total and differential cellularity determination. Results: A total of 54 patients were included. Upon testing negative for any etiologic agent, 7 patients were excluded, resulting in a total of 54 patients studied. A total of 60 infectious agents were isolated. Among the etiologic agents isolated, 46.7% were P. jiroveci, 33.5 were pyogenic bacteria and 16.7% were Mycobacterium tuberculosis. Sputum induction presented 57.5% sensitivity, 42.9% specificity, 87.1% predictive positive value, 13% predictive negative value and 55.6% overall accuracy. Conclusions: In this population, sputum induction proved to be a technique that is safe and easily performed, with a good diagnostic yield.

Keywords: HIV, Acquired Immunodeficiency Syndrome, Bronchoscopy, Sputum, Lung Disease/diagnosi.

Since the beginning of the use of anti-TNF in the treatment of rheumatoid arthritis and other inflammatory diseases, cases of pulmonary tuberculosis and extrapulmonary tuberculosis have been reported in patients receiving such treatment. In most cases, the disease develops by the time the patient has received the sixth infusion. Every patient should be evaluated for latent tuberculosis infection prior to the use of a TNF inhibitor. However, the diagnosis of latent tuberculosis infection is a challenge. The tuberculin test, which was the only test available to detect latent tuberculosis infection for nearly a century, presents a number of limitations. Tests based on the detection of the in-vitro production of IFN-γ by mononuclear cells activated by specific antigens appear to be more accurate and have been studied in patients with rheumatoid arthritis.

Keywords: Tuberculosis, pulmonary; Arthritis, rheumatoid; Tumor necrosis factor-alpha; Infection.

Objective: To compare gastric lavage (GL) performed in inpatients with GL performed in outpatients in terms of its accuracy in diagnosing pulmonary tuberculosis (TB) in children. Methods: A prospective study was carried out in the state of Espírito Santo, Brazil, from 1999 to 2003. A total of 230 children suspected of having TB (103 inpatients and 127 outpatients) were selected to undergo GL. Those thus diagnosed with TB (n = 53) were divided into two groups: inpatient GL (n = 30) and outpatient GL (n = 23). All 53 children were monitored for 6 months in order to evaluate the accuracy of the diagnosis. Accuracy was determined based on any change in diagnosis, cure rate, and the percentage of positive cultures in the two groups studied. Results: The cure rate was 100% in both groups, and there was no change in diagnosis in the 53 children studied. No significant difference was found between the two groups studied in terms of detection of Mycobacterium tuberculosis (RR = 1.47; 95% CI: 0.95-2.27; p = 0.095), although the outpatient group presented a greater rate of positive cultures. Conclusions: Our results show that the accuracy of GL performed in an inpatient setting is similar to that of GL performed in an outpatient setting. This indicates that hospitalization is required only in more severe cases in which GL cannot be performed as an outpatient procedure.

Keywords: Gastric lavage; Tuberculosis; Diagnosis.

Objective: To evaluate the accuracy of bacteriological methods and of polymerase chain reaction (with primers specific for IS6110 of the Mycobacterium tuberculosis complex) in testing sputum samples from indigenous (Amerindian) and non-indigenous patients. Methods: A total of 214 sputum samples (154 from indigenous patients and 60 from non-indigenous patients) were analyzed in order to determine the accuracy of smear microscopy (direct and concentrated versions) for acid-fast bacilli, culture, and polymerase chain reaction. Results: Both microscopy methods presented low sensitivity in comparison with culture and polymerase chain reaction. Specificity ranged from 91% to 100%, the concentrated acid-fast smear technique being the least specific. Nontuberculous mycobacteria were isolated three times more frequently in samples from indigenous patients than in those from non-indigenous patients. False-positive and false-negative polymerase chain reaction results were more common in the indigenous population. Conclusion: Positivity and isolation of nontuberculous mycobacteria in the acid-fast smear in conjunction with polymerase chain reaction positivity raise the following hypotheses: nontuberculous mycobacteria species with DNA regions homologous to, or even still possessing, the M. tuberculosis IS6110 exist in the Amazon; colonization of the oropharynx or of a tuberculous lesion accelerates the growth of the nontuberculous mycobacteria present in the sputum samples, making it impossible to isolate M. tuberculosis; A history of tuberculosis results in positivity for M. tuberculosis DNA. The absence of bacteriological positivity in the presence of polymerase chain reaction positivity raises questions regarding the inherent technical characteristics of the bacteriological methods or regarding patient history of tuberculosis.

Keywords: Tuberculosis, pulmonary/diagnosis; Mycobacterium tuberculosis, Polymerase chain reaction/methods; Indians, south american

Purpose: To determine the effectiveness of alternative regimens for treating confirmed MDR TB cases in outpatient units: Methods: MDR TB cases were defined as culture isolation of M. tuberculosis resistant in vitro to at least rifampin/isoniazide and a third drug of standard regimens in Brazil, according to both the conventional method and the BACTEC system. Design: Multicentric non-randomized controlled clinical trial. From April 95 to December 97 187 patients were enrolled. As of April 98, there were 36 patients under treatment. The authors analyzed 149 patients that had an average 14 months of treatment duration. The regimens used were chosen according to sensitivity tests: 1) streptomycin (S)/ofloxacin (OFX)/terizidon (TZ)/ethambutol (E)/clofazimine (CZ) or capreomycin (CM)/OFX/TZ/CZ/E or amicacyn/OFX/TZ/E/CZ. Demography: Male, 68.4%; female, 31.5%; mean age-36.9 years; HIV prevalence 1.9%; primary resistance rate - 8%. Outcomes: cured-treated for 12 months with six months after two consecutive negative culture; abandoned-discontinued treatment and consultations; died - deaths due to TB after two months of treatment; failed - remained positive in culture throughout the 12 months. Results: 120 (79.5%) patients converted to negative culture within 3 months. Cured: 53%, failed 31%, died 6%, abandoned 10%. Conclusions: The major predictor to MDR TB in Brazil is previous irregular and/or incomplete treatment. Sputum conversion rate was high and favorable overall response was 53%. Clinical implications: Because TB is endemic in Brazil and the number of MDR cases due to acquired resistance is increasing, greater efforts are needed to implement supervised treatment in tuberculosis particularly for non compliant patients.

Keywords: Tuberculosis, treatment. Multidrug resistant tuberculosis.

Objective: To evaluate Brazilian studies by summarizing the accuracy of adenosine deaminase in the diagnosis of the pleural tuberculosis, with the objective of lending support to the movement to make the test part of the routine in the investigation of pleural effusions. Methods: A search for Brazilian studies related to the determination of adenosine deaminase levels in the pleural liquid was carried out. These studies were evaluated and included in this study. The data were analyzed using summary receiver operating characteristic (SROC) curves, which enabled the studies to be collected and evaluated regarding the accuracy of the diagnosis. As for the global values of sensitivity and specificity, the Bayes' theorem was applied to calculate the post-test probabilities in different prevalences of the disease. Results: Twenty-five studies dating from 1987 to 2005 and including enough information to be used in the meta-analysis were identified. After evaluation, nine studies were included, totaling 1674 patients. According to the SROC curve, a sensitivity of 91.8% (95% CI: 89.8‑93.6%) and a specificity of 88.4% (95% CI: 86.0-90.5%) were found, with an area of 0.969 below the curve. The overall odds ratio was 112.0 (95% CI: 51.6-243.2). Considering a prevalence of tuberculosis of 50% (considered neutral), the post-test probability was 88.7% for a positive test and 91.5% for a negative test. Conclusion: Despite the differences found among studies, it is possible to conclude that the determination of adenosine deaminase levels has high accuracy in the diagnosis of the pleural tuberculosis and should be used as a routine test in its investigation.

Keywords: Pleural effusion; Tuberculosis; Diagnosis; Adenosine deaminase; Meta-analysis.

Objective: To estimate the total time elapsed between symptom onset and diagnosis of pulmonary tuberculosis (patient delay plus health care system delay), analyzing the factors associated with delayed diagnosis in the state of Rio de Janeiro, Brazil. Methods: We conducted a questionnaire-based survey involving 218 pulmonary tuberculosis patients treated for two months at 20 health care clinics and 3 hospitals in eight cities within the state of Rio de Janeiro. We collected socioeconomic and demographic data, as well as data regarding the health care system and the medical history of the patients. Results: The median time elapsed from the onset of symptoms to diagnosis was 68 days (interquartile range [IQR]: 35-119 days). The median patient delay (time from symptom onset to initial medical visit) was 30 days (IQR: 15-60 days), and the median health care system delay (time from initial medical visit to diagnosis) was 21 days (IQR: 8-47 days). A cut-off point of 21 days was adopted. The factors independently associated with patient delay were female gender, cough, and unemployment [adjusted OR (95% CI) = 2.7 (1.3-5.6); 11.6 (2.3-58.8); and 2.0 (1.0-3.8), respectively], whereas only female gender was independently associated with health care system delay (OR= 3.2; 95% CI: 1.7-6.0). Conclusions: Delayed diagnosis of pulmonary tuberculosis remains a problem in Rio de Janeiro, increasing the risk of transmission and mortality, that risk being greater for women and the socioeconomically disadvantaged. Patients might not recognize the significance of chronic cough as a health problem. Tuberculosis education programs targeting women might improve this situation.

Keywords: Lung neoplasms; Neoplasm metastasis; Antineoplastic combined chemotherapy protocols; Radiotherapy, computer-assisted.

Background: In Brazil, tuberculosis is the major cause of pleural effusion. In more than 50% of cases, treatment has been initiated prior to confirmation of the diagnosis. Our objective was to identify factors that can contribute to the diagnosis. Method: We studied 215 consecutive patients with pleural effusion: 104 from tuberculosis (TB) and 111 from other causes (41 were from malignancies, 29 involved transudation, 28 were parapneumonic and 13 were from other etiologies). Clinical, radiological and laboratorial variables were evaluated for differences between the two groups, individually or in combination. Results: Male gender and PPD > 10 mm were significantly more frequent in the tuberculosis group. Radiological features were similar in both groups. Among the continuous variables, adenosine deaminase (ADA), percentile of cells, protein and age performed better as isolated diagnostic criteria. Between the group with tuberculosis and that with pleural effusion from other causes, no significant differences were found in Lactate dehydrogenase, total leukocytes or duration of disease. The correlation of ADA with any other welldeveloped continuous variable showed an LR+ > 10 and an LR- < 0.1, which effectively confirmed or ruled out a diagnosis of tuberculous pleural effusion. Conclusions: In patients with ADA levels > 39 at 95% sensitivity, the specificity can be improved to more than 90% if we consider non purulent effusion or effusion with a predominance of lymphocytes (> 50%).

Keywords: Tuberculosis, pleural/diagnosis. Adenosine deaminase/diagnosis use. Sensitivity and specificity.

Objective: To evaluate the quality of diagnosis and the epidemiological profile of patients with pleural tuberculosis in the state of Roraima, Brazil, in order to provide technical support for the development and implementation of public policies to combat the disease. Methods: This was a cross-sectional study designed to determine the prevalence of pleural forms of tuberculosis in Roraima between 2005 and 2013 and to evaluate the diagnostic criteria used, as well as their determinants. This study was based on secondary data from the Brazilian Case Registry Database, including all reported cases of pleural tuberculosis in the state during the study period. Diagnoses based on bacteriological or histopathological confirmation were defined as high-quality diagnoses. Results: Among the 1,395 cases of tuberculosis reported during the study period, 116 (8.3%) were cases of pleural tuberculosis, accounting for 38.9% of all cases of extrapulmonary tuberculosis in the sample. The incidence rate of pleural tuberculosis did not follow the downward trend observed for the pulmonary form of the disease during the same period. The prevalence of cases with a high-quality diagnosis was 28.5% (95% CI: 20.4-37.6%). In a univariate analysis, none of the demographic or clinical characteristics collected from the database were found to have a significant impact on the outcome (as explanatory variables). Conclusions: The quality of the diagnoses in our study sample was considered unsatisfactory. Limited access to specific diagnostic methods might have contributed to these results.

Keywords: Tuberculosis/diagnosis; Tuberculosis/epidemiology; Tuberculosis, pleural.