Objective: To evaluate the rapid diagnosis of multidrug-resistant tuberculosis, by using a commercial line probe assay for rifampicin and isoniazid detection (LPA-plus), in the routine workflow of a tuberculosis reference laboratory. Methods: The LPA-plus was prospectively evaluated on 341 isolates concurrently submitted to the automated liquid drug susceptibility testing system. Results: Among 303 phenotypically valid results, none was genotypically rifampicin false-susceptible (13/13; 100% sensitivity). Two rifampicin-susceptible isolates harboured rpoB mutations (288/290; 99.3% specificity) which, however, were non-resistance-conferring mutations. LPA-plus missed three isoniazid-resistant isolates (23/26; 88.5% sensitivity) and detected all isoniazid-susceptible isolates (277/277; 100% specificity). Among the 38 (11%) invalid phenotypic results, LPA-plus identified 31 rifampicin- and isoniazid-susceptible isolates, one isoniazid-resistant and six as non-Mycobacterium tuberculosis complex. Conclusions: LPA-plus showed excellent agreement (≥91%) and accuracy (≥99%). Implementing LPA-plus in our setting can speed up the diagnosis of multidrug-resistant tuberculosis, yield a significantly higher number of valid results than phenotypic drug susceptibility testing and provide further information on the drug-resistance level.

Keywords: Tuberculosis, multidrug-resistant; Molecular diagnostic techniques; Microbial sensitivity tests; Mycobacterium tuberculosis.

Objective: To assess predictive factors for improved diagnostic accuracy with the use of radial-probe EBUS (RP-EBUS). Methods: This was a retrospective review of consecutive patients undergoing RP-EBUS between February of 2012 and January of 2020. Parameters including the presence of a bronchus sign on CT scans, the position of the radial EBUS probe, lesion size, lesion location, and lesion type were analyzed in relation to two defined outcomes (final diagnosis or no diagnosis). Univariate analysis was used in order to explore the individual effects of each parameter on diagnostic accuracy. Multivariate logistic regression was performed to identify significant predictors of diagnostic accuracy. Results: RP-EBUS was used for diagnostic purposes in 101 patients. The lesion was < 3 cm in size in 59 patients (58.4%) and predominantly solid in 60.3%. There was a positive correlation between radial EBUS probe position and diagnostic accuracy (p = 0.036), with 80.9% of the patients showing a bronchus sign on CT scans. Furthermore, 89% of the patients showed a bronchus sign on CT scans and a correlation with diagnostic accuracy (p = 0.030), with 65.8% of the lesions being located in the left/right upper lobe (p = 0.046). When the radial EBUS probe was within the target lesion, the diagnostic yield was = 80.8%. When the probe was adjacent to the lesion, the diagnostic yield was = 19.2%. A bronchus sign on CT scans was the only parameter that independently influenced diagnostic accuracy (adjusted OR, 3.20; 95% CI, 1.081-9.770; p = 0.036). Conclusions: A bronchus sign on CT scans is a powerful predictor of successful diagnosis by RP-EBUS.

Keywords: Diagnostic techniques, respiratory system; Ultrasonography; Bronchoscopy.

Objective: Conventional bronchoscopy has a low diagnostic yield for peripheral pulmonary lesions. Radial-probe EBUS employs a rotating ultrasound transducer at the end of a probe that is passed through the working channel of the bronchoscope. Radial-probe EBUS facilitates the localization of peripheral pulmonary nodules, thus increasing the diagnostic yield. The objective of this study was to present our initial experience using radial-probe EBUS in the diagnosis of peripheral pulmonary lesions at a tertiary hospital. Methods: We conducted a retrospective analysis of 54 patients who underwent radial-probe EBUS-guided bronchoscopy for the investigation of pulmonary nodules or masses between February of 2012 and September of 2013. Radial-probe EBUS was performed with a flexible 20-MHz probe, which was passed through the working channel of the bronchoscope and advanced through the bronchus to the target lesion. For localization of the lesion and for collection procedures (bronchial brushing, transbronchial needle aspiration, and transbronchial biopsy), we used fluoroscopy. Results: Radial-probe EBUS identified 39 nodules (mean diameter, 1.9 ± 0.7 cm) and 19 masses (mean diameter, 4.1 ± 0.9 cm). The overall sensitivity of the method was 66.7% (79.5% and 25.0%, respectively, for lesions that were visible and not visible by radial-probe EBUS). Among the lesions that were visible by radial-probe EBUS, the sensitivity was 91.7% for masses and 74.1% for nodules. The complications were pneumothorax (in 3.7%) and bronchial bleeding, which was controlled bronchoscopically (in 9.3%). Conclusions: Radial-probe EBUS shows a good safety profile, a low complication rate, and high sensitivity for the diagnosis of peripheral pulmonary lesions.

Keywords: Diagnostic techniques, respiratory system; Lung/ultrasonography; Bronchoscopy/methods; Bronchoscopy/instrumentation.

Objective: To evaluate the implications of the proportion of annual family income spent in the pre- and post-diagnosis periods in tuberculosis patients followed for after at least one year after completing tuberculosis treatment in Brazil. Methods: This was a cross-sectional study of tuberculosis patients followed for at least one year after completing tuberculosis treatment in five Brazilian capitals (one in each region of the country). Results: A total of 62 patients were included in the analysis. The overall average cost of tuberculosis was 283.84 Brazilian reals (R$) in the pre-diagnosis period and R$4,161.86 in the post-diagnosis period. After the costs of tuberculosis disease, 71% of the patients became unemployed, with an overall increase in unemployment; in addition, the number of patients living in nonpoverty decreased by 5%, the number of patients living in poverty increased by 6%, and the number of patients living in extreme poverty increased by 5%. The largest proportion of annual household income to cover the total costs of tuberculosis was for the extremely poor (i.e., 40.37% vs. 11.43% for the less poor). Conclusions: Policies to mitigate catastrophic costs should include interventions planned by the health care system and social protection measures for tuberculosis patients with lower incomes in order to eliminate the global tuberculosis epidemic by 2035-a WHO goal in line with the United Nations Sustainable Development Goals.

Keywords: Tuberculosis/diagnosis; Tuberculosis/therapy; Costs and cost analysis; Financial stress; Brazil.

Objective: To evaluate cases of tuberculosis occurring in the Entorno region of the state of Goiás but reported in the Federal District (FD) and to analyze the influence that this has on the effectiveness of the local tuberculosis control program, as well as on the socioeconomic and demographic data related to tuberculosis incidence rates. Methods: Rates of tuberculosis incidence, cure, noncompliance, treatment failure, mortality and referral, as well as socioeconomic and demographic data, were reviewed for patients from ten cities in Goiás. Results: From 2000 to 2004 in the cities under study, 714 new cases of tuberculosis were reported, 436 (61.0%) of which were treated in the FD, and therefore, were not included in the Goiás database. Among patients treated only in Goiás, the mean incidence of tuberculosis ranged from 4.40 to 10.02/100,000 inhabitants. When those treated in the FD were included, the incidence significantly increased, ranging from 15.16 to 20.54/100,000 inhabitants (p < 0.001). The rate at which contacts of tuberculosis patients were investigated was low, and treatment outcomes were unsatisfactory in Goiás and in the DF. Socioeconomic and demographic data were consistent with the tuberculosis incidence. Conclusion: The number of tuberculosis patients treated in the city in which they reside was lower than expected. Treatment in another city might compromise tuberculosis control. The recalculated tuberculosis incidence is consistent with the socioeconomic and demographic profile of the region. A federal surveillance system can be efficiently optimized, improving the control of this disease.

Keywords: Tuberculosis/epidemiology; Epidemiologic studies; Government programs.

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.

We compared the nitrate reductase assay with the proportion method, which is considered the gold standard, in 57 Mycobacterium tuberculosis strains isolated from patients treated at the Federal University of Minas Gerais Hospital das Clínicas, located in the city of Belo Horizonte, Brazil. For rifampin and isoniazid, the sensitivity, specificity, and accuracy of the nitrate reductase assay were all 100%, whereas they were 100%, 88.9%, and 66.7%, respectively, for streptomycin and 98.0%, 100%, and 98.2%, respectively, for ethambutol. The mean time to results was ten days. In the study sample, the nitrate reductase assay proved highly accurate and showed excellent concordance with the gold standard.

Keywords: Mycobacterium tuberculosis; Microbial sensitivity tests; Tuberculosis, multidrug-resistant; Nitrate reductase.

Background: The appearance of tuberculosis/human immunodeficiency virus co-infection and the growing number of diseases caused by nontuberculous mycobacteria, as well as the confusion that these can cause in relation to emerging multidrug-resistant strains, require more accurate and rapid laboratory results, not only in the isolation of strains but also in their identification. Objective: A comparative study evaluating a new tool of molecular identification, which uses a genetic probe based on the 16S rDNA sequence of the Mycobacterium tuberculosis gene (Gen-Probe Accuprobe® Gen Probe, Inc.), and the classic methodology. Method: Fifty-five Mycobacterium strains, isolated from the sputum of patients treated at a tuberculosis reference clinic, were selected for study. Subcultures were performed in three tubes: one submitted to genetic identification, one analyzed through classical tests (production and accumulation of niacin; growth in the Lowenstein-Jensen medium with the inhibitor agents p-nitrobenzoic acid and thiophene-2-carboxylic acid hydrazide added), and one held in reserve. Results: The probe identified 51 cases as belonging to the M. tuberculosis complex (one associated with M. kansasii) and the other 4 as nontuberculous mycobacteria, later identified as M. kansasii (3) and M. avium (1). Using traditional methods, 47 samples were identified as belonging to the M. tuberculosis complex, 4 were classified as fitting the profile of nontuberculous mycobacteria (in agreement with the genetic probe results), and 4 were unidentified, 1 of which presented the exact characteristics that 2 mycobacterium species have in common. Conclusion: The benefits of the molecular biology technique justify its implementation and routine use, in combination with classical methods, in a high-traffic clinic where complex cases of tuberculosis are treated.

Keywords: Mycobacterium tuberculosis. Molecular probe techniques.

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 clinical and epidemiological profile of patients who are candidates for TNF-α inhibitor use and are classified as having latent tuberculosis (LTB), as well as to evaluate the outcomes of prophylactic treatment with isoniazid. Methods: A prospective descriptive analysis followed by an analytical, observational, cross-sectional study of the outcomes of prophylactic treatment in a group of 45 candidates for TNF-α inhibitor use. We evaluated the patients through anamnesis, clinical examination, chest X-ray, and tuberculin skin test (TST) using the Mantoux method. Results: The mean age was 45 years, and 56.0% of the patients were female. Chronic rheumatic diseases, chronic dermatological diseases, and Crohn's disease were present in 46.7%, 40.0%, and 13.3% of the patients, respectively. The mean TST induration was 14.6 mm (range: 5-30 mm). The majority (n = 30) of the 45 patients (66.7%) had an induration > 10 mm. In the 16 patients with BCG vaccination scars, the mean induration was 15.7 mm, and 14 of those patients had an induration > 10 mm. Chest X-ray results were considered normal, with minimal alterations, in 64.4% and 35.6% of the patients, respectively. The treatment with isoniazid was abandoned by 1 patient (2.2%) and completed by 41 (91.2%), whereas it was interrupted because of drug-induced hepatitis in 2 (4.4%), and 1 patient (2.2%) was transferred to another hospital. Of those who completed the treatment, 5 experienced mild side effects. Conclusions: Determining the profile of candidates for TNF-α inhibitor use is important for the management of LTB treatment and for the establishment of clinical protocols for the use and monitoring of the use of these medications.

Keywords: Tuberculosis; Latent tuberculosis; Tuberculin test; Isoniazid; Tumor necrosis factor-alpha.

Objective: The present study aims at describing the frequency of nontuberculous mycobacteria (NTM) species identified through laboratory testing of samples collected from non-sterile sites (sputum), as well as its frequency in HIV-infected and non-HIV-infected individuals in the Baixada Santista region of the state of São Paulo, Brazil, in the period from 2000 to 2005. Methods: Retrospective analysis of sputum smear microscopy results and culture was conducted based on the records on file at the Instituto Adolfo Lutz-Santos, the regional tuberculosis laboratory. Results: We analyzed 194 NTM strains isolated from 125 individuals, of whom 73 (58.4%) were HIV-negative and 52 (41.6%) were HIV-positive. Thirteen different species were identified: Mycobacterium kansasii; M. avium complex; M. fortuitum; M. peregrinum; M. gordonae; M. terrae; M. nonchromogenicum; M. intracellulare; M. flavescens; M. bohemicum; M. chelonae; M. shimoidei; and M. lentiflavum. In 19.2% of the cases, the bacteriological diagnosis was confirmed by isolation of the same species in at least two consecutive samples. Conclusions: Our results show the importance of including systematic identification of NTM in the laboratory routine, and that its integration into the clinical routine could improve the characterization of the disease, thereby informing the planning of effective control measures in specific populations, such as individuals presenting tuberculosis/HIV co-infection.

Keywords: Mycobacteria, atypical; Laboratory techniques and procedures; HIV; Tuberculosis.

Objective: To develop a system for the molecular diagnosis of tuberculosis by polymerase chain reaction (PCR), constructing primers based on the difference in gene organization of the intergenic region of phospholipase C (plcB-plcC region), which differentiates Mycobacterium tuberculosis from other mycobacteria. Methods: A PCR product of the expected size (432 bp) was obtained from M. tuberculosis and M. africanum only. A total of 33 mycobacterial isolates and 273 clinical samples from patients suspected of having tuberculosis were examined. These were used in the comparative study of the PCR technique versus culture. Results: For PCR versus culture, the data showed 93.8% accuracy (p < 0.0001), 93.1% sensitivity (CI: 88.7-96.0), and 96.4% specificity (CI: 96.1-99.4). The Kappa value (0.82) shows that there was a near-perfect concordance between the two tests. Conclusion: The use of the plcB-plcC region in PCR amplification was found to be an important and reliable tool for the specific diagnosis of tuberculosis in the samples analyzed.

Keywords: Polymerase chain reaction; Diagnosis; Tuberculosis; Mycobacterium tuberculosis

Objective: To identify spatial patterns in hospitalizations for pneumonia in infants under one year of age in the Vale do Paraíba region of Brazil. Methods: This was an ecological exploratory study using a georeferencing technique based on data from the Information Technology Department of the Brazilian Unified Health Care System on the number of hospitalizations for pneumonia among infants under one year of age in the Vale do Paraíba region between 2004 and 2005. Based on the distribution of the rates of hospitalizations for pneumonia per 1,000 live births, thematic maps were created. Moran's spatial autocorrelation coefficient was estimated, and the cities with the highest rates were identified using box maps. Results: During the study period, 2,227 infants under one year of age were hospitalized for pneumonia. Moran's coefficient was 0.37 (p = 0.02), demonstrating a spatial autocorrelation for these hospitalizations. Eight cities deserving special attention for future interventions were identified. Conclusions: The spatial analysis was successful in determining the spatial autocorrelation, as well as in identifying the cities in which an intervention is necessary regarding the number of hospitalizations for pneumonia in infants under one year of age.

Keywords: Pneumonia; Geographic information systems; Child health (Public health); Infant.

Objective: To evaluate the prevalence of and describe the methods used to control the smoking habit among a geographically-specific population of physicians. Methods: Questionnaires were distributed to physicians practicing in a region of the greater metropolitan area of São Paulo area known as the "ABC Paulista" (comprising the municipalities of Santo Andre, São Bernardo and São Caetano), and completed questionnaires were received from 678 physicians, all registered with the São Paulo State Regional Council of Medicine. Results: Of the 678 responding physicians, 58 (8.6%) were smokers, 183 (27.0%) were former smokers, and 437 (64.5%) were nonsmokers. No gender-based differences were found. Nor were there any significant differences in prevalence based on medical specialty. Most of the smokers had tried to stop smoking. Among the smokers, cessation methods were used by 7%: nicotine replacement therapy by 4.3%; and acupuncture by 2.7%. Most of the former smokers (88.1%) had successfully quit smoking without using any cessation methods. Conclusion: The prevalence of smoking among physicians in the ABC Paulista region was 8.6%. In this region, the majority of physicians who quit smoking did so without the aid of smoking cessation methods. Among those who did use such methods, nicotine replacement therapy was the method of choice.

Keywords: Prevalence; Smoking; Physicians; Smoking cessation

Objective: To analyze the prevalence of asthma and asthma symptoms in students of two distinct age brackets residing in the city of Tangará da Serra, Brazil. Methods: Cross-sectional, population-based study of the prevalence of asthma in children from 6 to 7 years of age and adolescents from 13 to 14, using the standardized International Study of Asthma and Allergies in Childhood, phase 1 questionnaire, validated for use in Brazil. Students who responded affirmatively to question 2 (presence of wheezing in the preceding 12 months) were classified as suffering from asthma. Results: The study comprised 3,362 students, of whom 1,634 (48.6%) were children and 1,728 (51.4%) were adolescents. Of the 1,634 children, 816 (49.9%) were male and 818 (50.1%) were female. Of the 1,728 adolescents, 773 (45.0%) were male and 955 (55.0%) were female. The prevalence of asthma among the children was 25.2%, whereas that among the adolescents was 15.9% (χ2 = 8.34; p = 0.00). The children presented higher prevalences of the following symptoms of asthma than did the adolescents: wheezing ever (54.3%), nocturnal dry cough (43.9%), wheezing in the preceding 12 months (25.2%), and from 1 to 3 attacks of wheezing in the preceding 12 months (19.1%). There were no differences between the two groups regarding physician-diagnosed asthma (approximately 4.5%). There were no statistical differences regarding the prevalence of asthma by gender in the two groups. Conclusions: Tangará da Serra has a high prevalence of asthma in children and adolescents, and this result is compatible with other studies carried out in Brazil and Latin America using the same methodology.

Keywords: Asthma/epidemiology; Child; Adolescent.