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.

Keywords: Tuberculosis; Post-infectious disorders; Disease management.

Objective: To analyze and compare the mutations in two different regions of the katG gene, which is responsible for isoniazid (INH) resistance. Methods: We analyzed 97 multidrug-resistant Mycobacterium tuberculosis strains isolated in cultures of sputum samples obtained from the Professor Hélio Fraga Referral Center, in Brasília, Brazil. Another 6 INH-sensitive strains did not present mutations and were included as controls. We used PCR to amplify two regions of the katG gene (GenBank accession no. U06258)-region 1, (from codon 1 to codon 119) and region 2 (from codon 267 to codon 504)-which were then sequenced in order to identify mutations. Results: Seven strains were resistant to INH and did not contain mutations in either region. Thirty strains carried mutations in region 1, which was characterized by a high number of deletions, especially at codon 4 (24 strains). Region 2 carried 83 point mutations, especially at codon 315, and there was a serine-to-threonine (AGC-to-ACC) substitution in 73 of those cases. The analysis of region 2 allowed INH resistance to be diagnosed in 81.4% of the strains. Nine strains had mutations exclusively in region 1, which allowed the proportion of INH-resistant strains identified to be increased to 90.6%. Conclusions: The number of mutations at codon 315 was high, which is consistent with cases described in Brazil and in other countries, and the analysis of region 1 resulted in a 9.2% increase in the rate at which mutations were identified.

Keywords: Isoniazid; Mutation; Tuberculosis; Drug resistance, multiple.

Objective: To analyze the temporal trend of tuberculosis cure indicators in Brazil. Methods: An ecological time-series study using administrative data of reported cases of the disease nationwide between 2001 and 2022. We estimated cure indicators for each federative unit (FU) considering individuals with pulmonary tuberculosis, tuberculosis-HIV coinfection, and those in tuberculosis retreatment. We used regression models using joinpoint regression for trend analysis, reporting the annual percentage change and the average annual percentage change. Results: For the three groups analyzed, we observed heterogeneity in the annual percentage change in the Brazilian FUs, with a predominance of significantly decreasing trends in the cure indicator in most FUs, especially at the end of the time series. When considering national indicators, an average annual percentage change of -0.97% (95% CI: -1.23 to -0.74) was identified for the cure of people with pulmonary tuberculosis, of -1.11% (95% CI: -1.42 to -0.85) for the cure of people with tuberculosis-HIV coinfection, and of -1.44% (95% CI: -1.62 to -1.31) for the cure of people in tuberculosis retreatment. Conclusions: The decreasing trends of cure indicators in Brazil are concerning and underscore a warning to public authorities, as it points to the possible occurrence of other treatment outcomes, such as treatment discontinuity and death. This finding contradicts current public health care policies and requires urgent strategies aiming to promote follow-up of patients during tuberculosis treatment in Brazil.

Keywords: Tuberculosis; Time factors; Retrospective studies; Brazil.

Objective: To investigate the reported cases of tuberculosis and of tuberculosis-HIV co-infection in Brazil between 2002 and 2012. Methods: This was an observational study based on secondary time series data collected from the Brazilian Case Registry Database for the 2002-2012 period. The incidence of tuberculosis was stratified by gender, age group, geographical region, and outcome, as was that of tuberculosis-HIV co-infection. Results: Nationally, the incidence of tuberculosis declined by 18%, whereas that of tuberculosis-HIV co-infection increased by 3.8%. There was an overall decrease in the incidence of tuberculosis, despite a significant increase in that of tuberculosis-HIV co-infection in women. The incidence of tuberculosis decreased only in the 0- to 9-year age bracket, remaining stable or increasing in the other age groups. The incidence of tuberculosis-HIV co-infection increased by 209% in the ≥ 60-year age bracket. The incidence of tuberculosis decreased in all geographical regions except the south, whereas that of tuberculosis-HIV co-infection increased by over 150% in the north and northeast. Regarding the outcomes, patients with tuberculosis-HIV co-infection, in comparison with patients infected with tuberculosis only, had a 48% lower chance of cure, a 50% greater risk of treatment nonadherence, and a 94% greater risk of death from tuberculosis. Conclusions: Our study shows that tuberculosis continues to be a relevant public health issue in Brazil, because the goals for the control and cure of the disease have yet to be achieved. In addition, the sharp increase in the incidence of tuberculosis-HIV co-infection in women, in the elderly, and in the northern/northeastern region reveals that the population of HIV-infected individuals is rapidly becoming more female, older, and more impoverished.

Keywords: Tuberculosis/epidemiology; HIV infections/epidemiology; Comorbidity.

Objective: Lung cancer (LC) is the leading cause of cancer-related death and represents a major public health problem worldwide. Another major cause of morbidity and mortality, especially in developing countries, is tuberculosis. The simultaneous or sequential occurrence of pulmonary tuberculosis and LC in the same patient has been reported in various case series and case-control studies. The objective of this study was to describe the characteristics of patients developing tuberculosis and LC, either simultaneously or sequentially. Methods: This was a cross-sectional study based on the review of medical charts. Results: The study involved 24 patients diagnosed with tuberculosis and LC between 2009 and 2012. The diagnoses of tuberculosis and LC occurred simultaneously in 10 patients, whereas tuberculosis was diagnosed prior to LC in 14. The median time between the two diagnoses was 5 years (interquartile range: 1-30 years). Fourteen patients (58.3%) were male, 20 (83.3%) were White, and 22 (91.7%) were smokers or former smokers. The most common histological type was adenocarcinoma, identified in 14 cases (58.3%), followed by epidermoid carcinoma, identified in 6 (25.0%). Seven patients (29.2%) presented with distant metastases at diagnosis; of those 7 patients, 5 (71%) were diagnosed with LC and tuberculosis simultaneously. Conclusions: In the present study, most of the patients with tuberculosis and LC were smokers or former smokers, and tuberculosis was diagnosed either before or simultaneously with LC. Non-small cell lung cancer, especially adenocarcinoma, was the most common histological type.

Keywords: Tuberculosis/diagnosis; Lung neoplasms/diagnosis; Comorbidity.

The objective of this study was to analyze trends in the tuberculosis mortality rate in Brazil (1990-2015) in an ecological time-series analysis. The indicators were obtained from the Brazilian National Ministry of Health. A joinpoint regression model was applied for the temporal analysis, with a level of significance of 5%. During the period in question, there was a trend toward a reduction in mortality in the country as a whole (p < 0.001) and in each of its five regions. The states with the highest tuberculosis mortality rates were Rio de Janeiro (7.0/100,000 population) and Pernambuco (5.0/100,000 population). Eleven states and the Federal District of Brasília showed downward trends. Only the state of Alagoas showed a significant increase (p < 0.001). The temporal behavior observed indicates that tuberculosis continues to be a major public health problem in Brazil.

Keywords: Tuberculosis/epidemiology; Tuberculosis/mortality; Mortality/trends; Epidemiologic studies.

Objective: To analyze the impact that the 2009 changes in tuberculosis treatment in Brazil had on the rates of cure, tuberculosis recurrence, mortality, treatment abandonment, and multidrug-resistant tuberculosis (MDR-TB). Methods: An ordinary least squares regression model was used in order to perform an interrupted time series analysis of secondary data collected from the Brazilian Tuberculosis Case Registry Database for the period between January of 2003 and December of 2014. Results: The 2009 changes in tuberculosis treatment in Brazil were found to have no association with reductions in the total number of cases (β = 2.17; 95% CI: −3.80 to 8.14; p = 0.47) and in the number of new cases (β = −0.97; 95% CI: −5.89 to 3.94; p = 0.70), as well as having no association with treatment abandonment rates (β = 0.40; 95% CI: −1.12 to 1.93; p = 0.60). The changes in tuberculosis treatment also showed a trend toward an association with decreased cure rates (β = −4.14; 95% CI: −8.63 to 0.34; p = 0.07), as well as an association with increased mortality from pulmonary tuberculosis (β = 0.77; 95% CI: 0.16 to 1.38; p = 0.01). Although there was a significant increase in MDR-TB before and after the changes (p < 0.0001), there was no association between the intervention (i.e., the changes in tuberculosis treatment) and the increase in MDR-TB cases. Conclusions: The changes in tuberculosis treatment were unable to contain the decrease in cure rates, the increase in treatment abandonment rates, and the increase in MDR-TB rates, being associated with increased mortality from pulmonary tuberculosis during the study period.

Keywords: Tuberculosis, pulmonary/epidemiology; Tuberculosis, pulmonary/drug therapy; Tuberculosis, pulmonary/mortality; Interrupted time series analysis; Drug resistance, multiple; Drug compounding.

Background: The diagnosis of pleural tuberculosis continues to be a challenge due to the low sensitivity of traditional diagnostic methods. Histopathological examination of pleural tissue is the most accurate method, with a sensitivity of up to 80%. Determination of adenosine deaminase levels is a recently introduced method, although its usefulness in the diagnosis of pleural tuberculosis in Brazil has yet to better elucidated. Objective: To verify the sensitivity and specificity of an experimental method of measuring adenosine deaminase activity in pleural fluid in a series of patients with pleural effusion patients evaluated between August 1998 and November 2002 in Rio de Janeiro (RJ). Results: Out of 137 cases, 111 pleural fluid samples were available. Of those, 83 were from pleural tuberculosis patients. Among the 67 pleural tuberculosis patients tested, 10 (14.9%) presented human immunodeficiency virus. The adenosine deaminase cutoff value of 35U/L was determined by a receiver operator characteristic curve. The sensitivity, specificity and likelihood ratios (positive and negative) were 92.8%, 93.3%, 25.8 and 13.9, respectively. Mean adenosine deaminase in the pleural tuberculosis group was 84.7 ± 43.1 U/L, versus 15.9 ± 11.1 U/L in the group with other diseases. There was no significant difference in adenosine deaminase activity between patients with and without human immunodeficiency virus co-infection. Conclusions: Adenosine deaminase measurement in pleural fluid is a sensitive and specific method for the diagnosis of pleural tuberculosis and its use can preclude the need for pleural biopsy in the initial workup of pleural effusion patients. An adenosine deaminase cutoff value of 35U/L is recommended.

Keywords: Pleural fluid. Adenosine deaminase. Diagnosis. Tuberculosis. HIV

Objective: To evaluate the accuracy of rapid molecular testing as a diagnostic tool and estimate the incidence of smear-positive pulmonary tuberculosis among the indigenous population. Methods: This is an epidemiological study based on secondary data. We calculated the incidence of smear-positive pulmonary tuberculosis between January 1st, 2011 and December 31, 2016, and the performance of bacilloscopy and rapid molecular testing in diagnosing pulmonary tuberculosis compared to sputum culture (standard test). Results: We included 4,048 cases of indigenous people with respiratory symptoms who provided sputum samples for analysis. Among them, 3.7%, 6.7%, and 3.7% had positive results for bacilloscopy, sputum culture, and rapid molecular testing, respectively. The mean incidence of pulmonary tuberculosis was 269.3/100 thousand inhabitants. Rapid molecular testing had 93.1% sensitivity and 98.2% specificity, compared to sputum culture. Bacilloscopy showed 55.1% sensitivity and 99.6% specificity. Conclusions: Rapid molecular testing can be useful in remote areas with limited resources and a high incidence of tuberculosis, such as indigenous villages in rural regions of Brazil. In addition, the main advantages of rapid molecular testing are its easy handling, fast results, and the possibility of detecting rifampicin resistance. Together, these attributes enable the early start of treatment, contributing to reduce the transmission in communities recognized as vulnerable to infection and disease.

Keywords: Tuberculosis; Molecular diagnostic testing; Diagnostic tests, routine; Indians, South American.

Background: Bronchiectasis is a frequently found disease in medical practice in Brazil leading to significant morbidity and decrease in quality of life of the affected individuals. Objectives: To study diagnostic and therapeutic aspects in a series of hospitalized patients with bronchiectasis in a department of pulmonary diseases. Methods: Signs, symptoms, microbiological and radiographic data, and therapeutic results were studied in 170 hospitalized patients between 1978 and 2001 - females 62.4%, males 37.6%, and aged from 12 to 88 years (mean age 36.8 yrs). Previous history of pneumonia in childhood was detected in 52.5% of the patients, tuberculosis in 19.8%; 8.8% had bronchial asthma, and 2 had Kartagener's syndrome. Results: The most common symptoms were cough (100.0%), expectoration (96.0%) and pulmonary rales (66.0%). The pulmonary lesions were unilateral in 46.5% of the cases. Pneumococcus, H. influenzae or mixed flora were found in 85.0% of the examined sputa. All 170 patients received antibiotics and postural drainage, and 88 of them (younger and with a higher functional reserve) were also submitted to pulmonary resections (82 unilateral and 6 bilateral). Two deaths occurred, and repetitive hospitalizations were more frequent among the clinically treated patients. The follow up showed that most of the surgically treated patients had significant symptoms improvement and rarely needed to be re-hospitalized. Conclusions: In the majority of the patients, lung resection surgery improved permanently the prolonged bronchopulmonary symptoms of patients with bronchiectasis, differently from the patients who received only clinical treatment.

Keywords: Bronchiectasis/diagnosis. Bronchiectasis/therapy. Bronchiectasis/surgery. Bronchiectasis/complications. Tomography X-ray computed/methods. Inpatients. Retrospective studies.

Background: Mycobacterium kansasii is a nontuberculous mycobacterium that can colonize the lungs and cause pulmonary infection. Objective: To report authors' study of 6 patients with pulmonary disease caused by M. kansasii infection in a series of 6 patients diagnosed over 5 years. Method: Between June 1995 and June 2000, 1,349 patients diagnosed with tuberculosis were admitted to the Ipiranga Ari Nogueira da Silva Sanitarium. M. kansasii was identified in the sputum cultures of six (0.44%) of these patients. Results: Patient ages ranged from 25 to 77 years, 5 of the 6 were male, and all presented symptomatic chronic lung disease. All patients tested negative for HIV. Chest radiographs confirmed a history of lung disease; all presented thin walled cavities and adjacent pleural thickening was seen in 2. All patients were initially treated with isoniazid-rifampin-pyrazinamide. In 2 patients, intolerance to pyrazinamide necessitated the substitution of pyrazinamide with ethambutol. Based on the culture results, pyrazinamide was also replaced by ethambutol in 2 other patients. All patients were treated for 9 months or longer, and only one patient suffered recurrence of the disease. After being considered cured of the M. kansasii infection, 1 patient died of respiratory insufficiency due to silicosis. Conclusions: Mycobacteriosis due to M. kansasii was found only rarely and may be attributable to the characteristics of our patients. Therapy with isoniazid, rifampin and pyrazinamide with eventual replacement of the latter by ethambutol was shown to be effective.

Keywords: Mycobacterium kansaii. Lung diseases. Respiratory insufficiency.

Objective: Pulmonary alveolar proteinosis (PAP) is a rare disease, characterized by the alveolar accumulation of surfactant, which is composed of proteins and lipids. PAP is caused by a deficit of macrophage activity, for which the main treatment is whole-lung lavage (WLL). We report the experience at a referral center for PAP in Brazil. Methods: This was a retrospective study involving patients with PAP followed between 2002 and 2016. We analyzed information regarding clinical history, diagnostic methods, treatments, and outcomes, as well as data on lung function, survival, and complications. Results: We evaluated 12 patients (8 of whom were women). The mean age was 41 ± 15 years. Most of the patients were diagnosed by means of BAL and transbronchial biopsy. The mean number of WLLs performed per patient was 2.8 ± 2.5. One third of the patients never underwent WLL. Four patients (33.3%) had associated infections (cryptococcosis, in 2; nocardiosis, in 1; and tuberculosis, in 1), and 2 (16.6%) died: 1 due to lepidic adenocarcinoma and 1 due to complications during anesthesia prior to WLL. When we compared baseline data with those obtained at the end of the follow-up period, there were no significant differences in the functional data, although there was a trend toward an increase in SpO2. The median follow-up period was 45 months (range, 1-184 months). The 5-year survival rate was 82%. Conclusions: To our knowledge, this is the largest case series of patients with PAP ever conducted in Brazil. The survival rate was similar to that found at other centers. For symptomatic, hypoxemic patients, the treatment of choice is still WLL. Precautions should be taken in order to avoid complications, especially opportunistic infections.