The resurgence of tuberculosis as one of the most important infectious diseases to affect mankind came after the illusion that the disease was under control and would be eradicated before the end of the 20th Century. Over the last 10 years, in association with American and European research centers, our group at the Universidade Federal do Rio de Janeiro has been dedicated to investigating the pathogenic mechanisms involved in pulmonary tuberculosis. Due to its frequency and role in transmission, pulmonary tuberculosis is the most serious form of the disease. Our hypothesis is that the establishment of latent infection and its progression to active disease depend on an imbalance between activating and deactivating cytokines at the disease site. Despite the presence of protective mechanisms such as the macrophage expression of phenotypes (denoting cellular and molecular activation of agents involved in protection, such as nitric oxide and interferon-ã), tuberculosis progresses. A possible explanation for this is the concomitant presence at the site of infection of molecules such as interleukin-10 and TGF-â, which are able to deactivate previously activated macrophages. Recent data suggest that mycobacteria secrete proteins capable of inducing interleukin-10, thus contributing to overcoming host protective mechanisms. Susceptible individuals would be more able to produce larger amounts of these molecules due to genetic polymorphisms that facilitate interleukin-10 production at infection onset. The understanding of these mechanisms could advance the prevention and discovery of new therapeutic targets for the control of tuberculosis.

Keywords: Tuberculosis/ethiology. Tuberculosis pulmonary/pathology.

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.

Objective: To evaluate surveillance of contacts of new tuberculosis cases in the state of Mato Grosso from 1999 to 2004. Methods: This was a descriptive epidemiological study based on data from the Tuberculosis Case Registry Database. The number of new tuberculosis cases, the number of contacts (estimated, investigated, and uninvestigated), and the tuberculosis incidence rate were analyzed by age bracket. The mean rate of contacts investigated for each case of tuberculosis by age bracket was calculated per year of study. The cases of pulmonary tuberculosis with and without contacts investigated were analyzed by sputum smear microscopy results. Results: In 2004, there were 41.3 cases of tuberculosis per 100,000 inhabitants in the state of Mato Grosso. The south-central region presented the highest incidence rate (57 cases/100,000 inhabitants) and a 15% rate of contacts investigated. Among those younger than 15 years, 63 contacts (60.5%) were investigated, whereas among those aged 15 or older, 389 (8.9%) were investigated. In 1999, the mean rate of contacts investigated statewide was 0.02 (0.5%), and, in 2004, it reached 0.42 (10.5%). The percentage of contacts investigated was 40% higher among the contacts of contagious cases (OR = 1.4; 95% CI: 1.08-1.83). Conclusions: The percentage of contacts investigated is very low, principally among adults. The adoption of the standards for investigation of tuberculosis contacts proposed by the Brazilian National Ministry of Health Department of Health Surveillance has not ensured that this group at highest risk of developing active tuberculosis be given priority at health care facilities in the state of Mato Grosso.

Keywords: Contact tracing; Epidemiologic surveillance; Tuberculosis/prevention & control.

Objective: To describe treatment outcomes (cure, noncompliance or death) after the implementation of the Directly Observed Treatment, Short-course (DOTS) strategy for tuberculosis control in the city of São José do Rio Preto, Brazil, between 1998 and 2003. Methods: A descriptive study, based on secondary data (National Case Registry database, Tuberculosis Epidemiology database, and the 'Black Book' Registry), was conducted using a specific instrument. The data were analyzed using descriptive statistics. Results: After the implementation of the DOTS strategy, there was a decrease in noncompliance and case detection rates as well as an increase in cure and death rates. The increase in the number of tuberculosis-related deaths might be attributable to three factors: the predominance of the disease in individuals over 50 years of age, tuberculosis/HIV co-infection, and the presence of accompanying diseases. Conclusion: The implementation of the DOTS strategy strengthened the decentralization of the tuberculosis control plans as well as the integration of the Basic Health Care Clinic teams with the Tuberculosis Control Program team. Political commitment of the administrator to tuberculosis control, in conjunction with the policy of benefits and incentives, is essential for the sustainability of the DOTS strategy.

Keywords: Tuberculosis; Epidemiology; Health services; Politics; Directly observed therapy.

Objective: Evaluate the impact of the instrument of the "Stratification by Degree of Clinical Severity and Abandonment Risk of Tuberculosis Treatment" (SRTB) on the tuberculosis outcome. Methods: This study was a pragmatic clinical trial involving patients with a confirmed diagnosis of tuberculosis treated at one of the 152 primary health care units in the city of Belo Horizonte, Brazil, between May of 2016 and April of 2017. Cluster areas for tuberculosis were identified, and the units and their respective patients were divided into intervention (use of SRTB) and nonintervention groups. Results: The total sample comprised 432 participants, 223 and 209 of whom being allocated to the nonintervention and intervention groups, respectively. The risk of treatment abandonment in the nonintervention group was significantly higher than was that in the intervention group (OR = 15.010; p < 0.001), regardless of the number of risk factors identified. Kaplan-Meier curves showed a hazard ratio of 0.0753 (p < 0.001). Conclusions: The SRTB instrument was effective in reducing abandonment of tuberculosis treatment, regardless of the number of risk factors for that. This instrument is rapid and easy to use, and can be adapted to different realities. Its application showed characteristics predisposing to a non-adherence to the treatment and established bases to mitigate its impact.

Keywords: Tuberculosis; Patient compliance; Risk factors; Treatment adherence.

Abstract Objective: To compare four laboratory methods in the diagnosis of pulmonary tuberculosis. Methods: Respiratory secretion specimens were collected from 160 patients suspected of having pulmonary tuberculosis. Direct testing for Mycobacterium tuberculosis was carried out using Ziehl-Neelsen staining, auramine staining, culture on Löwenstein-Jensen (LJ) medium and polymerase chain reaction (PCR). The strains isolated were identified by means of a radiometric method using p-nitro-alpha-acetylamino-beta-hydroxypropiophenone (NAP) and classical methods. The sensitivity of the methods was compared to the gold standard for the diagnosis of pulmonary tuberculosis, based on clinical, radiological and microbiological criteria. Results: Of the 160 patients, 142 were diagnosed with pulmonary tuberculosis according to the gold standard. The sensitivity of Ziehl-Neelsen staining, auramine staining, culture on LJ medium and PCR was 54.2%, 58.4%, 67.6% and 77.5%, respectively, when compared with the diagnostic criterion adopted. All four methods presented 100% specificity. In the identification of mycobacteria, there was high (96.8%) concordance between PCR and the radiometric method using NAP. The sensitivity of PCR was 50.8% in samples with negative sputum smear microscopy results and 98.8% in those with positive results. The sensitivity of PCR was lower in specimens with negative results in sputum smear microscopy and culture than in those with positive results (25.6% and 99.0%, respectively). Conclusions: We found PCR to be a promising method for the diagnosis of pulmonary tuberculosis, even in paucibacillary specimens. Simultaneous identification and faster results are additional advantages of this method.

Keywords: Tuberculosis, pulmonary/diagnosis; Culture media; Polymerase chain reaction; Sputum/microbiology.

For diagnostic purposes of pleural tuberculosis, three pleural fragments are routinely obtained from a single site by needle biopsy. The objective of this study is to compare the diagnostic yield of the routine procedure with two different approaches: harvesting five fragments on a single site (A), and collection of fragments at an additional site (B); from the same cutaneous orifice, the needle was partially removed up to the subcutaneous tissue and redirected at a 45o angle. The authors performed a prospective study in 115 patients submitted to pleural biopsy. The first three pleural fragments were placed in a vial (VA1-3), the 5 subsequent fragments obtained at the same site were placed in a second vial (VA4-8), and the five fragments from the second site were placed in a third vial (VB1-5). Analysis of fragments from VA1-3 revealed granuloma in 72/92 tuberculosis cases (78.3%), whereas in fragments VA5-8 and VB1-5, granuloma was observed in 74/92 cases (80.5%). In 6/92 patients the diagnosis at VA1-3 was non-specific pleuritis, but granuloma was found in VA4-8, resulting in a diagnosis increment of 8.3% (adding six to the 72 patients). In 7/92 patients (7.6%) the histopathological examination at site A led to a non-specific result but granuloma was found at site B, leading to a diagnostic increment of 9.0% (7 to 78 patients). Histological concordance of two examinations by the same pathologist had a kappa index of 0.62 (0.54 to 0.7) whereas concordance between two different pathologists had a kappa index of 0.64 (0.56 to 0.72). The performance of multiple biopsies at two different sites at the pleural surface led to an additional diagnosis of 13 patients, i.e., an increase of 18% (13 to 72) relative to the routine procedure. Considering the low cost increase of obtaining the fragments, adoption of this method is recommended in routine pleural tuberculosis diagnosis.

Keywords: Tuberculosis, pleural tuberculosis, biopsy, diagnosis.

Objective: To evaluate the impact of smoking on pulmonary tuberculosis (PTB) treatment outcomes and the two-month conversion rates for Mycobacterium tuberculosis sputum cultures among patients with culture-confirmed PTB in an area with a moderate incidence of tuberculosis in Brazil. Methods: This was a retrospective cohort study of PTB patients diagnosed and treated at the Thoracic Diseases Institute of the Federal University of Rio de Janeiro between 2004 and 2012. Results: Of the 298 patients diagnosed with PTB during the study period, 174 were included in the outcome analysis: 97 (55.7%) were never-smokers, 31 (17.8%) were former smokers, and 46 (26.5%) were current smokers. Smoking was associated with a delay in sputum culture conversion at the end of the second month of TB treatment (relative risk = 3.58 [95% CI: 1.3-9.86]; p = 0.01), as well as with poor treatment outcomes (relative risk = 6.29 [95% CI: 1.57-25.21]; p = 0.009). The association between smoking and a positive culture in the second month of treatment was statistically significant among the current smokers (p = 0.027). Conclusions: In our sample, the probability of a delay in sputum culture conversion was higher in current smokers than in never-smokers, as was the probability of a poor treatment outcome.

Keywords: Tuberculosis; Treatment outcome; Smoking.

Tumors of the anterior mediastinum include several entities with different radiological and clinical manifestations, constituting a heterogeneous group of congenital, inflammatory, and neoplastic conditions. Among these lesions, the most common primary tumor of the mediastinum is thymoma, nearly followed by germ cell tumors and lymphomas. Tuberculosis of the thymus, an extremely rare condition, typically involves the mediastinal lymph nodes. We present, in this study, pathological, radiological, and clinical findings of one case of tuberculosis of the thymus in an 18-year-old patient who presented thoracic pain, dyspnea upon minimal effort, and progressive worsening of the symptoms in one week. The chest X-ray showed a large mass in the mediastinum, and computed tomography scans indicated that it was located anteriorly. The patient was submitted to surgery in order to excise the mass. Microscopy revealed a massive inflammatory response and granulomas in the thymic tissue. Ziehl-Neelsen staining for acid-fast bacilli yielded positive results, and a diagnosis of tuberculosis was made. Surgeons and pathologists should remain alert for this condition and should include it in the differential diagnosis of mediastinal masses.

Keywords: Thymus; Tuberculosis; Thoracic surgery; Pathology.

Chronic obstructive pulmonary disease is highly prevalent the world over. An estimated 7% to 10% of the global adult population is affected. In Brazil, the incidence of chronic bronchitis is 12.7% among individuals over the age of 40. Economic studies have great relevance in devising policies for dealing with diseases of such high prevalence. The majority of data related to the costs of chronic obstructive pulmonary disease is culled from national health databases. There have been only a few studies evaluating the direct public health costs of the disease. In analyzing those studies, one can conclude that a chronic obstructive pulmonary disease patient generates a direct annual expenditure of 1200 to 1800 USD. However, the cost is correlated with the severity of the disease. Patients suffering from the more severe forms can require as much as double that expenditure, and early diagnosis is therefore vital. The most cost-effective strategy is early detection of the disease, in concert with anti-smoking campaigns. In the most advanced stages of the disease, the greatest costs are incurred due to hospitalization. In such cases, correct treatment of the acute exacerbations of the disease is crucial to minimizing costs. The average cost of a hospital stay in Brazil is 2761 Brazilian reals, which is equal to that of one full year of outpatient treatment. Antibiotic therapy accounts for only a small fraction of the total cost of treating such acute exacerbations. The use of more efficacious antibiotics may represent a more cost-effective strategy for reducing the rate of treatment failure. Economic analysis should allow for the identification and implementation of the most cost-effective strategies for treating this disease.

Keywords: Smoking/adverse effects. Tobacco use cessation/methods. Pregnancy.

Objective: To evaluate changes in health-related quality of life (HRQoL) after twelve months of smoking cessation. Methods: This was a prospective study to evaluate the effectiveness of a smoking cessation program on the quality of life of 60 self-referred subjects, at a public hospital, during the period of August 2006 to December 2007. The program consisted of 2-h group sessions once a week during the first month and then every 15 days over six months, followed by monthly phone contacts for another six months. The treatment was based on behavior modification and the use of bupropion in combination with nicotinic replacement therapy. Abstinence was verified by exhaled CO measurements. Patient HRQoL was quantified using the Medical Outcomes Study 36-item Short-Form Health Survey (SF-36) questionnaire. Differences in quality of life scores between quitters and non-quitters at twelve months after the initial intervention were evaluated using analysis of covariance with baseline characteristics as covariates. Results: Self-reported quality of life scores were significantly higher among the 40 quitters than among the 20 non-quitters. The following SF-36 domains were most affected: role-emotional (p = 0.008); general health (p = 0.006); vitality (p < 0.001); and mental health (p = 0.002). At twelve months after the smoking cessation intervention, the SF-36 mental component and physical component summary scores were higher among quitters than among non-quitters (p = 0.004 and p = 0.001, respectively). Conclusions: Our findings illustrate that smoking abstinence is related to better HRQoL, especially in aspects of mental health.

Keywords: Quality of life; Smoking cessation; Questionnaires.