Background: Host genetic factors may play a role in the susceptibility to active tuberculosis (TB), and several polymorphisms in different cytokine coding genes have been described and associated with diseases to date. Objectives: To investigate whether polymorphisms within the promoter region of the TNF-á (-238/-308) coding genes are associated to the occurrence of active TB. Methods: SNPs within the TNF-á gene were analyzed by PCR-RFLP among two groups of individuals: patients with TB (n = 234, and patients non TB (n = 113). Results: In this study, the presence of the -238A allele was associated with susceptibility to TB disease occurrence and severity (p = 0,00002; OR = 0,15; IC = 0,06-0,36. On the contrary, the -308A allele was associated with protection to the occurrence of another pulmonary diseases. Conclusions: These results suggest the importance of genetics studies on TB occurrence. Further studies are needed pursuing a better understanding of the human pathogenesis of M. tb.

Keywords: Tuberculosis/genetics. Polymorphism, single nucleotide/genetics. Tumor necrosis factor/genetics. Alleles. Genotype. Lung diseases.

New scientific articles about tuberculosis (TB) are published daily worldwide. However, it is difficult for health care workers, overloaded with work, to stay abreast of the latest research findings and to discern which information can and should be used in their daily practice on assisting TB patients. The purpose of the III Brazilian Thoracic Association (BTA) Guidelines on TB is to critically review the most recent national and international scientific information on TB, presenting an updated text with the most current and useful tools against TB to health care workers in our country. The III BTA Guidelines on TB have been developed by the BTA Committee on TB and the TB Work Group, based on the text of the II BTA Guidelines on TB (2004). We reviewed the following databases: LILACS (SciELO) and PubMed (Medline). The level of evidence of the cited articles was determined, and 24 recommendations on TB have been evaluated, discussed by all of the members of the BTA Committee on TB and of the TB Work Group, and highlighted. The first version of the present Guidelines was posted on the BTA website and was available for public consultation for three weeks. Comments and critiques were evaluated. The level of scientific evidence of each reference was evaluated before its acceptance for use in the final text.

Keywords: Tuberculosis; Mycobacterium infections; Diagnosis; Tuberculosis, multidrug-resistant.

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 describe the factors associated with nonadherence to TB chemoprophylaxis in patients older than 15 years of age treated via referral TB control programs. Methods: A historical cohort study was carried out based on medical charts related to cases treated via referral TB control programs in the city of Vitória, Brazil, between 2002 and 2007. Cases of infection with Mycobacterium tuberculosis were stratified into two groups: health care workers (HCW group); and individuals who were not health care workers (NHCW group). Results: A total of 395 patients were included in the study: 35 in the HCW group and 360 in the NHCW group. The mean age in the HCW and NHCW groups was 34.8 and 32.4 years, respectively (p = 0.36). Of the 35 patients in the HCW group, 29 (82.9%) were female, compared with 180 (50.0%) of the 360 patients in the NHCW group. In the HCW and NHCW groups, respectively, 15 (42.9%) and 169 (46.9%) of the patients were contacts of TB cases. In addition, 9 (25.7%) and 157 (78.5%) the HCW and NHCW group patients, respectively, were HIV-infected. Nonadherence to chemoprophylaxis was 37.1% and 21.9% in the HCW and NHCW groups, respectively (p = 0.045). In the multivariate analysis, the factors associated with nonadherence were being a health care worker (OR = 8.60; 95% CI: 2.09-35.41), being HIV-infected (OR = 4.57; 95% CI: 1.2-17.5) and having had contact with a TB patient (OR = 2.65; 95% CI: 1.15-6.12). Conclusions: In order to improve adherence to TB chemoprophylaxis, new TB control program strategies are needed, especially for health care workers and HIV-infected patients.

Keywords: Tuberculosis; Chemoprevention; Isoniazid.

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.

Objective: To evaluate the impact that Family Health Program (FHP) team training and active surveillance have on the detection of TB cases in a low-income community in the city of Fortaleza, Brazil. Methods: The study was performed in an area with approximately 25,000 inhabitants, served by a health care center with five FHP teams, in the city of Fortaleza, Brazil. Although all of the teams were trained, active surveillance was carried out only in one of the areas (area 5). We compared the number of TB cases detected in each of the five areas prior to and after the intervention. We also compared the number of TB cases detected in area 5 to the number of those detected in the other areas, as well as to the citywide number of reported TB cases in Fortaleza, within the same period. Results: The number of TB cases detected in the area studied increased from 1 in 2002 to 22 in 2004 (p < 0.05). There was no significant difference between the number of TB cases in area 5 and that observed for each of the other four areas (p > 0.05). There was a significant increase in the number of TB cases detected in the area studied when compared to the city as a whole (p < 0.05). Conclusions: Training and sensitization of FHP professionals were effective in promoting an increase in the number of TB cases detected in a low-income community.

Keywords: Tuberculosis; Communicable disease control; Family health program; Epidemiologic surveillance.

Objective: To evaluate the incidence of Mycobacterium tuberculosis infection, using tuberculin skin test, among community health agents (CHAs) monitoring TB patients in the city of Cachoeiro de Itapemirim, Brazil. Methods: We included 30 CHAs acting in the Family Health Program and 30 of their family members residing in the same household. The tuberculin skin test results of each CHA were compared with those of the corresponding family member. Results: Of the 30 CHAs, 27 (90.0%) were female, compared with 23 (76.7%) of the 30 family members (p = 0.299). The mean age of the CHA group and of the family member group was, respectively, 36.8 and 39.7 years. No statistically significant difference was found between the groups regarding the level of education. Regarding M. tuberculosis exposure, the same number of participants in the two groups reported having known or had contact with a TB patient (17 individuals; 56.7%). There was a statistically significant difference regarding positive tuberculin skin test results (26.7% in the CHA group and 3.3% in the family member group; p = 0.011). Conclusions: M. tuberculosis infection was significantly higher among CHAs than among their family members, fueling the debate on the occupational risk involved in the activities of these professionals.

Keywords: Community health aides; Tuberculosis; Tuberculin test.

In this study, we analyzed the number of TB cases in an emergency room (ER) and the susceptibility profile of Mycobacterium tuberculosis strains. Patients were selected from among those treated at the Hospital das Clínicas, in the city of Belo Horizonte, Brazil. Between 2002 and 2005, 240 TB patients were identified. Of those, 117 patients (48.7%) were diagnosed in the ER, 72 (61.5%) presenting positive sputum smear microscopy. Drug susceptibility testing was carried out in 90 strains, of which 80 (89%) were sensitive, 9 (10%) were resistant, and 1 (1%) was multidrug resistant. The incidence of positive smear sputum microscopy and resistant TB strains was high, which calls for the immediate adoption of TB control measures in the ER.

Keywords: Tuberculosis; Disease transmission, infectious; Drug resistance.

Objective: To determine the prevalence of latent and active TB among detainees in a prison hospital in Bahia, Brazil. Methods: A cross-sectional study with prospective data collection was carried out comprising 237 inmates in the Bahia State Prison Hospital between July 2003 and April 2004. A standardized questionnaire was applied and completed by medical students. The detainees were systematically submitted to the following tests: tuberculin skin test, chest X-ray (anteroposterior), sputum smear microscopy and culture for mycobacteria. The events of interest were active TB and latent TB. Results: The mean age of the participants was 36.6 years, and 89.9% were male. Smoking and alcohol consumption were reported by 70.0% and 43.9% of the inmates, respectively. A history of treatment for TB was reported by 11.3% of the inmates. Of the inmates evaluated, 36.3% reported cough and 31.4% reported expectoration. Other less common symptoms were asthenia (in 26.2%), weight loss (in 23.1%), loss of appetite (in 17.7%), fever (in 11.3%) and hemoptysis (in 6.7%). Of the 86 inmates tested, none presented positive HIV serology. The prevalence of latent TB was 61.5% (96 of the 156 inmates submitted to tuberculin skin tests), whereas that of active TB was 2.5% (6 of the 237 inmates evaluated). The presence of cough was a determinant of active TB (prevalence ratio = 8.8; 95% CI: 1.04-73.9; p = 0.025). Conclusions: Active and latent TB are highly prevalent among inmates hospitalized in the Bahia State Prison Hospital. Our findings justify the need to implement public policies specifically directed towards the control of TB in this population.

Keywords: Tuberculosis; Prisons; Hospitals; Prevalence.

The objective of this study was to provide access to and disseminate a questionnaire used as an instrument to assess the organizational elements and the performance of primary health care clinics regarding TB control in Brazil, comparing selected organizational dimensions by health care clinic, by municipality and by actor (patients, health care workers and managers). The results show that municipalities where the coverage of supervised treatment was more extensive presented more favorable indicators regarding access to TB treatment. The organizational format of the health care clinics involved in TB treatment-family health programs and referral centers with specialized teams in TB control programs (TCPs)-was not a factor that expanded access to diagnosis. The TCPs involving a smaller number of patients presented better performance regarding the health care professional-patient relationship. The majority of the patients faced economic and social difficulties, and most managers were unaware of the amount of resources allocated to TB control activities. The instrument proved to be viable and to have the potential to adequately assess the performance of health care clinics in the urban areas studied.

Keywords: Questionnaires; Patient satisfaction; Primary health care; Family health program; Tuberculosis.

Objective: To determine the epidemiological profile of inpatients at a TB referral hospital. Methods: This was a descriptive, retrospective study of the medical charts of patients with TB hospitalized at the Hospital Estadual Santa Maria (HESM), in the city of Rio de Janeiro, Brazil, between January of 2002 and December of 2003. Data were collected using a standardized form. Results: Of the 451 patients included in the study, 313 (69.4%) had been referred to the HESM from health care clinics, and 302 (67.0%) were male. Most of the patients were in the 30-59  year age bracket, 443 (98.2%) lived in the greater metropolitan region of Rio de Janeiro, and 298 (66.1%) lived in the city of Rio de Janeiro itself. The most common reason for hospitalization was poor health status (in 237, 52.5%). The most common comorbidity was AIDS (in 137, 30.4%). The most common signs and symptoms at admission were weight loss, fever and productive cough. Sputum smear microscopy was positive in 122 (71.0%) of the patients presenting with productive cough at admission. Of the 212 patients being retreated, 156 (73.6%) reported noncompliance with previous treatment. Regarding the outcome, 273 (65.8%) of the patients were referred to municipal health care centers, 83 (18.4%) died, 44 (9.8%) were cured, and 27 (6%) were discharged against medical advice. Conclusions: Providing hospitals specializing in TB is relevant for TB control, especially in metropolitan regions. In addition to taking biosafety measures, these hospitals must be prepared to treat patients with TB-related comorbidities and social problems. This study has resulted in improvements at the HESM.

Keywords: Tuberculosis; Epidemiology; Hospitalization.

Tuberculosis continues to be a public health priority in many countries. In 2015, tuberculosis killed 1.4 million people, including 210,000 children. Despite the recent progress made in the control of tuberculosis in Brazil, it is still one of the countries with the highest tuberculosis burdens. In 2015, there were 69,000 reported cases of tuberculosis in Brazil and tuberculosis was the cause of 4,500 deaths in the country. In 2014, the World Health Organization approved the End TB Strategy, which set a target date of 2035 for meeting its goals of reducing the tuberculosis incidence by 90% and reducing the number of tuberculosis deaths by 95%. However, to achieve those goals in Brazil, there is a need for collaboration among the various sectors involved in tuberculosis control and for the prioritization of activities, including control measures targeting the most vulnerable populations. Children are highly vulnerable to tuberculosis, and there are particularities specific to pediatric patients regarding tuberculosis development (rapid progression from infection to active disease), prevention (low effectiveness of vaccination against the pulmonary forms and limited availability of preventive treatment of latent tuberculosis infection), diagnosis (a low rate of bacteriologically confirmed diagnosis), and treatment (poor availability of child-friendly anti-tuberculosis drugs). In this review, we discuss the epidemiology, clinical manifestations, and prevention of tuberculosis in childhood and adolescence, highlighting the peculiarities of active and latent tuberculosis in those age groups, in order to prompt reflection on new approaches to the management of pediatric tuberculosis within the framework of the End TB Strategy.

Keywords: Tuberculosis, pulmonary/prevention & control; Mycobacterium tuberculosis; Lung diseases/etiology; Child; Adolescent.

Objective: To compare clinical, radiological and laboratory aspects of household contacts, aged 15 or younger, of patients presenting a positive culture for Mycobacterium tuberculosis. Methods: This was a cohort study comparing children and adolescents (≤ 15 years of age) who were household contacts of TB cases presenting positive sputum smear and positive culture results (exposed group, n = 100) or negative sputum smear and positive culture results (unexposed group, n = 55). All of the contacts were evaluated via the TB control program of a university hospital in the city of Vitória, Brazil, between July of 2003 and December of 2006. Results: Of the 155 minors evaluated, 87 (56.1%) were female and 68 (43.9%) were male. Of those 155, 28 (18%) were aged 5 or younger, 62 (40%) were aged 5-9, and 65 (42%) were aged 10-15. Symptoms of the disease were found in 17 (17%) of the 100 contacts in the exposed group and in 9 (16%) of the 55 in the unexposed group (p = 0.86). Chest X-rays showed alterations in 20 (21%) and 2 (4%) of the contacts in the exposed and unexposed groups, respectively (RR = 6.9; p = 0.004). In the exposed and unexposed groups, respectively, 35 (38%) and 10 (18%) of the contacts presented positive results on the tuberculin skin test (RR = 2.8; p = 0.01). Of the 100 contacts in the exposed group, 5 (5%) were diagnosed with TB, which was not diagnosed in any of those in the unexposed group (p = 0.08). Conclusions: Although no significant difference was found between the two groups regarding the incidence of TB, it is of note that there is a greater risk of becoming infected with M. tuberculosis if the bacterial load of the index case is high.

Keywords: Tuberculosis; Mycobacterium tuberculosis; Tuberculosis, pulmonary; Child; Adolescent.

Objective: To analyze the clinical characteristics and evolution of a group of patients with positive sputum cultures for multidrug-resistant (MDR) Mycobacterium tuberculosis and treated at a referral center in the city of Rio de Janeiro, Brazil. Methods: Based on the positive results in sputum cultures for MDR M. tuberculosis, 50 patients were selected, and their clinical data were obtained from the Brazilian Ministry of Health MDR-TB Database. The frequencies of noncompliance, relapses, failures and previous treatments for TB up to diagnosis of MDR-TB were compiled. The radiological patterns were classified as unilateral or bilateral, and with or without cavitation. Two years after the end of the standard treatment for MDR-TB, the outcome (cure, failure, noncompliance or death) for each patient was evaluated and reassessed every two years. The post-treatment follow-up period was eight years. Results: The mean number of previous treatments was 2.3 ± 0.9. The mean interval between the initial diagnosis and the development of MDR-TB was 2.0 ± 1.7 years. Two years after the initial treatment for MDR-TB, 2 patients had abandoned treatment, 8 had died, 18 had been cured, and 22 had presented treatment failure. The bivariate analysis showed that bilateral pulmonary involvement and cavitary pattern markedly reduced the chances for cure, with a relative risk of 1-0.6 (40%) and 1-0.7 (30%), respectively. At the end of the follow-up period, 2 patients had abandoned treatment, 9 had presented treatment failure, 17 had been cured, and 22 had died. Conclusions: Bilateral pulmonary involvement and cavity pattern greatly reduced the chances for cure of the patients with MDR-TB. Most patients who presented treatment failure died within the 8-year follow-up period.

Keywords: Tuberculosis, multidrug-resistant; Treatment outcome; Disease-free survival; Treatment refusal; Treatment failure.

Objective: To investigate the effects of age on pulmonary emphysema, based on the values of the emphysema index (EI) in a cohort of patients who had never smoked and who had no recognizable lung disease. Methods: We reviewed the CT scans, reported as normal, of 315 patients. Exclusion criteria were a history of smoking, cardiorespiratory disease, and exposure to drugs that could cause lung disease. From this cohort, we selected 32 patients (16 men and 16 women), matched for gender and body mass index, who were divided equally into two groups by age (< 50 years and  50 years). We quantified emphysema using a computer program specific to that task. The EI was calculated with a threshold of −950 HU. We also evaluated total lung volume (TLV) and mean lung density (MLD). Results: The overall means for TLV, MLD, and EI were 5,027 mL, −827 HU, and 2.54%, respectively. Mean values in the older and younger groups, respectively, were as follows: for TLV, 5,229 mL vs. 4,824 mL (p > 0.05); for MLD, −846 HU vs. −813 HU (p < 0.04); and for EI, 3.30% vs. 1.28% (p < 0.001). Significant correlations were found between EI and age (r = 0.66; p = 0.001), EI and TLV (r = 0.58; p = 0.001), and EI and MLD (r = −0.67; p < 0.001). The predicted EI per age was defined by the regression equation (r2 = 0.43): p50(EI) = 0.049 × age − 0.5353. Conclusions: It is important to consider the influence of age when quantifying emphysema in patients over 50 years of age. Based on the regression analysis, EI values of 2.6%, 3.5%, and 4.5% can be considered normal for patients 30, 50, and 70 years of age, respectively.

Keywords: Pulmonary emphysema; Tomography, spiral computed; Aging; Pulmonary disease, chronic obstructive.

Objective: To estimate the prevalence of primary resistance to the drugs in the basic treatment regimen for tuberculosis in treatment-naïve patients with pulmonary tuberculosis and no known risk factors for such resistance, as well as to identify factors potentially associated with drug resistance. Methods: This was an exploratory cross-sectional study. We analyzed the medical records of the subjects enrolled in two clinical trials of treatments for drug-susceptible tuberculosis between November 1, 2004 and March 31, 2011 at the Prof. Newton Bethlem Outpatient Clinic of the Federal University of Rio de Janeiro Thoracic Diseases Institute, located in the city of Rio de Janeiro, Brazil. The inclusion criteria were being ≥ 18 years of age, testing positive for AFB in the first sputum sample, having a positive culture for Mycobacterium tuberculosis, having undergone drug susceptibility testing, and being treatment-naïve. Patients with a history of imprisonment or hospitalization were excluded, as were those who had been in contact with drug-resistant tuberculosis patients. Results: We included 209 patients. The overall prevalence of primary drug resistance was 16.3%. The overall prevalence of resistance to isoniazid and streptomycin was, respectively, 9.6% and 9.1%, compared with 5.8% and 6.8% for single-drug resistance to isoniazid and streptomycin, respectively. The prevalence of resistance to two or more drugs was 3.8%, and the prevalence of multidrug resistance was 0.5%. No statistically significant associations were found between the variables studied and drug susceptibility testing results. Conclusions: In this sample, the prevalence of primary drug resistance was high despite the absence of known risk factors.

Keywords: Tuberculosis, pulmonary; Tuberculosis, multidrug-resistant; Risk factors.