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.

Mycobacterium tuberculosis is one of the most successful human pathogens. Highly virulent strains, which are more easily transmitted than are less virulent strains, elicit variable immune responses. We evaluated the Th1 responses (IFN-γ production) in healthy volunteers after stimulation with various strains. Our results show that the individuals with negative tuberculin skin test (TST) results were not necessarily naive to all of the strains tested, whereas individuals with positive TST results did not respond to all of the strains tested. Drug-resistant strains induced a lower mean level of IFN-γ production than did drug-sensitive strains. One possible practical application of this finding would be for the prediction of responses to treatment, in which it might be advantageous to have knowledge of the estimated IFN-γ production elicited by a specific isolated strain.

Keywords: Tuberculosis; Polymorphism, restriction fragment length; Mycobacterium tuberculosis; Immunity, cellular; Interferon-gamma.

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.

Background: Surveys of patients diagnosed with mycobacteriosis, taken at the Laboratory of Mycobacteriology of the Hospital das Clínicas da Universidade Federal de Minas Gerais, have shown that lack of information concerning diagnosis prevented 42% from initiating treatment. Objective: To evaluate the profile of patients with mycobacterial infection attending the Hospital das Clínicas da Universidade Federal de Minas Gerais. To describe the follow up of those patients and compare it to the guidelines made by the National Program for the Control of Tuberculosis. Methods: The files of patients diagnosed with mycobacterium infection during 2002 were selected from the archives of the Laboratory of Mycobacteriology of the Hospital das Clínicas da Universidade Federal de Minas Gerais. An active search for these patients was carried out and follow-up exams were then performed. Results: Of the 66 patients selected, 62 (94%) were positive for Mycobacterium tuberculosis and 4 (6%) had nontuberculous mycobacteriosis. Another 4 (6%) had been transferred to other institutions. Of the remaining 58, 37 (63%) had been cured, 1 (2%) had refused treatment, 9 (16%) were not found and 11 (19%) had died. Of the 11 deaths, 7 (64%) had tested positive for HIV. Conclusion: Patients failed to receive treatment not due to lack of diagnosis, but to inadequate structure, low awareness levels of all parties, and lack of tuberculosis control organization at the hospital level. Due to the high number of HIV-positive patients, the number of patients cured was lower than that required by the National Health Ministry. Deaths were attributed to HIV infection and lack of knowledge about the disease. In order to identify and address the problems associated with clinical laboratory practice, laboratory professionals must work in concert with their clinical counterparts when carrying out operational research on tuberculosis.

Keywords: Tuberculosis/diagnosis. Mycobacterium infections/complications.

Objective: To investigate the effects of manual chest compression (MCC) on the expiratory flow bias during the positive end-expiratory pressure-zero end-expiratory pressure (PEEP-ZEEP) airway clearance maneuver applied in patients on mechanical ventilation. The flow bias, which influences pulmonary secretion removal, is evaluated by the ratio and difference between the peak expiratory flow (PEF) and the peak inspiratory flow (PIF). Methods: This was a crossover randomized study involving 10 patients. The PEEP-ZEEP maneuver was applied at four time points, one without MCC and the other three with MCC, which were performed by three different respiratory therapists. Respiratory mechanics data were obtained with a specific monitor. Results: The PEEP-ZEEP maneuver without MCC was enough to exceed the threshold that is considered necessary to move secretion toward the glottis (PEF − PIF difference > 33 L/min): a mean PEF − PIF difference of 49.1 ± 9.4 L/min was achieved. The mean PEF/PIF ratio achieved was 3.3 ± 0.7. Using MCC with PEEP-ZEEP increased the mean PEF − PIF difference by 6.7 ± 3.4 L/min. We found a moderate correlation between respiratory therapist hand grip strength and the flow bias generated with MCC. No adverse hemodynamic or respiratory effects were found. Conclusions: The PEEP-ZEEP maneuver, without MCC, resulted in an expiratory flow bias superior to that necessary to facilitate pulmonary secretion removal. Combining MCC with the PEEP-ZEEP maneuver increased the expiratory flow bias, which increases the potential of the maneuver to remove secretions.

Keywords: Physical therapy modalities; Critical care; Respiration, artificial; Bodily secretions.

Objective: Bone disease is a common comorbidity in patients with cystic fibrosis (CF). We sought to determine risk factors and identify potential biochemical markers for CF-related bone disease (CFBD) in a unique cohort of CF patients with end-stage lung disease undergoing lung transplantation (LTx) evaluation. Methods: All of the CF patients who were evaluated for LTx at our center between November of 1992 and December of 2010 were included in the study. Clinical data and biochemical markers of bone turnover, as well as bone mineral density (BMD) at the lumbar spine and femoral neck, were evaluated. Spearman's rho and multivariate logistic regression analysis were used. Results: A total of 102 adult CF patients were evaluated. The mean age was 28.1 years (95% CI: 26.7-29.5), and the mean body mass index was 17.5 kg/m2 (95% CI: 17.2-18.2). Mean T-scores were −2.3 and −1.9 at the lumbar spine and femoral neck, respectively, being lower in males than in females (−2.7 vs. −2.0 at the lumbar spine and −2.2 vs. −1.7 at the femoral neck). Overall, 52% had a T-score of < −2.5 at either skeletal site. The homozygous Phe508del genotype was found in 57% of patients without osteoporosis and in 60% of those with low BMD. Mean T-scores were not particularly low in patients with severe CFTR mutations. Although the BMI correlated with T-scores at the femoral neck and lumbar spine, serum 25-hydroxyvitamin D and parathyroid hormone levels did not. Conclusions: CFBD is common in CF patients with end-stage lung disease, particularly in males and patients with a low BMI. It appears that CF mutation status does not correlate with CFBD. In addition, it appears that low BMD does not correlate with other risk factors or biochemical parameters. The prevalence of CFBD appears to have recently decreased, most likely reflecting increased efforts at earlier diagnosis and treatment.

Keywords: Lung transplantation; Cystic fibrosis; Bone density; Osteoporosis.

Objective: To evaluate the prevalence of pulmonary function abnormalities and to investigate the factors affecting lung function in patients treated for pulmonary tuberculosis. Methods: A total of 214 consecutive patients (132 men and 82 women; 20-82 years of age), treated for pulmonary tuberculosis and followed at a local dispensary, underwent spirometry and plethysmography at least one year after treatment. Results: Pulmonary impairment was present in 102 (47.7%) of the 214 patients evaluated. The most common functional alteration was obstructive lung disease (seen in 34.6%). Of the 214 patients, 60 (28.0%) showed reduced pulmonary function (FEV1 below the lower limit of normal). Risk factors for reduced pulmonary function were having had culture-positive pulmonary tuberculosis in the past, being over 50 years of age, having recurrent tuberculosis, and having a lower level of education. Conclusions: Nearly half of all tuberculosis patients evolve to impaired pulmonary function. That underscores the need for pulmonary function testing after the end of treatment.

Keywords: Respiratory function tests; Tuberculosis, pulmonary; Spirometry; Lung diseases, obstructive.

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.