Objective: To describe the incidence of active tuberculosis and the occurrence of adverse events after isoniazid treatment in patients with latent tuberculosis infection (LTBI) who also had chronic inflammatory diseases and were treated with immunobiologic agents in an endemic area in Brazil. Methods: The diagnosis of LTBI was based on anamnesis, clinical examination, chest X-ray, and a tuberculin skin test (TST). Patients received prophylactic treatment (isoniazid for six months) in accordance with the Brazilian guidelines. Results: A total of 101 patients were evaluated between July of 2011 and July of 2015. Of those, 55 (54.46%) were women (mean age, 53.16 ± 1.76 years) and 46 (45.54%) were men (mean age, 45.39 ± 2.13 years). A total of 79 patients (78.22%) were being treated with immunobiologic agents and 22 (21.78%) were being treated with immunomodulatory or immunosuppressive agents. In the screening for LTBI, 53 patients (52.48%) had a TST induration ≥ 10 mm. Chest X-ray findings consistent with LTBI were observed in 36 patients (35.64%). Isoniazid preventive therapy was effective in 96 (95.05%) of the 101 patients evaluated. It is of note that 84 (83.17%) of the patients experienced no adverse effects from the use of isoniazid and that 83 (98.81%) of those patients completed the prophylactic treatment (p = 0.002). Active tuberculosis was diagnosed in 5 (6.33%) of the 79 patients treated with immunobiologic agents and in 1 (4.55%) of the 22 patients treated with other immunomodulators/immunosuppressants. Conclusions: A six-month course of isoniazid proved to be safe and effective in the treatment of LTBI, which is essential to reducing the risk of developing active tuberculosis.

Keywords: Latent tuberculosis; Tuberculin test; Tumor necrosis factors/antagonists & inhibitors; Isoniazid.

Objective: To determine the prevalence of latent tuberculosis infection (LTBI) and the risk of infection in patients with chronic kidney disease treated at a hemodialysis center. Methods: We included 307 patients with chronic kidney disease undergoing hemodialysis at the Mineiro Institute of Nephrology, located in the city of Belo Horizonte, Brazil. All of the patients were submitted to tuberculin skin tests (TSTs). We investigated the booster effect and TST conversion. If the initial TST (TST1) was negative, a second TST (TST2) was performed 1-3 weeks later in order to investigate the booster effect. If TST2 was also negative, a third TST (TST3) was performed one year after TST2 in order to determine whether there was TST conversion. Results: When we adopted a cut-off induration of 5 mm, the prevalence of LTBI was 22.2% on TST1, increasing by 11.2% on TST2. When we adopted a cut-off induration of 10 mm, the prevalence of LTBI was 28.5% on TST1, increasing by 9.4% on TST2. The prevalence of LTBI increased significantly from TST1 to TST2 (booster effect), as well as from TST2 to TST3 (p < 0.01 for both). In our sample, the mean annual risk of infection was 1.19%. Conclusions: In the population studied, the prevalence of LTBI was high, and the mean annual risk of infection was similar to that reported for the general population of Brazil, which suggests recent infection.

Keywords: Tuberculosis; Renal insufficiency, chronic; Tuberculin test.

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.

Coccidioidomycosis, a fungal illness acquired by the inhalation of arthroconidia of Coccidioides sp., was first described in 1894. Coccidioidomycosis is mainly restricted to areas with arid climate, alkaline soil and low rainfall. Consequently, most of the reported cases in Brazil have occurred in the northeastern region. We report three cases of pulmonary coccidioidomycosis occurring between 2005 and 2006 in an endemic area in the state of Ceará, Brazil. The three patients were immunocompetent adult males, hunters of armadillos (Dasypus novemcinctus), with complaints of cough, fever, dyspnea and pleuritic pain. All three patients presented pulmonary involvement, and one also presented cutaneous lesions. Chest X-rays and CT scans of the patients revealed characteristic coccidioidomycosis lesions. The diagnosis was confirmed by serological testing. All of the patients evolved to cure after antifungal treatment.

Keywords: Coccidioidomycosis; Lung diseases, fungal; Coccidioides.

Since the beginning of the use of anti-TNF in the treatment of rheumatoid arthritis and other inflammatory diseases, cases of pulmonary tuberculosis and extrapulmonary tuberculosis have been reported in patients receiving such treatment. In most cases, the disease develops by the time the patient has received the sixth infusion. Every patient should be evaluated for latent tuberculosis infection prior to the use of a TNF inhibitor. However, the diagnosis of latent tuberculosis infection is a challenge. The tuberculin test, which was the only test available to detect latent tuberculosis infection for nearly a century, presents a number of limitations. Tests based on the detection of the in-vitro production of IFN-γ by mononuclear cells activated by specific antigens appear to be more accurate and have been studied in patients with rheumatoid arthritis.

Keywords: Tuberculosis, pulmonary; Arthritis, rheumatoid; Tumor necrosis factor-alpha; Infection.

Most people infected by Mycobacterium tuberculosis (Mtb) do not have any signs or disease symptoms, a condition known as latent tuberculosis infection (LTBI). The introduction of biological agents, mainly tumor necrosis factor (TNF) inhibitors, for the treatment of immune-mediated diseases such as Rheumatoid Arthritis (RA) and other rheumatic diseases, increased the risk of reactivation of LTBI, leading to development of active TB. Thus, this review will approach the aspects related to LTBI in patients with rheumatologic diseases, especially those using iTNF drugs. For this purpose it will be considered the definition and prevalence of LTBI, mechanisms associated with diseases and medications in use, criteria for screening, diagnosis and treatment. Considering that reactivation of LTBI accounts for a large proportion of the incidence of active TB, adequate diagnosis and treatment are crucial, especially in high-risk groups such as patients with rheumatologic diseases.

Keywords: Tuberculosis; Latent tuberculosis; Tuberculin skin test; Anti-TNF therapy; Tumor necrosis factor-alpha; Rheumatoid arthritis.

Evidence-based techniques have been increasingly used in the creation of clinical guidelines and the development of recommendations for medical practice. The use of levels of evidence allows the reader to identify the quality of scientific information that supports the recommendations made by experts. The objective of this review was to address current concepts related to the clinical impact, diagnosis, and treatment of Pseudomonas aeruginosa infections in patients with cystic fibrosis. For the preparation of this review, the authors defined a group of questions that would be answered in accordance with the principles of PICO-an acronym based on questions regarding the Patients of interest, Intervention being studied, Comparison of the intervention, and Outcome of interest. For each question, a structured review of the literature was performed using the Medline database in order to identify the studies with the methodological design most appropriate to answering the question. The questions were designed so that each of the authors could write a response. A first draft was prepared and discussed by the group. Recommendations were then made on the basis of the level of scientific evidence, in accordance with the classification system devised by the Oxford Centre for Evidence-Based Medicine, as well as the level of agreement among the members of the group.

Keywords: Cystic fibrosis/diagnosis; Cystic fibrosis/drug therapy; Pseudomonas aeruginosa; Evidence-based medicine.

Objective: To compare the frequency of unfavorable outcome (death or default and treatment failure) between tuberculosis (TB)/HIV co-infected patients treated for TB after laboratory confirmation of the diagnosis and TB/HIV co-infected patients who were so treated without diagnostic confirmation. Methods: A retrospective cohort of TB/HIV co-infected patients who started TB treatment between July of 2002 and June of 2004 at an HIV/AIDS referral center in Recife, Brazil. The main exposure variable, laboratory confirmation of TB, was adjusted for three different sets of variables: sociodemographic variables; HIV/AIDS-related variables; and TB-related variables. In order to evaluate the statistical significance of the results, we calculated odds ratios, with 95% confidence intervals, and p values (from chi-square tests and likelihood ratio tests). Results: A total of 262 patients were studied. No association was found between laboratory confirmation of the diagnosis of TB at treatment outset and unfavorable outcome, even after adjustment for confounders. In the final multiple logistic regression model, the following variables remained: the presence of other opportunistic diseases; CD4 lymphocyte count below 50 cells/mm3; viral load between 10,000 and 100,000 copies/mL; dyspnea; the disseminated form of TB; and change in the TB treatment regimen due to adverse reactions or intolerance. Conclusions: Our results suggest that TB treatment in TB/HIV co-infected patients without etiologic confirmation of TB, at the discretion of experienced physicians in referral centers, did not increase the risk of unfavorable outcomes. In addition, it allowed the identification of groups that should be closely monitored due to a greater risk of unfavorable outcomes.

Keywords: Tuberculosis; Diagnosis; Therapeutics; Treatment outcome; HIV infections.

Objective: Preventive treatment of active tuberculosis is one of the main strategies for reducing the incidence of tuberculosis. We sought to evaluate the rates of latent tuberculosis infection (LTBI) treatment completion with three months of once-weekly isoniazid plus rifapentine (3HP) and compare them with those for six to nine months of daily isoniazid (6H/9H). Methods: This was a retrospective cross-sectional study. Consecutive patients undergoing LTBI treatment with 3HP or 6H/9H were included in the study. Treatment completion rates and adverse effects were analyzed. Results: A total of 226 patients were included in the study: 113 in the 3HP group and 113 in the 6H/9H group. The frequency of adverse effects was not significantly different between the 3HP and 6H/9H groups. The 3HP group had a higher treatment completion rate (93.8%) than did the 6H/9H group (84.1%), the difference being significant. Conclusions: The rates of LTBI treatment completion appear to be higher with 3HP than with 6H/9H. Health care professionals should be vigilant in managing adverse effects to further maximize LTBI treatment completion.

Keywords: Tuberculosis, pulmonary; Latent tuberculosis/prevention & control; Mycobacterium tuberculosis.

Setting: Philanthropic health center specialized in lung diseases, including tuberculosis. Background: Directly-observed treatment (DOT) is the chief measure to insure improvement in cure levels and to reduce acquired resistance. This unit adopted DOT in the past, but financial difficulties prevent its maintenance. Objectives: Compare abandon levels in DOT and auto-administered treatment (AT) and identify predictive factors associated to abandonment. Type of study: Retrospective; patients observed in different years and selected at random. Material and methods: 1,226 patients were selected (613 patients in DOT and 613 in AT). Abandonment was compared in DOT and TA; in each group, abandonment was compared to sex, age, alcoholism, previous treatment, direction of symptoms, sputum and extension of the disease. Main results: Patients in DOT and in AT differ in some aspects. In AT, males, older age, positive sputum and more extensive disease were detected, previous treatment predominantly DOT. No difference was detected in relation to duration of symptoms, race, alcoholism and call up. Abandon was more frequent in AT (5.0% vs. 17.0%), p < 0.01, OR 3.90, CI 95% (2.50-5.88); one abandom in AT may be prevented by treating 8.4 patients in DOT. In AT, abandonment was related to male, black race, previous treatment, duration of symptoms, alcoholism and to age; duration of symptoms in DOT. Conclusion and proposal: 1) As abandonment is more common in AT, it is necessary to begin DOT immediately in structured units. 2) Cooperation with company medical facilities, community leaders and pharmacist will make it easier DOT adoption. 3) Punitive measures must be adopted for uncooperative patients.

Keywords: Tuberculosis. Abandonment. Directly-observed treatment (DOT).

Objective: Many biologic agents cause some degree of immunosuppression, which can increase the risk of reactivation of tuberculosis infection (TBI). This risk is variable between individual biologics. We aimed to assess current (and recommended) clinical practice of TBI screening and treatment among patients initiating treatment with biologic agents. Methods: An online questionnaire was distributed via email to members of the Global Tuberculosis Network and associated professional organisations to seek insights into the screening for and treatment of TBI in patients treated with biologics. Results: A total of 163 respondents in 27 countries answered at least one question. For all biologics described in the questionnaire, respondents advised increasing screening relative to current practice. Observed and supported TBI screening rates in patients treated with TNF-a inhibitors were high, especially for older TNF-a inhibitors. Most participants supported TBI screening in patients treated with B- or T-cell inhibitors but not in those treated with interleukin inhibitors. Guideline awareness was higher for TNF-a inhibitors than for other biologic classes (79% vs. 34%). Conclusions: Although respondents stated that TBI screening rates are lower than what they consider ideal, there was a tendency to recommend TBI screening in patients treated with biologics not known to be associated with an increased risk of TBI. As a result, there is a potential risk of over-screening and over-treatment of TBI, potentially causing harm, in patients treated with biologics other than TNF-a inhibitors. There is a need to research the risk of TBI associated with biologics and for guidelines to address the spectrum of TBI risk across all types of biologics.

Keywords: Latent tuberculosis; Biological products; Immunosuppression therapy; Recurrence; Mass screening.

Objective: To estimate the prevalence of latent Mycobacterium tuberculosis infection (LTBI) in renal transplant recipients and to assess sociodemographic, behavioral, and clinical associations with positive tuberculin skin test (TST) results. Methods: This was a cross-sectional study of patients aged ≥ 18 years who underwent renal transplantation at the Renal Transplant Center of the Federal University of Minas Gerais Hospital das Clínicas, located in the city of Belo Horizonte, Brazil. We included renal transplant recipients who underwent the TST between January 2011 and July 2013. If the result of the first TST was negative, a second TST was administered. Bivariate and multivariate analyses using logistic regression were used to determine factors associated with positive TST results. Results: The sample included 216 patients. The prevalence of LTBI was 18.5%. In the multivariate analysis, history of contact with a tuberculosis case and preserved graft function (estimated glomerular filtration rate ≥ 60 mL/min/1.73 m2) were associated with positive TST results. TST induration increased by 5.8% from the first to the second test, which was considered significant (p = 0.012). Conclusions: The prevalence of LTBI was low in this sample of renal transplant recipients. The TST should be administered if renal graft function is preserved. A second TST should be administered if the first TST is negative.

Keywords: Tuberculosis; Tuberculin test; Immunocompromised host.

Objective: To determine the prevalence of and the factors associated with latent Mycobacterium tuberculosis infection (LTBI) in prisoners in the state of Minas Gerais, Brazil. Methods: This was a cross-sectional cohort study conducted in two prisons in Minas Gerais. Tuberculin skin tests were performed in the individuals who agreed to participate in the study. Results: A total of 1,120 individuals were selected for inclusion in this study. The prevalence of LTBI was 25.2%. In the multivariate analysis, LTBI was associated with self-reported contact with active tuberculosis patients within prisons (adjusted OR = 1.51; 95% CI: 1.05-2.18) and use of inhaled drugs (adjusted OR = 1.48; 95% CI: 1.03-2.13). Respiratory symptoms were identified in 131 (11.7%) of the participants. Serological testing for HIV was performed in 940 (83.9%) of the participants, and the result was positive in 5 (0.5%). Two cases of active tuberculosis were identified during the study period. Conclusions: Within the prisons under study, the prevalence of LTBI was high. In addition, LTBI was associated with self-reported contact with active tuberculosis patients and with the use of inhaled drugs. Our findings demonstrate that it is necessary to improve the conditions in prisons, as well as to introduce strategies, such as chest X-ray screening, in order to detect tuberculosis cases and, consequently, reduce M. tuberculosis infection within the prison system.

Keywords: Prisons; Tuberculin test; Latent tuberculosis, HIV.

Objective: To describe the frequency of popular myths about and features of asthma treatment in children and adolescents in an urban area in southern Brazil. Methods: The parents or legal guardians of public school students (8-16 years of age) completed a specific questionnaire regarding their understanding of asthma, asthma control, and treatment characteristics. The sample included parents or legal guardians of students with asthma (n = 127) and healthy controls (n = 124). Results: The study involved 251 parents or legal guardians, of whom 127 (68.5%) were the mothers and 130 (51.8%) were White. The mean age of these participants was 38.47 ± 12.07 years. Of the participants in the asthma and control groups, 37 (29.1%) and 26 (21.0%), respectively, reported being afraid of using asthma medications, whereas 61 (48%) and 56 (45.2%), respectively, believed that using a metered dose inhaler can lead to drug dependence. However, only 17 (13.4%) and 17 (13.7%) of the participants in the asthma and control groups, respectively, reported being afraid of using oral corticosteroids. In the asthma group, 55 students (43.3%) were diagnosed with uncontrolled asthma, only 41 (32.3%) had a prescription or written treatment plan, and 38 (29.9%) used asthma medications regularly. Conclusions: Popular myths about asthma treatment were common in our sample, as were uncontrolled asthma and inappropriate asthma management. Further studies in this field should be conducted in other developing countries, as should evaluations of pediatric asthma treatment programs in public health systems.

Keywords: Asthma/therapy; Asthma/prevention & control; Child health.

Abstract Objectives: To determine the frequency of adverse effects related to the use of the tuberculosis treatment regimen designated Regimen I and the need for regimen alterations due to these effects. Methods: A retrospective analysis of 329 medical charts of patients who were treated with Regimen I and discharged after cure between March 2000 and April 2006 was carried out at the Tuberculosis Outpatient Clinic, Department of Pulmonology of the Santa Casa de Misericórdia de São Paulo Hospital in the city of São Paulo, Brazil. Adverse effects and the timing of their appearance, as well as subsequent modifications in the treatment regimen, were investigated. Results: We included 297 patients, 146 (49.1%) of whom presented one or more adverse effects related to antituberculosis medications. The frequency of minor side effects was 41.1%, and that of major side effects was 12.8%. The most common reactions were those involving the gastrointestinal tract (40.3%) and the skin (22.1%). Adverse effects were more common in the first and second months of treatment (58.4%). Modification of the treatment regimen was necessary in 11 cases (3.7% of the total sample). Drug-induced hepatitis was the adverse effect that demanded the most regimen changes. Conclusions: In this group of patients, the frequency of adverse effects related to treatment with Regimen I was 49.1%. However, in most of the cases, it was not necessary to modify the treatment regimen due to side effects.

Keywords: Tuberculosis/therapy; Antitubercular agents/adverse effects; Hepatitis, toxic.