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 evaluate the perspectives of tuberculosis experts from different countries regarding national screening procedures. Methods: This was a qualitative descriptive study. Data were collected by using electronic, anonymized surveys with experts in tuberculosis in seven different countries within two World Health Organization regions (Europe and Africa). Thematic analysis was employed. Results: The survey results indicate that there are varied perceptions of and experiences with national guidelines on screening for and treatment of tuberculosis (especially in the population tested), the appropriate timing of screening, types of tests, best practices, barriers, and limitations of the screening. The participants highlighted the importance of integrating health care services into the community to achieve people-centered health care. The study also sheds light on the importance of involving trained nurses and social workers in the screening process and of networks to ensure continuity of care. Conclusions: The overall perceptions of the respondents underscore the importance of standardized screening guidelines. The ongoing collaboration between public health services, the private sector, and the community is essential to reduce tuberculosis transmission, as well as to provide substantial public health and economic benefits.

Keywords: Europe; Communicable diseases; Transients and migrants; Public health; Tuberculosis.

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.

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.

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: Mycobacteriosis is frequently diagnosed among HIV-infected patients. In Mozambique, where few patients are under antiretroviral therapy and the prevalence of tuberculosis is high, there is need for better characterization of mycobacteria at the species level, as well as for the identification of patterns of resistance to antituberculous drugs. Methods: We studied a sample of 503 HIV-infected individuals suspected of having pulmonary tuberculosis. Of those 503, 320 tested positive for mycobacteria through sputum smear microscopy or culture of bronchoalveolar lavage fluid. Results: Acid-fast bacilli were observed in the sputum of 73% of the individuals presenting positive cultures. Of 277 isolates tested, only 3 were nontuberculous mycobacteria: 2 were identified as Mycobacterium avium and one was identified as M. simiae. Strains initially characterized as M. tuberculosis complex through polymerase chain reaction restriction analysis (PRA) of the hsp65 gene were later confirmed as such through PRA of the gyrB gene. Among the M. tuberculosis isolates, resistance patterns were as follows: to isoniazid, 14%; to rifampin, 6%; and multidrug resistance, 5%. Previously treated cases showed significantly higher rates of resistance to first-line antituberculous drugs. The most common radiological pattern was interstitial infiltrate (in 67%), followed by mediastinal lymph node enlargement (in 30%), bronchiectasis (in 28%), miliary nodules (in 18%) and cavitation (in 12%). Patients infected with nontuberculous mycobacteria presented clinical profiles indistinguishable from those of other patients. The median CD4 lymphocyte count in this group was 134 cells/mm3. Conclusions: There is a strong association between tuberculosis and AIDS in Mozambique, as expected in a country with a high prevalence of tuberculosis. Although drug resistance rates are high, the isoniazid-rifampin regimen continues to be the appropriate choice for initial therapy.

Keywords: Tuberculosis; Mycobacteria, atypical; HIV; Acquired immunodeficiency syndrome; Drug Resistance, Multiple; Mozambique.

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.

Objectives: To verify the prevalence of tuberculosis (TB)/HIV co-infection and the ability of the clinical history to detect the HIV infection in TB inpatients. Setting: Eduardo de Menezes Hospital, reference for both TB and AIDS. Patients and methods: All patients admitted with TB in a pneumology ward were evaluated prospectively from 1/1/1997 to 1/31/1998. The clinical history was directed to the presence of risk factors for AIDS or TB, previous treatments or abandoned treatments for TB, and TB clinical forms. Patients with AIDS defining illnesses, except for TB, and with previous anti-HIV tests were excluded. All patients had an ELISA anti-HIV serology, and when positive, a Western-Blot test was performed to confirm the previous result. X-square test and Fisher test were used for statistical analysis. Results: Sixty-five patients were divided into group I (positive serology for HIV, n = 6) and group II (negative serology for HIV, n = 59). There were no statistical differences between the groups comparing the risk factors for AIDS and TB, previous treatments or abandoned treatments for TB, or TB clinical forms. Conclusions: The high prevalence of TB/HIV co-infection (9.2%) reinforces that: 1) the clinical history was not able to detect a significant number of patients with TB/HIV co-infection and that: 2) anti-HIV serology should be performed in all patients with active TB forms.

Keywords: tuberculosis, acquired immundeficiency syndrome, prevalence

Background: Empyema is a serious disease classically characterized by purulence within the pleural cavity. Early diagnosis demands immediate treatment, although there is still great controversy surrounding the question of what is the best therapy. Objective: To analyze the method of using thoracentesis and pleural irrigation, combined with the intrapleural application of an antimicrobial agent, to treat empyema - and to compare this method with others described in the literature. Method: Between January 1999 and May 2000, 17 patients diagnosed with loculated or diffuse pleural empyema were submitted to thoracentesis, followed by thorough washing of the pleural cavity with isotonic solution and intrapleural administration of a non-irritating antimicrobial agent to the pleura. Results: The group of patients studied consisted of 15 men and 2 women, and the average age was 44. The most common clinical symptoms were fever, productive cough, chest pain and dyspnea, and the most common cause was pneumonia. Macroscopically, 12 patients presented obviously purulent pleural fluid. In 4 (26.67%) of the patients, the etiological agent was identified, the most frequent being Staphylococcus sp. Pulmonary decortication was indicated in 2 cases, and those 2 patients were therefore excluded. The average length of hospitalization was 17.1 days, although 3 patients received the treatment as outpatients. No recurrence or mortality was observed with the use of this methodology. Conclusion: This approach reduced the need for invasive procedures, proving to be safe and efficient, with lower rates of morbidity and mortality than other modalities of treatment.

Keywords: Empyema/Pleural, Pleura/Blood Supply, Treatment Outcome, Treatment Effectiveness.

Background: Multidrug resistant tuberculosis is a threat to tuberculosis control worldwide. In many studies, it has been suggested that inadequate treatment is a risk factor for the development of multidrug resistent tuberculosis. Objective: To identify the factors associated with inadequate treatment in a group of patients with multidrug resistent tuberculosis. Method: The authors identified all drug sensitivity test for tuberculosis performed at the Central Laboratory of the state of Ceará from 1990 to 1999. Retrospective and prospective analysis was performed, comparing the characteristics of adequately treated patients with those of inadequately treated patients. Multidrug resistance was defined as resistance to 2 drugs (rifampin and isoniazid) or more, using the Cox proportional hazards model. Results: Of the 1,500 sensitivity test performed at the Central Laboratory of Public Health of the state of Ceará, 266 revealed multidrug-resistant strains. Of those 266 patients, the authors were able to identify only 153, of whom 19 were excluded. Thus, our sampling consisted of 134 patients. Univariate analysis demonstrated that the significant factors associated with inadequate treatment were: noncompliance with the treatment, extreme poverty, drug intolerance, mistakes in the management of the patients, lack of medication being supplied by the health service, two or more previous treatments, pronounced lung cavities and bilateral lesions on chest X-rays. They found a further association (p < 0.0010) between alcoholism or smoking and noncompliance with the treatment. In the multivariate analysis, the factors associated with an outcome of inadequate treatment were: two or more previous treatments (p < 0.0001, OR = 5.9; CI 95%: 2.5-13.7), pronounced cavitation (p < 0.0217, OR = 2.7; CI 95%: 1.2-6.1) and bilateral chest X-ray lesions (p < 0.0226, OR = 3.2; CI 95%: 1.4-7.4) Conclusion: In the study, the authors observed that factors related to inadequate treatment are wide-ranging. An attempt at better control of the disease is warranted, especially in those patients with pronounced cavitation or bilateral lesions in chest X-rays. And those with 2 or more previous treatments.

Keywords: Tuberculosis, multidrug-resistant. Risk factors.

Background: The risk for nosocomial transmission of tuberculosis exists in health care institutions. Objective: To evaluate indicators of transmission risk among patients with pulmonary tuberculosis treated at a university hospital. Method: A retrospective study covering the January 1997 to September of 1999 period and evaluating patients admitted to the Hospital de Clínicas of the Universidade Estadual de Campinas with pulmonary tuberculosis. Three intervals were determined: from admission to collection of sputum for acid-fast bacilli microscopy; from admission to implementation of airborne infection control measures; from sputum collection to the initiation of treatment. Results: The final sample included 63 cases. Concomitant human immunodeficiency virus-positivity was found in 31.7%. Forty patients (63.5%) were admitted through the emergency room. In 42 (66.7%) patients, TB was suspected at admission. The interval between admission and sputum collection exceeded 12 hours in 27.5% of cases admitted through the emergency room and in 30.4% of those admitted directly to wards (p = 0.803). Delayed respiratory isolation occurred in 31 cases (49.2%). The delay in isolation was correlated to no diagnosis of tuberculosis at admission (p < 0.000) and lower bacillary load in the sputum (p = 0.032). Co-infection with human immunodeficiency virus (p = 0.530), hospitalization ward (p = 0.284) and underlying diseases (p = 0.541) were not correlated with delayed isolation. The interval between sputum collection and initiation of treatment was greater than 24 hours in 15.9% of the cases. Conclusion: Delayed isolation was observed in many cases. Policies of continuing education are called for, especially in high-risk areas.

Keywords: Tuberculosis. Infection Control. Brazil. Delay. Diagnosis.

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: To characterize the prevalence of latent tuberculosis infection (LTBI) in patients with interstitial lung diseases (ILDs) requiring immunosuppression. Only 5 to 10% of individuals infected with Mycobacterium tuberculosis develop tuberculosis, and certain groups of patients have an increased risk of illness, such as the immunocompromised. Patients with ILDs are frequently treated with immunosuppressants and, therefore, might have a higher risk of developing the disease. Methods: Prospective study conducted at the ILD reference center of the Federal University of Paraná from January 2019 to December 2020. The screening of LTBI was performed with the use of the tuberculin skin test (TST). Results: The sample consisted of 88 patients, of whom 64.8% were women, with a mean age of 61.4 years. The most frequent diagnoses were autoimmune rheumatic disease ILD (38.6%) and hypersensitivity pneumonitis (35.2%). The most common immunosuppressant in use at the time of the TST was prednisone, either in combination with mycophenolate (19.3%) or alone (17.1%). The majority of participants had fibrotic lung disease, characterized by a reticular interstitial pattern on chest computed tomography (79.5%) and moderate to severe functional impairment (mean FVC 69.2%). A prevalence of LTBI of 9.1% (CI 95%, 2.1%-15.1%) was found, with a TST median of 13. Conclusion: Patients with ILD who are treated with immunosuppressants are not commonly screened for LTBI, despite being under a greater risk of progression to active disease. This study suggests the need for a more cautious approach to these patients.

Keywords: Latent tuberculosis infection; Interstitial lung diseases; Immunosuppression; Tuberculin test.

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.

Objective: To identify risk factors for the development of hospital-acquired pneumonia (HAP) caused by multidrug-resistant (MDR) bacteria in non-ventilated patients. Methods: This was a retrospective observational cohort study conducted over a three-year period at a tertiary-care teaching hospital. We included only non-ventilated patients diagnosed with HAP and presenting with positive bacterial cultures. Categorical variables were compared with chi-square test. Logistic regression analysis was used to determine risk factors for HAP caused by MDR bacteria. Results: Of the 140 patients diagnosed with HAP, 59 (42.1%) were infected with MDR strains. Among the patients infected with methicillin-resistant Staphylococcus aureus and those infected with methicillin-susceptible S. aureus, mortality was 45.9% and 50.0%, respectively (p = 0.763). Among the patients infected with MDR and those infected with non-MDR gram-negative bacilli, mortality was 45.8% and 38.3%, respectively (p = 0.527). Univariate analysis identified the following risk factors for infection with MDR bacteria: COPD; congestive heart failure; chronic renal failure; dialysis; urinary catheterization; extrapulmonary infection; and use of antimicrobial therapy within the last 10 days before the diagnosis of HAP. Multivariate analysis showed that the use of antibiotics within the last 10 days before the diagnosis of HAP was the only independent predictor of infection with MDR bacteria (OR = 3.45; 95% CI: 1.56-7.61; p = 0.002). Conclusions: In this single-center study, the use of broad-spectrum antibiotics within the last 10 days before the diagnosis of HAP was the only independent predictor of infection with MDR bacteria in non-ventilated patients with HAP.

Keywords: Pneumonia, bacterial; Drug resistance, bacterial; Cross infection.