Objective: To determine the current use and potential acceptance (by tuberculosis experts worldwide) of novel rapid tests for the diagnosis of tuberculosis that are in line with World Health Organization target product profiles. Methods: A multilingual survey was disseminated online between July and November of 2016. Results: A total of 723 individuals from 114 countries responded to the survey. Smear microscopy was the most commonly used rapid tuberculosis test (available to 90.9% of the respondents), followed by molecular assays (available to 70.7%). Only a small proportion of the respondents in middle- and low-income countries had access to interferon-gamma-release assays. Serological and lateral flow immunoassays were used by more than a quarter (25.4%) of the respondents. Among the respondents who had access to molecular tests, 46.7% were using the Xpert assay overall, that proportion being higher in lower middle-income countries (55.6%) and low-income countries (76.6%). The data also suggest that there was some alignment of pricing for molecular assays. Respondents stated they would accept novel rapid tuberculosis tests if available, including molecular assays (acceptable to 86.0%) or biomarker-based serological assays (acceptable to 81.7%). Simple biomarker-based assays were more commonly deemed acceptable in middle- and low-income countries. Conclusions: Second-generation molecular assays have become more widely available in high- and low-resource settings. However, the development of novel rapid tuberculosis tests continues to be considered important by tuberculosis experts. Our data also underscore the need for additional training and education of end users.

Keywords: Tuberculosis/diagnosis; Surveys and questionnaires; Income; Mycobacterium tuberculosis/isolation & purification; Molecular diagnostic techniques/methods; Serologic tests/methods.

Objective: To evaluate the impact of the use of the molecular test for Mycobacterium tuberculosis and its resistance to rifampin (Xpert MTB/RIF), under routine conditions, at a referral hospital in the Brazilian state of Bahia. Methods: This was a descriptive study using the database of the Mycobacteriology Laboratory of the Octávio Mangabeira Specialized Hospital, in the city of Salvador, and georeferencing software. We evaluated 3,877 sputum samples collected from symptomatic respiratory patients, under routine conditions, between June of 2014 and March of 2015. All of the samples were submitted to sputum smear microscopy and the Xpert MTB/RIF test. Patients were stratified by gender, age, and geolocation. Results: Among the 3,877 sputum samples evaluated, the Xpert MTB/RIF test detected M. tuberculosis in 678 (17.5%), of which 60 (8.8%) showed resistance to rifampin. The Xpert MTB/RIF test detected M. tuberculosis in 254 patients who tested negative for sputum smear microscopy, thus increasing the diagnostic power by 59.9%. Conclusions: The use of the Xpert MTB/RIF test, under routine conditions, significantly increased the detection of cases of tuberculosis among sputum smear-negative patients.

Keywords: Tuberculosis/diagnosis; Molecular diagnostic techniques; Sputum.

Background: Although pulmonary tuberculosis is the principal predisposing factor for intracavitary fungal colonization, the coexistence of the two diseases is rare. Simultaneity of fungal colonization and active mycobacteriosis in the same cavity (acid-fast bacilli found among hyphal masses) is highly unusual. Objective: To describe clinical findings, diagnostic procedures, radiographic aspects, accompanying conditions and evolution in patients with tuberculosis and fungus ball. Method: We reviewed, retrospectively, the records of 625 patients diagnosed with fungus ball between 1974 and 2002. All of the patients had been diagnosed through immunodiffusion or mycological study, or both. The inclusion criterion was positivity for acid-fast bacilli in sputum smear microscopy or histopathology. Results: The charts of 14 patients were selected. All had presented hemoptysis, followed by productive cough, dyspnea, weight loss, fever, asthenia and chest pain. In one patient colonized by Aspergillus niger and in another colonized by Scedosporium apiospermum (Teleomorph, Pseudallescheria boydii), active tuberculosis was seen concomitant to the fungus ball. In the remaining cases, the mycobacteria were found in the adjacent parenchyma or in the contralateral lung. Conclusion: This study corrobates the assertion that antagonism exists between Mycobacterium tuberculosis and Aspergillus fumigatus. The potential for fungal colonization and mycobacteriosis to occur concomitantly is demonstrated in other fungal agents, S. apiospermum (P. boydii) and A. niger in particular.

Keywords: Key words: Aspergillosis. Aspergillus fumigatus. Aspergillus niger. Pseudallescheria. Mycobacterium tuberculosis. Scedosporium apiospermum.

Tuberculosis is one of the major infectious diseases in developing countries, and the length of time for which the chain of transmission is maintained has been implicated as a major factor in the perpetuation of the disease. In this context, regulatory agencies in such countries have approved new diagnostic tools, which have been almost immediately incorporated into the national tuberculosis control programs. Health interventions have been increasingly investigated in clinical trials, including explanatory trials (in order to evaluate the beneficial effects of such interventions) and pragmatic trials (in order to aid in the decision-making process). We argue that the evaluation of new diagnostic techniques for the detection of tuberculosis should not escape this same logic of evaluation.

Keywords: Tuberculosis/diagnosis; Tuberculosis/prevention & control; Controlled clinical trial as topic.

Objective: To evaluate the accuracy of rapid molecular testing as a diagnostic tool and estimate the incidence of smear-positive pulmonary tuberculosis among the indigenous population. Methods: This is an epidemiological study based on secondary data. We calculated the incidence of smear-positive pulmonary tuberculosis between January 1st, 2011 and December 31, 2016, and the performance of bacilloscopy and rapid molecular testing in diagnosing pulmonary tuberculosis compared to sputum culture (standard test). Results: We included 4,048 cases of indigenous people with respiratory symptoms who provided sputum samples for analysis. Among them, 3.7%, 6.7%, and 3.7% had positive results for bacilloscopy, sputum culture, and rapid molecular testing, respectively. The mean incidence of pulmonary tuberculosis was 269.3/100 thousand inhabitants. Rapid molecular testing had 93.1% sensitivity and 98.2% specificity, compared to sputum culture. Bacilloscopy showed 55.1% sensitivity and 99.6% specificity. Conclusions: Rapid molecular testing can be useful in remote areas with limited resources and a high incidence of tuberculosis, such as indigenous villages in rural regions of Brazil. In addition, the main advantages of rapid molecular testing are its easy handling, fast results, and the possibility of detecting rifampicin resistance. Together, these attributes enable the early start of treatment, contributing to reduce the transmission in communities recognized as vulnerable to infection and disease.

Keywords: Tuberculosis; Molecular diagnostic testing; Diagnostic tests, routine; Indians, South American.

Background: Since the first years of antituberculosis chemotherapy, there has been controversy regarding the transmissibility, infectiousness, virulence and pathogenicity of susceptible and drug-resistant strains of Mycobacterium tuberculosis. Objective: To determine the incidence of active tuberculosis (TB) among individuals cohabiting with patients infected with susceptible and multidrug-resistant tuberculosis (MDR-TB). Methods: A case-control study was conducted. Cases of MDR-TB were defined as those infected with M. tuberculosis strains resistant to at least rifampin and isoniazid. Susceptible TB cases (controls) were defined as those first treated at approximately the same time as the first treatment of the MDR-TB cases - and cured by the time of the interview. Study cases were selected on the basis of the results of susceptibility tests, using the proportion method, carried out at the Central Laboratory of Public Health of the State of Ceará. The control group consisted of patients enrolled in the Tuberculosis Control Program between 1990 and 1999. Results: We evaluated 126 patients and 176 controls. The number of individuals sharing the household with patients was 557 in the MDR-TB group and 752 in the controls. The average number of exposed individuals per index case was 4.42 and 4.27 among patients and controls, respectively. Of the 557 MDR-TB-exposed individuals, 4.49% (25)received antituberculosis treatment after the respective index case had begun treatment, compared to 5.45% (41/752) among the controls ( p = 0.4468). Microepidemics of MDRTB were confirmed in eight families. Conclusion: Our results suggest that the incidence of active TB is comparable between households inhabited by MDRTB patients and those inhabited by susceptible-TB patients.

Keywords: Tuberculosis, multidrug-resistant/epidemiology. Tuberculosis/trasmission.

Objective: To analyze the temporal trends of the incidence and prevalence of tuberculosis, with and without HIV co-infection, as well as of the associated mortality, in Brazil, the Americas, and worldwide. Methods: We collected data related to tuberculosis, with and without HIV co-infection, between 1990 and 2010, in Brazil, the Americas, and worldwide. Temporal trends were estimated by linear regression. Results: We identified a trend toward a decrease in tuberculosis prevalence and mortality, and that trend was more pronounced in Brazil and the Americas than worldwide. There was also a trend toward an increase in the incidence of tuberculosis/HIV co-infection, as well as in the rates of detection of new cases of active and latent tuberculosis. The incidence of tuberculosis was found to trend downward in Brazil, whereas it trended upward worldwide. Tuberculosis incidence rates correlated positively with poverty rates and with HIV incidence rates. Conclusions: Social inequality and the advent of AIDS are the major factors that aggravate the current situation of tuberculosis. In this context, methodical approaches to the assessment of surveillance activities are welcome, because they will identify situations in which the reported tuberculosis data do not reflect the true incidence of this disease.

Keywords: Tuberculosis/epidemiology; HIV; Socioeconomic factors.

Objective: To evaluate the prevalence of and factors associated with experimentation with and current use of water pipes and e-cigarettes among medical students. Methods: This was a cross-sectional multicentric study involving a convenience sample of students from medical schools in most Brazilian geographic regions. Information about experimentation with and current use of conventional cigarettes, water pipes, and e-cigarettes; beliefs and attitudes toward tobacco products; religiosity; and demographics were collected by means of an online structured questionnaire. We used descriptive statistics and logistic regression to analyze the association of those factors. Results: Our sample comprised 700 individuals from four Brazilian regions. Prevalence of experimentation with and current use of cigarettes, water pipes, and e-cigarettes were, respectively, 39.1% and 7.9%; 42.6% and 11.4%; and 13.1% and 2.3%. Water pipe experimentation was higher among those who had a sibling (adjusted OR = 2.64; 95% CI, 1.24-5.61) or friends (adjusted OR = 2.33; 95% CI, 1.63-3.31) who smoke. The same occurred regarding e-cigarette experimentation: siblings (adjusted OR = 2.76; 95% CI, 1.17-6.50) and friends (adjusted OR = 2.47; 95% CI, 1:45-4.22). Curiosity and scent/taste were the major reasons for water pipe use and e-cigarette experimentation. Although 93% of the responders learned about health damages of smoking during medical school classes, 51.4% reported having experimented with at least one of these tobacco products. Most responders who reported feeling the presence of God/the Holy Spirit in their lives were never experimenters of water pipes (59.2%) or e-cigarettes (55.3%). Conclusions: There is a high prevalence of experimentation with tobacco products among medical students whose siblings or friends smoke, despite their knowledge about smoking harms.

Keywords: Education, medical; Health knowledge, attitudes, and practice; Electronic nicotine delivery systems; Smoking water pipes; Religion.

Objective: To evaluate tuberculin test results and relate them to the presence or absence of active tuberculosis, as well as to CD4+ and CD8+ T-lymphocyte counts. Method: The charts of 802 patients with acquired immunodeficiency syndrome treated between August of 1985 and March of 2003 were reviewed. Of the 185 patients submitted to tuberculin tests (23.1%), 107 (57.8%) were male, and 78 (42.2%) were female. Patients were divided into two study groups: tuberculin test reactors (n = 28); and tuberculin test non-reactors (n = 157). Among the reactors, the mean age was 30.60 years, with a standard deviation of 6.62 years, compared with 34.45 years, with a standard deviation of 10.32 years, among the non-reactors. Results: Most of the individuals tested presented only a mild response to the tuberculin test. We found that, at the time of the test, the percentage of individuals with active tuberculosis was greater in the reactor group than in the non-reactor group. During the test period, 10 reactor group patients and 11 non-reactor group patients presented some clinical form of active tuberculosis. In addition, CD4+ T-lymphocyte counts were lower than 200 cells/mm3 in 6 reactor group patients and in 8 non-reactor group patients. Conclusion: Indurations greater than 5 mm were unrelated to higher absolute CD4+ T-cell counts.

Keywords: Tuberculin test; Acquired immunodeficiency syndrome; Tuberculosis; CD4-positive T-lymphocytes; CD8-positive T-lymphocytes

Step tests are typically used to assess exercise capacity. Given the diversity of step tests, the aim of this review was to describe the protocols that have been used in healthy subjects and in patients with chronic lung disease. Step tests for use in healthy subjects have undergone a number of modifications over the years. In most step tests, the duration is variable (90 s-10 min), but the step height (23.0-50.8 cm) and stepping rate (22.5-35.0 steps/min) remain constant throughout the test. However, the use of a fixed step height and constant stepping rate might not provide adequate work intensity for subjects with different levels of fitness, the workload therefore being above or below individual capacity. Consequently, step test protocols have been modified by introducing changes in step heights and stepping rates during the test. Step tests have been used in patients with chronic lung diseases since the late 1970s. The protocols are quite varied, with adjustments in step height (15-30 cm), pacing (self-paced or externally paced), and test duration (90 s-10 min). However, the diversity of step test protocols and the variety of outcomes studied preclude the determination of the best protocol for use in individuals with chronic lung disease. Shorter protocols with a high stepping rate would seem to be more appropriate for assessing exercise-related oxygen desaturation in chronic lung disease. Symptom-limited testing would be more appropriate for evaluating exercise tolerance. There is a need for studies comparing different step test protocols, in terms of their reliability, validity, and ability to quantify responses to interventions, especially in individuals with lung disease.

Keywords: Pulmonary disease, chronic obstructive; Asthma; Cystic fibrosis; Idiopathic pulmonary fibrosis; Exercise tolerance; Exercise test.

Tuberculosis continues to be a major public health problem. Although efforts to control the epidemic have reduced mortality and incidence, there are several predisposing factors that should be modified in order to reduce the burden of the disease. This review article will address some of the risk factors associated with tuberculosis infection and active tuberculosis, including diabetes, smoking, alcohol use, and the use of other drugs, all of which can also contribute to poor tuberculosis treatment results. Tuberculosis can also lead to complications in the course and management of other diseases, such as diabetes. It is therefore important to identify these comorbidities in tuberculosis patients in order to ensure adequate management of both conditions.

Keywords: Tuberculosis/epidemiology; Tuberculosis/prevention & control; Diabetes mellitus/prevention & control; Smoking/adverse effects; Alcohol drinking/adverse effects; Street drugs/adverse effects.

Objective: Most studies of tuberculosis originate from high-income countries with a low incidence of tuberculosis. A review of the scientific production on tuberculosis in Latin American countries, most of which are low- or middle-income countries (some with high or intermediate tuberculosis incidence rates), would improve the understanding of public health challenges, clinical needs, and research priorities. The aims of this systematic review were to determine what has been published recently in Latin America, to identify the leading authors involved, and to quantify the impact of international collaborations. Methods: We used PubMed to identify relevant manuscripts on pulmonary tuberculosis (PTB), drug-resistant tuberculosis (DR-TB), or multidrug-resistant tuberculosis (MDR-TB), published between 2013 and 2018. We selected only studies conducted in countries with an annual tuberculosis incidence of ≥ 10,000 reported cases and an annual MDR-TB incidence of ≥ 300 estimated cases, including Brazil, Peru, Mexico, Colombia, and Argentina. Articles were stratified by country, type, and topic. Results: We identified as eligible 395 studies on PTB and 188 studies on DR/MDR-TB-of which 96.4% and 96.8%, respectively, were original studies; 35.5% and 32.4%, respectively, had an epidemiological focus; and 52.7% and 36.2%, respectively, were conducted in Brazil. The recent Latin American Thoracic Association/European Respiratory Society/Brazilian Thoracic Association collaborative project boosted the production of high-quality articles on PTB and DR/MDR-TB in Latin America. Conclusions: Most of the recent Latin American studies on tuberculosis were conducted in Brazil, Mexico, or Peru. Collaboration among medical societies facilitates the production of scientific papers on tuberculosis. Such initiatives are in support of the World Health Organization call for intensified research and innovation in tuberculosis.

Keywords: Tuberculosis, pulmonary; Tuberculosis, multidrug-resistant; Latin America.