In view of the fact that the World Health Organization has recommended the use of the mycobacteria growth indicator tube (MGIT) 960 system for the diagnosis of tuberculosis and that there is as yet no evidence regarding the clinical impact of its use in health care systems, we conducted a pragmatic clinical trial to evaluate the clinical performance and cost-effectiveness of the use of MGIT 960 at two health care facilities in the city of Rio de Janeiro, Brazil, where the incidence of tuberculosis is high. Here, we summarize the methodology and preliminary results of the trial. (ISRCTN.org Identifier: ISRCTN79888843 [http://isrctn.org/])

Keywords: Controlled clinical trial; Tuberculosis; Diagnostic tests, routine.

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 level of access to health care clinics of a population of patients hospitalized for tuberculosis (TB) at two hospitals in the city of São Paulo, Brazil, comparing them with a population of TB patients under outpatient treatment only. Methods: We compiled sociodemographic, clinical and epidemiological data related to patients hospitalized for TB at two hospitals in the city of São Paulo, Brazil, between January and December of 2007, using a structured questionnaire. We also identified the outpatient clinics to which the patients were referred at discharge. The same variables were evaluated for TB outpatients during the same period, using a database. Results: The study sample consisted of 474 patients (166 inpatients and 308 outpatients: mean age, 41.0 and 39.1 years, respectively). The univariate analysis showed positive associations between hospitalization due to TB and the following variables: 30-39 year age bracket (OR = 2.17); 50-59 year age bracket (OR = 2.17); combination of pulmonary and extrapulmonary forms of TB (OR = 5.31); TB re-treatment (OR = 2.66); seeking treatment at other health care facilities prior to the diagnosis of TB (OR = 2.05); symptom duration of more than 12 weeks (OR = 2.23); and TB diagnosed at hospitals or in emergency rooms (OR = 4.68). The proportion of inpatients who resided in the same regional health district area as that in which the respective hospital was located was 77.6% and 36.8%. The proportion of discharged patients who were referred to outpatient clinics in the same areas was 67.1% and 39.7%, respectively. Conclusions: Patients hospitalized for TB should be monitored from discharge until their admission to the outpatient clinic.

Keywords: Tuberculosis; Health services accessibility; Inpatients; Outpatients.

Objective: To identify nontuberculous mycobacteria (NTM) isolated from sterile sites in patients hospitalized between 2001 and 2006 at the Clementino Fraga Filho University Hospital, located in the city of Rio de Janeiro, Brazil. Methods: During the study period, 34 NTM isolates from sterile sites of 14 patients, most of whom were HIV-positive, were submitted to phenotypic identification and hsp65 PCR-restriction enzyme analysis (PRA). Results: Most isolates were identified as Mycobacterium avium, followed by M. monacense, M. kansasii, and M. abscessus. Conclusions: The combination of PRA, a relatively simple and inexpensive method, with the evaluation of a few phenotypic characteristics can allow NTM to be accurately identified in the routine of clinical laboratories.

Keywords: Mycobacteria, atypical; Molecular biology; Polymerase chain reaction.

Objective: To estimate the rates of recurrence, cure, and treatment abandonment in patients with pulmonary tuberculosis treated with a four-drug fixed-dose combination (FDC) regimen, as well as to evaluate possible associated factors. Methods: This was a retrospective observational study involving 208 patients with a confirmed diagnosis of pulmonary tuberculosis enrolled in the Hospital Tuberculosis Control Program at the Institute for Thoracic Diseases, located in the city of Rio de Janeiro, Brazil. Between January of 2007 and October of 2010, the patients were treated with the rifampin-isoniazid-pyrazinamide (RHZ) regimen, whereas, between November of 2010 and June of 2013, the patients were treated with the rifampin-isoniazid-pyrazinamide-ethambutol FDC (RHZE/FDC) regimen. Data regarding tuberculosis recurrence and mortality in the patients studied were retrieved from the Brazilian Case Registry Database and the Brazilian Mortality Database, respectively. The follow-up period comprised two years after treatment completion. Results: The rates of cure, treatment abandonment, and death were 90.4%, 4.8%, and 4.8%, respectively. There were 7 cases of recurrence during the follow-up period. No significant differences in the recurrence rate were found between the RHZ and RHZE/FDC regimen groups (p = 0.13). We identified no factors associated with the occurrence of recurrence; nor were there any statistically significant differences between the treatment groups regarding adverse effects or rates of cure, treatment abandonment, or death. Conclusions: The adoption of the RHZE/FDC regimen produced no statistically significant differences in the rates of recurrence, cure, or treatment abandonment; nor did it have any effect on the occurrence of adverse effects, in comparison with the use of the RHZ regimen.

Keywords: Tuberculosis, pulmonary, Drug combinations; Recurrence.

Objective: To evaluate deaths attributed to multiple causes in which tuberculosis was one of the causes listed. Methods: All deaths among residents of the state of Rio de Janeiro, Brazil, occurring between 1999 and 2001 and for which the death certificate mentioned tuberculosis, were investigated. The World Health Organization guidelines were used in characterizing the underlying and associated (non-underlying) causes of death. Results: In deaths from tuberculosis, conditions related to its natural history were the principal associated causes, together with alcoholism and diabetes. In approximately three-fifths of all deaths for which tuberculosis was listed as an associated cause, the underlying cause of death was acquired immunodeficiency syndrome. High proportion of ill-defined causes of death, low values found for the number of causes informed per death certificate and for TB as an associated cause point towards a certain degree of underestimation of the actual number of TB-related deaths in Rio de Janeiro State. Conclusion: The study shows that the rates of tuberculosis-related mortality in the state of Rio de Janeiro, calculated based on the number of times tuberculosis was listed as a cause of death (underlying or associated), are the highest in the country. Epidemiological studies of mortality are recommended as a means of guiding the activities of the tuberculosis control program.

Keywords: Tuberculosis/mortality; Acquired immunodeficiency syndrome; Multipe cause of death; Brazil

In 2005 and 2006, 8,121 clinical specimens submitted to the Mycobacteriology Laboratory of the Clementino Fraga Filho University Hospital/Thoracic Diseases Institute, in the city of Rio de Janeiro, Brazil, were inoculated on Löwenstein-Jensen medium containing glycerol and pyruvate. There were 79 mycobacteria isolates that presented growth only on pyruvate-containing medium, and those isolates were selected for the presumptive identification of Mycobacterium bovis. The selected isolates were screened with biochemical tests, PCR amplification (with the specific primers Rv0577 and Rv1510), and pyrazinamide susceptibility tests. All of the strains isolated showed specific phenotypical and genotypical patterns characteristic of M. tuberculosis, and no M. bovis strains were detected.

Keywords: Tuberculosis; Mycobacterium bovis; Polymerase chain reaction.

Objective: To evaluate the prevalence of asthma attacks treated in public health facilities in the city of Juiz de Fora, Brazil from February 1, 2002 to January 31, 2003. Methods: This was a cross-sectional study involving monthly analyses performed in order to evaluate the asthma attacks treated. The variables analyzed were patient gender, age, and place of residence, as well as the profile of the visits by age bracket and by the site of the visit. In addition, we attempted to determine whether asthma attacks correlated with temperature or relative humidity. Results: A total of 25,243 patients were treated for asthma attacks, accounting for 11.1% of the total number of visits to pediatric clinics and 2.7% of the total number visits to medical clinics. The mean age of the patients was 11.6 years (median, 4 years), and 52.9% of the patients were male. The analysis of the annual distribution revealed an increase in the number of asthma attacks treated in the months of May (11.5%), June (10.8%), and July (10.9%). Asthma attack presented a strong inverse correlation with temperature (-0.86) and a weak inverse correlation with relative humidity (-0.27). Statistically significant differences, in terms of mean age and gender, were found between patients with asthma attacks treated in emergency rooms and those treated in basic health clinics. The evaluation by age bracket revealed a predominance of males among patients younger than 12 years of age and a predominance of females among those aged 12 or older. Conclusion: We found that asthma represents a significant public health problem in this city. Local strategies are urgently needed in order to increase in the availability of prophylactic treatment.

Keywords: Asthma/epidemiology; Prevalence; Public Hospitals; Brazil

Objective: To describe the clinical and therapeutic aspects of pulmonary tuberculosis and compare the adverse effects of the treatment and its outcome in elderly and nonelderly patients. Methods: This was a case-control study of 117 elderly individuals (over the age of 60 years) and 464 nonelderly individuals (aged 15-49 years). All subjects presented pulmonary tuberculosis that had been diagnosed and treated at the Thoracic Diseases Institute of the Federal University of Rio de Janeiro between 1980 and 1996. Results: In the elderly group, pulmonary tuberculosis was found to be correlated with diabetes (OR = 3.98; 95% CI = 2.07-7.65; p = 0.001), lung disease (OR = 7.24; 95% CI = 3.64‑14.46; p = 0.001) and heart disease (OR = 5.86; 95% CI = 2.88-11.95; p = 0.001). Smoking (OR = 2.07; 95% CI = 1.26‑3.42; p = 0.002) and alcohol abuse (OR = 1.63; 95% CI = 1.01-2.68; p = 0.041) were also more common in the elderly group. In the elderly group, the treatment more frequently resulted in adverse reactions (OR = 1.62; 95% CI = 1.04-2.54; p = 0.024), especially gastrointestinal reactions (OR = 1.64; 95% CI = 1.01-2.77; p = 0.047), and treatment efficacy was lower: cure rate, 51%; mortality rate, 24%. Treatment adherence was low (approximately 77%) in both groups. Conclusions: In the elderly group, adverse reactions were more common, treatment outcomes were less favorable, there was a greater frequency of clinical complications and deaths related to drug toxicity, and the prevalence of concomitant diseases was higher.

Keywords: Tuberculosis, pulmonary; Aged; Drug therapy; Treatment outcome.

Objective: Nontuberculous mycobacteria (NTM) are a heterogeneous group of bacteria that are widely distributed in nature and associated with opportunistic infections in humans. The aims of this study were to identify NTM in patients with suspected tuberculosis who pre-sented positive cultures and to evaluate the genetic diversity of strains identified as Myco-bacterium avium. Methods: We studied pulmonary and extrapulmonary samples obtained from 1,248 patients. The samples that tested positive on culture and negative for the M. tu-berculosis complex by molecular identification techniques were evaluated by detection of the hsp65 and rpoB genes and sequencing of conserved fragments of these genes. All strains identified as M. avium were genotyped using the eight-locus mycobacterial interspersed repetitive unit-variable-number tandem-repeat method. Results: We found that NTM ac-counted for 25 (7.5%) of the 332 mycobacteria isolated. Of those 25, 18 (72%) were M. avium, 5 (20%) were M. abscessus, 1 (4%) was M. gastri, and 1 (4%) was M. kansasii. The 18 M. avium strains showed high diversity, only two strains being genetically related. Conclusions: These results highlight the need to consider the investigation of NTM in patients with suspected active tuberculosis who present with positive cultures, as well as to evaluate the genetic di-versity of M. avium strains.

Keywords: Mycobacterium avium; Nontuberculous mycobacteria; HIV; Genotyping techniques.

The objective of this study was to compare gender differences among tuberculosis patients in a city with a high incidence of tuberculosis. This was a cross-sectional questionnaire-based study involving 560 tuberculosis patients (373 males and 187 females). Sociodemographic and clinical data, as well as data related to diagnostic criteria and treatment outcome, were collected (from the questionnaires and medical records) and subsequently compared between the genders. The median time from symptom onset to diagnosis was 90 days. There were no differences between the genders regarding the clinical presentation, diagnostic criteria, previous noncompliance with treatment, time from symptom onset, number of medical appointments prior to diagnosis, or treatment outcome. Gender-specific approaches are not a priority in Brazil. However, regardless of patient gender, the delay in diagnosis is a major concern.

Keywords: Poverty; Tuberculosis; Income.

Objective: To evaluate the performance of nested PCR (nPCR) in detecting the Mycobacterium tuberculosis complex in blood samples of patients suspected of having TB, in order to determine its potential for use as an auxiliary tool in the laboratory diagnosis of TB in children. Methods: Detection of the M. tuberculosis complex in blood samples using as a target the insertion sequence IS6110 of the genomic DNA of the bacillus. Blood samples of 120 patients were evaluated. All of the patients were under 15 years of age at the time of their treatment at public hospitals in the city of Recife, Brazil (between January of 2003 and August of 2005). Attending physicians at the hospitals diagnosed TB based on the criteria recommended by the American Thoracic Society. The nPCR amplified a 123-bp fragment with outer oligonucleotides (IS1/IS2) and, in the subsequent reaction, using inner oligonucleotides (IS3/IS4), generating an 81-bp amplicon. Results: Active or latent TB was found in 65 patients, TB was ruled out in 28 suspected cases, and 27 patients were TB-free (controls). The sensitivity of nPCR was 26.15% and was significantly higher for the extrapulmonary form of the disease (55.56%) than for the pulmonary form (18.18%). The specificity was 92.73%. Conclusions: Despite the difficulties in diagnosing TB in children and the low number of cases evaluated in the present study, nPCR in blood samples proved to be a rapid and specific technique, albeit one with low sensitivity. In order to establish its true usefulness in the diagnosis of paucibacillary forms, especially extrapulmonary TB, further studies need to be carried out with a larger sample of children and analyzing biological specimens other than blood.

Keywords: Tuberculosis; Diagnosis; Blood; Polymerase chain reaction.

This retrospective molecular study involving restriction fragment length polymorphism, using insertion sequence 6110 as a marker, was conducted in order to provide an initial insight into the genetic diversity of Mycobacterium tuberculosis strains isolated in the slums of the Complexo de Manguinhos, located in the city of Rio de Janeiro, Brazil. Of the 67 strains evaluated, 23 (34.3%) were found to belong to clusters (total clusters, 10). Household and social chains of transmission were associated with clustering, in 20% and 60%, respectively. Living in the Conjunto Habitacional Programado 2 slum was associated with clustering. Although not significant, it is relevant that 26% of the clustered strains presented primary resistance. These findings, although possibly underestimating the prevalence due to the failure to analyze all strains, could help improve the local tuberculosis control program.

Keywords: Tuberculosis; Epidemiology, molecular; Mycobacterium tuberculosis/transmission; Polymorphism, Restriction Fragment Length.

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.

The objective of this study was to determine the prevalence of HIV infection among individuals ≥ 15 years of age with a confirmed diagnosis of tuberculosis and treated at family health care clinics in the city of Fortaleza, Brazil. We evaluated a random sample of 110 patients with tuberculosis, treated at a total of 26 family health care clinics between January and May of 2009. All of the participants completed a questionnaire regarding sociodemographic and clinical data, and all underwent HIV testing. In this sample, the prevalence of tuberculosis/HIV co-infection was 3.6% (95% CI: 0.2-7.0).

Keywords: Tuberculosis; HIV seroprevalence; Primary health care.

Objective: To estimate the total time elapsed between symptom onset and diagnosis of pulmonary tuberculosis (patient delay plus health care system delay), analyzing the factors associated with delayed diagnosis in the state of Rio de Janeiro, Brazil. Methods: We conducted a questionnaire-based survey involving 218 pulmonary tuberculosis patients treated for two months at 20 health care clinics and 3 hospitals in eight cities within the state of Rio de Janeiro. We collected socioeconomic and demographic data, as well as data regarding the health care system and the medical history of the patients. Results: The median time elapsed from the onset of symptoms to diagnosis was 68 days (interquartile range [IQR]: 35-119 days). The median patient delay (time from symptom onset to initial medical visit) was 30 days (IQR: 15-60 days), and the median health care system delay (time from initial medical visit to diagnosis) was 21 days (IQR: 8-47 days). A cut-off point of 21 days was adopted. The factors independently associated with patient delay were female gender, cough, and unemployment [adjusted OR (95% CI) = 2.7 (1.3-5.6); 11.6 (2.3-58.8); and 2.0 (1.0-3.8), respectively], whereas only female gender was independently associated with health care system delay (OR= 3.2; 95% CI: 1.7-6.0). Conclusions: Delayed diagnosis of pulmonary tuberculosis remains a problem in Rio de Janeiro, increasing the risk of transmission and mortality, that risk being greater for women and the socioeconomically disadvantaged. Patients might not recognize the significance of chronic cough as a health problem. Tuberculosis education programs targeting women might improve this situation.

Keywords: Lung neoplasms; Neoplasm metastasis; Antineoplastic combined chemotherapy protocols; Radiotherapy, computer-assisted.

Objective: The sweat test (ST) measures chloride levels in sweat and is considered the gold standard for the diagnosis of cystic fibrosis (CF). However, the reliability of a ST depends on their being performed by experienced technicians and in accordance with strict guidelines. Our aim was to evaluate how sweat stimulation, sweat collection, and chloride measurement are performed at 14 centers (9 public centers and 5 private centers) that routinely perform STs in the state of São Paulo, which has the highest frequency of CF in Brazil. Methods: This was a cross-sectional cohort study, using a standardized questionnaire administered in loco to the staff responsible for conducting STs. Results: No uniformity regarding the procedures was found among the centers. Most centers were noncompliant with the international guidelines, especially regarding the collection of sweat (the samples were insufficient in 10-50% of the subjects tested); availability of stimulation equipment (which was limited at 2 centers); modernity and certification of stimulation equipment (most of the equipment having been used for 3-23 years); and written protocols (which were lacking at 12 centers). Knowledge of ST guidelines was evaluated at only 1 center. Conclusions: Our results show that STs largely deviate from internationally accepted guidelines at the participating centers. Therefore, there is an urgent need for standardization of STs, training of qualified personnel, and acquisition/certification of suitable equipment. These are essential conditions for a reliable diagnosis of CF, especially with the increasing demand due to newborn screening nationwide, and for the assessment of a possible clinical benefit from the use of modulator drugs.

Keywords: Cystic fibrosis/diagnosis; Cystic fibrosis/prevention & control; Sweat.