Background: Tuberculosis is an ancient disease, which still remains one of the major ills faced by mankind in the 21st century. In recent decades, new technologies employing the knowledge gained from molecular biology studies have allowed for more accurate detection of tuberculosis and increased investigation of the etiology and epidemiology of the disease. Aim: Evaluating the degree of similarity among strains of Mycobacterium tuberculosis provided by the Phthisiology Sector of Centro de Saúde Navegantes (Navegantes Health Clinic) in Porto Alegre, RS, Brazil. Method: A retrospective study was performed involving RFLP typing of 55 sputum samples from outpatients examined at the Centro de Saúde Navegantes. The results of the genotyping were correlated to the conventional epidemiology data. Results: A single pattern was seen in 39 (70.9%) of the isolates, whereas 16 isolates (29.1%) showed clustering patterns and were grouped into 8 clusters of 2 patients each. An epidemiological link was found for 6 (37.5%) of the 16 patients in the clusters. Conclusion: The appropriate combination of conventional epidemiology and genotyping of M. tuberculosis contributes to a better understanding of the dynamics of tuberculosis transmission even when such a study is performed in a single, isolated health clinic.

Keywords: Mycobacterium tuberculosis. Transmission. Polymorphism, Restriction Fragment Length. Epidemiology.

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 and compare the mutations in two different regions of the katG gene, which is responsible for isoniazid (INH) resistance. Methods: We analyzed 97 multidrug-resistant Mycobacterium tuberculosis strains isolated in cultures of sputum samples obtained from the Professor Hélio Fraga Referral Center, in Brasília, Brazil. Another 6 INH-sensitive strains did not present mutations and were included as controls. We used PCR to amplify two regions of the katG gene (GenBank accession no. U06258)-region 1, (from codon 1 to codon 119) and region 2 (from codon 267 to codon 504)-which were then sequenced in order to identify mutations. Results: Seven strains were resistant to INH and did not contain mutations in either region. Thirty strains carried mutations in region 1, which was characterized by a high number of deletions, especially at codon 4 (24 strains). Region 2 carried 83 point mutations, especially at codon 315, and there was a serine-to-threonine (AGC-to-ACC) substitution in 73 of those cases. The analysis of region 2 allowed INH resistance to be diagnosed in 81.4% of the strains. Nine strains had mutations exclusively in region 1, which allowed the proportion of INH-resistant strains identified to be increased to 90.6%. Conclusions: The number of mutations at codon 315 was high, which is consistent with cases described in Brazil and in other countries, and the analysis of region 1 resulted in a 9.2% increase in the rate at which mutations were identified.

Keywords: Isoniazid; Mutation; Tuberculosis; Drug resistance, multiple.

Introduction: A considerable increase in asthma and atopy prevalence has been noticed worldwide through the last decades, however, in our country, epidemiological data are still insufficient. Objective: This study was carried out to determine the prevalence of asthma and atopy in a group of students, and compare these data with those found in two previous studies undertaken in Porto Alegre, Rio Grande do Sul. Methods: Asthma prevalence was identified through a questionnaire applied to 855 students from five schools of Porto Alegre. The students submitted to skin tests who presented, at least, one positive reaction were considered atopic. The signature of an informed consent from one of the parents was required for the skin test performance. Results: Prevalence was found to be 42.5% and 22% of cumulative and active asthma, respectively, with predominance in females. Atopy was identified in 50.1% of the sample. These results were significantly higher than the 6.7% (1980) and 16% (1989) of cumulative asthma, 10.9% (1989) of active asthma and 15.8% (1980) of atopy found in the two previous studies. Conclusion: A high prevalence of asthma and atopy was identified in our students. Future studies should be performed to elucidate the phenomenon herein demonstrated.

Keywords: Asthma. Epidemiology. Atopy.

Objective: To describe the outcomes of retreatment in tuberculosis patients receiving the regimen known, in Brazil, as regimen 3 (streptomycin, ethambutol, ethionamide, and pyrazinamide for 3 months + ethambutol and ethionamide for 9 months) after treatment failure with the basic regimen (rifampin, isoniazid, and pyrazinamide for 2 months + rifampin and isoniazid for 4 months). Methods: A descriptive, uncontrolled, historical cohort study involving adult tuberculosis patients treated with regimen 3. We evaluated adverse drug effects, recurrence, treatment outcomes, and associated factors. Results: The study included 229 patients. The overall cure rate was 62%. For the patients who used the medications regularly and those who did not, the cure rate was 88% and 31%, respectively. Adverse events occurred in 95 patients (41.5%), and most of those events were related to the gastrointestinal tract. In the five-year follow-up period, relapse occurred in 17 cases (12.0%). Conclusions: Overall, the outcomes of treatment with regimen 3 were unsatisfactory, in part because this regimen was administered to a selected population of patients at high risk for noncompliance with treatment, as well as because it presents high rates of adverse effects, especially those related to the gastrointestinal tract, which might be caused by ethionamide. However, for those who took the medications regularly, the cure rate was satisfactory. The recurrence rate was higher than that recommended in international consensus guidelines, which might be attributable to the short (12-month) treatment period. We believe that regimen 3, extended to 18 months, represents an option for patients with proven treatment compliance.

Keywords: Tuberculosis, pulmonary/therapy; Treatment outcome; Retreatment.

Objective: The aim of this study was to determine the prevalence of macrolide-resistant S. pneumoniae and to identify its phenotypic and genotypic characteristics. Methods: Strains of S. pneumoniae isolated in the city of Porto Alegre between May 2002 and August 2004 from samples collected from different anatomical sites were analyzed. For the agar diffusion test, disks of erythromycin, clarithromycin, azithromycin and clindamycin were used. The minimum inhibitory concentrations of erythromycin were determined for macrolide-resistant isolates by the agar dilution method. Macrolide-resistant isolates were phenotyped by agar diffusion test and genotyped by polymerase chain reaction. Results: A total of 229 pneumococcal strains were evaluated, 12 (5.2%) of which were macrolide-resistant. Among the 12 resistant strains, 9 (75%) presented the MLSB phenotype, and 3 (25%) presented the M phenotype. Polymerase chain reaction testing indicated that 8 MLSB phenotype isolates harbored the ermB gene only, whereas the mefE gene was present in all 3 M phenotype isolates. One MLSB phenotype isolate presented both genes. Conclusion: In Porto Alegre, the S. pneumoniae resistance to macrolides is still low since such resistance is due primarily to the presence of the ermB gene expressing the MLSB phenotype.

Background: Tuberculosis become important challenge to health care settings. Brazil has high prevalence of the disease and Rio de Janeiro has high incidence rates with 30% of cases notified at hospitals. Objective: To evaluate prevalence of initial and acquired drug resistance at a general hospital, reference for aids treatment in Rio de Janeiro and to identify associated factors. Methods: Mycobacterium tuberculosis strains from 165 patients were analyzed, between August 1996 and February 1998. Results: Twenty per cent (33/165) were resistant to at least one drug; 13% (12/165) to isoniazid; 3.64% (6/ 165) to rifampin and 3.64% (6/165) to both. Among HIV seropositive subjects (52/165); 28.85% (15/52) were resistant to at least one drug. Acquired resistance occurred in 15.79% of 19 patients that mentioned previous antiTB treatment. Association statistically significant was found with non cavitation on X-ray in bivariate analyses ( P=0.05). Eighty four patients refereed no previous treatment (NPT). Resistance to 1 or more drugs was found in 28.57% (24/84) of NPT patients. Association statistically significant with initial resistance was found with health care workers (P=0.004), unemployment (P=0.03), and diarrhea (P=0.01) in bivariate analyses. On multivariate analyses, health care workers ( P=0.002) remained significantly associated with initial resistance. Conclusions: High resistance rates was found. It corroborates that hospitals needs attention for TB control especially which concerns to health care works infection.

Keywords: Mycobacterium tuberculosis. Drug resistance. Disease transmission, patient to professional. Hospitals.

We compared the nitrate reductase assay with the proportion method, which is considered the gold standard, in 57 Mycobacterium tuberculosis strains isolated from patients treated at the Federal University of Minas Gerais Hospital das Clínicas, located in the city of Belo Horizonte, Brazil. For rifampin and isoniazid, the sensitivity, specificity, and accuracy of the nitrate reductase assay were all 100%, whereas they were 100%, 88.9%, and 66.7%, respectively, for streptomycin and 98.0%, 100%, and 98.2%, respectively, for ethambutol. The mean time to results was ten days. In the study sample, the nitrate reductase assay proved highly accurate and showed excellent concordance with the gold standard.

Keywords: Mycobacterium tuberculosis; Microbial sensitivity tests; Tuberculosis, multidrug-resistant; Nitrate reductase.

This study aimed to assess drug resistance in Mycobacterium tuberculosis strains isolated from sputum samples. To that end, sputum samples were collected from 263 patients suspected of having tuberculosis. All subjects lived in the Complexo de Manguinhos, which is located in the city of Rio de Janeiro, Brazil. Cultures testing positive between October of 2000 and December of 2002 were tested to determine strain susceptibility to isoniazid, rifampicin, streptomycin, ethionamide, and ethambutol. Of the 75 patients diagnosed with tuberculosis, resistance to at least one of the drugs was found in 16 (21.4%). Of those 16 patients, 8 (50%) were new cases, and 8 (50%) had previously been treated. Multidrug-resistant tuberculosis was identified in 8 (10.6%) of the 75 patients, being associated with previous treatment in 6 (8%). The incidence of multidrug-resistant tuberculosis might have been underestimated, since M. tuberculosis was not isolated from all of the samples testing positive for acid-fast bacilli. However, at least, our findings shed some light on the problem.

Keywords: Tuberculosis; Drug resistance; Drug resistance, multiple.

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.

Introduction: Silicosis is the most prevalent pneumoconiosis in Brazil, with most of the registered cases occurring in the State of Minas Gerais. Although it is a preventable disease, silicosis is still epidemic in some areas. Objective: To describe the profile of workers seen at the Clinics Hospital of the Federal University of Minas Gerais. Patients and methods: 300 medical records of silica-exposed workers in different occupations, seen between 1989-2000, were reviewed. Clinical and occupational information, radiographic and spirometric data were analyzed. Statistical methods included univariate analyses with chi-square and t tests. Results and conclusion: The mean age of the exposed patients was 51 years, with mean exposure duration of 15.6 years. 126/300 (42%) were radiologically classified as cases of silicosis. Increasing grades of profusion were associated with lower spirometric indices and more frequent associations with tuberculosis and chronic airflow limitation. Most of the workers were regularly registered employees and the main occupational activity was mining, accounting for the exposure of 197 (66%) workers. Non-registered workers presented more severe radiological grades of silicosis, suggesting, possibly, worse conditions of silica exposure in this group of workers.

Background: In recent decades, the prevalence of asthma has increased. Objectives: To determine the prevalence of asthma symptoms in children and adolescents from 2 to 14 years of age living in Porto Alegre (in the state of Rio Grande do Sul, Brazil) and to determine any potential correlations with socioeconomic profile, treatment and smoking in the home. Methods: A transversal study based on interviews of all families seeking medical attention in June of 2000. Results: The prevalence of asthma symptoms was 49.5%. In 66.8% of families, total income was less than four times the minimum wage, and in more than 50% of homes, the parents had had less than five years of schooling. In 98.5%, prophylactic asthma treatment was not used. In the 174 families studied, 38.7% of mothers and 43.7% of fathers were smokers (32.7% overall). Correlations were found between the following variables: exposure to smoking in the home and number of asthma attacks in the last year (p = 0.02; RR = 2.9; CI: 1.1 - 4.5); maternal level of education and number of attacks in the last year (p = 0.03; RR = 2.03; CI: 1.01 - 4.19); close living quarters and number of attacks in the last year among children exposed to second-hand smoke (p = 0.04; RR = 2.7; CI: 1.4 - 5.1); hospitalization and number of attacks in the last year (p = 0.004; RR = 1.46; CI: 1.15 -1.86); hospitalization and close living quarters (p = 0.03; RR = 1.47; CI: 1.15 -1.86). In children below the age of five, there was correlation between maternal smoking and number of attacks in the last year (p = 0.03; RR = 1.79; CI: 1.04 - 3.08). Conclusion: The prevalence of asthma symptoms was high. The community studied has limited socioeconomic resources, and there is therefore a lack of adequate treatment for asthma. Our results demonstrate the need for prioritized, standardized treatment programs that would give healthcare workers access to the appropriate materials and means of evaluation necessary for asthma control.

Keywords: Key words: Asthma. Prevalence. Smoking in the home. Treatment between episodes of asthma.

Objective: To discuss the main aspects of co-infection with Mycobacterium tuberculosis and human immunodeficiency virus in the city of Taubaté (located in the state of São Paulo, Brazil) in 2001 and 2002. Methods: This study presents epidemiological data on tuberculosis cases occurring in Taubaté in 2001 and 2002. Results: Of the 250 cases of tuberculosis analyzed, 70 (28%) presented human immunodeficiency virus seropositivity, 95 (38%) presented human immunodeficiency virus seronegativity, and 85 (34%) were patients who had not been submitted to serological testing. In the first group (tuberculosis and human immunodeficiency virus seropositivity), males from 30 to 40 years of age predominated, the most common clinical presentation of tuberculosis was pulmonary (65.71%), and the cure rate was 59.38%. In the group of tuberculosis patients presenting human immunodeficiency virus seronegativity, males from 30 to 40 years of age also predominated, the most common clinical presentation of tuberculosis was also pulmonary (70.55%), and the cure rate was 81.63%. Conclusion: We conclude that the human immunodeficiency virus plays an important role in the epidemiology of tuberculosis. Therefore, serological testing for human immunodeficiency virus should be carried out when a diagnosis of tuberculosis is made.

Keywords: Tuberculosis/epidemiology; HIV infections; HIV; Prevalence

Objective: To compare clinical, radiological, and laboratory characteristics of individuals with pulmonary tuberculosis co-infected or not with HIV. Methods: A cross-sectional study, in which signs and symptoms were assessed by anamnesis and physical examination in patients hospitalized with pulmonary tuberculosis. The results of sputum smear microscopy and culture for Mycobacterium tuberculosis, as well as hemoglobin levels and CD4+ T-cell counts, were obtained from medical records, and chest X-ray reports were consulted. Results: We included 50 pulmonary tuberculosis patients, who were divided into two groups (HIV-positive and HIV-negative; n = 25 per group). The mean age of the participants was 38.4 ± 10.5 years; 46 (92%) were males; and 27 (54%) were White. Expectoration was presented by 21 (84%) and 13 (52%) of the patients in the HIV-negative and HIV-positive groups, respectively (p = 0.016). Radiological findings of cavitation were present in 10 (43%) and 2 (10%) of the patients in the HIV-negative and HIV-positive groups, respectively (p = 0.016), whereas an interstitial pattern was observed in 18 (78%) and 8 (40%), respectively (p = 0.012). The mean hemoglobin level was 11.1 ± 2.9 g/dL and 9.3 ± 2.2 g/dL in the HIV-negative and HIV-positive groups, respectively (p = 0.015). Conclusions: In our sample of tuberculosis patients, expectoration was less prevalent, hemoglobin levels were lower, and cavitation was less common, as was an interstitial pattern, among those co-infected with HIV than among those without HIV co-infection.

Keywords: HIV; Tuberculosis; Acquired immunodeficiency syndrome.

Objectives: The purpose of this study is to establish the prevalence of pulmonary thromboembolism (PTE) in autopsies and its rate of antemortem suspicion at Hospital de Clínicas de Porto Alegre (HCPA). Design: Cohort study with historical data. Setting: School hospital with 728 beds. Patients and methods: The adult autopsy reports were studied from 1985 to 1995 as well as the records of patients whose autopsies diagnosed PTE. Antemortem suspicion of PTE was considered from explicit notes on patients records, from requests of lung scan, or from full anticoagulation. Results: In the period mentioned, 9,607 deaths occurred, and 767 (7.98%) autopsies were performed. Significant PTE (> 1 pulmonary subsegment) in 30 (3.9%) patients. In 3 (10%) patients, PTE was considered the effective cause of death. Clinic suspicion was present in 5 (16.6%) patients; in 25 (83.4%) patients, there were only postmortem findings. Conclusion: PTE rates in autopsies were similar to those found in international literature. The rates of clinical suspicion were half of the ones mentioned in school hospitals in the United States and Europe. PTE was subsuspected in life in patients hospitalized at HCPA.

Keywords: Venous thromboembolism. Deep venous thrombosis. Pulmonary artery. Pulmonary infarction.

Objective: To describe the prevalence of multidrug-resistant tuberculosis (MDR-TB) among tuberculosis patients in a major Brazilian city, evaluated via the Second National Survey on Antituberculosis Drug Resistance, as well as the social, demographic, and clinical characteristics of those patients. Methods: Clinical samples were collected from tuberculosis patients seen between 2006 to 2007 at three hospitals and five primary health care clinics participating in the survey in the city of Porto Alegre, Brazil. The samples were subjected to drug susceptibility testing. The species of mycobacteria was confirmed using biochemical methods. Results: Of the 299 patients included, 221 (73.9%) were men and 77 (27.3%) had a history of tuberculosis. The mean age was 36 years. Of the 252 patients who underwent HIV testing, 66 (26.2%) tested positive. The prevalence of MDR-TB in the sample as a whole was 4.7% (95% CI: 2.3-7.1), whereas it was 2.2% (95% CI: 0.3-4.2) among the new cases of tuberculosis and 12.0% (95% CI: 4.5-19.5) among the patients with a history of tuberculosis treatment. The multivariate analysis showed that a history of tuberculosis and a longer time to diagnosis were both associated with MDR-TB. Conclusions: If our results are corroborated by other studies conducted in Brazil, a history of tuberculosis treatment and a longer time to diagnosis could be used as predictors of MDR-TB.

Keywords: Tuberculosis/diagnosis; Drug resistance; HIV.

Background: Knowledge of the rates of drug resistance is one of the pillars of tuberculosis control program evaluation. Data from low-resource countries are scarce and results are delayed due to the techniques employed. There is therefore an urgent need for evaluation of faster and less onerous testing methods. Objective: To compare the performance of rapid colorimetric assays for phenotyping that employ oxidationreduction indicators to determine the susceptibility profile of Mycobacterium tuberculosis with the gold-standard proportion method on Lowenstein-Jensen Medium. Method: We analyzed 166 M. tuberculosis strains of known susceptibility. Minimal inhibition concentrations for isoniazid and rifampicin were determined in microplates, using a liquid medium and Alamar Blue and tetrazolium bromide indicators. To measure agreement the Kappa value was used. Cutoff values between sensitive and resistant strains were defined as 0.2µg/mL and 1.0µg/mL for isoniazid and rifampicin, respectively. Results: There was 100% concordance between Alamar Blue and tetrazolium bromide methods in the determination of minimal inhibition concentrations. Agreement between the colorimetric method and the Lowenstein-Jensen was 95% for isoniazid and rifampicin. Using the colorimetric method, results were obtained within 7 days, in contrast to the 28 days required for the conventional method. Conclusions: Assays to determine minimal inhibition concentrations in liquid medium and employing oxidationreduction indicators proved to be rapid and inexpensive. This method has the potential to become a faster, alternative method for determining susceptibility of M. tuberculosis strains in developing countries.

Keywords: Mycobacterium tubercolis. Disease susceptibility. Isoniazid/therapeutic use. Rifampin/therapeutic use.

Objective: To compare the accuracy of the amplified Mycobacterium tuberculosis direct (AMTD) test with reference methods for the laboratory diagnosis of tuberculosis in HIV-infected patients. Methods: This was a study of diagnostic accuracy comparing AMTD test results with those obtained by culture on Löwenstein-Jensen (LJ) medium and by the BACTEC Mycobacteria Growth Indicator Tube 960 (BACTEC MGIT 960) system in respiratory samples analyzed at the Bioassay and Bacteriology Laboratory of the Oswaldo Cruz Foundation Evandro Chagas Clinical Research Institute in the city of Rio de Janeiro, Brazil. Results: We analyzed respiratory samples collected from 118 patients, of whom 88 (74.4%) were male. The mean age was 36.6 ± 10.6 years. Using the AMTD test, the BACTEC MGIT 960 system, and LJ culture, we identified M. tuberculosis complex in 31.0%, 29.7%, and 27.1% of the samples, respectively. In comparison with LJ culture, the AMTD test had a sensitivity, specificity, positive predictive value, and negative predictive value of 87.5%, 89.4%, 75.7%, and 95.0%, respectively, for LJ culture, whereas, in comparison with the BACTEC MGIT 960 system, it showed values of 88.6%, 92.4%, 83.8%, and 94.8%, respectively. Conclusions: The AMTD test showed good sensitivity and specificity in the population studied, enabling the laboratory detection of M. tuberculosis complex in paucibacillary respiratory specimens.

Keywords: Molecular diagnostic techniques; Tuberculosis; HIV; Molecular probe techniques.