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.

Objective: The present study aims at describing the frequency of nontuberculous mycobacteria (NTM) species identified through laboratory testing of samples collected from non-sterile sites (sputum), as well as its frequency in HIV-infected and non-HIV-infected individuals in the Baixada Santista region of the state of São Paulo, Brazil, in the period from 2000 to 2005. Methods: Retrospective analysis of sputum smear microscopy results and culture was conducted based on the records on file at the Instituto Adolfo Lutz-Santos, the regional tuberculosis laboratory. Results: We analyzed 194 NTM strains isolated from 125 individuals, of whom 73 (58.4%) were HIV-negative and 52 (41.6%) were HIV-positive. Thirteen different species were identified: Mycobacterium kansasii; M. avium complex; M. fortuitum; M. peregrinum; M. gordonae; M. terrae; M. nonchromogenicum; M. intracellulare; M. flavescens; M. bohemicum; M. chelonae; M. shimoidei; and M. lentiflavum. In 19.2% of the cases, the bacteriological diagnosis was confirmed by isolation of the same species in at least two consecutive samples. Conclusions: Our results show the importance of including systematic identification of NTM in the laboratory routine, and that its integration into the clinical routine could improve the characterization of the disease, thereby informing the planning of effective control measures in specific populations, such as individuals presenting tuberculosis/HIV co-infection.

Keywords: Mycobacteria, atypical; Laboratory techniques and procedures; HIV; Tuberculosis.

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 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 describe the clinical manifestations of patients with pulmonary infection caused by mycobacteria of the Mycobacterium abscessus complex (MABSC), and to compare these manifestations with those of patients infected with other nontuberculous mycobacteria (NTM). Methods: This was a retrospective cohort study involving 43 patients divided into two groups: the MABSC group, consisting of patients with pulmonary infection caused by MABSC (n = 17); and the NTM group, consisting of patients with pulmonary infection caused by NTM other than MABSC (n = 26). Patients were previously treated with a regimen of rifampin, isoniazid, pyrazinamide, and ethambutol before the diagnosis of NTM was confirmed by two culture-positive sputum samples. The nucleotide sequences of the hsp65, 16S rRNA, and/or rpoB genes were analyzed to identify the mycobacteria. Data were collected on demographic, clinical, and radiological characteristics, as well as on treatment responses and outcomes. Results: Loss of appetite was the only clinical manifestation that was significantly more common in the MABSC group than in the NTM group (p = 0.0306). The chance of having to use a second treatment regimen was almost 12 times higher in the MABSC group than in the NTM group. Treatment success was significantly higher in the NTM group than in the MABSC group (83.2% vs. 17.6%; p < 0.0001). The chance of recurrence was approximately 37 times higher in the MABSC group than in the NTM group. Conclusions: In the study sample, treatment response of pulmonary disease caused by MABSC was less favorable than that of pulmonary disease caused by other NTM.

Keywords: Nontuberculous mycobacteria/classification; Nontuberculous mycobacteria/drug effects; Lung diseases.

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: 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 identify mycobacterial species in the sputum of patients suspected of having pulmonary tuberculosis and to determine the impact that the acquisition of this knowledge has on the therapeutic approach. Methods: We evaluated 106 patients suspected of having pulmonary tuberculosis and referred to the pulmonology department of a public hospital in the city of Teresina, Brazil. Morning sputum specimens were evaluated for the presence of mycobacteria by sputum smear microscopy and culture. We used PCR and restriction enzyme analysis of the hsp65 gene (PRA-hsp65) to identify the strains of mycobacteria isolated in culture. Results: A total of 206 sputum samples were analyzed. Patient ages ranged from 15 to 87 years, and 67% were male. There was cough in 100% of the cases. The predominant radiographic pattern was moderate disease, observed in 70%. Smear positivity was 76%, and isolation in culture occurred in 91% of the cultures. Traditional tests identified nontuberculous mycobacteria (NTM) in 9% of the isolates. The PRA-hsp65 method confirmed these data, showing seven band patterns that were able to identify the isolated species of NTM: Mycobacterium kansasii; M. abscessus 1; M. abscessus 2; M. smegmatis; M. flavescens 1; M. gordonae 5; and M. gordonae 7. All of the patients with NTM were over 60 years of age, and bronchiectasis was seen in 88% of the X-rays. There were two cases of reinfection, initially attributed to M. abscessus and M. kansasii. Conclusions: In immunocompetent patients, NTM can infect the lungs. It is important to identify the specific NTM in order to establish the correct diagnosis and choose the most appropriate therapeutic regimen. The PRA-hsp65 method is useful in identifying NTM species and can be implemented in molecular biology laboratories that do not specialize in the identification of mycobacteria. Keywords:

Keywords: Tuberculosis; Mycobacteria, atypical; Polymerase chain reaction; Brazil.

Background: Synergism between tuberculosis and HIV is responsible for the increased morbidity-mortality rate in AIDS patients. Objective: To delineate the profile of patients with tuberculosis and AIDS in the city of Rio Grande by relating demographic, clinical and laboratory data. Method: The sample comprised all cases of tuberculosis defined by identification of Mycobacterium tuberculosis that occurred in the AIDS Service of the University Hospital/FURG between September, 1997 and December, 2000, which added to a total of 31 patients confirmed as definite cases of AIDS. Using the Ogawa-Kudoh culture method and the Kinyoun bacilloscopy, 33 clinical pulmonary and extrapulmonary specimens were analyzed. Identification of M. tuberculosis was made by the usual phenotype methods. The method of proportions was chosen to establish resistance of isolated strains. Results: The mean age was of 33.8±9.9 years, with a man/woman ratio of 2.87:1 and 80.7% of Caucasians. All patients (n=31) exhibited overall or specific clinical manifestations of turberculosis at the time of suspicion diagnosis. In 20 of the cases risk factors were observed: use of injected drugs, alcoholism, malnutrition, imprisonment. Pulmonary disease occurred in 19 cases, extrapulmonary in 10 and the association of both in two. Lymph node commitment was more frequent among those with extrapulmonary disease. The isolated strains (33) were identified as M. tuberculosis and 28 were tested and showed sensibility to Isoniazid and Rifampin. Conclusion: In AIDS patients, tuberculosis appeared with various clinical manifestations, jeopardizing both men and women of less favored social conditions while at a fully productive stage of their lives.

Keywords: Tuberculosis/epidemiology. Tuberculosis/complications. Acquired immunodeficiency syndorme/tuberculosis. Mycobacterium tuberculosis/indicators of morbidity and mortality.

Objective: This case study, conducted in the state of Rio Grande do Sul (RS), Brazil, aims to determine the local profile of sarcoidosis, describing patient characteristics, clinical presentation and pulmonary function, as well as analyzing the results of radiological, histopathological and biochemical tests, at the time of diagnosis in a series of sarcoidosis patients. Methods: A retrospective study of 92 patients with sarcoidosis treated on the Pavilhão Pereira Filho (Pereira Filho [Respiratory Diseases] Ward) of the Hospital Santa Casa, in the city of Porto Alegre, RS, between 1990 and 2003. The protocol included the collection of clinical, biochemical, radiological, spirometric and histological data. Results: There was no significant gender-based difference in frequency (men, 42%; women, 58%). Mean age was 41.8 ± 14.1 years, with 87% of patients being between 20 and 60 years old. Caucasians predominated (84%). Most patients (61%) had never smoked, 29% were former smokers, and 10% were current smokers. The majority (33%) of the diagnoses were made in winter. Among the clinical findings, it is of note that 12% were asymptomatic, 18% presented pulmonary symptoms only, 22% presented extrapulmonary symptoms only, and 48% presented pulmonary and extrapulmonary symptoms. Spirometry was performed in 79% of patients at the time of diagnosis. In 45% of those patients, abnormal results were obtained: a restrictive pattern was seen in 23%, an obstructive pattern in 18% and a mixed pattern in 4%. Classification by radiological type revealed that 30% were stage I, 48% were stage II, and 22% were stage III. Conclusion: The findings of this study are quite similar to those of other studies in the literature, particularly those conducted in Europe.

Keywords: Sarcoidosis, pulmonary/diagnosis; Sarcoidosis, pulmonary/pathology; Lung diseases/pathology; Prognosis; Retrospective studies

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

Background: The appearance of tuberculosis/human immunodeficiency virus co-infection and the growing number of diseases caused by nontuberculous mycobacteria, as well as the confusion that these can cause in relation to emerging multidrug-resistant strains, require more accurate and rapid laboratory results, not only in the isolation of strains but also in their identification. Objective: A comparative study evaluating a new tool of molecular identification, which uses a genetic probe based on the 16S rDNA sequence of the Mycobacterium tuberculosis gene (Gen-Probe Accuprobe® Gen Probe, Inc.), and the classic methodology. Method: Fifty-five Mycobacterium strains, isolated from the sputum of patients treated at a tuberculosis reference clinic, were selected for study. Subcultures were performed in three tubes: one submitted to genetic identification, one analyzed through classical tests (production and accumulation of niacin; growth in the Lowenstein-Jensen medium with the inhibitor agents p-nitrobenzoic acid and thiophene-2-carboxylic acid hydrazide added), and one held in reserve. Results: The probe identified 51 cases as belonging to the M. tuberculosis complex (one associated with M. kansasii) and the other 4 as nontuberculous mycobacteria, later identified as M. kansasii (3) and M. avium (1). Using traditional methods, 47 samples were identified as belonging to the M. tuberculosis complex, 4 were classified as fitting the profile of nontuberculous mycobacteria (in agreement with the genetic probe results), and 4 were unidentified, 1 of which presented the exact characteristics that 2 mycobacterium species have in common. Conclusion: The benefits of the molecular biology technique justify its implementation and routine use, in combination with classical methods, in a high-traffic clinic where complex cases of tuberculosis are treated.

Keywords: Mycobacterium tuberculosis. Molecular probe techniques.

Objective: To determine the prevalence of alternative diagnoses based on chest CT angiography (CTA) in patients with suspected pulmonary thromboembolism (PTE) who tested negative for PTE, as well as whether those alternative diagnoses had been considered prior to the CTA. Methods: This was a cross-sectional, retrospective study involving 191 adult patients undergoing CTA for suspected PTE between September of 2009 and May of 2012. Chest X-rays and CTAs were reviewed to determine whether the findings suggested an alternative diagnosis in the cases not diagnosed as PTE. Data on symptoms, risk factors, comorbidities, length of hospital stay, and mortality were collected. Results: On the basis of the CTA findings, PTE was diagnosed in 47 cases (24.6%). Among the 144 patients not diagnosed with PTE via CTA, the findings were abnormal in 120 (83.3%). Such findings were consistent with an alternative diagnosis that explained the symptoms in 75 patients (39.3%). Among those 75 cases, there were only 39 (20.4%) in which the same alterations had not been previously detected on chest X-rays. The most common alternative diagnosis, made solely on the basis of the CTA findings, was pneumonia (identified in 20 cases). Symptoms, risk factors, comorbidities, and the in-hospital mortality rate did not differ significantly between the patients with and without PTE. However, the median hospital stay was significantly longer in the patients with PTE than in those without (18.0 and 9.5 days, respectively; p = 0.001). Conclusions: Our results indicate that chest CTA is useful in cases of suspected PTE, because it can confirm the diagnosis and reveal findings consistent with an alternative diagnosis in a significant number of patients.

Keywords: Pulmonary embolism/diagnosis; Pulmonary embolism/epidemiology; Angiography.

Malignant mesothelioma (MM) is a highly aggressive form of cancer, has a long latency period, and is resistant to chemotherapy. It is extremely fatal, with a mean survival of less than one year. The development of MM is strongly correlated with exposure to asbestos and erionite, as well as to simian virus 40. Although various countries have banned the use of asbestos, MM has proven to be difficult to control and there appears to be a trend toward an increase in its incidence in the years to come. In Brazil, MM has not been widely studied from a genetic or biochemical standpoint. In addition, there have been few epidemiological studies of the disease, and the profile of its incidence has yet to be well established in the Brazilian population. The objective of this study was to review the literature regarding the processes of malignant transformation, as well as the respective mechanisms of tumorigenesis, in MM.

Keywords: Occupational diseases; Mesothelioma; Genes, tumor suppressor; Oncogenes; Signal transduction.

Objective: To determine the prevalence and profile of smoking among hospitalized patients at a university hospital in the south of Brazil. Methods: This was a descriptive cross-sectional study involving patients over 18 years of age hospitalized for over 24 h at the Federal University of Santa Catarina University Hospital, located in the city of Florianópolis, Brazil. The patients were interviewed on two distinct occasions. We collected demographic data, socioeconomic data, and data regarding smoking. Results: We interviewed 235 patients: 44 (18.7%) were smokers; 77 (32.8%) were former smokers; 114 (48.5%) were nonsmokers; and 109 (46.7%) were passive smokers. The mean age of the smokers was 45.7 ± 15.2 years, and 29 (65.9%) were male. Among the smokers, the median age at smoking initiation was 15 years; the mean smoking history was 32 ± 30.2 pack-years; 36 (81.9%) smoked up to 20 cigarettes/day; 20 (45.4%) had a high or very high degree of nicotine dependence; 32 (72.7%) had already tried to quit smoking; 39 (88.7%) would like to quit smoking; 32 (72.7%) would accept smoking cessation treatment; 13 (29.5%) smoked during hospitalization; and 13 (29.5%) suffered withdrawal syndrome. Regarding the motivation to quit smoking, the number of patients in the "preparation" and "action" stages of change increased from admission to discharge (from 31.8% to 54.8%). Conclusions: The prevalence of smoking in this study was similar to that reported in other studies conducted in Brazil. The results suggest that our sample was significant regarding the population of hospitalized smokers, who are motivated to quit smoking during hospitalization and require a systematized approach for doing so.

Keywords: Smoking/epidemiology; Hospitalization; Smoking cessation.

Objective: To study the incidence of nontuberculous mycobacteria and the range of species isolated between 1996 and 2005 at a regional branch of the Adolfo Lutz Institute-located in the city of São José do Rio Preto, Brazil-and to show the importance of laboratory testing. Methods: Mycobacteria were isolated from pulmonary and extrapulmonary specimens and identified through phenotyping and molecular methods (polymerase chain reaction-restriction enzyme analysis). Results: We isolated 317 nontuberculous mycobacterium strains: ­Mycobacterium avium complex, 182 (57.4%); M. gordonae, 33 (10.4%); M. fortuitum, 25 (7.9%); M. chelonae, 8 (2.5%); M. terrae complex, 8 (2.5%); M. kansasii, 7 (2.2%); and less frequent species, 54 (17%). During this period, 72 cases (33.3%) were characterized as mycobacteriosis, according to bacteriological criteria established by the American Thoracic Society in 2007. Of those 72 cases, 56 were attributed to M. avium complex. Of those 56, 29 (51.8%) were characterized as disseminated disease. Six cases were attributed to M. fortuitum, 3 to M. gordonae, 2 to M. chelonae, 1 to M. abscessus, 1 to M. kansasii, 1 to M. intracellulare, 1 to M. malmoense and 1 to ­Mycobacterium ssp. Conclusions: These results show the importance of the bacteriological diagnosis, since identification of the species enables early and appropriate treatment.

Keywords: Mycobacteria, atypical/isolation & purification; Mycobacteria, atypical/classification; Diagnostic techniques and procedures.

Objective: Silicosis is a pneumoconiosis characterized by fibrosis of the lung parenchyma caused by inhalation of silica particles. Genetic factors might play a role in the severity silicosis. We sought to evaluate the influence of polymorphisms in the ACE, FAS, FASLG, NOS2, IL1RN, FAM13A, TGFB1, and TNF genes on the severity of silicosis. Methods: Nine polymorphisms were genotyped by PCR in a sample of 143 patients with silicosis in the state of Rio de Janeiro, Brazil. Results: Fifty-seven patients (40%) were classified as having simple silicosis and 86 (60%) were classified as having complicated silicosis. The TT genotype of rs1800469 in the TGFB1 gene showed a protective effect for complicated silicosis (OR = 0.35; 95% CI, 0.14-0.92; p = 0.028) when compared with the other two genotypes (CC+CT). The polymorphic T allele of rs763110 in the FASLG gene (OR = 0.56; 95% CI, 0.31-0.99; p = 0.047), as well as a dominant model for the T allele (TT+CT: OR = 0.37; 95% CI, 0.15-0.96; p = 0.037), also showed a protective effect. When patients with simple silicosis despite having been exposed to silica for a longer time (> 44,229 hours) were compared with patients with complicated silicosis despite having been exposed to silica for a shorter time, the T allele of rs763110 in the FASLG gene (OR = 0.20; 95% CI, 0.08-0.48; p < 0.0001), as well as dominant and recessive models (OR = 0.06; 95% CI, 0.00-0.49; p = 0.01 and OR = 0.22; 95% CI, 0.06-0.77; p = 0.014, respectively), showed a protective effect against the severity of silicosis. Conclusions: It appears that rs1800469 polymorphisms in the TGFB1 gene and rs763110 polymorphisms in the FASLG gene are involved in the severity of silicosis. Given the lack of studies relating genetic polymorphisms to the severity of silicosis, these results should be replicated in other populations.

Keywords: Silicosis; Polymorphism, genetic; Genetic association studies; Cytokines.

Objectives: To characterize the main identified mutations on cystic fibrosis transmembrane conductance regulator (CFTR) in a group of children and adolescents at a cystic fibrosis center and its association with the clinical and laboratorial characteristics. Method: Descriptive cross-sectional study including patients with cystic fibrosis who had two alleles identified with CFTR mutation. Clinical, anthropometrical, laboratorial and pulmonary function (spirometry) data were collected from patients' records in charts and described with the results of the sample genotyping. Results: 42 patients with cystic fibrosis were included in the study. The most frequent mutation was F508del, covering 60 alleles (71.4%). The second most common mutation was G542X (six alleles, 7.1%), followed by N1303K and R1162X mutations (both with four alleles each). Three patients (7.14%) presented type III and IV mutations, and 22 patients (52.38%) presented homozygous mutation for F508del. Thirty three patients (78.6%) suffered of pancreatic insufficiency, 26.2% presented meconium ileus, and 16.7%, nutritional deficit. Of the patients in the study, 59.52% would be potential candidates for the use of CFTR-modulating drugs. Conclusions: The mutations of CFTR identified more frequently were F508del and G542X. These are type II and I mutations, respectively. Along with type III, they present a more severe cystic fibrosis phenotype. More than half of the sample (52.38%) presented homozygous mutation for F508del, that is, patients who could be treated with Lumacaftor/Ivacaftor. Approximately 7% of the patients (7.14%) presented type III and IV mutations, therefore becoming candidates for the treatment with Ivacaftor.

Keywords: Cystic fibrosis; Mutations; Genetics; Phenotype; Child

Objective: To determine the drug resistance profile of Mycobacterium tuberculosis in the state of Mato Grosso do Sul, Brazil, between 2000 and 2006. Methods: Descriptive study of reported tuberculosis cases in the Brazilian Case Registry Database. We included only those cases in which M. tuberculosis culture was positive and sensitivity to drugs (rifampicin, isoniazid, streptomycin and ethambutol) was tested. Löwenstein-Jensen and Ogawa-Kudoh solid media were used for cultures, as was an automated liquid medium system. Sensitivity tests were based on the proportion method. Results: Among the 783 cases evaluated, males predominated (69.7%), as did patients in the 20-49 year age bracket (70%), a diagnosis of pulmonary tuberculosis (94.4%) and positive HIV serology (8.6%); 645 (82.4%) were new cases, and 138 (17.6%) had previously been treated. Resistance to at least one drug was found in 143 cases (18.3%). The primary resistance (PR) rate was, respectively, 8.1%, 1.6%, 2.8% and 12.4%, for monoresistance, multidrug resistance (MDR), other patterns of resistance and resistance to at least one drug, whereas the acquired resistance (AR) rate was 14.5%, 20.3%, 10.9% and 45.7%, respectively, and the combined resistance (CR) rate was 9.2%, 4.9%, 4.2% and 18.3%, respectively. In PR, streptomycin was the most common drug, whereas isoniazid was the most common in AR and CR (7.2% and 3.7%, respectively). Conclusions: These high levels of resistance undermine the efforts for tuberculosis control in Mato Grosso do Sul. Acquired MDR was 12.7 times more common than was primary MDR, demonstrating that the previous use of drug therapy is an indicator of resistance. These levels reflect the poor quality of the health care provided to these patients, showing the importance of using the directly observed treatment, short course strategy, as well as the need to perform cultures and sensitivity tests for the early diagnosis of drug resistance.

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