Tuberculosis remains a serious social and public health problem, affecting millions of people annually. The bacille Calmette-Guerin (BCG) vaccine, used prophylactically, does not impede the progression of the disease, which usually manifests as decreased cellular immunity. Early diagnosis, together with polychemotherapy, can control the dissemination of the tuberculosis infection. The current diagnostic methods present certain problems. Such problems include the low sensitivity of sputum smear microscopy, the fact that performing microbiological cultures is quite time-consuming, and the low specificity of the skin test with the purified protein derivative of Mycobacterium tuberculosis. New diagnostic methods, which use specific antigens such as the early secreted antigenic target 6-kDa and culture filtrate protein 10‑kDa, are being evaluated. The genes that encode these antigens are located in the DNA region of difference 1 of M. tuberculosis, M. africanum and M. bovis. However, they are absent from the M. bovis (BCG) and from most environmental mycobacteria. Diagnostic methods such as QuantiFERON-TB® and T SPOT.TB®, which are based on the production of interferon-gamma by T lymphocytes, in response to those antigens, are being tested and have been found to outstrip the purified protein derivative skin test in the following characteristics: greater sensitivity; lower cross-reactivity due to BCG vaccination or infection with environmental mycobacteria; and execution time. The introduction of diagnostic methods that are more specific and sensitive, together with gaining a better understanding of the molecular and cellular mechanisms that regulate the parasite-host interaction, can increase the efficiency of strategies devised to combat tuberculosis.

Keywords: Tuberculosis; Mycobacterium tuberculosis; Diagnosis; Antigens, bacterial/ESAT-6 protein; Immunity.

The objective of this study was to review the literature, focusing on difficulties encountered in asthma diagnosis and in the establishment of initial inhaled corticosteroid treatment in children under five years of age. The search was limited to studies published between 1991 and 2002 in Portuguese, Spanish, or English and included in the LILACS and MEDLINE databases. Symptoms of asthma, the most common chronic childhood disease, typically appear in the first years of life. There are currently no diagnosis means of making a certain diagnosis of asthma in children under the age of five. Clinical manifestations, when present in toddlers and preschoolers, may require treatment such as that given for asthma, assuming that it is preceded by a critical evaluation. We can conclude that diagnosis of asthma in the first years of life is complex and predominantly clinical. Inhaled corticosteroid treatment is an effective tool, although its risks and benefits must be carefully evaluated.

Keywords: Asthma. Adrenal cortex hormones. Infant. Preschool.

Since the beginning of the use of anti-TNF in the treatment of rheumatoid arthritis and other inflammatory diseases, cases of pulmonary tuberculosis and extrapulmonary tuberculosis have been reported in patients receiving such treatment. In most cases, the disease develops by the time the patient has received the sixth infusion. Every patient should be evaluated for latent tuberculosis infection prior to the use of a TNF inhibitor. However, the diagnosis of latent tuberculosis infection is a challenge. The tuberculin test, which was the only test available to detect latent tuberculosis infection for nearly a century, presents a number of limitations. Tests based on the detection of the in-vitro production of IFN-γ by mononuclear cells activated by specific antigens appear to be more accurate and have been studied in patients with rheumatoid arthritis.

Keywords: Tuberculosis, pulmonary; Arthritis, rheumatoid; Tumor necrosis factor-alpha; Infection.

Objective: To evaluate the impact that Family Health Program (FHP) team training and active surveillance have on the detection of TB cases in a low-income community in the city of Fortaleza, Brazil. Methods: The study was performed in an area with approximately 25,000 inhabitants, served by a health care center with five FHP teams, in the city of Fortaleza, Brazil. Although all of the teams were trained, active surveillance was carried out only in one of the areas (area 5). We compared the number of TB cases detected in each of the five areas prior to and after the intervention. We also compared the number of TB cases detected in area 5 to the number of those detected in the other areas, as well as to the citywide number of reported TB cases in Fortaleza, within the same period. Results: The number of TB cases detected in the area studied increased from 1 in 2002 to 22 in 2004 (p < 0.05). There was no significant difference between the number of TB cases in area 5 and that observed for each of the other four areas (p > 0.05). There was a significant increase in the number of TB cases detected in the area studied when compared to the city as a whole (p < 0.05). Conclusions: Training and sensitization of FHP professionals were effective in promoting an increase in the number of TB cases detected in a low-income community.

Keywords: Tuberculosis; Communicable disease control; Family health program; Epidemiologic surveillance.

Objective: To translate the Breathing Problems Questionnaire (BPQ) into Portuguese and adapt it to the Brazilian culture, as well as to evaluate its reproducibility in patients with COPD. Methods: After the BPQ had been translated and adapted to the Brazilian culture, it was administered to a subgroup of 8 patients in order to identify their uncertainties and difficulties. The questionnaire was reviewed by an expert committee, and its final version was arrived at. A second translator back-translated the final version into English, which was sent to the original author in order to verify that the original meaning of the questionnaire had been maintained. After the approval of the original author, the final Portuguese-language version of the questionnaire was administered to 50 patients with COPD, in order to evaluate its reproducibility. Results: The mean response time was 9.5 min. Of the 50 patients, 21 were female and 29 were male. The mean age was 65.8 ± 7.5 years. Most of the patients were classified as having moderate COPD (29.16%) or severe COPD (52%). The intraclass correlation coefficient (ICC) for the total score was 0.94. The ICCs for the eleven BPQ domains and its two subscales were also above 0.70. Moderate correlations were found between the BPQ domains and subscales. Conclusions: The translation and cultural adaptation of the BPQ for use in Brazil was deemed appropriate, because the patients could easily understand and answer the questions. In addition, the Brazilian version of the BPQ questionnaire was found to be reliable, showing good reproducibility.

Keywords: Pulmonary disease; chronic obstructive; Quality of life; Reproducibility of results.

Objective: To evaluate patient profiles and factors associated with successful treatment. Methods: A retrospective study of patients enrolled in the smoking cessation program at the Hospital de Messejana, located in the state of Ceará, Brazil, from October of 2002 to April of 2005. The treatment was evaluated based on patient profile, type of medication prescribed and time on that medication. Results: Of the 320 patients enrolled, 65.5% were women. The mean age at the outset of treatment was 48 years, and the mean duration of the smoking habit was 33 years. More than 90% of the patients had started smoking before the age of 20. Of the 258 individuals who had enrolled in the program at least one year prior, 50.8% had achieved treatment success; 17.8% had relapsed, and 31.4% had not quit smoking. On average, partial success was achieved in the fifth week of the treatment, and relapse occurred predominantly in the fourth month. Approximately 60% of the patients were treated with medication. Conclusion: Quitting smoking was significantly associated with the use of medication, regardless of the profile of the smoker evaluated. In the second year of the program, quitting smoking was more strongly associated with the use of bupropion and nicotine replacement, resulting in a higher success rate and a trend toward a reduction in the relapse rate.

Keywords: Smoking/therapy; Tobacco use cessation; Bupropion; Nicotine

Silicosis, the most prevalent of the pneumoconioses, is caused by inhalation of crystalline silica particles. Silica-exposed workers, with or without silicosis, are at increased risk for tuberculosis and nontuberculous mycobacteria-related diseases. The risk of a patient with silicosis developing tuberculosis is higher (2.8 to 39 times higher, depending on the severity of the silicosis) than that found for healthy controls. Various regimens for tuberculosis chemoprophylaxis in patients with silicosis have been studied, all of which present similar efficacy and overall risk reduction to about one half of that obtained with placebo. Long-term regimens have potential side effects (particularly hepatotoxicity). In addition, the use of such regimens can jeopardize adherence to treatment. The current guidelines recommend that tuberculin skin tests be performed, and, if positive, that chemoprophylaxis be instituted. There are several possible regimens, varying in terms of the drugs prescribed, as well as in terms of treatment duration. We recommend the use of isoniazid at 300 mg/day (or 10 mg/kg/day) for six months for patients with silicosis, as well as for healthy patients with periods of exposure to silica longer than 10 years and strongly positive tuberculin skin test results (induration ≥ 10 mm). Nevertheless, further studies are necessary so that indications, drugs, doses and duration of chemoprophylaxis regimens can be more properly defined.

Keywords: Silicosis; Tuberculosis; Diagnostic techniques and procedures; Chemoprevention.

The epidemiological relevance of tuberculosis is directly related to the socioeconomic profile of a given country. Vulnerability to tuberculosis is influenced by biological factors (e.g., malnutrition, HIV infection, and age) and social factors (e.g., unhealthy housing, high population density, inappropriate working conditions, and lack of access to health services). In many cases, multiple vulnerabilities occur in conjunction. We propose here a reflection on tuberculosis from the point of view of the social determinants of health, as well as the costs associated with its diagnosis and treatment in Brazil, based not only on data in the international literature but also on evidence related to the national context. Given the magnitude of tuberculosis as a socially mediated disease, there is an evident need for greater involvement of health professionals and of the scientific community to implement relevant operational and research measures to understand the social conditions influencing the health-illness continuum for tuberculosis patients. Although the recent economic crisis in Brazil has contributed to increased mortality from all causes, including tuberculosis, health and social protection expenditures have mitigated detrimental health effects. The evidence presented here underscores the importance of public social protection policies for minimizing the effects of tuberculosis indicators, with the aim of eliminating tuberculosis in Brazil.

Keywords: Tuberculosis; Social determinants of health; Cost of illness; Costs and cost analysis.

Objective: The present study aimed to describe the clinical forms and the time taken to diagnose new tuberculosis cases and to statistically analyze the isolated and combined forms of the disease in children and adolescents treated at a university hospital in Rio de Janeiro during the first year of the COVID-19 pandemic in Brazil. Methods: This was a cross-sectional study that used retrospective data on children (0-9 years old) and adolescents (10-18 years old) with pulmonary (PTB), extrapulmonary (EPTB), and combined tuberculosis (PTB + EPTB) followed up at the outpatient clinic from January 2019 to March 2021. Categorical data were analyzed by descriptive statistics and expressed as frequency and proportions. Categorical variables were compared using the Chi-square test, and numerical variables using Student's T-test. Results: A total of 51 cases were included, 63% (32/51) of which comprised patients in the year of the pandemic (group A), while 37% (19/51) were patients attended in previous years (group B). In group A, 19% (6/32) of the patients presented PTB, 59% (16/32) had EPTB, and 31% (10/32) had PTB+EPTB. In group B, 42% (8/19) of the patients presented PTB, 42% (8/19) had EPTB, and 16% (3/19) had PTB+EPTB. Conclusion: Our study revealed more tuberculosis cases in the first year of the pandemic than in the same period of the previous year, with greater variation of sites affected by the disease, including rarer and more severe forms.

Keywords: pandemic, children, adolescents, tuberculosis, coronavirus.

Objective: To compare gastric lavage (GL) performed in inpatients with GL performed in outpatients in terms of its accuracy in diagnosing pulmonary tuberculosis (TB) in children. Methods: A prospective study was carried out in the state of Espírito Santo, Brazil, from 1999 to 2003. A total of 230 children suspected of having TB (103 inpatients and 127 outpatients) were selected to undergo GL. Those thus diagnosed with TB (n = 53) were divided into two groups: inpatient GL (n = 30) and outpatient GL (n = 23). All 53 children were monitored for 6 months in order to evaluate the accuracy of the diagnosis. Accuracy was determined based on any change in diagnosis, cure rate, and the percentage of positive cultures in the two groups studied. Results: The cure rate was 100% in both groups, and there was no change in diagnosis in the 53 children studied. No significant difference was found between the two groups studied in terms of detection of Mycobacterium tuberculosis (RR = 1.47; 95% CI: 0.95-2.27; p = 0.095), although the outpatient group presented a greater rate of positive cultures. Conclusions: Our results show that the accuracy of GL performed in an inpatient setting is similar to that of GL performed in an outpatient setting. This indicates that hospitalization is required only in more severe cases in which GL cannot be performed as an outpatient procedure.

Keywords: Gastric lavage; Tuberculosis; Diagnosis.

Objective: To investigate the characteristics of and risk factors for mortality among non-HIV-infected immunocompromised patients with an in-hospital diagnosis of tuberculosis. Methods: This was a two-year, retrospective cohort study of patients with an in-hospital diagnosis of tuberculosis. The predictive factors for mortality were evaluated. Results: During the study period, 337 hospitalized patients were diagnosed with tuberculosis, and 61 of those patients presented with immunosuppression that was unrelated to HIV infection. Extrapulmonary tuberculosis was found in 47.5% of cases. In the latter group, the in-hospital mortality rate was 21.3%, and the mortality rate after discharge was 18.8%. One-year survival was significantly higher among the immunocompetent patients than among the HIV patients (p = 0.008) and the non-HIV-infected immunocompromised patients (p = 0.015), although there was no such difference between the two latter groups (p = 0.848). Among the non-HIV-infected immunocompromised patients, the only factor statistically associated with mortality was the need for mechanical ventilation. Among the patients over 60 years of age, fibrosis/atelectasis on chest X-rays and dyspnea were more common, whereas fever and consolidations were less common. Fever was also less common among the patients with neoplasms. The time from admission to the initiation of treatment was significant longer in patients over 60 years of age, as well as in those with diabetes and those with end-stage renal disease. Weight loss was least common in patients with diabetes and in those using corticosteroids. Conclusions: The lower prevalence of classic symptoms, the occurrence of extrapulmonary tuberculosis, the delayed initiation of treatment, and the high mortality rate reflect the diagnostic and therapeutic challenges of tuberculosis in non-HIV-infected immunocompromised patients.

Keywords: Hospitalization; Immunosuppression; Risk factors; Tuberculosis/mortality; Immunocompromised host.

Background: In Brazil, tuberculosis is the major cause of pleural effusion. In more than 50% of cases, treatment has been initiated prior to confirmation of the diagnosis. Our objective was to identify factors that can contribute to the diagnosis. Method: We studied 215 consecutive patients with pleural effusion: 104 from tuberculosis (TB) and 111 from other causes (41 were from malignancies, 29 involved transudation, 28 were parapneumonic and 13 were from other etiologies). Clinical, radiological and laboratorial variables were evaluated for differences between the two groups, individually or in combination. Results: Male gender and PPD > 10 mm were significantly more frequent in the tuberculosis group. Radiological features were similar in both groups. Among the continuous variables, adenosine deaminase (ADA), percentile of cells, protein and age performed better as isolated diagnostic criteria. Between the group with tuberculosis and that with pleural effusion from other causes, no significant differences were found in Lactate dehydrogenase, total leukocytes or duration of disease. The correlation of ADA with any other welldeveloped continuous variable showed an LR+ > 10 and an LR- < 0.1, which effectively confirmed or ruled out a diagnosis of tuberculous pleural effusion. Conclusions: In patients with ADA levels > 39 at 95% sensitivity, the specificity can be improved to more than 90% if we consider non purulent effusion or effusion with a predominance of lymphocytes (> 50%).

Keywords: Tuberculosis, pleural/diagnosis. Adenosine deaminase/diagnosis use. Sensitivity and specificity.

Objective: To evaluate the accuracy of bacteriological methods and of polymerase chain reaction (with primers specific for IS6110 of the Mycobacterium tuberculosis complex) in testing sputum samples from indigenous (Amerindian) and non-indigenous patients. Methods: A total of 214 sputum samples (154 from indigenous patients and 60 from non-indigenous patients) were analyzed in order to determine the accuracy of smear microscopy (direct and concentrated versions) for acid-fast bacilli, culture, and polymerase chain reaction. Results: Both microscopy methods presented low sensitivity in comparison with culture and polymerase chain reaction. Specificity ranged from 91% to 100%, the concentrated acid-fast smear technique being the least specific. Nontuberculous mycobacteria were isolated three times more frequently in samples from indigenous patients than in those from non-indigenous patients. False-positive and false-negative polymerase chain reaction results were more common in the indigenous population. Conclusion: Positivity and isolation of nontuberculous mycobacteria in the acid-fast smear in conjunction with polymerase chain reaction positivity raise the following hypotheses: nontuberculous mycobacteria species with DNA regions homologous to, or even still possessing, the M. tuberculosis IS6110 exist in the Amazon; colonization of the oropharynx or of a tuberculous lesion accelerates the growth of the nontuberculous mycobacteria present in the sputum samples, making it impossible to isolate M. tuberculosis; A history of tuberculosis results in positivity for M. tuberculosis DNA. The absence of bacteriological positivity in the presence of polymerase chain reaction positivity raises questions regarding the inherent technical characteristics of the bacteriological methods or regarding patient history of tuberculosis.

Keywords: Tuberculosis, pulmonary/diagnosis; Mycobacterium tuberculosis, Polymerase chain reaction/methods; Indians, south american

Objective: To evaluate the quality of diagnosis and the epidemiological profile of patients with pleural tuberculosis in the state of Roraima, Brazil, in order to provide technical support for the development and implementation of public policies to combat the disease. Methods: This was a cross-sectional study designed to determine the prevalence of pleural forms of tuberculosis in Roraima between 2005 and 2013 and to evaluate the diagnostic criteria used, as well as their determinants. This study was based on secondary data from the Brazilian Case Registry Database, including all reported cases of pleural tuberculosis in the state during the study period. Diagnoses based on bacteriological or histopathological confirmation were defined as high-quality diagnoses. Results: Among the 1,395 cases of tuberculosis reported during the study period, 116 (8.3%) were cases of pleural tuberculosis, accounting for 38.9% of all cases of extrapulmonary tuberculosis in the sample. The incidence rate of pleural tuberculosis did not follow the downward trend observed for the pulmonary form of the disease during the same period. The prevalence of cases with a high-quality diagnosis was 28.5% (95% CI: 20.4-37.6%). In a univariate analysis, none of the demographic or clinical characteristics collected from the database were found to have a significant impact on the outcome (as explanatory variables). Conclusions: The quality of the diagnoses in our study sample was considered unsatisfactory. Limited access to specific diagnostic methods might have contributed to these results.

Keywords: Tuberculosis/diagnosis; Tuberculosis/epidemiology; Tuberculosis, pleural.

Abstract Objective: To compare four laboratory methods in the diagnosis of pulmonary tuberculosis. Methods: Respiratory secretion specimens were collected from 160 patients suspected of having pulmonary tuberculosis. Direct testing for Mycobacterium tuberculosis was carried out using Ziehl-Neelsen staining, auramine staining, culture on Löwenstein-Jensen (LJ) medium and polymerase chain reaction (PCR). The strains isolated were identified by means of a radiometric method using p-nitro-alpha-acetylamino-beta-hydroxypropiophenone (NAP) and classical methods. The sensitivity of the methods was compared to the gold standard for the diagnosis of pulmonary tuberculosis, based on clinical, radiological and microbiological criteria. Results: Of the 160 patients, 142 were diagnosed with pulmonary tuberculosis according to the gold standard. The sensitivity of Ziehl-Neelsen staining, auramine staining, culture on LJ medium and PCR was 54.2%, 58.4%, 67.6% and 77.5%, respectively, when compared with the diagnostic criterion adopted. All four methods presented 100% specificity. In the identification of mycobacteria, there was high (96.8%) concordance between PCR and the radiometric method using NAP. The sensitivity of PCR was 50.8% in samples with negative sputum smear microscopy results and 98.8% in those with positive results. The sensitivity of PCR was lower in specimens with negative results in sputum smear microscopy and culture than in those with positive results (25.6% and 99.0%, respectively). Conclusions: We found PCR to be a promising method for the diagnosis of pulmonary tuberculosis, even in paucibacillary specimens. Simultaneous identification and faster results are additional advantages of this method.

Keywords: Tuberculosis, pulmonary/diagnosis; Culture media; Polymerase chain reaction; Sputum/microbiology.

Objective: To compare the frequency of unfavorable outcome (death or default and treatment failure) between tuberculosis (TB)/HIV co-infected patients treated for TB after laboratory confirmation of the diagnosis and TB/HIV co-infected patients who were so treated without diagnostic confirmation. Methods: A retrospective cohort of TB/HIV co-infected patients who started TB treatment between July of 2002 and June of 2004 at an HIV/AIDS referral center in Recife, Brazil. The main exposure variable, laboratory confirmation of TB, was adjusted for three different sets of variables: sociodemographic variables; HIV/AIDS-related variables; and TB-related variables. In order to evaluate the statistical significance of the results, we calculated odds ratios, with 95% confidence intervals, and p values (from chi-square tests and likelihood ratio tests). Results: A total of 262 patients were studied. No association was found between laboratory confirmation of the diagnosis of TB at treatment outset and unfavorable outcome, even after adjustment for confounders. In the final multiple logistic regression model, the following variables remained: the presence of other opportunistic diseases; CD4 lymphocyte count below 50 cells/mm3; viral load between 10,000 and 100,000 copies/mL; dyspnea; the disseminated form of TB; and change in the TB treatment regimen due to adverse reactions or intolerance. Conclusions: Our results suggest that TB treatment in TB/HIV co-infected patients without etiologic confirmation of TB, at the discretion of experienced physicians in referral centers, did not increase the risk of unfavorable outcomes. In addition, it allowed the identification of groups that should be closely monitored due to a greater risk of unfavorable outcomes.

Keywords: Tuberculosis; Diagnosis; Therapeutics; Treatment outcome; HIV infections.