Family health team knowledge concerning the health needs of people with tuberculosis

The purposes of the study were to get to know conceptions on tuberculosis and health needs and to describe the care provided to people with tuberculosis, according to health professionals' perspective. Qualitative study developed at family health units in Capao Redondo, Sao Paulo. The data were collected through open interviews in January 2010 and submitted to discourse analysis, resulting in three categories: meanings attributed to tuberculosis and health needs and care characteristics. The conceptions regarding the disease are supported by the multi-causal theory of the health-disease process. The care is characterized by interventions that go beyond the biological dimension. The precarious living conditions define the needs of most people with tuberculosis, and can be more important to the ill than the very diagnosis of the disease, influencing treatment adherence, and should gain relevance in care.

Classification and regression tree (CART) model to predict pulmonary tuberculosis in hospitalized patients

Background: Tuberculosis (TB) remains a public health issue worldwide. The lack of specific clinical symptoms to diagnose TB makes the correct decision to admit patients to respiratory isolation a difficult task for the clinician. Isolation of patients without the disease is common and increases health costs. Decision models for the diagnosis of TB in patients attending hospitals can increase the quality of care and decrease costs, without the risk of hospital transmission. We present a predictive model for predicting pulmonary TB in hospitalized patients in a high prevalence area in order to contribute to a more rational use of isolation rooms without increasing the risk of transmission. Methods: Cross sectional study of patients admitted to CFFH from March 2003 to December 2004. A classification and regression tree (CART) model was generated and validated. The area under the ROC curve (AUC), sensitivity, specificity, positive and negative predictive values were used to evaluate the performance of model. Validation of the model was performed with a different sample of patients admitted to the same hospital from January to December 2005. Results: We studied 290 patients admitted with clinical suspicion of TB. Diagnosis was confirmed in 26.5% of them. Pulmonary TB was present in 83.7% of the patients with TB (62.3% with positive sputum smear) and HIV/AIDS was present in 56.9% of patients. The validated CART model showed sensitivity, specificity, positive predictive value and negative predictive value of 60.00%, 76.16%, 33.33%, and 90.55%, respectively. The AUC was 79.70%. Conclusions: The CART model developed for these hospitalized patients with clinical suspicion of TB had fair to good predictive performance for pulmonary TB. The most important variable for prediction of TB diagnosis was chest radiograph results. Prospective validation is still necessary, but our model offer an alternative for decision making in whether to isolate patients with clinical suspicion of TB in tertiary health facilities in countries with limited resources.

Spatio-temporal patterns of tuberculosis incidence in Ribeirao Preto, State of Sao Paulo, southeast Brazil, and their relationship with social vulnerability: a Bayesian analysis

Introduction: The purpose of this ecological study was to evaluate the urban spatial and temporal distribution of tuberculosis (TB) in Ribeirao Preto, State of Sao Paulo, southeast Brazil, between 2006 and 2009 and to evaluate its relationship with factors of social vulnerability such as income and education level. Methods: We evaluated data from TBWeb, an electronic notification system for TB cases. Measures of social vulnerability were obtained from the SEADE Foundation, and information about the number of inhabitants, education and income of the households were obtained from Brazilian Institute of Geography and Statistics. Statistical analyses were conducted by a Bayesian regression model assuming a Poisson distribution for the observed new cases of TB in each area. A conditional autoregressive structure was used for the spatial covariance structure. Results: The Bayesian model confirmed the spatial heterogeneity of TB distribution in Ribeirao Preto, identifying areas with elevated risk and the effects of social vulnerability on the disease. We demonstrated that the rate of TB was correlated with the measures of income, education and social vulnerability. However, we observed areas with low vulnerability and high education and income, but with high estimated TB rates. Conclusions: The study identified areas with different risks for TB, given that the public health system deals with the characteristics of each region individually and prioritizes those that present a higher propensity to risk of TB. Complex relationships may exist between TB incidence and a wide range of environmental and intrinsic factors, which need to be studied in future research.

Tuberculosis and latent tuberculosis in prison inmates

OBJECTIVE: To estimate the prevalences of tuberculosis and latent tuberculosis ill inmates. METHODS: Observational study was carried out with inmates of a prison and a jail in the State of Sao Paulo, Southeastern Brazil, between March and December of 2008. Questionnaires were used to collect sociodemographic and epidemiological data. Tuberculin skin testing was administered (PPD-RT23-2TU/0.1 mL), and the following laboratory tests were also performed: sputum smear examination, sputum culture, identification of strains isolated and drug susceptibility testing. The variables were compared using Pearson's chi-square (chi(2)) association test, Fisher's exact test and the proportion test. RESULTS: Of the 2,435 inmates interviewed, 2,237(91.9%) agreed to submit to tuberculin skin testing and of these, 73.0% had positive reactions. The prevalence of tuberculosis was 830.6 per 100,000 inmates. The coefficients of prevalence were 1,029.5/100,000 for inmates of the prison and 525.7/100,000 for inmates of the jail. The sociodemographic characteristics of the inmates in the two groups studied were similar; most of the inmates were young and single with little schooling. The epidemiological characteristics differed between the prison units, with the number of cases of previous tuberculosis and of previous contact with the disease greater in the prison and coughing, expectoration and smoking more common in the jail. Among the 20 Mycobacterium tuberculosis strains identified, 95.0% were sensitive to anti-tuberculosis drugs, and 5.0% were resistant to streptomycin. CONCLUSIONS: The prevalences of tuberculosis and latent tuberculosis were higher in the incarcerated population than in the general population, and they were also higher in the prison than in the jail.

Delays in the diagnosis of tuberculosis in a town at the triple border of Brazil, Paraguay, and Argentina

Objective. To identify the factors linked to patients and health services in delays in the diagnosis of tuberculosis. Methods. Epidemiological study in Foz do Iguacu, Parana, Brazil, 2009. The Primary Care Assessment Tool, adapted for appraising tuberculosis treatment, was the instrument used. Descriptive statistics techniques were used, such as frequency distributions, central tendency and dispersion measurements (median and interquartile intervals), and odds ratios. Results. There were greater delays in seeking health services for those in the age group 60 years and older, for females, for patients with low levels of education, and for patients with poor knowledge of the disease. Clinical variables (being a new case and HIV infection) and behavioral variables (use of tobacco and alcohol consumption) were not linked with delays in diagnosis. The median time delays before diagnosis attributable to patients and to the health services were 30 days and 10 days, respectively. Emergency 24-hour medical services and primary health care services were not effective in identifying suspicious cases of tuberculosis and requesting tests to confirm the diagnosis, with a high percentage of referrals to the Tuberculosis Control Program clinic. Conclusions. Going to primary health care services for diagnosis increased the time before diagnosis of the disease was reached. The Tuberculosis Control Program clinic was more effective in diagnosis of tuberculosis, due to the training of the staff and to an organized process for receiving patients, including the availability of tests to support the diagnosis.

Exploration of the parameter space in an agent-based model of tuberculosis spread: emergence of drug resistance in developing vs developed countries

In this work we present an agent-based model for the spread of tuberculosis where the individuals can be infected with either drug-susceptible or drug-resistant strains and can also receive a treatment. The dynamics of the model and the role of each one of the parameters are explained. The whole set of parameters is explored to check their importance in the numerical simulation results. The model captures the beneficial impact of the adequate treatment on the prevalence of tuberculosis. Nevertheless, depending on the treatment parameters range, it also captures the emergence of drug resistance. Drug resistance emergence is particularly likely to occur for parameter values corresponding to less efficacious treatment, as usually found in developing countries.

Protection conferred by heterologous vaccination against tuberculosis is dependent on the ratio of CD4(+)/CD4(+) Foxp3(+) cells

CD4(+) Foxp3(+) regulatory T cells inhibit the production of interferon-?, which is the major mediator of protection against Mycobacterium tuberculosis infection. In this study, we evaluated whether the protection conferred by three different vaccines against tuberculosis was associated with the number of spleen and lung regulatory T cells. We observed that after homologous immunization with the 65 000 molecular weight heat-shock protein (hsp 65) DNA vaccine, there was a significantly higher number of spleen CD4(+) Foxp3(+) cells compared with non-immunized mice. Heterologous immunization using bacillus Calmette Guerin (BCG) to prime and DNA-hsp 65 to boost (BCG/DNA-hsp 65) or BCG to prime and culture filtrate proteins (CFP)-CpG to boost (BCG/CFP-CpG) induced a significantly higher ratio of spleen CD4(+)/CD4(+) Foxp3(+) cells compared with non-immunized mice. In addition, the protection conferred by either the BCG/DNA-hsp 65 or the BCG/CFP-CpG vaccines was significant compared with the DNA-hsp 65 vaccine. Despite the higher ratio of spleen CD4(+)/CD4(+) Foxp3(+) cells found in BCG/DNA-hsp 65-immunized or BCG/CFP-CpG-immunized mice, the lungs of both groups of mice were better preserved than those of DNA-hsp 65-immunized mice. These results confirm the protective efficacy of BCG/DNA-hsp 65 and BCG/CFP-CpG heterologous prime-boost vaccines and the DNA-hsp 65 homologous vaccine. Additionally, the prime-boost regimens assayed here represent a promising strategy for the development of new vaccines to protect against tuberculosis because they probably induce a proper ratio of CD4(+) and regulatory (CD4(+) Foxp3(+)) cells during the immunization regimen. In this study, this ratio was associated with a reduced number of regulatory cells and no injury to the lungs.

Bronchoscopy for the diagnosis of pulmonary tuberculosis in patients with negative sputum smear microscopy results

Objective: To evaluate the diagnostic accuracy of bronchoscopy in patients with clinical or radiological suspicion of tuberculosis who were unable to produce sputum or with negative sputum smear microscopy results. Methods: A prospective cross-sectional study involving 286 patients under clinical or radiological suspicion of having pulmonary tuberculosis and submitted to bronchoscopy-BAL and transbronchial biopsy (TBB). The BAL specimens were submitted to direct testing and culture for AFB and fungi, whereas the TBB specimens were submitted to histopathological examination. Results: Of the 286 patients studied, 225 (79%) were diagnosed on the basis of bronchoscopic findings, as follows: pulmonary tuberculosis, in 127 (44%); nonspecific chronic inflammation, in 51 (18%); pneumocystis, fungal infections, or nocardiosis, in 20 (7%); bronchiolitis obliterans organizing pneumonia, alveolites, or pneumoconiosis, in 14 (5%); lung or metastatic neoplasms, in 7 (2%); and nontuberculous mycobacterium infections, in 6 (2%). For the diagnosis of tuberculosis, BAL showed a sensitivity and a specificity of 60% and 100%, respectively. Adding the TBB findings significantly increased this sensitivity (to 84%), as did adding the post-bronchoscopy sputum smear microscopy results (total sensitivity, 94%). Minor post-procedure complications occurred in 5.6% of the cases. Conclusions: Bronchoscopy is a reliable method for the diagnosis of pulmonary tuberculosis, with low complication rates. The combination of TBB and BAL increases the sensitivity of the method and facilitates the differential diagnosis with other diseases.

Audiometric evaluation of patients treated for pulmonary tuberculosis

Objective: To evaluate the hearing status of patients being treated for pulmonary tuberculosis at referral hospitals in Brazil. Methods: This was a descriptive study involving 97 male and female inpatients/outpatients between 18 and 60 years of age who were undergoing treatment for active pulmonary tuberculosis at one of two referral hospitals in the state of Rio de Janeiro. After being interviewed, all of the patients underwent pure tone audiometry. Results: OF the 97 patients studied, 65 (67%) were male, 52 (54%) were receiving first-line treatment, and 45 (46%) were receiving second-line treatment, which included aminoglycosides. Smoking, alcohol consumption, exposure to noise, and ototoxic medication use were identified in 65 (67%), 51 (53%), 53 (55%), and 45 (46.4%) of the patients, respectively. The most common auditory and vestibular complaints were dizziness, in 28 patients (28.8%); tinnitus, in 27 (27.8%); and hypoacusis, in 23 (23.7%). Conclusions: Due to the great number of patients with hearing loss in the present study, we recommend that all patients under tuberculosis treatment be submitted to auditory monitoring.

Access to healthcare services for tuberculosis: analysis of patient satisfaction

Tuberculosis remains a pubic health challenge. Uncountable efforts are made to control the disease, and patient treatment and accessibility to healthcare can hinder reaching a cure. The objective of this article is to analyze the satisfaction of tuberculosis patients regarding tuberculosis control services. This is an epidemiological, prospective study, using both a quantitative and qualitative approach. Data were collected using a semi-structured questionnaire. Participants included 77 patients. The quantitative data were positively evaluated, and the qualitative data permitted an understanding of the patients' experience regarding their accessibility and treatment. Aspects such as the criteria for performing Directly Observed Treatment and the proximity of the healthcare facility to the patients' residence affected their satisfaction, which implies the need to reorganize healthcare services in order to provide more appropriate care to tuberculosis patients.

Synthesis, Biological Evaluation, And Molecular Modeling of Chalcone Derivatives As Potent Inhibitors of Mycobacterium tuberculosis Protein Tyrosine Phosphatases (PtpA and PtpB)

Tuberculosis (TB) is a major infectious disease caused by Mycobacterium tuberculosis (Mtb). According to the World Health Organization (WHO), about 1.8 million people die from TB and 10 million new cases are recorded each year. Recently, a new series of naphthylchalcones has been identified as inhibitors of Mtb protein tyrosine phosphatases (PTPs). In this work, 100 chalcones were designed, synthesized, and investigated for their inhibitory properties against MtbPtps. Structure-activity relationships (SAR) were developed, leading to the discovery of new potent inhibitors with IC50 values in the low-micromolar range. Kinetic studies revealed competitive inhibition and high selectivity toward the Mtb enzymes. Molecular modeling investigations were carried out with the aim of revealing the most relevant structural requirements underlying the binding affinity and selectivity of this series of inhibitors as potential anti-TB drugs.

Infliximab partially impairs the anti-Mycobacterium tuberculosis immune responses of severe psoriasis patients with positive tuberculin skin-test

Background Infliximab and etarnecept are now widely used for treating severe psoriasis. However, these drugs, especially infliximab, increased the risk of tuberculosis reactivation. Surprisingly, epidemiological data suggest that the tuberculosis rate in patients taking infliximab in Sao Paulo State, Brazil, is similar to that of some developed, non-endemic countries. Objective The aim of this study was to better understand the effect of infliximab on Mycobacterium tuberculosis (Mtb) immune responses of psoriasis patients in an endemic setting (Brazil). Methods We evaluated the tuberculosis-specific immune responses of severe psoriasis patients and healthy individuals, both tuberculin skin test (TST) positive, in the presence/absence of infliximab. Patients had untreated severe psoriasis, no co-morbidities affecting the immune responses and a TST >10 mm. Healthy TST+ (>10 mm) individuals were evaluated in parallel. PBMC cultures from both groups were stimulated with different Mycobacterium tuberculosis (Mtb) antigens (ESAT-6, 85B and Mtb lysate) and phytohemagglutinin, with or without infliximab (5 mu g/mL). Parameters evaluated were TNF-alpha, IFN-gamma and IL-10 secretion by ELISA, overnight IFN-gamma ELISpot and lymphocyte proliferative response (LPR). Results Infliximab almost abolished TNF-alpha detection in PBMC supernatants of both groups. It also significantly reduced the LPR to phytohemagglutinin and the Mtb antigens as well as the IFN-gamma levels secreted into day 5 supernatants in both groups. There was no concomitant exaggerated IL-10 secretion that could account for the decreases in these responses. ELISpot showed that, contrasting with the central-memory responses above, infliximab did not affect effector-memory INF-gamma-releasing T-cell numbers. Conclusions Infliximab affected some, but not all aspects of the in vitro antituberculosis immune responses tested. The preserved effector-memory responses, putatively related to exposure to environmental mycobacteria, may help to explain the lower than expected susceptibility to tuberculosis reactivation in our setting. Received: 29 December 2010; Accepted: 9 March 2011

1,3-Azoles from ortho-naphthoquinones: Synthesis of aryl substituted imidazoles and oxazoles and their potent activity against Mycobacterium tuberculosis

Twenty-three naphthoimidazoles and six naphthoxazoles were synthesised and evaluated against susceptible and rifampicin- and isoniazid-resistant strains of Mycobacterium tuberculosis. Among all the compounds evaluated, fourteen presented MIC values in the range of 0.78 to 6.25 mu g/mL against susceptible and resistant strains of M. tuberculosis, Five structures were solved by X-ray crystallographic analysis. These substances are promising antimycobacterial prototypes. (C) 2012 Elsevier Ltd. All rights reserved.

Predicting smear negative pulmonary tuberculosis with classification trees and logistic regression: a cross-sectional study

Abstract Background Smear negative pulmonary tuberculosis (SNPT) accounts for 30% of pulmonary tuberculosis cases reported yearly in Brazil. This study aimed to develop a prediction model for SNPT for outpatients in areas with scarce resources. Methods The study enrolled 551 patients with clinical-radiological suspicion of SNPT, in Rio de Janeiro, Brazil. The original data was divided into two equivalent samples for generation and validation of the prediction models. Symptoms, physical signs and chest X-rays were used for constructing logistic regression and classification and regression tree models. From the logistic regression, we generated a clinical and radiological prediction score. The area under the receiver operator characteristic curve, sensitivity, and specificity were used to evaluate the model's performance in both generation and validation samples. Results It was possible to generate predictive models for SNPT with sensitivity ranging from 64% to 71% and specificity ranging from 58% to 76%. Conclusion The results suggest that those models might be useful as screening tools for estimating the risk of SNPT, optimizing the utilization of more expensive tests, and avoiding costs of unnecessary anti-tuberculosis treatment. Those models might be cost-effective tools in a health care network with hierarchical distribution of scarce resources.

PCR colorimetric dot-blot assay and clinical pretest probability for diagnosis of Pulmonary Tuberculosis in Smear-Negative patients

Abstract Background Smear-negative pulmonary tuberculosis (SNPTB) accounts for 30% of Pulmonary Tuberculosis (PTB) cases reported annually in developing nations. Polymerase chain reaction (PCR) may provide an alternative for the rapid detection of Mycobacterium tuberculosis (MTB); however little data are available regarding the clinical utility of PCR in SNPTB, in a setting with a high burden of TB/HIV co-infection. Methods To evaluate the performance of the PCR dot-blot in parallel with pretest probability (Clinical Suspicion) in patients suspected of having SNPTB, a prospective study of 213 individuals with clinical and radiological suspicion of SNPTB was carried out from May 2003 to May 2004, in a TB/HIV reference hospital. Respiratory specialists estimated the pretest probability of active disease into high, intermediate, low categories. Expectorated sputum was examined by direct microscopy (Ziehl-Neelsen staining), culture (Lowenstein Jensen) and PCR dot-blot. Gold standard was based on culture positivity combined with the clinical definition of PTB. Results In smear-negative and HIV subjects, active PTB was diagnosed in 28.4% (43/151) and 42.2% (19/45), respectively. In the high, intermediate and low pretest probability categories active PTB was diagnosed in 67.4% (31/46), 24% (6/25), 7.5% (6/80), respectively. PCR had sensitivity of 65% (CI 95%: 50%–78%) and specificity of 83% (CI 95%: 75%–89%). There was no difference in the sensitivity of PCR in relation to HIV status. PCR sensitivity and specificity among non-previously TB treated and those treated in the past were, respectively: 69%, 43%, 85% and 80%. The high pretest probability, when used as a diagnostic test, had sensitivity of 72% (CI 95%:57%–84%) and specificity of 86% (CI 95%:78%–92%). Using the PCR dot-blot in parallel with high pretest probability as a diagnostic test, sensitivity, specificity, positive and negative predictive values were: 90%, 71%, 75%, and 88%, respectively. Among non-previously TB treated and HIV subjects, this approach had sensitivity, specificity, positive and negative predictive values of 91%, 79%, 81%, 90%, and 90%, 65%, 72%, 88%, respectively. Conclusion PCR dot-blot associated with a high clinical suspicion may provide an important contribution to the diagnosis of SNPTB mainly in patients that have not been previously treated attended at a TB/HIV reference hospital.