Functional impact of sequelae in drug-susceptible and multidrug-resistant tuberculosis.

BACKGROUND: Evidence on the impact of tuberculosis (TB) treatment on lung function is scarce. The aim of this study was to evaluate post-treatment sequelae in drug-susceptible and drug-resistant-TB (DR-TB) cases in Mexico and Italy.METHODS: At the end of TB treatment the patients underwent complete clinical assessment, functional evaluation of respiratory mechanics, gas exchange and a 6-minute walking test. Treatment regimens (and definitions) recommended by the World Health Organization were used throughout.RESULTS: Of 61 patients, 65.6% had functional impairment, with obstruction in 24/61 patients (39.4%), and 78% with no bronchodilator response. These effects were more prevalent among DR-TB cases (forced expiratory volume in 1 s/forced vital capacity [FEV1/FVC] < lower limit of normality, 14/24 vs. 10/34; P = 0.075). DR-TB patients showed moderately severe (FEV1 < 60%) and severe obstruction (FEV1 < 50%) (P = 0.008). Pre- and post-bronchodilator FEV1 and FEV1/FVC (% of predicted) were significantly lower among DR-TB cases. Plethysmography abnormalities (restriction, hyperinflation and/or air trapping) were more frequent among DR-TB cases (P = 0.001), along with abnormal carbon monoxide diffusing capacity (DLCO) (P = 0.003).CONCLUSION: The majority of TB patients suffer the consequences of post-treatment sequelae (of differing levels), which compromise quality of life, exercise tolerance and long-term prognosis. It is therefore important that lung function is comprehensively evaluated post-treatment to identify patient needs for future medication and pulmonary rehabilitation.

Team approach to manage difficult-to-treat TB cases: Experiences in Europe and beyond.

As recommended by the World Health Organization (WHO), optimal management of MDR-TB cases can be ensured by a multi-speciality consultation body known as 'TB Consilium'. This body usually includes different medical specialities, competences and perspectives (e.g., clinical expertise both for adults and children; surgical, radiological and public health expertise; psychological background and nursing experience, among others), thus lowering the risk of making mistakes - or managing the patients inappropriately, in order to improve their clinical outcomes. At present, several high MDR-TB burden countries in the different WHO regions (and beyond) have introduced TB Consilium-like bodies at the national or subnational level to reach consensus on the best treatment approach for their patients affected by TB. In addition, in countries/settings where a formal system of consultation does not exist, specialized staff from MDR-TB reference centres or international organizations usually spend a considerable amount of their working time responding to phone or e-mail clinical queries on how to manage M/XDR-TB cases. The aim of this manuscript is to describe the different experiences with the TB Consilia both at the international level (European Respiratory Society - ERS/WHO TB Consilium) and in some of the countries where this experience operates successfully in Europe and beyond. The Consilium experiences are described around the following topics: (1) history, aims and focus; (2) management and funding; (3) technical functioning and structure; (4) results achieved. In addition a comparative analysis of the TB Consilia in the different countries has been performed.

Novel role for IL-22 in protection during chronic Mycobacterium tuberculosis HN878 infection.

Approximately 2 billion people are infected with Mycobacterium tuberculosis (Mtb), resulting in 1.4 million deaths every year. Among Mtb-infected individuals, clinical isolates belonging to the W-Beijing lineage are increasingly prevalent, associated with drug resistance, and cause severe disease immunopathology in animal models. Therefore, it is exceedingly important to identify the immune mechanisms that mediate protection against rapidly emerging Mtb strains, such as W-Beijing lineage. IL-22 is a member of the IL-10 family of cytokines with both protective and pathological functions at mucosal surfaces. Thus far, collective data show that IL-22 deficient mice are not more susceptible to aerosolized infection with less virulent Mtb strains. Thus, in this study we addressed the functional role for the IL-22 pathway in immunity to emerging Mtb isolates, using W-Beijing lineage member, Mtb HN878 as a prototype. We show that Mtb HN878 stimulates IL-22 production in TLR2 dependent manner and IL-22 mediates protective immunity during chronic stages of Mtb HN878 infection in mice. Interestingly, IL-22-dependent pathways in both epithelial cells and macrophages mediate protective mechanisms for Mtb HN878 control. Thus, our results project a new protective role for IL-22 in emerging Mtb infections.

Comparison of bacteriological conversion and treatment outcomes among MDR-TB patients with and without diabetes in Mexico: Preliminary data.

Diabetes mellitus (DM) is a well-known risk factor for tuberculosis (TB). However, it is not known to what extent DM affects the outcome in patients with multidrug-resistant (MDR-TB) and extensively drug-resistant TB (XDR-TB) treated with second-line anti-TB drugs. The objective of this study was to compare the microbiological evolution (sputum smear and culture conversion) and final outcomes of MDR/XDR-TB patients with and without DM, managed at the national TB reference centre in Mexico City. RESULTS: Ninety patients were enrolled between 2010 and 2015: 73 with MDR-TB (81.1%), 11 with pre-XDR-TB (e.g. MDR-TB with additional resistance to one injectable drug or a fluoroquinolone, 12.2%) and 6 (6.7%) with XDR-TB. Out of these, 49 (54.4%) had DM and 42 (86%) were undergoing insulin treatment. No statistically significant differences were found in treatment outcomes comparing DM vs. non-DM MDR-TB cases: 18/32 (56.3%) of DM cases and 19/24 (79.2%) non DM patients achieved treatment success (p=0.07). The time to sputum smear and culture conversion was longer (although not statistically) in patients without DM, as follows: the mean (±SD) time to sputum smear conversion was 53.9 (±31.4) days in DM patients and 65.2 (±34.8) days in non-DM ones (p=0.15), while the time to culture conversion was 66.2 (±27.6) days for DM and 81.4 (±37.7) days for non-DM MDR-TB cases (p=0.06). CONCLUSIONS: The study results support the Mexican National TB programme to strengthen its collaboration with the DM programme, as an entry point for TB (and latent TB infection) screening and management.

Atypical radiological images of pulmonary tuberculosis in 192 diabetic patients: a comparative study.

SETTING: Comparative studies of pulmonary tuberculosis images in diabetics have yielded conflicting results. OBJECTIVE: To assess radiological images of pulmonary tuberculosis in a large population of diabetic patients. DESIGN: Radiographs from in-patients admitted with pulmonary tuberculosis and diabetes (TBDM group, n = 192) were reviewed and compared with a control group of patients with pulmonary tuberculosis alone (TB group, n = 130). RESULTS: Both groups had a similar evolution time of tuberculosis (approximately 2 years). Statistical differences were observed as follows: TBDM patients were older (51.3+/-0.9 vs. TB group 44.9+/-1.8 years, mean +/- SEM), and had a decreased frequency of upper (17% vs. 56%), and an increased frequency of lower (19% vs. 7%) and upper + lower (64% vs. 36%) lung field lesions. More TBDM patients developed cavitations (82% vs. 59%) more often in the lower lung fields (29% vs. 3%). More multiple cavities were seen in TBDM patients (25% vs. 2%). TBDM group had a lower total leukocyte count (8836.7+/-219.5 vs. 10013.1+/-345.2 cells/mm3), mainly due to a lower number of non-lymphocyte cells (6815.8+/-221.8 vs. 8095.7+/-321.9 cells/mm3). Multiple logistic regression showed that being a diabetic patient was the most important factor determining lower lung field lesions and cavities. CONCLUSIONS: This study in a large number of diabetics with pulmonary tuberculosis confirmed that their chest X-ray images significantly depart from the typical presentation. Clinicians must keep this in mind to avoid misdiagnosis.

Diagnostic methods of primary tuberculous pleural effusion in a region with high prevalence of tuberculosis. A study in Mexican population.

STUDY OBJECTIVES: 1) To determine the age distribution of the patients with pleural tuberculosis in a region with high prevalence of tuberculosis; and 2) to evaluate the efficiency of the methods used in its diagnosis. SETTING: The National Institute of Respiratory Diseases in Mexico City, a tertiary reference center for pulmonary diseases. DESIGN: A retrospective study. PATIENTS: 452 consecutive inpatients with diagnosis of pleural effusion from January 1991 to September 1996 were reviewed: 133 patients had a diagnosis of tuberculous pleural effusion of primary origin without parenchymal abnormalities by chest roetgenogram. The others were excluded because of reactivated tuberculosis or non-tuberculous effusion. MEASUREMENTS AND RESULTS: The patients had a mean age of 42 +/- 17 years (98 male, 35 female). Pleural granulomas in the morphological study were found in 87% whereas the baciloscopy and the culture of the fluid were positive in only 8% and 19% respectively. The determination of adenosine deaminase (ADA) gave a diagnostic yield of 84%. CONCLUSIONS: 1) Primary tuberculosis pleural effusion, reported in the English literature, was also present in our adults; 2) the pleural biopsy continued to be the most effective method in the diagnosis of the pathology; and 3) the determination of ADA in an area with high prevalence of the disease was a reliable and unexpensive diagnostic method.

PIP: It is often difficult to diagnose tuberculosis (TB) pleural effusion because the search for Mycobacterium tuberculosis in fluid, or the identification of historical alterations in the pleural biopsy are often false negative. The diagnosis, however, must be timely since 43-65% of patients may develop an active pulmonary TB in the next 3-5 years. To determine the age distribution of patients with pleural TB, the authors reviewed the charts of 452 consecutive inpatients from January 1991 to September 1996 hospitalized at Mexico's National Institute of Respiratory Diseases with a diagnosis of the condition. 133 patients were diagnosed with TB pleural effusion of primary origin without parenchymal abnormalities according to chest roentgenogram. These 98 men and 35 women were of mean age 42 years. Pleural granulomas were identified in 87% of subjects while fluid baciloscopy and culture were positive in only 8% and 19%, respectively. The determination of adenosine deaminase (ADA) produced a diagnostic yield of 84%. Based upon their findings, the authors stress that primary TB pleural effusion may also be seen in adults, closed pleural biopsy remains the most effective diagnostic method, and ADA level is a cheap diagnostic method in countries with a high prevalence of TB.

[Tuberculosis associated with HIV infection]. / Tuberculosis asociada a infección por el virus VIH.

Tuberculosis and human immunodeficiency virus (HIV) infection are two important linked public health problems in the world of today. Tuberculosis in HIV infected patients is frequently atypical in its clinical and radiological findings and commonly has an extrapulmonary dissemination. Atypical mycobacteriosis have also been reported in patients with HIV infection. We review here all the patients admitted from 1986 to 1991 with definitive diagnosis of tuberculosis and HIV infection at the National Institute of Respiratory Diseases in Mexico City. Out of 220 patients with HIV infection and pulmonary complications, 19 had proven tuberculosis. Their mean age was 34 +/- 8 years and seven were homosexual males. In 16 patients (84%), respiratory symptoms (cough with sputum) and fever were the first manifestations of the HIV infection. Only two patients had the typical cavitary lesions but also coexisting with miliary tuberculosis. The rest had several types of non cavitated pulmonary opacities or other thoracic or pleural alterations. Eleven patients (58%) had, in addition, extrapulmonary tuberculosis. Mycobacterium tuberculosis was cultured in 11 of 12 patients but no atypical mycobacteria were isolated. Only seven of the 19 patients completed at least six months of treatment and two of them relapsed. Three patients died in their first admission; the rest were lost in the follow up. Our results show that the clinical features of tuberculosis associated to HIV infection are similar to those described in other countries.

Adenosine deaminase in the diagnosis of tuberculous pleural effusions. A report of 218 patients and review of the literature.

The activity of adenosine deaminase in the pleural fluid of 218 consecutive patients was studied. According to the etiology of exudative pleural effusions, the patients were divided into the following five groups: (1) tuberculosis; (2) lung cancer; (3) pneumonias; (4) miscellaneous; and (5) idiopathic. Patients with pleural tuberculosis presented significantly higher ADA activity than patients with nontuberculous pleural effusions (p less than 0.0001). The results indicated that in a population with a relatively high prevalence of tuberculosis, the analysis of ADA levels in pleural effusions constitutes a useful marker for the diagnosis which, in addition, can be made quickly and cheaply. Additionally, a comprehensive review of the literature on the role of ADA in the diagnosis of tuberculous pleural effusions is presented.