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Comparison of the performance among three screening tests (skin tuberculin test, PPD; quantiferon-test and ELISPOT) for detection of latent tuberculosis infection (LTBI) in patients with active chronic inflammatory arthritis using TNF alfa blockers

Grant number: 11/02771-9
Support type:Regular Research Grants
Duration: October 01, 2011 - September 30, 2013
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Marcelo de Medeiros Pinheiro
Grantee:Marcelo de Medeiros Pinheiro
Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
Assoc. researchers:Carina Mori Frade Gomes ; Cassia Maria Passarelli Lupoli Barbosa ; Maria Isabel de Moraes Pinto ; Maria Teresa de Sande e Lemos Ramos Ascensão Terreri

Abstract

The World Health Organization estimates that approximately one third of the world population is infected with M. tuberculosis, particularly in Brazil, with annual incidence of 30-50 cases per 100,000 inhabitants. Approximately 3-5% of the population has some type of chronic inflammatory arthropathy (CIA), and 30 to 50% of them will need to use some TNF-blockers to achieve better clinical control of the disease.The TNFa plays a central role in the initial host response against mycobacterial infections, especially in the formation and maintenance of the granuloma, mediated through IFN-gamma and Th1-dependent response. In the presence of anti-TNFa therapy, there is disintegration of the granulomatous structure, causing dissemination of its content, with increased bacillary load. Most active cases of tuberculosis-related to TNFa blockers are associated with reactivation of latent infection.The incidence rate of cases of active TB was significantly reduced after the introduction of guidelines for testing of latent tuberculosis infection (LTBI) before the beginning of the anti-TNFa. Isoniazid is used in those cases with positive evidence for LTBI. However, the great debate now is if a tuberculin test non reactor really mean a negative result and a lower risk of active tuberculosis or whether it represents a state of anergy related to immunosuppression of the disease itself or associated with its treatment. In the latter case, the risk of developing active infection by mycobacteria is a relevant concern and an issue of safety for physicians and patients. According our data, after 60 months of follow up, we found six cases (2.83%) incidents of TB in a total of 212 patients with AIC, exposed to TNF blockers. Importantly, all of them had no history or risk factors for this type of infection, as well as had negative TST and normal chest X-ray.Therefore, new strategies for better identification of LTBI are needed. Currently, there are new tests being used, such as IGRAs (QuantiFERON-TB Gold test/ Gold In-tube test and the T-Spot), which are based on the crucial role of IFNg on the cellular response against specific peptides from M. tuberculosis (ESAT-6 and CFP-10). These proteins are present in all M. tuberculosis and are not found in BCG and most other nontuberculous mycobacteria.A total of 100 patients (70 adults and 30 children and adolescents), from 5 to 60 years old, both sexes, with a diagnosis of rheumatoid arthritis (ACR 1987), psoriatic arthritis (CASPAR, 2006), ankylosing spondylitis (modified New York, 1984) and juvenile idiopathic arthritis (ILAR, 2004), will be enrolled in this study. All of them should have an indication or be using anti-TNF agents for at least 6 months. Demographic, socioeconomic and clinical data will be captured through a specific questionnaire, including details on symptoms related to mycobacterial infection as well as epidemiological,professional and family information. In addition, patients will perform chest X-ray and TST, following current international recommendations, with the inoculation of 0.1 mL (2 UT) of PPD RT-23, intradermally in the middle third of the anterior left forearm, approximately 8 cm below the elbow fold, with readings after 72 hours. Area of induration equal or above than 5 mm is defined as a reactor. In negative cases, the test will be repeated in contralateral forearm, following the same methodology, with until three weeks after the first reading. Booster phenomenon is set if there is greater than 10 mm induration or greater increase than 6mm in comparison with the first one. Almost 8 mL of blood will be collected into two vials of heparin for testing SPOT.TB® and more 3 mL distributed into 3 tubes for testing QuantiFERN-TB Gold-In tube test®. (AU)