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Comparision 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 chronic active inflammatory arthritis using TNF alfa blockers

Grant number: 11/15940-3
Support Opportunities:Scholarships in Brazil - Master
Effective date (Start): April 01, 2012
Effective date (End): March 31, 2014
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal Investigator:Marcelo de Medeiros Pinheiro
Grantee:Carina Mori Frade Gomes
Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil


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), including rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis (PsoA) and juvenile idiopathic arthritis (JIA) and 30 to 50 % of them will need to use anti-TNF therapy at some point, for better control of disease activity.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-³ 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 TNFa blockers are associated with reactivation of latent infection and usually occur in the first six months of use, as well as varies according to the agent used, being lower in patients exposed etanercept compared to users of monoclonal antibodies.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 and includes verification of epidemiologic data, tuberculin skin test (TST) and chest X-ray. 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 tuberculosis 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. Thus, the incidence rate was not low, and to dealing with potentially severe and more frequent treatment resistance. Moreover, the clinical management of this patient was more limited and treatment with glucocorticosteroids, drugs can alter the course of disease and the TNF-blockers were delayed, with the patient complaining of pain and disability.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.

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