Paradoxical Reactions in Non Immuno-compromized Patients With Extrapulmonary Tuberculosis

Primary objective :

Search for predictive factors of tuberculous paradoxical reaction (PR), with assessment of clinical, radiological and biological factors.

Secondary objectives :

• Descriptive study of PR : incidence, clinical and radiological presentation, clinical course ; characterization of mycobacteria strains- Search for genetic predictive factors of PR
• Characterization of the specific immune antigene response during PR et analysis of different cell subsets implicated in peripheral blood and locally- Characterization of the anti-bacterial immune response before and after antituberculous treatment
• Preliminary search for new diagnosis criteria including clinical, biological (immune and genetic) and radiological factors.Methodology : Multicentric cohort study for a total of 5 years (4 years of enrolment and one year of follow-up, with biological collection for scientific purpose

Inclusion Status of patients (determined by a validation comity at M6)

• PR+ : PR with clinical symptoms
• rPR : pure radiological PR
• PR- : absence of RP after 6 months of treatment Development of the study

Primary outcome :

• Association between PR+ occurrence and clinical, biological and radiological factors harvested at the diagnosis of tuberculosis..

Secondary outcomes :

• Association between PR+ and rPR
• occurrence and the above quoted factors.- Descriptive study : clinical, biological, and radiological presentation of PR+ and rPR, characterization of isolated BK strains in PR+ patients
• Immunological study in 20 PR+ patients and 20 RP- : 20 patients per group will allow a 80% power to detect, by means of bilateral Mann-Whitney test with alpha=5%, any difference in the count of specific cells corresponding to at least one standard deviation of the primary immunological outcome
• controls: variation between tuberculosis diagnostic and either PR time or M2 (in absence of PR), of the specific cells, macrophages, dendritic cells, gamma-delta lymphocytes, NK et CD4 cells counts
• Preliminary search for diagnostic criteria that can be used at the time of PR occurrence: variation between D0 and the PR of clinical, biological, radiological immunological et genomic of PR+ patients.
• Evolution specific and non specific immune response of mycobacterial antigen at tuberculosis diagnosis during tuberculosis treatment and after. Sample size calculation
• prognostic study : Patients will be recruited and followed until the achievement of a 20 PR+ sample. The investigators will have to analyze 200 patients.

Inclusion criteria

• Extrapulmonary tuberculosis, with associated pulmonary localization or not
• Treatment started less than 5 days ago
• Negative HIV serology
• Social insurance
• Age >= 18- Foreseeable follow-up of at last one year
• Signed Free Inform Consent

Exclusion criteria

• HIV infection
• immuno-suppressive treatment (including corticosteroids > 10 mg /d prednisone equivalent, however patients with corticotherapy could be included during the phase 2 of the study)
• central neurological system tuberculosis and tuberculous pericarditis - pure pulmonary tuberculosis
• multiresistant tuberculosis
• pregnancy or breast feeding