Paradoxical Reactions in Non Immuno-compromized Patients With Extrapulmonary Tuberculosis (PARATB)

• Risk factors of paradoxical reaction [ Time Frame: at 6 months ] [ Designated as safety issue: No ]
  Risk factors of paradoxical reaction : clinical, radiological immune and genetic factors
  
  

• Incidence and natural history of paradoxical reactions [ Time Frame: during the first 6 months ] [ Designated as safety issue: No ]
  
• Immune description of paradoxical reactions [ Time Frame: during the first 6 months ] [ Designated as safety issue: No ]
  
• Preliminary study of Diagnosis factors of paradoxical reaction [ Time Frame: during the first 6 months ] [ Designated as safety issue: No ]
  

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 100 PR+ sample. Expecting the PR+ incidence in extra-pulmonary tuberculosis to be 25%, we will have to analyze 400 patients. The sample size of 100 PR+ patients and 300 controls will allow detection of the effect of a factor displaying a prevalence of 0.2 in the control population, conferring a relative risk of PR >2, with a 80% power and an alpha risk of 0.0025 (i.e. a global alpha= 0.05, after BONFERRONI correction for 20 tests). In the genetic association study, the additive effect of a causal allele of frequency 0.2 with an Odds ratio >2, will be detected with a 80% power and an alpha risk of 0.001. Foreseeing that 20% of included patients won't be analysable (diagnosis non confirmed, lost to follow-up etc…), we shall eventually include 500 patients at D0.