Paradoxical Reactions in Non Immuno-compromized Patients With Extrapulmonary Tuberculosis

Summary

Tuberculous paradoxical reactions (PR) are immune reactions occurring during the course of antituberculous treatment and leading to a worsening of tuberculous symptoms after an initial improvement. This phenomenon has very extensively studied in HIV infected patients where it corresponds to the so called IRIS (immune reconstitution syndrome). However, it laso occurs in non immuno-compromized patients, especially those with extra-pulmonary localization of tuberculosis. The aim of the study is to look for risk factors of paradoxical reaction in non immuno-compromized patients with extra-pulmonary tuberculosis. The investigators will consider clinical, radiological and biological variables, including specific immune and genetic markers. Our secondary goals are to estimate the incidence of PR, describe their natural history; characterize the type of immune response they correspond to, and look for better diagnostic tools.The immunological characterization and the finding of predictive factors of PR, especially the genetic ones will allow a better understanding of biological mechanisms that lead to their occurrence during extra-pulmonary tuberculosis treatment. The establishment of predictive criteria could permit a better surveillance of at risk patients for a rapid treatment, or even a prevention of PR. The establishment of new diagnostic criteria at the time of PR could avoid numerous invasive diagnostic procedures, surgery and/or useless prolongation of antibiotic treatment.

Conditions

• Extrapulmonary Tuberculosis

Interventions

GENETIC

Genetic analysis

1. identification of candidates genes by a differential analysis of the whole transcriptome of the peripheral leucocytes of 20 PR+ patients and 20 RP- controls, at D0, D15, M2,; 2. Genetic association analysis: comparison of allelic distributions of SNPs (diallelic markers) within the candidate genes, between PR+ and PR- patients, in the whole cohort. One supplementary ACD tube of 5 ml à D0, D15, M2, PR+, for RNA extraction.

RADIATION

Body scan (CERVICO THORACO ABDOMINAL) + Cranian IRM

at day 0, Month 2, paradoxical reaction, end of treatment, read by an independent radiologist

OTHER

Immunologic analysis

For patients included until 20 PR+ : blood puncture of 4 ACD tubes of 10 ml, 1 EDTA tube of 7,5 ml et 1 heparinate lithium tube of 7,5ml at D0, D15, M2, and M6 and at the time of an potential RP+

OTHER

QuantiferonTB Gold test

at M0, M2, M6 and in case of PR+.

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris

  lead OTHER

Principal Investigators

• Anne BOURGARIT, MD, PhD · Assistance Publique - Hôpitaux de Paris

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2011-03-14

Primary Completion

2018-02-21

Completion

2018-02-21

Countries

• France

Study Locations