Temporal Dynamics of Interferon Gamma Responses in Children Evaluated for Tuberculosis

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Abstract
Development of T-cells based-Interferon gamma (IFNγ) assays has offered new possibilities for the diagnosis of latent tuberculosis infection (LTBI) and active disease in adults. Few studies have been performed in children, none in France. With reference to the published data on childhood TB epidemiology in the Paris and Ile de France Region, we considered it important to evaluate the performance of IGRA (QuantiFERON TB Gold In Tube®, QF-TB-IT) in the diagnosis and the follow-up through treatment of LTBI and active TB in a cohort of French children. 131 children were recruited during a prospective and multicentre study (October 2005 and May 2007; Ethical Committee St Louis Hospital, Paris, study number 2005/32). Children were sampled at day 0, 10, 30, 60 (except Healthy Contacts, HC) and 90 for LTBI and HC, and a further day 120, and day 180 for active TB children. Median age was 7.4 years, with 91% of the children BCG vaccinated. LTBI and active TB children undergoing therapy produced significant higher IFNγ values after 10 days of treatment (p = 0.035). In addition, IFNγ values were significantly lower at the end of treatment compared to IFNγ values at day 0, although the number of positive patients was not significantly different between day 0 and end of treatment. By following quantitative IFNγ values in each enrolled child with LTBI or active TB and receiving treatment, we were able to detect an increase in the IFNγ response at day 10 of treatment which might allow the confirmation of a diagnosis. In addition, a decline in IFNγ values during treatment makes it possible for clinicians to monitor the effect of preventive or curative therapy.