Abstract
Lack of biomarkers for treatment monitoring is listed among the main requirements for next generation assays, as identified globally among tuberculosis (TB) researchers. In this study, we evaluated in a low TB endemic country such as Italy, the effect of preventive therapy on the results obtained in the QuantiFERON TB Plus (QFT-Plus), in a cohort of subjects with latent TB infection (LTBI) and active TB. We found that TB therapy significantly decreased IFN-γ values and number of responders to TB1- and TB2- peptides stimulation in both LTBI and active TB patients. Stratifying LTBI subjects according to the type of preventive TB therapy used, we found that INH treatment but not INH and RIF significantly decreased IFN-γ production. Stratifying the active TB patients according the microbiological status, we found that TB therapy significantly decreased IFN-γ response to antigen present in QFT-Plus test in patients with clinical diagnosis compared to those with a microbiological diagnosis. In conclusions, we demonstrated that TB therapy decreases IFN-γ level in response to antigen present in QFT-Plus test in LTBI and active TB patients. Future studies are needed to better characterize Mtb-specifc response as a potential marker for monitoring TB therapy and preventive treatment effects.
Highlights
Tuberculosis (TB) has been responsible for 10.4 million cases and 1.7 million deaths in 2017, representing one of the major public health problem[1]
In latent TB infection (LTBI) we found that the median of TB1 response (4.6 IU/mL, interquartile ranges (IQRs): 1.3–10) at baseline was significantly higher than that observed at the end of preventive therapy (2.1 IU/mL, IQR: 0.7–6.4) (p = 0.0004)
To further analyze the QFT-Plus results of subjects scored negative at the end of treatment, we showed the IFN-γ values expressed as IU/mL of LTBI subjects (Table 2) and active TB patients (Table 3)
Summary
Tuberculosis (TB) has been responsible for 10.4 million cases and 1.7 million deaths in 2017, representing one of the major public health problem[1]. In case of extra-pulmonary TB, being impossible to detect M. tuberculosis (Mtb) in a “relative easy to take” sample as sputum[6], it is not possible to correlate the sputum result to the clinical outcome. It is even more difficult in LTBI subjects, in which is not possible to isolate Mtb despite its presence. On the base of these evidences, aim of this study is to evaluate the effect of treatment on QFT-Plus response of patients with different stages of Mtb infection, followed overtime during treatment for active TB or LTBI
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