Biomarkers for risk of developing active tuberculosis in contacts of TB patients: a prospective cohort study

Abstract

Identifying those Mycobacterium tuberculosis latent-infected individuals most at risk of developing active tuberculosis (TB) using routine clinical and laboratory tests remains a huge challenge in TB control efforts. We conducted a prospective longitudinal study of clinical and laboratory markers associated with the risk of developing active TB in contacts with latent M. tuberculosis infection.HIV-negative household contacts (n=296) of pulmonary TB patients underwent monitoring of clinical features, full blood cell counts, tuberculin skin text (TST) and chest radiography performed regularly during 18 months of follow-up. Paired statistical tests, a Kaplan-Meier analysis and Cox proportional hazard modelling were performed on variables between contacts progressing or not progressing to active TB.The appearance of TB disease symptoms in contacts was significantly associated with an elevated peripheral percentage of blood monocytes (adjusted hazard ratio (aHR) 6.25, 95% CI 1.63-23.95; p<0.01), a ⩾14 mm TST response (aHR 5.72, 95% CI 1.22-26.80; p=0.03) and an increased monocyte:lymphocyte ratio (aHR 4.97, 95% CI 1.3-18.99; p=0.03). Among contacts having TST ⩾14 mm, a strong association with risk of progression to TB was found with an elevated blood monocyte percentage (aHR 8.46, p<0.01).Elevated percentage of peripheral blood monocytes plus an elevated TST response are potential biomarkers for identifying contacts of TB patients at highest risk of developing active TB. @ERSpublications Tuberculin skin tests combined with monocyte count improve evaluation of disease progression risk among TB contacts

An Integrated Workflow To Assess Technical and Biological Variability of Cell Population Frequencies in Human Peripheral Blood by Flow Cytometry

“…We thus provide primary evidence that ex vivo immune signatures in PBMC can discriminate between LTBI and non-TB infected donors, which could potentially be applied as an additional tool to IGRAs for improving the specificity of LTBI diagnosis. Recent studies have also shown differences in whole blood cell counts of infants and adults with various TB status (32, 33). Specifically, a high monocyte/lymphocyte ratio was associated with an increased risk of developing active TB (32, 33).…”

“…Recent studies have also shown differences in whole blood cell counts of infants and adults with various TB status (32, 33). Specifically, a high monocyte/lymphocyte ratio was associated with an increased risk of developing active TB (32, 33). Thus, we predict that combining whole blood counts to our newly defined ex vivo PBMC signature of LTBI will improve its discriminatory power.…”

Can we predict tuberculosis cure? What tools are available?

“…In the 1920s it was shown in a rabbit model that a higher ratio between peripheral blood monocytes and lymphocytes, known as the monocyte/lymphocyte (M/L) ratio, was associated with progressive active TB [137,138]. This finding was confirmed in humans [139,140] and, recently, it was shown that the M/L ratio returned to levels found in healthy donors upon TB cure [141]. This finding may be related to decreased inflammation during effective TB treatment, leading to decreased myelopoiesis in the bone marrow, which is known to be driven by IFN-γ produced during the antimycobacterial response [139,142].…”

First evaluation of QuantiFERON-TB Gold Plus performance in contact screening

“…The use of IFN-γ response to the latency antigen heparin-binding-haemoagglutinin [13,14], immunoprofiling [15,16], gene expression pattern (i.e. interleukin-13 and autoimmune regulator (AIRE)) [17,18] and proportion of peripheral blood monocytes [19] have been studied as possible biomarkers for incipient TB. However, all of these approaches are still confined to research fields and currently have minimal impact on patient management.…”