Abstract
Tuberculosis (TB) epidemiology is changing in Western and Central Europe due to the rise in immigration and refugees fleeing high-TB-burden areas of war and devastation. The change in local demography and the lack of sensitive and specific TB diagnostic and monitoring tools, especially for cases of childhood TB, leads to either missed cases or over-treatment of this group. Here we present a promising new diagnostic approach, the T cell activation marker (TAM)-TB assay, and its performance in a case of extra-pulmonary TB occurring in a 16 year old refugee from Afghanistan. This assay is based on the characterization of 3 activation markers (CD38, HLA-DR, and Ki67) and one maturation marker (CD27) on M. tuberculosis-specific CD4 T cells. It was performed at time-points T0 (10 days), T1 (1 month), T2 (6 months), and T3 (12 months) post-treatment initiation. All markers were able to detect active tuberculosis (aTB) within this patient at T0 and reverted to a healthy/LTBI phenotype at the end of treatment. Tantalizingly, there was a clear trend toward the healthy/LTBI phenotype for the markers at T1 and T2, indicating a potential role in monitoring anti-TB treatment in the future. This assay may therefore contribute to improved TB diagnostic algorithms and TB treatment monitoring, potentially allowing for individualization of TB treatment duration in the future.
Highlights
Childhood TB, in its extra-pulmonary form, is very challenging to diagnose, let alone to monitor treatment response [1, 2]
Culture method, and the PCR technique (GeneXpert Mycobacterium tuberculosis (MTB)/RIF R, Cepheid) both of which involve the detection of MTB in sputum or other clinical samples
Liquid culture methods require weeks for results to be available, and as treatment progresses the production of sputum and detection of live MTB in sputum becomes more difficult [5]
Summary
Childhood TB, in its extra-pulmonary form, is very challenging to diagnose, let alone to monitor treatment response [1, 2]. In addition to the described sampling issues the liquid culture method is a long process, requiring weeks for results to be available, a major limitation of all currently available diagnostic tools is their inability to monitor treatment response. The GeneXpert MTB/RIF R method, though being a very sensitive method is hampered by its inability to differentiate between live and dead bacilli, not allowing for evaluating success of treatment [6] This has led to a presumed overtreatment of a majority of pulmonary TB patients, shown in previous studies reporting that at least 80% of pulmonary TB patients had been cured within 4 month of anti-TB treatment not showing any signs of relapse within the defined study period [7,8,9]. An optimal monitoring tool would be rapid and dynamic to allow in vivo measurement of changes of biomarkers to mirror treatment progress in each individual patient, this opens the avenue toward a personalized medicine approach in TB care— in children and adolescents
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