Abstract
BackgroundDiagnosing tuberculosis (TB) in children is challenging due to paucibacillary disease, and lack of ability for microbiologic confirmation. Hence, we measured the plasma chemokines as biomarkers for diagnosis of pediatric tuberculosis.MethodsWe conducted a prospective case control study using children with confirmed, unconfirmed and unlikely TB. Multiplex assay was performed to examine the plasma CC and CXC levels of chemokines.ResultsBaseline levels of CCL1, CCL3, CXCL1, CXCL2 and CXCL10 were significantly higher in active TB (confirmed TB and unconfirmed TB) in comparison to unlikely TB children. Receiver operating characteristics curve analysis revealed that CCL1, CXCL1 and CXCL10 could act as biomarkers distinguishing confirmed or unconfirmed TB from unlikely TB with the sensitivity and specificity of more than 80%. In addition, combiROC exhibited more than 90% sensitivity and specificity in distinguishing confirmed and unconfirmed TB from unlikely TB. Finally, classification and regression tree models also offered more than 90% sensitivity and specificity for CCL1 with a cutoff value of 28 pg/ml, which clearly classify active TB from unlikely TB. The levels of CCL1, CXCL1, CXCL2 and CXCL10 exhibited a significant reduction following anti-TB treatment.ConclusionThus, a baseline chemokine signature of CCL1/CXCL1/CXCL10 could serve as an accurate biomarker for the diagnosis of pediatric tuberculosis.
Highlights
Diagnosing tuberculosis (TB) in children is challenging due to paucibacillary disease, and lack of ability for microbiologic confirmation
It has been reported in a few studies that IP-10 detection could be useful for diagnosing active TB and LTBI in children [8] and even in the adult population, IP-10 and MCP-2 [9] can be used as biomarkers for tuberculosis
Plasma levels of chemokines are elevated in children with active TB disease To determine the levels of plasma chemokines in children with active TB disease and with no TB disease, we measured the plasma
Summary
Diagnosing tuberculosis (TB) in children is challenging due to paucibacillary disease, and lack of ability for microbiologic confirmation. Mycobacterium tuberculosis (M.tb) exposed children acquire infection, which is described as immunological evidence of sensitisation to M.tb, and some of these children may develop TB disease with signs and symptoms with microbiological evidence of disease [7] It has been reported in a few studies that IP-10 detection could be useful for diagnosing active TB and LTBI in children [8] and even in the adult population, IP-10 and MCP-2 [9] can be used as biomarkers for tuberculosis. In this proofof-concept study, we aimed to determine the plasma concentrations of CC (CCL1, CCL2, CCL3, CCL4 and CCL11) and CXC (CXCL1 CXCL2, CXCL9, CXCL10 and CXCL11) chemokines as markers capable of discriminating among children who were microbiology positive (confirmed TB) or those negative but clinically diagnosed and treated (unconfirmed TB) compared with unlikely TB children in a prospectively recruited cohort for the study
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