IJID regions · 2026
Blood kynurenine pathway metabolites show limited diagnostic utility for tuberculosis among adults living with human immunodeficiency virus and children in Uganda.
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Kasule George W, Nsubuga Joachim, Lutter René, Semugenze Derrick, Vaz Frederic, Kolader Marion, Cobelens Frank, Mwachan Patricia, Sserubiri James, Jamal Youssra, Joloba Moses, García-Basteiro Alberto L, Ssengooba Willy, Hermans Sabine, Stool4TB Global Partnership2
Аннотация
OBJECTIVES: Traditional sputum-based diagnostics often demonstrate suboptimal diagnostic performance in people living with human immunodeficiency virus and children presenting with paucibacillary tuberculosis (TB). This study evaluated the diagnostic accuracy of circulating kynurenine-pathway metabolites against an authentic symptomatic control cohort in Uganda.
METHODS: Tryptophan, kynurenine, and the kynurenine-to-tryptophan ratio were quantified via ultra-performance liquid chromatography-tandem mass spectrometry in 70 adult people living with human immunodeficiency virus and 23 children presenting with presumptive TB.
RESULTS: Median biomarker concentrations demonstrated no statistically significant differences between participants with laboratory-confirmed TB and symptomatic controls. The kynurenine-to-tryptophan ratio yielded an area under the curve of 0.51 (95% confidence interval: 0.34-0.69) in adults and 0.62 (95% confidence interval: 0.36-0.87) in children, indicating limited diagnostic discrimination with substantial uncertainty, particularly in the small pediatric cohort. At the evaluated cutoff points, none of the biomarkers met the minimum sensitivity and specificity requirements defined by the World Health Organization target product profiles for diagnostic and screening tests.
CONCLUSION: Blood kynurenine pathway metabolites demonstrated limited clinical utility as standalone diagnostic biomarkers for active TB in these vulnerable populations. In addition, larger diagnostic performance studies are needed to address the uncertainty associated with the small sample size and to further validate our findings.
METHODS: Tryptophan, kynurenine, and the kynurenine-to-tryptophan ratio were quantified via ultra-performance liquid chromatography-tandem mass spectrometry in 70 adult people living with human immunodeficiency virus and 23 children presenting with presumptive TB.
RESULTS: Median biomarker concentrations demonstrated no statistically significant differences between participants with laboratory-confirmed TB and symptomatic controls. The kynurenine-to-tryptophan ratio yielded an area under the curve of 0.51 (95% confidence interval: 0.34-0.69) in adults and 0.62 (95% confidence interval: 0.36-0.87) in children, indicating limited diagnostic discrimination with substantial uncertainty, particularly in the small pediatric cohort. At the evaluated cutoff points, none of the biomarkers met the minimum sensitivity and specificity requirements defined by the World Health Organization target product profiles for diagnostic and screening tests.
CONCLUSION: Blood kynurenine pathway metabolites demonstrated limited clinical utility as standalone diagnostic biomarkers for active TB in these vulnerable populations. In addition, larger diagnostic performance studies are needed to address the uncertainty associated with the small sample size and to further validate our findings.