Bih H Chendi1,2, Candice I Snyders2, Kristian Tonby1,3, Synne Jenum3, Martin Kidd4, Gerhard Walzl2, Novel N Chegou2, Anne M Dyrhol-Riise1,3. 1. Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway. 2. Division of Molecular Biology and Human Genetics, Department of Science and Technology-National Research Foundation (DST-NRF) Centre of Excellence for Biomedical Tuberculosis Research, Faculty of Medicine and Health Sciences, South African Medical Research Council Centre for Tuberculosis Research, Stellenbosch University, Cape Town, South Africa. 3. Department of Infectious Diseases, Oslo University Hospital, Oslo, Norway. 4. Department of Statistics and Actuarial Sciences, Centre for Statistical Consultation, Stellenbosch University, Cape Town, South Africa.
Abstract
Background: Several host inflammatory markers have been proposed as biomarkers for diagnosis and treatment response in Tuberculosis (TB), but few studies compare their utility in different demographic, ethnic, and TB endemic settings. Methods: Fifty-four host biomarkers were evaluated in plasma samples obtained from presumed TB cases recruited at the Oslo University Hospital in Norway, and a health center in Cape Town, South Africa. Based on clinical and laboratory assessments, participants were classified as having TB or other respiratory diseases (ORD). The concentrations of biomarkers were analyzed using the Luminex multiplex platform. Results: Out of 185 study participants from both study sites, 107 (58%) had TB, and 78 (42%) ORD. Multiple host markers showed diagnostic potential in both the Norwegian and South African cohorts, with I-309 as the most accurate single marker irrespective of geographical setting. Although study site-specific biosignatures had high accuracy for TB, a site-independent 5-marker biosignature (G-CSF, C3b/iC3b, procalcitonin, IP-10, PDGF-BB) was identified diagnosing TB with a sensitivity of 72.7% (95% CI, 49.8-82.3) and specificity of 90.5% (95% CI, 69.6-98.8) irrespective of geographical site. Conclusion: A 5-marker host plasma biosignature has diagnostic potential for TB disease irrespective of TB setting and should be further explored in larger cohorts.
Background: Several host inflammatory markers have been proposed as biomarkers for diagnosis and treatment response in Tuberculosis (TB), but few studies compare their utility in different demographic, ethnic, and TB endemic settings. Methods: Fifty-four host biomarkers were evaluated in plasma samples obtained from presumed TB cases recruited at the Oslo University Hospital in Norway, and a health center in Cape Town, South Africa. Based on clinical and laboratory assessments, participants were classified as having TB or other respiratory diseases (ORD). The concentrations of biomarkers were analyzed using the Luminex multiplex platform. Results: Out of 185 study participants from both study sites, 107 (58%) had TB, and 78 (42%) ORD. Multiple host markers showed diagnostic potential in both the Norwegian and South African cohorts, with I-309 as the most accurate single marker irrespective of geographical setting. Although study site-specific biosignatures had high accuracy for TB, a site-independent 5-marker biosignature (G-CSF, C3b/iC3b, procalcitonin, IP-10, PDGF-BB) was identified diagnosing TB with a sensitivity of 72.7% (95% CI, 49.8-82.3) and specificity of 90.5% (95% CI, 69.6-98.8) irrespective of geographical site. Conclusion: A 5-marker host plasma biosignature has diagnostic potential for TB disease irrespective of TB setting and should be further explored in larger cohorts.
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