<p>Non-sputum-based tests are urgently needed for rapid tuberculosis (TB) diagnosis. While the World Health Organization (WHO) recommends C-reactive protein (CRP) in serum as a TB screening tool for people living with HIV, it falls short of meeting the minimum target product profile (TPP) criteria for a triage test. We hypothesized that combining CRP with Myeloperoxidase (MPO) as a two-protein signature, would diagnose TB with improved accuracy. Using the Meso Scale Discovery platform, we measured CRP and MPO levels in 109 serum samples from adults presenting with TB-like symptoms at primary healthcare centres in South Africa, Uganda, and The Gambia. Diagnoses were based on clinical, laboratory, and radiological findings. Receiver Operator Characteristic (ROC) curve analysis assessed the biomarkers’ diagnostic accuracy. CRP and MPO levels differed significantly between TB and other respiratory diseases (ORD). Individually, CRP and MPO achieved areas under the ROC curve (AUCs) of 0.90 and 0.66, respectively. Combined, the AUC remained 0.90, but sensitivity and specificity improved to 91.3% and 77.8% after leave-one-out cross-validation. MPO only increased CRP sensitivity by 2.2%. Concurrent measurement of MPO may improve the accuracy of CRP when used together as a TB diagnostic signature. However, the evidence from our study was not strong and our preliminary findings require validation in larger studies.</p>

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Diagnostic accuracy of CRP and myeloperoxidase as a 2-marker biosignature for the diagnosis of symptomatic TB

  • Lesego Rantho,
  • Bih H. Chendi,
  • Megan-Lee Burger,
  • Marika Flinn,
  • Belinda Kriel,
  • Candice I. Synders,
  • Kim Stanley,
  • Shalena Naidoo,
  • Simona John von Freyend,
  • Maynard Meiring,
  • Tejas Shah,
  • Stephanus Malherbe,
  • Martin Kidd,
  • Harriet Mayanja-Kizza,
  • Jayne S. Sutherland,
  • Gerhard Walzl,
  • Adrian Woolfson,
  • Novel N. Chegou

摘要

Non-sputum-based tests are urgently needed for rapid tuberculosis (TB) diagnosis. While the World Health Organization (WHO) recommends C-reactive protein (CRP) in serum as a TB screening tool for people living with HIV, it falls short of meeting the minimum target product profile (TPP) criteria for a triage test. We hypothesized that combining CRP with Myeloperoxidase (MPO) as a two-protein signature, would diagnose TB with improved accuracy. Using the Meso Scale Discovery platform, we measured CRP and MPO levels in 109 serum samples from adults presenting with TB-like symptoms at primary healthcare centres in South Africa, Uganda, and The Gambia. Diagnoses were based on clinical, laboratory, and radiological findings. Receiver Operator Characteristic (ROC) curve analysis assessed the biomarkers’ diagnostic accuracy. CRP and MPO levels differed significantly between TB and other respiratory diseases (ORD). Individually, CRP and MPO achieved areas under the ROC curve (AUCs) of 0.90 and 0.66, respectively. Combined, the AUC remained 0.90, but sensitivity and specificity improved to 91.3% and 77.8% after leave-one-out cross-validation. MPO only increased CRP sensitivity by 2.2%. Concurrent measurement of MPO may improve the accuracy of CRP when used together as a TB diagnostic signature. However, the evidence from our study was not strong and our preliminary findings require validation in larger studies.