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The Role of C-Reactive Protein as a Triage Tool for Pulmonary Tuberculosis in Children
Devan Jaganath1,2,3, Tania F Reza2,3, Peter Wambi4
1Division of Pediatric Infectious Diseases, University of California, San Francisco, San Francisco, California, USA.
Insights
C-reactive protein (CRP) showed low accuracy for triaging childhood pulmonary tuberculosis (TB). This study found CRP levels were insufficient to meet the required sensitivity and specificity for a reliable TB diagnostic tool in children.
Area of Science:
- Pediatric infectious diseases
- Biomarker research
- Global health
Background:
- C-reactive protein (CRP) is a promising triage tool for pulmonary tuberculosis (TB) in HIV-positive adults.
- This study is the first to evaluate CRP's utility for TB triage specifically in children.
Purpose of the Study:
- To assess the accuracy of C-reactive protein (CRP) as a triage tool for identifying pulmonary tuberculosis (TB) in children.
- To determine optimal CRP cut-off points for TB triage in pediatric populations.
Main Methods:
- Prospective enrollment of symptomatic children under 15 years old in Kampala, Uganda.
- Standard TB evaluation and point-of-care CRP measurement.
- Analysis of CRP sensitivity and specificity at 10 mg/L and 5 mg/L cut-offs, and ROC curve generation.
Main Results:
- 332 children were included; median CRP was 3.0 mg/L, higher in confirmed TB cases (9.5 mg/L) vs. unlikely TB (2.9 mg/L).
- At 10 mg/L cut-off: sensitivity 50.0%, specificity 63.3%. At 5 mg/L cut-off: sensitivity 56.5%, specificity 54.0%.
- Area under the ROC curve was 0.59; maximum sensitivity achieved was 66.1% at 46.8% specificity.
Conclusions:
- C-reactive protein (CRP) levels were generally low in children with pulmonary TB.
- CRP did not achieve the target accuracy (≥90% sensitivity, ≥70% specificity) for a reliable TB triage test in this pediatric cohort.
Background:
C-reactive protein (CRP) has shown promise as a triage tool for pulmonary tuberculosis (TB) in adults living with the human immunodeficiency virus. We performed the first assessment of CRP for TB triage in children.
Methods:
Symptomatic children less than 15 years old were prospectively enrolled in Kampala, Uganda. We completed a standard TB evaluation and measured CRP using a point-of-care assay. We determined the sensitivity and specificity of CRP to identify pulmonary TB in children using 10 mg/L and 5 mg/L cut-off points and generated a receiver operating characteristic (ROC) curve to determine alternative cut-offs that could approach the target accuracy for a triage test (≥90% sensitivity and ≥70% specificity).
Results:
We included 332 children (median age 3 years old, interquartile range [IQR]: 1-6). The median CRP level was low at 3.0 mg/L (IQR: 2.5-26.6) but was higher in children with Confirmed TB than in children with Unlikely TB (9.5 mg/L vs. 2.9 mg/L, P-value = .03). At a 10 mg/L cut-off, CRP sensitivity was 50.0% (95% confidence interval [CI], 37.0-63.0) among Confirmed TB cases and specificity was 63.3% (95% CI, 54.7-71.3) among children with Unlikely TB. Sensitivity increased to 56.5% (95% CI, 43.3-69.0) at the 5 mg/L cut-off, but specificity decreased to 54.0% (95% CI, 45.3-62.4). The area under the ROC curve was 0.59 (95% CI, 0.51-0.67), and the highest sensitivity achieved was 66.1% at a specificity of 46.8%.
Conclusions:
CRP levels were low in children with pulmonary TB, and CRP was unable to achieve the accuracy targets for a TB triage test.
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