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Published on: June 28, 2018
Performance Evaluation of Host Biomarker Combinations for the Diagnosis of Serious Bacterial Infection in Young
Aurélie Portefaix1,2, Sylvie Pons3,4, Antoine Ouziel5
1Clinical Investigation Center (CIC 1407), Hospices Civils de Lyon, 69677 Bron, France.
Insights
Identifying new protein marker combinations can help diagnose serious bacterial infections (SBI) in febrile children. While some combinations showed promise, further optimization is needed for accurate diagnosis in young children.
Area of Science:
- Pediatric Infectious Diseases
- Biomarker Discovery
- Computational Biology
Background:
- Diagnosing serious bacterial infections (SBI) in young febrile children is complex.
- Current diagnostic methods require improvement for accurate differentiation between bacterial and viral infections.
Purpose of the Study:
- To identify novel protein marker combinations for differentiating bacterial from viral infections in young children.
- To evaluate the diagnostic performance of these combinations against established biomarkers like CRP and PCT.
Main Methods:
- Prospective, multicentre observational study involving 983 children (7 days-36 months) with suspected SBI.
- Measurement of seven protein markers (CRP, PCT, IL-6, NGAL, MxA, TRAIL, IP-10) in blood.
- Application of computational modeling with independent training and validation cohorts to assess marker combinations.
Main Results:
- Several protein marker combinations showed potential to outperform CRP and PCT individually.
- No combination met the targeted performance criteria (LR+ ≥ 5.67, LR- ≤ 0.5) in the overall 7-36 month population.
- The CRP/MxA/TRAIL combination demonstrated promising performance in younger infants (7-91 days old) with AUC 0.895, LR+ 10.46, LR- 0.16.
Conclusions:
- Computational modeling of protein marker combinations is a promising approach for SBI diagnosis.
- Further optimization is required to enhance the diagnostic accuracy of these models in young febrile children.
- The CRP/MxA/TRAIL combination shows potential for improved diagnosis in a specific subgroup of very young infants.
Abstract:
The diagnosis of serious bacterial infection (SBI) in young febrile children remains challenging. This prospective, multicentre, observational study aimed to identify new protein marker combinations that can differentiate a bacterial infection from a viral infection in 983 children, aged 7 days-36 months, presenting with a suspected SBI at three French paediatric emergency departments. The blood levels of seven protein markers (CRP, PCT, IL-6, NGAL, MxA, TRAIL, IP-10) were measured at enrolment. The patients received the standard of care, blinded to the biomarker results. An independent adjudication committee assigned a bacterial vs. viral infection diagnosis based on clinical data, blinded to the biomarker results. Computational modelling was applied to the blood levels of the biomarkers using independent training and validation cohorts. Model performances (area under the curve (AUC), positive and negative likelihood ratios (LR+ and LR-)) were calculated and compared to those of the routine biomarkers CRP and PCT. The targeted performance for added value over CRP or PCT was LR+ ≥ 5.67 and LR- ≤ 0.5. Out of 652 analysed patients, several marker combinations outperformed CRP and PCT, although none achieved the targeted performance criteria in the 7 days-36 months population. The models seemed to perform better in younger (7-91 day-old) patients, with the CRP/MxA/TRAIL combination performing best (AUC 0.895, LR+ 10.46, LR- 0.16). Although computational modelling using combinations of bacterial- and viral-induced host-protein markers is promising, further optimisation is necessary to improve SBI diagnosis in young febrile children.
