Evaluation of 16s Deoxyribonucleic acid, Procalcitonin, High sensitive C-reactive Protein and Presepsin as early diagnostic markers for Paediatric Sepsis

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AUGUST, 2016.
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Abstract
Sepsis is one of the commonest diseases of the paediatric population with significant morbidity and mortality especially in developing countries. Its diagnosis however, remains a challenge despite the advances in medicine. This study evaluated the individual and combined diagnostic accuracy of 16S deoxyribonucleic acid (16S DNA), procalcitonin (PCT), presepsin (sCD14-ST) and high sensitive C-reactive protein (hs-CRP) in septic Ghanaian paediatrics. A total of 90 paediatrics consisting of 60 cases and 30 controls from the Paediatric Emergency Unit and the Mother and Baby Unit of the Komfo Anokye Teaching Hospital were recruited for the study after ethical approval for the study was obtained. Diagnosis of sepsis was done using blood cultures, 16S DNA, PCT, sCD14-ST and hs-CRP. Evaluation of the biomarkers was done on individual and combinational basis using receiver operating characteristics curve and multiple logistic regression analysis was used to select independent predictors. Bacterial sepsis was diagnosed in 14 patients (23.3%) using blood cultures (BC). Significant elevations in PCT, sCD14-ST and hs-CRP levels were observed among cases in comparison to controls (p<0.0001). PCT showed a better accuracy (AUC=78.7%) followed by hs-CRP (AUC=78.4%) and sCD14-ST (AUC=74.8%) respectively for the individual performances. PCT+hs-CRP had the highest accuracy (AUC =80.1%) followed by hs-CRP+ sCD14-ST (AUC =77.2%), PCT+sCD14-ST+hs-CRP (AUC=77.0%) and PCT+sCD14-ST (AUC=75.9%) when bioscore for the combination of the biomarkers were fitted into logistic regression model. The best significant odd ratios (OR) for the combination was PCT+sCD14-ST+hs-CRP at 15.8 followed by hs-CRP+sCD14-ST at 13.5, hs-CRP+PCT at 13.3 and PCT+sCD14-ST at 11.7. Using BC as a gold standard, the 16S DNA had a high level of sensitivity (85.7%) but was poorly specific (32.6%) in the diagnosis of sepsis. PCT and hs-CRP were significantly higher in 16S DNA diagnosed septic patients than those who tested negative for 16S DNA (p<0.005). Though no statistically significant, we observed increased levels of sCD14-ST in 16S DNA proven sepsis 26.76 (19.14-93.59) than those that were negative for 16S DNA 22.43 (18.74-27.08). Using PCR to diagnose sepsis among paediatrics may not be specific enough to replace microbiologically proven sepsis (blood cultures) but can be performed as an additional test especially for detection of resistant as well as culture unfriendly bacteria strains. This study showed that combined diagnostic performance of hs-CRP+PCT poses a better diagnostic accuracy in the diagnosis of paediatric sepsis. Bioscores combination of the biomarkers were significantly associated with increasing odds of bacterial sepsis. The incorporation of the combination of these three biomarkers into routine diagnostic tests for paediatric sepsis will aid in the prompt diagnosis of paediatric sepsis and will be of immense help in Ghana since all the biomarkers were independent predictors of bacterial sepsis.
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A thesis submitted in fulfillment of the requirements for the Degree of Master of philosophy in the Department of Molecular Medicine, School of Medical Sciences College of Health.
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