|Publication Type||Journal Article|
|Year of Publication||2021|
|Authors||Gillette, MA, Mani, DR, Uschnig, C, Pellé, KG, Madrid, L, Acácio, S, Lanaspa, M, Alonso, P, Valim, C, Carr, SA, Schaffner, SF, MacInnis, B, Milner, DA, Bassat, Q, Wirth, DF|
|Journal||Clin Infect Dis|
|Date Published||2021 Feb 03|
BACKGROUND: Differential etiologies of pediatric acute febrile respiratory illness pose challenges for all populations globally but especially in malaria-endemic settings because the pathogens responsible overlap in clinical presentation and frequently occur together. Rapid identification of bacterial pneumonia with high quality diagnostic tools would enable appropriate, point of care antibiotic treatment. Current diagnostics are insufficient, and the discovery and development of new tools is needed. We report a unique biomarker signature identified in blood samples to accomplish this.
METHODS: Blood samples from 195 pediatric Mozambican patients with clinical pneumonia were analyzed with an aptamer-based, high dynamic range, quantitative assay (~1200 proteins). We identified new biomarkers using a training set of samples from patients with established bacterial, viral, or malarial pneumonia. Proteins with significantly variable abundance across etiologies (FDR<0.01) formed the basis for predictive diagnostic models derived from machine learning techniques (Random Forest, Elastic Net). Validation on a dedicated test set of samples was performed.
RESULTS: Significantly different abundances between bacterial and viral infections (219 proteins) and bacterial infections and mixed (viral and malaria) infections (151 proteins) were found. Predictive models achieved >90% sensitivity and >80% specificity, regardless of number of pathogen classes. Bacterial pneumonia was strongly associated with neutrophil markers, in particular degranulation including HP, LCN2, LTF, MPO, MMP8, PGLYRP1, RETN, SERPINA1, S100A9, and SLPI.
CONCLUSION: Blood protein signatures highly associated with neutrophil biology reliably differentiated bacterial pneumonia from other causes. With appropriate technology, these markers could provide the basis for a rapid diagnostic for field-based triage for antibiotic treatment of pediatric pneumonia.
|Alternate Journal||Clin Infect Dis|