Biomarkers to Distinguish Bacterial From Viral Pediatric Clinical Pneumonia in a Malaria-Endemic Setting.
Clin Infect Dis
; 73(11): e3939-e3948, 2021 12 06.
Article
em En
| MEDLINE
| ID: mdl-33534888
ABSTRACT
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 (false discovery rate <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.CONCLUSIONS:
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pneumonia Viral
/
Viroses
/
Pneumonia Bacteriana
/
Malária
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Child
/
Humans
Idioma:
En
Revista:
Clin Infect Dis
Assunto da revista:
DOENCAS TRANSMISSIVEIS
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Estados Unidos