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PLoS One. 2015 Sep 14;10(9):e0137592. doi: 10.1371/journal.pone.0137592. eCollection 2015.

Biomarkers of Host Response Predict Primary End-Point Radiological Pneumonia in Tanzanian Children with Clinical Pneumonia: A Prospective Cohort Study.

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Sandra Rotman Centre for Global Health, University Health Network-Toronto General Hospital, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
Swiss Tropical and Public Health Institute, University of Basel, Basel, Switzerland; Department of Ambulatory Care and Community Medicine, University of Lausanne, Lausanne, Switzerland.
Amana Regional Referral Hospital, Dar es Salaam, United Republic of Tanzania.
St-Francis Hospital, Ifakara, United Republic of Tanzania.
Department of Radiology, University Hospital of Lausanne (CHUV), Lausanne, Switzerland.
Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
Swiss Tropical and Public Health Institute, University of Basel, Basel, Switzerland; Department of Ambulatory Care and Community Medicine, University of Lausanne, Lausanne, Switzerland; Infectious Disease Service, University Hospital, Lausanne, Switzerland.



Diagnosing pediatric pneumonia is challenging in low-resource settings. The World Health Organization (WHO) has defined primary end-point radiological pneumonia for use in epidemiological and vaccine studies. However, radiography requires expertise and is often inaccessible. We hypothesized that plasma biomarkers of inflammation and endothelial activation may be useful surrogates for end-point pneumonia, and may provide insight into its biological significance.


We studied children with WHO-defined clinical pneumonia (n = 155) within a prospective cohort of 1,005 consecutive febrile children presenting to Tanzanian outpatient clinics. Based on x-ray findings, participants were categorized as primary end-point pneumonia (n = 30), other infiltrates (n = 31), or normal chest x-ray (n = 94). Plasma levels of 7 host response biomarkers at presentation were measured by ELISA. Associations between biomarker levels and radiological findings were assessed by Kruskal-Wallis test and multivariable logistic regression. Biomarker ability to predict radiological findings was evaluated using receiver operating characteristic curve analysis and Classification and Regression Tree analysis.


Compared to children with normal x-ray, children with end-point pneumonia had significantly higher C-reactive protein, procalcitonin and Chitinase 3-like-1, while those with other infiltrates had elevated procalcitonin and von Willebrand Factor and decreased soluble Tie-2 and endoglin. Clinical variables were not predictive of radiological findings. Classification and Regression Tree analysis generated multi-marker models with improved performance over single markers for discriminating between groups. A model based on C-reactive protein and Chitinase 3-like-1 discriminated between end-point pneumonia and non-end-point pneumonia with 93.3% sensitivity (95% confidence interval 76.5-98.8), 80.8% specificity (72.6-87.1), positive likelihood ratio 4.9 (3.4-7.1), negative likelihood ratio 0.083 (0.022-0.32), and misclassification rate 0.20 (standard error 0.038).


In Tanzanian children with WHO-defined clinical pneumonia, combinations of host biomarkers distinguished between end-point pneumonia, other infiltrates, and normal chest x-ray, whereas clinical variables did not. These findings generate pathophysiological hypotheses and may have potential research and clinical utility.

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