ArticlePLoS medicine2022
Immune and endothelial activation markers and risk stratification of childhood pneumonia in Uganda: A secondary analysis of a prospective cohort study.
Article in PLoS medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04726826 (Predictive Biomarkers of Mortality and Morbidity in Children Hospitalized for Acute Febrile Illness), which is not on this map. Cited by 10 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Predictive Biomarkers of Mortality and Morbidity in Children Hospitalized for Acute Febrile Illness
Who cites it
10 citing papers in PubMed, 13 citations in OpenAlex.
- Early Clinical and Inflammatory Predictors of Supplemental Oxygen Requirement in Children Hospitalized with Acute Lower Respiratory Infection: A Multivariable Analysis.Microorganisms · 2026Article
- Predicting referral need for febrile children in low-resource community settings in South and Southeast Asia.Nature medicine · 2026Article
- Association of the LncRNA TINCR rs2288947 polymorphism with survival outcomes in severe pneumonia among Han Chinese children.European journal of medical research · 2026Article
- Soluble triggering receptor expressed on myeloid cells 1 (sTREM-1) predicts mortality in patients with febrile illness in southern Mozambique.Communications medicine · 2025Article
- Soluble triggering receptor expressed on myeloid cells 1 is associated with hemoconcentration and endothelial activation in children and young adults with dengue virus infection in the Philippines.PLoS neglected tropical diseases · 2025Article
- Heparin-Binding Protein Stratifies Mortality Risk Among Ugandan Children Hospitalized With Respiratory Distress.Open forum infectious diseases · 2024Article
- sTREM-1: A Biomarker of Mortality in Severe Malaria Impacted by Acute Kidney Injury.The Journal of infectious diseases · 2024Article
- Research progress of biomarkers in evaluating the severity and prognostic value of severe pneumonia in children.Frontiers in pediatrics · 2024Review
- Defining the role of host biomarkers in the diagnosis and prognosis of the severity of childhood pneumonia: a prospective cohort study.Scientific reports · 2023Article
- Prognostic accuracy of biomarkers of immune and endothelial activation in Mozambican children hospitalized with pneumonia.PLOS global public health · 2023Article
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Authors and funding
12 authors at 7 institutions in 3 countries.
Funding
Abstract
backgroundDespite the global burden of pneumonia, reliable triage tools to identify children in low-resource settings at risk of severe and fatal respiratory tract infection are lacking. This study assessed the ability of circulating host markers of immune and endothelial activation quantified at presentation, relative to currently used clinical measures of disease severity, to identify children with pneumonia who are at risk of death. METHODS AND
findingsWe conducted a secondary analysis of a prospective cohort study of children aged 2 to 59 months presenting to the Jinja Regional Hospital in Jinja, Uganda between February 2012 and August 2013, who met the Integrated Management of Childhood Illness (IMCI) diagnostic criteria for pneumonia. Circulating plasma markers of immune (IL-6, IL-8, CXCL-10/IP-10, CHI3L1, sTNFR1, and sTREM-1) and endothelial (sVCAM-1, sICAM-1, Angpt-1, Angpt-2, and sFlt-1) activation measured at hospital presentation were compared to lactate, respiratory rate, oxygen saturation, procalcitonin (PCT), and C-reactive protein (CRP) with a primary outcome of predicting 48-hour mortality. Of 805 children with IMCI pneumonia, 616 had severe pneumonia. Compared to 10 other immune and endothelial activation markers, sTREM-1 levels at presentation had the best predictive accuracy in identifying 48-hour mortality for children with pneumonia (AUROC 0.885, 95% CI 0.841 to 0.928; p = 0.03 to p < 0.001) and severe pneumonia (AUROC 0.870, 95% CI 0.824 to 0.916; p = 0.04 to p < 0.001). sTREM-1 was more strongly associated with 48-hour mortality than lactate (AUROC 0.745, 95% CI 0.664 to 0.826; p < 0.001), respiratory rate (AUROC 0.615, 95% CI 0.528 to 0.702; p < 0.001), oxygen saturation (AUROC 0.685, 95% CI 0.594 to 0.776; p = 0.002), PCT (AUROC 0.650, 95% CI 0.566 to 0.734; p < 0.001), and CRP (AUROC 0.562, 95% CI 0.472 to 0.653; p < 0.001) in cases of pneumonia and severe pneumonia. The main limitation of this study was the unavailability of radiographic imaging.
conclusionsIn this cohort of Ugandan children, sTREM-1 measured at hospital presentation was a significantly better indicator of 48-hour mortality risk than other common approaches to risk stratify children with pneumonia. Measuring sTREM-1 at clinical presentation may improve the early triage, management, and outcome of children with pneumonia at risk of death.
trial registrationThe trial was registered at clinicaltrial.gov (NCT04726826).
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