Prognostic accuracy of biomarkers of immune and endothelial activation in Mozambican children hospitalized with pneumonia

PLOS Glob Public Health. 2023 Feb 23;3(2):e0001553. doi: 10.1371/journal.pgph.0001553. eCollection 2023.

Abstract

Pneumonia is a leading cause of child mortality. However, currently we lack simple, objective, and accurate risk-stratification tools for pediatric pneumonia. Here we test the hypothesis that measuring biomarkers of immune and endothelial activation in children with pneumonia may facilitate the identification of those at risk of death. We recruited children <10 years old fulfilling WHO criteria for pneumonia and admitted to the Manhiça District Hospital (Mozambique) from 2010 to 2014. We measured plasma levels of IL-6, IL-8, Angpt-2, sTREM-1, sFlt-1, sTNFR1, PCT, and CRP at admission, and assessed their prognostic accuracy for in-hospital, 28-day, and 90-day mortality. Healthy community controls, within same age strata and location, were also assessed. All biomarkers were significantly elevated in 472 pneumonia cases versus 80 controls (p<0.001). IL-8, sFlt-1, and sTREM-1 were associated with in-hospital mortality (p<0.001) and showed the best discrimination with AUROCs of 0.877 (95% CI: 0.782 to 0.972), 0.832 (95% CI: 0.729 to 0.935) and 0.822 (95% CI: 0.735 to 0.908), respectively. Their performance was superior to CRP, PCT, oxygen saturation, and clinical severity scores. IL-8, sFlt-1, and sTREM-1 remained good predictors of 28-day and 90-day mortality. These findings suggest that measuring IL-8, sFlt-1, or sTREM-1 at hospital presentation can guide risk-stratification of children with pneumonia, which could enable prioritized care to improve survival and resource allocation.

Grants and funding

We acknowledge funding support from the Bill and Melinda Gates Foundation (OPP50092), the Canadian Institutes of Health Research (CIHR) Foundation grant FDN-148439 (KCK), the Canada Research Chair Program (KCK), and donations from Kim Kertland and the Tesari Foundation. ISGlobal receives support from the Spanish Ministry of Science and Innovation through the “Centro de Excelencia Severo Ochoa 2019-2023” Program (CEX2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Program. CISM is supported by the Government of Mozambique and the Spanish Agency for International Development (AECID). NB is supported by an FPU predoctoral fellowship from the Spanish Ministry of Universities (FPU18/04260). BB is a Beatriu de Pinos postdoctoral fellow granted by the Government of Catalonia’s Secretariat for Universities and Research, and by Marie Sklodowska-Curie Actions COFUND Program (BP3, 801370). EL-V has received funding from the European Respiratory Society and the European Union’s H2020 research and innovation program under the Marie Sklodowska-Curie grant agreement No 847462. CRM, AMW, and JW are supported by CIHR Doctoral Awards. Funding bodies played no role in study design; collection, analysis, or interpretation of the data; writing of the report, or in submission of this article for publication.