Host-Based Prognostic Biomarkers to Improve Risk Stratification and Outcome of Febrile Children in Low- and Middle-Income Countries
Fever is one of the leading causes for pediatric medical consultation and the most common symptom at clinical presentation in low- and middle-income countries (LMICs). Most febrile episodes are due to self-limited infections, but a small proportion of children will develop life-threatening infection...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-09-01
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| Series: | Frontiers in Pediatrics |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fped.2020.552083/full |
| _version_ | 1818136318078615552 |
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| author | Núria Balanza Clara Erice Clara Erice Michelle Ngai Michelle Ngai Rosauro Varo Rosauro Varo Kevin C. Kain Kevin C. Kain Quique Bassat Quique Bassat Quique Bassat Quique Bassat Quique Bassat |
| author_facet | Núria Balanza Clara Erice Clara Erice Michelle Ngai Michelle Ngai Rosauro Varo Rosauro Varo Kevin C. Kain Kevin C. Kain Quique Bassat Quique Bassat Quique Bassat Quique Bassat Quique Bassat |
| author_sort | Núria Balanza |
| collection | DOAJ |
| description | Fever is one of the leading causes for pediatric medical consultation and the most common symptom at clinical presentation in low- and middle-income countries (LMICs). Most febrile episodes are due to self-limited infections, but a small proportion of children will develop life-threatening infections. The early recognition of children who have or are progressing to a critical illness among all febrile cases is challenging, and there are currently no objective and quantitative tools to do so. This results in increased morbidity and mortality among children with impending life-threatening infections, whilst contributing to the unnecessary prescription of antibiotics, overwhelming health care facilities, and harm to patients receiving avoidable antimicrobial treatment. Specific fever origin is difficult to ascertain and co-infections in LMICs are common. However, many severe infections share common pathways of host injury irrespective of etiology, including immune and endothelial activation that contribute to the pathobiology of sepsis (i.e., pathogen “agnostic” mechanisms of disease). Importantly, mediators of these pathways are independent markers of disease severity and outcome. We propose that measuring circulating levels of these factors can provide quantitative and objective evidence to: enable early recognition of severe infection; guide patient triage and management; enhance post-discharge risk stratification and follow up; and mitigate potential gender bias in clinical decisions. Here, we review the clinical and biological evidence supporting the clinical utility of host immune and endothelial activation biomarkers as components of novel rapid triage tests, and discuss the challenges and needs for developing and implementing such tools. |
| first_indexed | 2024-12-11T09:38:30Z |
| format | Article |
| id | doaj.art-e66f4d19808846349dce69caea967905 |
| institution | Directory Open Access Journal |
| issn | 2296-2360 |
| language | English |
| last_indexed | 2024-12-11T09:38:30Z |
| publishDate | 2020-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pediatrics |
| spelling | doaj.art-e66f4d19808846349dce69caea9679052022-12-22T01:12:45ZengFrontiers Media S.A.Frontiers in Pediatrics2296-23602020-09-01810.3389/fped.2020.552083552083Host-Based Prognostic Biomarkers to Improve Risk Stratification and Outcome of Febrile Children in Low- and Middle-Income CountriesNúria Balanza0Clara Erice1Clara Erice2Michelle Ngai3Michelle Ngai4Rosauro Varo5Rosauro Varo6Kevin C. Kain7Kevin C. Kain8Quique Bassat9Quique Bassat10Quique Bassat11Quique Bassat12Quique Bassat13ISGlobal, Hospital Clínic - Universitat de Barcelona, Barcelona, SpainSandra-Rotman Centre for Global Health, Toronto General Research Institute, University Health Network-Toronto General Hospital, Toronto, ON, CanadaTropical Disease Unit, Division of Infectious Diseases, Department of Medicine, University of Toronto, Toronto, ON, CanadaSandra-Rotman Centre for Global Health, Toronto General Research Institute, University Health Network-Toronto General Hospital, Toronto, ON, CanadaTropical Disease Unit, Division of Infectious Diseases, Department of Medicine, University of Toronto, Toronto, ON, CanadaISGlobal, Hospital Clínic - Universitat de Barcelona, Barcelona, SpainCentro de Investigação em Saúde de Manhiça, Manhiça, MozambiqueSandra-Rotman Centre for Global Health, Toronto General Research Institute, University Health Network-Toronto General Hospital, Toronto, ON, CanadaTropical Disease Unit, Division of Infectious Diseases, Department of Medicine, University of Toronto, Toronto, ON, CanadaISGlobal, Hospital Clínic - Universitat de Barcelona, Barcelona, SpainCentro de Investigação em Saúde de Manhiça, Manhiça, MozambiqueICREA, Barcelona, SpainPediatric Infectious Diseases Unit, Pediatrics Department, Hospital Sant Joan de Déu (University of Barcelona), Barcelona, SpainConsorcio de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, SpainFever is one of the leading causes for pediatric medical consultation and the most common symptom at clinical presentation in low- and middle-income countries (LMICs). Most febrile episodes are due to self-limited infections, but a small proportion of children will develop life-threatening infections. The early recognition of children who have or are progressing to a critical illness among all febrile cases is challenging, and there are currently no objective and quantitative tools to do so. This results in increased morbidity and mortality among children with impending life-threatening infections, whilst contributing to the unnecessary prescription of antibiotics, overwhelming health care facilities, and harm to patients receiving avoidable antimicrobial treatment. Specific fever origin is difficult to ascertain and co-infections in LMICs are common. However, many severe infections share common pathways of host injury irrespective of etiology, including immune and endothelial activation that contribute to the pathobiology of sepsis (i.e., pathogen “agnostic” mechanisms of disease). Importantly, mediators of these pathways are independent markers of disease severity and outcome. We propose that measuring circulating levels of these factors can provide quantitative and objective evidence to: enable early recognition of severe infection; guide patient triage and management; enhance post-discharge risk stratification and follow up; and mitigate potential gender bias in clinical decisions. Here, we review the clinical and biological evidence supporting the clinical utility of host immune and endothelial activation biomarkers as components of novel rapid triage tests, and discuss the challenges and needs for developing and implementing such tools.https://www.frontiersin.org/article/10.3389/fped.2020.552083/fullfebrile syndromesevere infectionsepsisrisk stratificationprognostic host-biomarkersangiopoietin-2 (Ang-2) |
| spellingShingle | Núria Balanza Clara Erice Clara Erice Michelle Ngai Michelle Ngai Rosauro Varo Rosauro Varo Kevin C. Kain Kevin C. Kain Quique Bassat Quique Bassat Quique Bassat Quique Bassat Quique Bassat Host-Based Prognostic Biomarkers to Improve Risk Stratification and Outcome of Febrile Children in Low- and Middle-Income Countries Frontiers in Pediatrics febrile syndrome severe infection sepsis risk stratification prognostic host-biomarkers angiopoietin-2 (Ang-2) |
| title | Host-Based Prognostic Biomarkers to Improve Risk Stratification and Outcome of Febrile Children in Low- and Middle-Income Countries |
| title_full | Host-Based Prognostic Biomarkers to Improve Risk Stratification and Outcome of Febrile Children in Low- and Middle-Income Countries |
| title_fullStr | Host-Based Prognostic Biomarkers to Improve Risk Stratification and Outcome of Febrile Children in Low- and Middle-Income Countries |
| title_full_unstemmed | Host-Based Prognostic Biomarkers to Improve Risk Stratification and Outcome of Febrile Children in Low- and Middle-Income Countries |
| title_short | Host-Based Prognostic Biomarkers to Improve Risk Stratification and Outcome of Febrile Children in Low- and Middle-Income Countries |
| title_sort | host based prognostic biomarkers to improve risk stratification and outcome of febrile children in low and middle income countries |
| topic | febrile syndrome severe infection sepsis risk stratification prognostic host-biomarkers angiopoietin-2 (Ang-2) |
| url | https://www.frontiersin.org/article/10.3389/fped.2020.552083/full |
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