{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T16:15:36Z","timestamp":1792512936149,"version":"4.5.0"},"reference-count":23,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2021,2,3]],"date-time":"2021-02-03T00:00:00Z","timestamp":1612310400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,12,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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 &amp;lt;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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>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 &amp;gt;90% sensitivity and &amp;gt;80% specificity, regardless of number of pathogen classes. Bacterial pneumonia was strongly associated with neutrophil markers\u2014in particular, degranulation including HP, LCN2, LTF, MPO, MMP8, PGLYRP1, RETN, SERPINA1, S100A9, and SLPI.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/cid\/ciaa1843","type":"journal-article","created":{"date-parts":[[2020,12,12]],"date-time":"2020-12-12T01:12:37Z","timestamp":1607735557000},"page":"e3939-e3948","source":"Crossref","is-referenced-by-count":25,"title":["Biomarkers to Distinguish Bacterial From Viral Pediatric Clinical Pneumonia in a Malaria-Endemic Setting"],"prefix":"10.1093","volume":"73","author":[{"given":"Michael A","family":"Gillette","sequence":"first","affiliation":[{"name":"Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA"},{"name":"Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA"},{"name":"Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D R","family":"Mani","sequence":"additional","affiliation":[{"name":"Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Uschnig","sequence":"additional","affiliation":[{"name":"Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA"},{"name":"Harvard T. H. Chan School of Public Health, Department of Immunology and Infectious Diseases, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karell G","family":"Pell\u00e9","sequence":"additional","affiliation":[{"name":"Harvard T. H. Chan School of Public Health, Department of Immunology and Infectious Diseases, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lola","family":"Madrid","sequence":"additional","affiliation":[{"name":"ISGlobal, Hospital Cl\u00ednic\u2013Universitat de Barcelona, Barcelona, Spain"},{"name":"Centro de Investiga\u00e7\u00e3o em Sa\u00fade de Manhi\u00e7a (CISM), Maputo, Mozambique"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sozinho","family":"Ac\u00e1cio","sequence":"additional","affiliation":[{"name":"Centro de Investiga\u00e7\u00e3o em Sa\u00fade de Manhi\u00e7a (CISM), Maputo, Mozambique"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"Lanaspa","sequence":"additional","affiliation":[{"name":"ISGlobal, Hospital Cl\u00ednic\u2013Universitat de Barcelona, Barcelona, Spain"},{"name":"Centro de Investiga\u00e7\u00e3o em Sa\u00fade de Manhi\u00e7a (CISM), Maputo, Mozambique"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro","family":"Alonso","sequence":"additional","affiliation":[{"name":"ISGlobal, Hospital Cl\u00ednic\u2013Universitat de Barcelona, Barcelona, Spain"},{"name":"Centro de Investiga\u00e7\u00e3o em Sa\u00fade de Manhi\u00e7a (CISM), Maputo, Mozambique"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clarissa","family":"Valim","sequence":"additional","affiliation":[{"name":"Harvard T. H. Chan School of Public Health, Department of Immunology and Infectious Diseases, Boston, Massachusetts, USA"},{"name":"Department of Global Health, Boston University School of Public Health, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven A","family":"Carr","sequence":"additional","affiliation":[{"name":"Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen F","family":"Schaffner","sequence":"additional","affiliation":[{"name":"Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA"},{"name":"Harvard T. H. Chan School of Public Health, Department of Immunology and Infectious Diseases, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bronwyn","family":"MacInnis","sequence":"additional","affiliation":[{"name":"Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA"},{"name":"Harvard T. 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Chan School of Public Health, Department of Immunology and Infectious Diseases, Boston, Massachusetts, USA"},{"name":"American Society for Clinical Pathology, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quique","family":"Bassat","sequence":"additional","affiliation":[{"name":"ISGlobal, Hospital Cl\u00ednic\u2013Universitat de Barcelona, Barcelona, Spain"},{"name":"Centro de Investiga\u00e7\u00e3o em Sa\u00fade de Manhi\u00e7a (CISM), Maputo, Mozambique"},{"name":"Catalan Institution for Research and Advanced Studies (ICREA) Barcelona, Spain"},{"name":"Pediatric Infectious Diseases Unit, Pediatrics Department, Hospital Sant Joan de D\u00e9u (University of Barcelona), Barcelona, Spain"},{"name":"Consorcio de Investigaci\u00f3n Biom\u00e9dica en Red de Epidemiolog\u00eda y Salud P\u00fablica (CIBERESP), Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8604-4455","authenticated-orcid":false,"given":"Dyann F","family":"Wirth","sequence":"additional","affiliation":[{"name":"Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA"},{"name":"Harvard T. 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