{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T21:25:09Z","timestamp":1770067509158,"version":"3.49.0"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2021,1,29]],"date-time":"2021-01-29T00:00:00Z","timestamp":1611878400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,1,29]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To compare the diagnostic accuracy of white blood cell-surface biomarkers (CD64, CD11b and HLA-DR), C-reactive protein (CRP) and hematological parameters to diagnose definite sepsis among pre-term neonates presenting with suspected late-onset neonatal sepsis (LONS).<\/jats:p><\/jats:sec><jats:sec><jats:title>Design<\/jats:title><jats:p>This was a prospective, single-gate, diagnostic study in a Level III neonatal unit. Fifty-three neonates (gestation, &amp;lt;34\u2009weeks) with LONS (onset, &amp;gt;72\u2009 age), were enrolled. Cell-surface biomarkers, CRP and haematological parameters were assayed at 0 and 48\u2009h after onset. The reference standard was definite sepsis, defined as a positive blood culture with a non-contaminant organism. The index tests (cell-surface biomarkers, CRP and haematological parameters) were compared between subjects with or without \u2018definite sepsis\u2019. The area under the receiver operator characteristics curves (AUC) generated for each index test at 0 and 48\u2009h was compared.<\/jats:p><\/jats:sec><jats:sec><jats:title>Setting<\/jats:title><jats:p>Level III neonatal unit in a tertiary care institute<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of 53 enrolled pre-term infants, 24 had definite sepsis. Among all the index tests evaluated, CRP at 48\u2009h had the highest AUC [0.82 (95% confidence interval, 0.69, 0.92)]. The expression of CD11b and HLA-DR was significantly reduced among the septic neonates. Among the cell-surface biomarkers, the maximum AUC was recorded for HLA-DR at 48\u2009 [0.68 (95% CI, 0.54, 0.81)]. Comparisons between index tests were not statistically significant.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>C-reactive protein is superior to other sepsis screen biomarkers and white blood cell-surface biomarkers in diagnosing culture-positive LONS among pre-term infants. CD64, CD11b and HLA DR as diagnostic tests in this group have limited discriminatory value.<\/jats:p><\/jats:sec><jats:sec><jats:title>LAY SUMMARY<\/jats:title><jats:p>The diagnosis of neonatal blood stream infections is a challenge. In response to bacterial blood stream infections, white blood cells are known to produce an excess of certain types of specialized proteins on their surface, including CD64, CD11b and HLA-DR. In this study we evaluated the concentration of these cell-surface proteins for diagnosing blood stream infections in pre-mature newborn babies, whose onset of infection was beyond 72\u2009h of life. We compared these tests against standard tests that are currently in clinical use, such as C-reactive protein and blood white cell counts. All tests were performed at the time of initially suspecting the infection and 48\u2009h later. The gold standard against which all these tests were evaluated was blood culture, in which the offending bacteria are grown in specialized laboratory media. Of 53 pre-mature babies with suspected infection, 24 had blood culture-proven infection. Among all tests, C-reactive protein at 48\u2009h had the best ability to distinguish definite infection from no infection. The expression of CD11b and HLA-DR was significantly reduced among infected neonates. We conclude that C-reactive protein is superior to white blood cell-surface proteins and white cell count in diagnosing definite late-onset infections among pre-term infants.<\/jats:p><\/jats:sec>","DOI":"10.1093\/tropej\/fmab016","type":"journal-article","created":{"date-parts":[[2021,2,20]],"date-time":"2021-02-20T12:18:15Z","timestamp":1613823495000},"source":"Crossref","is-referenced-by-count":4,"title":["Cell-Surface Biomarkers, C-Reactive Protein and Haematological Parameters for Diagnosing Late Onset Sepsis in Pre-term Neonates"],"prefix":"10.1093","volume":"67","author":[{"given":"Aradhana","family":"Rohil","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5595-8289","authenticated-orcid":false,"given":"Sourabh","family":"Dutta","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neelam","family":"Varma","sequence":"additional","affiliation":[{"name":"Department of Hematology, PGIMER, Chandigarh, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manupdesh Singh","family":"Sachdev","sequence":"additional","affiliation":[{"name":"Department of Hematology, PGIMER, Chandigarh, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arun","family":"Bansal","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Praveen","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2021,3,13]]},"reference":[{"key":"2021031307291625300_fmab016-B1","doi-asserted-by":"crossref","first-page":"19","DOI":"10.2471\/BLT.14.139790","article-title":"Neonatal cause-of-death estimates for the early and late neonatal periods for 194 countries: 2000-2013","volume":"93","author":"Oza","year":"2015","journal-title":"Bull World Health Organ"},{"key":"2021031307291625300_fmab016-B2","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/j.pcl.2012.12.003","article-title":"Neonatal infectious diseases: evaluation of neonatal sepsis","volume":"60","author":"Camacho-Gonzalez","year":"2013","journal-title":"Pediatr Clin North Am"},{"key":"2021031307291625300_fmab016-B3","doi-asserted-by":"crossref","first-page":"170","DOI":"10.4161\/viru.26906","article-title":"Neonatal sepsis: an old problem with new insights","volume":"5","author":"Shah","year":"2014","journal-title":"Virulence"},{"key":"2021031307291625300_fmab016-B4","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.jinf.2010.02.013","article-title":"Neutrophil CD64 expression as marker of bacterial infection: a systematic review and meta-analysis","volume":"60","author":"Cid","year":"2010","journal-title":"J Infect"},{"key":"2021031307291625300_fmab016-B5","first-page":"90","article-title":"Neutrophil-surface antigens CD11b and CD64 expression: a potential predictor of early-onset neonatal sepsis","volume":"2","author":"El-Raggal Nehal","year":"2004","journal-title":"Egypt J Pediatr Allergy Immunol"},{"key":"2021031307291625300_fmab016-B6","doi-asserted-by":"crossref","first-page":"1950","DOI":"10.1007\/s00134-009-1637-7","article-title":"Neutrophil and monocyte CD64 indexes, lipopolysaccharide-binding protein, procalcitonin and C-reactive protein in sepsis of critically ill neonates and children","volume":"35","author":"Groselj-Grenc","year":"2009","journal-title":"Intensive Care Med"},{"key":"2021031307291625300_fmab016-B7","doi-asserted-by":"crossref","first-page":"3914","DOI":"10.1128\/JCM.00628-09","article-title":"CD64 index provides simple and predictive testing for detection and monitoring of sepsis and bacterial infection in hospital patients","volume":"47","author":"Icardi","year":"2009","journal-title":"J Clin Microbiol"},{"key":"2021031307291625300_fmab016-B8","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1177\/0300060513489799","article-title":"Diagnostic accuracy of neutrophil CD64 expression in neonatal infection: a meta-analysis","volume":"41","author":"Jia","year":"2013","journal-title":"J Int Med Res"},{"key":"2021031307291625300_fmab016-B9","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1542\/peds.2007-1308","article-title":"Hematologic profile of sepsis in neonates: neutrophil CD64 as a diagnostic marker","volume":"121","author":"Bhandari","year":"2008","journal-title":"Pediatrics"},{"key":"2021031307291625300_fmab016-B10","doi-asserted-by":"crossref","first-page":"11","DOI":"10.3345\/kjp.2012.55.1.11","article-title":"Comparison of the accuracy of neutrophil CD64 and C-reactive protein as a single test for the early detection of neonatal sepsis","volume":"55","author":"Choo","year":"2012","journal-title":"Korean J Pediatr"},{"key":"2021031307291625300_fmab016-B11","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1002\/jcla.20370","article-title":"Predictive values of neutrophil CD64 expression compared with interleukin-6 and C-reactive protein in early diagnosis of neonatal sepsis","volume":"24","author":"Dilli","year":"2010","journal-title":"J Clin Lab Anal"},{"key":"2021031307291625300_fmab016-B12","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1515\/CCLM.2009.224","article-title":"Neutrophil CD64: a diagnostic marker for infection and sepsis","volume":"47","author":"Hoffmann","year":"2009","journal-title":"Clin Chem Lab Med"},{"key":"2021031307291625300_fmab016-B13","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1203\/00006450-200203000-00006","article-title":"Neutrophil CD64 expression: a sensitive diagnostic marker for late-onset nosocomial infection in very low birthweight infants","volume":"51","author":"Ng","year":"2002","journal-title":"Pediatr Res"},{"key":"2021031307291625300_fmab016-B14","doi-asserted-by":"crossref","first-page":"E12","DOI":"10.1542\/peds.108.1.e12","article-title":"Neutrophil CD11b expression and circulating interleukin-8 as diagnostic markers for early-onset neonatal sepsis","volume":"108","author":"Nupponen","year":"2001","journal-title":"Pediatrics"},{"key":"2021031307291625300_fmab016-B15","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1055\/s-0033-1334453","article-title":"Neutrophil CD64 with hematologic criteria for diagnosis of neonatal sepsis","volume":"31","author":"Streimish","year":"2014","journal-title":"Am J Perinatol"},{"key":"2021031307291625300_fmab016-B16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2013\/763191","article-title":"Flow cytometry in the detection of neonatal sepsis","volume":"2013","author":"Umlauf","year":"2013","journal-title":"Int J Pediatr"},{"key":"2021031307291625300_fmab016-B17","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1016\/S0022-3476(98)70018-6","article-title":"Neutrophil CD11b expression as a diagnostic marker for early-onset neonatal infection","volume":"132","author":"Weirich","year":"1998","journal-title":"J Pediatr"},{"key":"2021031307291625300_fmab016-B18","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1515\/JPM.2003.009","article-title":"Early markers of late-onset sepsis in premature neonates: clinical, hematological and cytokine profile","volume":"31","author":"Gonzalez","year":"2003","journal-title":"J Perinat Med"},{"key":"2021031307291625300_fmab016-B19","first-page":"470","article-title":"Determinants of blood pressure in infants admitted to neonatal intensive care units: a prospective multicenter study. Philadelphia Neonatal Blood Pressure Study Group","volume":"15","author":"Zubrow","year":"1995","journal-title":"J Perinatol"},{"key":"2021031307291625300_fmab016-B20","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1055\/s-0029-1243303","article-title":"Baseline illness severity does not alter accuracy of neonatal sepsis screen","volume":"27","author":"Mahale","year":"2010","journal-title":"Am. J. Perinatol"},{"key":"2021031307291625300_fmab016-B21","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1093\/tropej\/49.4.235","article-title":"Predictive clinical scores for diagnosis of late onset neonatal septicemia","volume":"49","author":"Singh","year":"2003","journal-title":"J Trop Pediatr"},{"key":"2021031307291625300_fmab016-B22","first-page":"93","article-title":"Evaluation of CD11b expression on peripheral blood neutrophils for early detection of neonatal sepsis","volume":"6","author":"Adib","year":"2007","journal-title":"Iran J Allergy Asthma Immunol"},{"key":"2021031307291625300_fmab016-B23","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1007\/s12519-011-0304-6","article-title":"Evaluation of adhesion molecules CD64, CD11b and CD62L in neutrophils and monocytes of peripheral blood for early diagnosis of neonatal infection","volume":"8","author":"Genel","year":"2012","journal-title":"World J Pediatr"},{"key":"2021031307291625300_fmab016-B24","first-page":"77","article-title":"Early diagnosis of neonatal sepsis: a molecular approach and detection of diagnostic markers versus conventional blood culture","volume":"4","author":"Labib Azza","year":"2013","journal-title":"Int J Microbiol Res"},{"key":"2021031307291625300_fmab016-B25","first-page":"53","article-title":"CD64 cell surface expression on neutrophils for diagnosis of neonatal sepsis","volume":"15","author":"Morsy","year":"2008","journal-title":"Egypt J Immunol"},{"key":"2021031307291625300_fmab016-B26","doi-asserted-by":"crossref","first-page":"299","DOI":"10.3109\/00365540903449832","article-title":"Evaluation of neutrophilic CD64, interleukin 10 and procalcitonin as diagnostic markers of early- and late-onset neonatal sepsis","volume":"42","author":"Zeitoun","year":"2010","journal-title":"Scand J Infect Dis"},{"key":"2021031307291625300_fmab016-B27","doi-asserted-by":"crossref","first-page":"25","DOI":"10.7196\/sajch.482","article-title":"Neutrophil CD64 has a high negative predictive value for exclusion of neonatal sepsis","volume":"7","author":"Dhlamini","year":"2013","journal-title":"S Afr J Child Health"},{"key":"2021031307291625300_fmab016-B28","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1097\/PCC.0b013e31826e726d","article-title":"Diagnostic performance of triggering receptor expressed on myeloid cells-1 and CD64 index as markers of sepsis in preterm newborns","volume":"14","author":"Mazzucchelli","year":"2013","journal-title":"Pediatr Crit Care Med"},{"key":"2021031307291625300_fmab016-B29","first-page":"54","article-title":"Assessment of the expression of neutrophil CD11b receptors in preterm infants","volume":"3","author":"Zieba Krzysztof","year":"2009","journal-title":"J Preclin Clin Res"},{"key":"2021031307291625300_fmab016-B30","first-page":"348","article-title":"Expression of neutrophil adhesion molecule CD11b as an early diagnostic marker for neonatal sepsis","volume":"41","author":"Cui","year":"2003","journal-title":"Zhonghua Er Ke Za Zhi"},{"key":"2021031307291625300_fmab016-B31","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1182\/blood.V83.4.1086.1086","article-title":"Deficient total cell content of CR3 (CD11b) in neonatal neutrophils","volume":"83","author":"Abughali","year":"1994","journal-title":"Blood"},{"key":"2021031307291625300_fmab016-B32","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1038\/sj.jp.7210906","article-title":"Age-related low expression of HLA-DR molecules on monocytes of term and preterm newborns with and without signs of infection","volume":"23","author":"Birle","year":"2003","journal-title":"J Perinatol"},{"key":"2021031307291625300_fmab016-B33","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/j.jinf.2009.12.004","article-title":"Monocyte HLA-DR expression as predictor of poor outcome in neonates with late onset neonatal sepsis","volume":"60","author":"Genel","year":"2010","journal-title":"J Infect"},{"key":"2021031307291625300_fmab016-B34","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1046\/j.1365-2249.2001.01471.x","article-title":"Flow cytometric measurement of HLA-DR expression on circulating monocytes in healthy and sick neonates using monocyte negative selection","volume":"123","author":"Kanakoudi-Tsakalidou","year":"2001","journal-title":"Clin Exp Immunol"},{"key":"2021031307291625300_fmab016-B35","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1159\/000088288","article-title":"Quantitative measurement of monocyte HLA-DR expression in the identification of early-onset neonatal infection","volume":"89","author":"Ng","year":"2006","journal-title":"Biol Neonate"}],"container-title":["Journal of Tropical Pediatrics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/tropej\/article-pdf\/67\/1\/fmab016\/36587631\/fmab016.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/tropej\/article-pdf\/67\/1\/fmab016\/36587631\/fmab016.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,18]],"date-time":"2022-12-18T08:52:54Z","timestamp":1671353574000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/tropej\/article\/doi\/10.1093\/tropej\/fmab016\/6169400"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,29]]},"references-count":35,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,1,29]]}},"URL":"https:\/\/doi.org\/10.1093\/tropej\/fmab016","relation":{},"ISSN":["0142-6338","1465-3664"],"issn-type":[{"value":"0142-6338","type":"print"},{"value":"1465-3664","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,2,1]]},"published":{"date-parts":[[2021,1,29]]},"article-number":"fmab016"}}