{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T11:05:00Z","timestamp":1790679900240,"version":"4.1.0"},"reference-count":48,"publisher":"BMJ","issue":"7","license":[{"start":{"date-parts":[[2020,7,23]],"date-time":"2020-07-23T00:00:00Z","timestamp":1595462400000},"content-version":"unspecified","delay-in-days":22,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"BioM\u00e9rieux Inc","award":["SEPSIS study"],"award-info":[{"award-number":["SEPSIS study"]}]},{"DOI":"10.13039\/501100002915","name":"Fondation pour la Recherche M\u00e9dicale","doi-asserted-by":"publisher","award":["ECO20160736054"],"award-info":[{"award-number":["ECO20160736054"]}],"id":[{"id":"10.13039\/501100002915","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003032","name":"Association Nationale de la Recherche et de la Technologie","doi-asserted-by":"publisher","award":["CIFRE number 2016\/1550"],"award-info":[{"award-number":["CIFRE number 2016\/1550"]}],"id":[{"id":"10.13039\/501100003032","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2020,6,12]]},"published-print":{"date-parts":[[2020,7]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Neonatal sepsis outreaches all causes of neonatal mortality worldwide and remains a major societal burden in low and middle income countries. In addition to limited resources, endemic morbidities, such as malaria and prematurity, predispose neonates and infants to invasive infection by altering neonatal immune response to pathogens. Nevertheless, thoughtful epidemiological, diagnostic and immunological evaluation of neonatal sepsis and the impact of gestational malaria have never been performed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>\n                      A prospective longitudinal multicentre follow-up of 580 infants from birth to 3\u2009months of age in urban and suburban Benin will be performed. At delivery, and every other week, all children will be examined and clinically evaluated for occurrence of sepsis. At delivery, cord blood systematic analysis of selected plasma and transcriptomic biomarkers (procalcitonin, interleukin (IL)-6, IL-10, IP10,\n                      <jats:italic>CD74<\/jats:italic>\n                      and\n                      <jats:italic>CX3CR1<\/jats:italic>\n                      ) associated with sepsis pathophysiology will be evaluated in all live births as well as during the follow-up, and when sepsis will be suspected. In addition, whole blood response to selected innate stimuli and extensive peripheral blood mononuclear cells phenotypic characterisation will be performed. Reference intervals specific to sub-Saharan neonates will be determined from this cohort and biomarkers performances for neonatal sepsis diagnosis and prognosis tested.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>Ethical approval has been obtained from the Comit\u00e9 d\u2019Ethique de la Recherche \u2013 Institut des Sciences Biom\u00e9dicales Appliqu\u00e9es (CER-ISBA 85 - 5 April 2016, extended on 3 February 2017). Results will be disseminated through international presentations at scientific meetings and publications in peer-reviewed journals.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>\n                      ClinicalTrials.gov registration number:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" specific-use=\"clinicaltrial pre-results\" xlink:href=\"NCT03780712\">NCT03780712<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2020-036905","type":"journal-article","created":{"date-parts":[[2020,7,24]],"date-time":"2020-07-24T07:09:45Z","timestamp":1595574585000},"page":"e036905","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":9,"title":["SEPSIS project: a protocol for studying biomarkers of neonatal sepsis and immune responses of infants in a malaria-endemic region"],"prefix":"10.1136","volume":"10","clinical-trial-number":[{"clinical-trial-number":"nct03780712","registry":"10.18810\/clinical-trials-gov","type":"preResults"}],"author":[{"given":"Nadine","family":"Fievet","sequence":"first","affiliation":[{"name":"Institut de Recherche pour le D\u00e9veloppement (IRD), M\u00e8re et enfant face aux infections tropicales (UMR216), Paris, France"},{"name":"COMUE Sorbonne Paris Cit\u00e9, Universite Paris Descartes, Paris, \u00cele-de-France, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sem","family":"Ezinmegnon","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Institut de Biologie Integrative de la Cellule, Gif-sur-Yvette, France"},{"name":"Medical Diagnostic Discovery Department (MD3), bioMerieux SA, Marcy l'Etoile, Rh\u00f4ne-Alpes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gino","family":"Agbota","sequence":"additional","affiliation":[{"name":"UMR216-MERIT, French National Research Institute for Sustainable Development (IRD), Universit\u00e9 Paris Descartes, Paris, France"},{"name":"Institut de Recherche Clinique du B\u00e9nin, Calavi, Benin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darius","family":"Sossou","sequence":"additional","affiliation":[{"name":"Institut de Recherche Clinique du B\u00e9nin, Calavi, Benin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodolphe","family":"Ladekpo","sequence":"additional","affiliation":[{"name":"Institut de Recherche Clinique du B\u00e9nin, Calavi, Benin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Komi","family":"Gbedande","sequence":"additional","affiliation":[{"name":"Institut de Recherche Clinique du Benin, Cotonou, Benin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerie","family":"Briand","sequence":"additional","affiliation":[{"name":"Institut de Recherche pour le D\u00e9veloppement (IRD), M\u00e8re et enfant face aux infections tropicales (UMR216), Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilles","family":"Cottrell","sequence":"additional","affiliation":[{"name":"UMR216, Institut de Recherche pour le D\u00e9veloppement, Cotonou, Benin"},{"name":"Facult\u00e9 de Pharmacie, Universit\u00e9 Paris Descartes, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence","family":"Vachot","sequence":"additional","affiliation":[{"name":"Medical Diagnostic Discovery Department (MD3), bioMerieux SA, Marcy l'Etoile, Rh\u00f4ne-Alpes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Yugueros Marcos","sequence":"additional","affiliation":[{"name":"Medical Diagnostic Discovery Department (MD3), bioMerieux SA, Marcy l'Etoile, Rh\u00f4ne-Alpes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre","family":"Pachot","sequence":"additional","affiliation":[{"name":"EA 7426 Pathophysiology of Injury-Induced Immunosuppression, bioMerieux, LYON cedex 03, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3821-9337","authenticated-orcid":false,"given":"Julien","family":"Textoris","sequence":"additional","affiliation":[{"name":"EA 7426 Pathophysiology of Injury-Induced Immunosuppression, bioMerieux, LYON cedex 03, France"},{"name":"D\u00e9partement d'Anesth\u00e9sie et de R\u00e9animation, Hospices Civils de Lyon, LYON Cedex 03, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Blein","sequence":"additional","affiliation":[{"name":"Medical Diagnostic Discovery Department (MD3), bioMerieux SA, Marcy l'Etoile, Rh\u00f4ne-Alpes, France"},{"name":"EA 7426 Pathophysiology of Injury-Induced Immunosuppression, bioMerieux, LYON cedex 03, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrik","family":"Lausten-Thomsen","sequence":"additional","affiliation":[{"name":"Pediatric Intensive Care, Hopitaux Universitaires Paris-Sud, Le Kremlin-Bicetre, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Achille","family":"Massougbodji","sequence":"additional","affiliation":[{"name":"Facult\u00e9 des Sciences de la Sant\u00e9 (FSS), Cotonou, Benin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lehila","family":"Bagnan","sequence":"additional","affiliation":[{"name":"Institut de Recherche Clinique du B\u00e9nin, Calavi, Benin"},{"name":"Department of Paediatric, National University Hospital Center (CNHU), Cotonou, Benin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Tchiakpe","sequence":"additional","affiliation":[{"name":"Institut de Recherche Clinique du B\u00e9nin, Calavi, Benin"},{"name":"Department of Paediatric, Centre Hospitalier Universitaire de la M\u00e8re et de l'Enfant Lagune (CHUMEL), Cotonou, Benin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marceline","family":"d'Almeida","sequence":"additional","affiliation":[{"name":"Department of Paediatric, National University Hospital Center (CNHU), Cotonou, Benin"},{"name":"Institut de Recherche Clinique du Benin, Calavi, \u00cele-de-France, Benin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jules","family":"Alao","sequence":"additional","affiliation":[{"name":"CHU-MEL Hospital, Cotonou, Benin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ida","family":"Dossou-Dagba","sequence":"additional","affiliation":[{"name":"Calavi Hospital, Calavi, Benin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5423-5532","authenticated-orcid":false,"given":"Pierre","family":"Tissieres","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Institut de Biologie Integrative de la Cellule, Gif-sur-Yvette, France"},{"name":"Pediatric Intensive Care, Hopitaux Universitaires Paris-Sud, Le Kremlin-Bicetre, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2020,7,23]]},"reference":[{"key":"2025121220194110000_10.7.e036905.1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(14)70804-7"},{"key":"2025121220194110000_10.7.e036905.2","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1111\/tmi.12048","article-title":"Addressing the challenge of neonatal mortality","volume":"18","author":"Blencowe","year":"2013","journal-title":"Trop Med Int Health"},{"key":"2025121220194110000_10.7.e036905.3","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)60820-4"},{"key":"2025121220194110000_10.7.e036905.4","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0092074"},{"key":"2025121220194110000_10.7.e036905.5","doi-asserted-by":"crossref","DOI":"10.1186\/s12884-017-1479-1","article-title":"Institutional maternal and perinatal deaths: a review of 40 low and middle income countries","volume":"17","author":"Bailey","year":"2017","journal-title":"BMC Pregnancy Childbirth"},{"key":"2025121220194110000_10.7.e036905.6","doi-asserted-by":"crossref","DOI":"10.1136\/bmjgh-2017-000347","article-title":"Economic burden of neonatal sepsis in sub-Saharan Africa","volume":"3","author":"Ranjeva","year":"2018","journal-title":"BMJ Glob Health"},{"key":"2025121220194110000_10.7.e036905.7","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0000442"},{"key":"2025121220194110000_10.7.e036905.8","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(11)70341-3"},{"key":"2025121220194110000_10.7.e036905.9","doi-asserted-by":"crossref","DOI":"10.1186\/s12936-016-1417-0","article-title":"Prenatal exposure to Plasmodium falciparum increases frequency and shortens time from birth to first clinical malaria episodes during the first two years of life: prospective birth cohort study","volume":"15","author":"Sylvester","year":"2016","journal-title":"Malar J"},{"key":"2025121220194110000_10.7.e036905.10","doi-asserted-by":"crossref","DOI":"10.1186\/s12936-016-1492-2","article-title":"Prevalence of malaria in pregnancy in southern Laos: a cross-sectional survey","volume":"15","author":"Briand","year":"2016","journal-title":"Malar J"},{"key":"2025121220194110000_10.7.e036905.11","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1093\/infdis\/jiy009","article-title":"Prevalence and associated risk factors of malaria in the first trimester of pregnancy: a preconceptional cohort study in Benin","volume":"217","author":"Accrombessi","year":"2018","journal-title":"J Infect Dis"},{"key":"2025121220194110000_10.7.e036905.12","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1016\/j.molmed.2016.08.005","article-title":"Impact of in utero exposure to malaria on fetal T cell immunity","volume":"22","author":"Odorizzi","year":"2016","journal-title":"Trends Mol Med"},{"key":"2025121220194110000_10.7.e036905.13","doi-asserted-by":"crossref","DOI":"10.3389\/fmicb.2019.00068","article-title":"Fetal-derived MyD88 signaling contributes to poor pregnancy outcomes during gestational malaria","volume":"10","author":"Barboza","year":"2019","journal-title":"Front Microbiol"},{"key":"2025121220194110000_10.7.e036905.14","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.aje.a009200"},{"key":"2025121220194110000_10.7.e036905.15","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cis490"},{"key":"2025121220194110000_10.7.e036905.16","doi-asserted-by":"publisher","DOI":"10.3109\/10253890.2013.876404"},{"key":"2025121220194110000_10.7.e036905.17","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.00288"},{"key":"2025121220194110000_10.7.e036905.18","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0095867"},{"key":"2025121220194110000_10.7.e036905.19","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1159\/000358550","article-title":"Hierarchical maturation of innate immune defences in very preterm neonates","volume":"106","author":"Sharma","year":"2014","journal-title":"Neonatology"},{"key":"2025121220194110000_10.7.e036905.20","doi-asserted-by":"publisher","DOI":"10.1086\/657143"},{"key":"2025121220194110000_10.7.e036905.21","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0032863"},{"key":"2025121220194110000_10.7.e036905.22","doi-asserted-by":"publisher","DOI":"10.1586\/1744666X.2013.857275"},{"key":"2025121220194110000_10.7.e036905.23","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2009-2959"},{"key":"2025121220194110000_10.7.e036905.24","doi-asserted-by":"publisher","DOI":"10.1159\/000343260"},{"key":"2025121220194110000_10.7.e036905.25","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2011.1829"},{"key":"2025121220194110000_10.7.e036905.26","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0182427","article-title":"Human leucocyte antigen (HLA-DR) gene expression is reduced in sepsis and correlates with impaired TNF\u03b1 response: a diagnostic tool for immunosuppression?","volume":"12","author":"Winkler","year":"2017","journal-title":"PLoS One"},{"key":"2025121220194110000_10.7.e036905.27","doi-asserted-by":"crossref","DOI":"10.1186\/s12879-019-4526-x","article-title":"Multicentric experience with interferon gamma therapy in sepsis induced immunosuppression. A case series","volume":"19","author":"Payen","year":"2019","journal-title":"BMC Infect Dis"},{"key":"2025121220194110000_10.7.e036905.28","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2013.05.006"},{"key":"2025121220194110000_10.7.e036905.29","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.9.6421"},{"key":"2025121220194110000_10.7.e036905.30","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1007\/s00134-017-4805-1","article-title":"Association between mRNA expression of CD74 and IL10 and risk of ICU-acquired infections: a multicenter cohort study","volume":"43","author":"Peronnet","year":"2017","journal-title":"Intensive Care Med"},{"key":"2025121220194110000_10.7.e036905.31","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1038\/pr.2012.199","article-title":"Low monocyte HLA-DR expression as an indicator of immunodepression in very low birth weight infants","volume":"73","author":"Paloj\u00e4rvi","year":"2013","journal-title":"Pediatr Res"},{"key":"2025121220194110000_10.7.e036905.32","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0200350","article-title":"Aetiology of neonatal sepsis in Nigeria, and relevance of group B Streptococcus: a systematic review","volume":"13","author":"Medugu","year":"2018","journal-title":"PLoS One"},{"key":"2025121220194110000_10.7.e036905.33","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0222864","article-title":"Maternal malaria but not schistosomiasis is associated with a higher risk of febrile infection in infant during the first 3 months of life: a mother-child cohort in Benin","volume":"14","author":"Agbota","year":"2019","journal-title":"PLoS One"},{"key":"2025121220194110000_10.7.e036905.34","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00237-13"},{"key":"2025121220194110000_10.7.e036905.35","doi-asserted-by":"crossref","DOI":"10.1186\/s12936-018-2315-4","article-title":"Malaria incidence and prevalence during the first year of life in Nanoro, Burkina Faso: a birth-cohort study","volume":"17","author":"Natama","year":"2018","journal-title":"Malar J"},{"key":"2025121220194110000_10.7.e036905.36","doi-asserted-by":"publisher","DOI":"10.1086\/591057"},{"key":"2025121220194110000_10.7.e036905.37","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0139606","article-title":"Infants' peripheral blood lymphocyte composition reflects both maternal and post-natal infection with Plasmodium falciparum","volume":"10","author":"Nouatin","year":"2015","journal-title":"PLoS One"},{"key":"2025121220194110000_10.7.e036905.38","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.12.7988-7995.2005"},{"key":"2025121220194110000_10.7.e036905.39","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0809742106"},{"key":"2025121220194110000_10.7.e036905.40","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1001188"},{"key":"2025121220194110000_10.7.e036905.41","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2017-019014"},{"key":"2025121220194110000_10.7.e036905.42","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)31444-7"},{"key":"2025121220194110000_10.7.e036905.43","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2875-10-223"},{"key":"2025121220194110000_10.7.e036905.44","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1302990"},{"key":"2025121220194110000_10.7.e036905.45","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1016\/j.jaci.2015.03.022","article-title":"Higher B-cell activating factor levels at birth are positively associated with maternal dairy farm exposure and negatively related to allergy development","volume":"136","author":"Lundell","year":"2015","journal-title":"J Allergy Clin Immunol"},{"key":"2025121220194110000_10.7.e036905.46","doi-asserted-by":"crossref","first-page":"2582","DOI":"10.1002\/eji.201445371","article-title":"Neonatal regulatory T cells have reduced capacity to suppress dendritic cell function","volume":"45","author":"Rueda","year":"2015","journal-title":"Eur J Immunol"},{"key":"2025121220194110000_10.7.e036905.47","doi-asserted-by":"publisher","DOI":"10.1016\/j.humimm.2014.10.016"},{"key":"2025121220194110000_10.7.e036905.48","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1111\/sji.12435","article-title":"Healthy preterm newborns show an increased frequency of CD4(+) CD25(high) CD127(low) FOXP3(+) regulatory T cells with a naive phenotype and high expression of gut-homing receptors","volume":"83","author":"Renn\u00f3","year":"2016","journal-title":"Scand J Immunol"}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2020-036905","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T04:19:49Z","timestamp":1765599589000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2020-036905"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7]]},"references-count":48,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2020,7,23]]},"published-print":{"date-parts":[[2020,7]]}},"alternative-id":["10.1136\/bmjopen-2020-036905"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2020-036905","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"value":"2044-6055","type":"print"},{"value":"2044-6055","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7]]}}}