SEPSIS project: a protocol for studying biomarkers of neonatal sepsis and immune responses of infants in a malaria-endemic region

Introduction 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...

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Main Authors: Karen Brengel-Pesce, Achille Massougbodji, Ida Dossou-Dagba, Dissou Affolabi, Darius Sossou, Benjamin Hounkpatin, Ulrik Lausten-Thomsen, Jules Alao, Nadine Fievet, Alexandre Pachot, Valerie Briand, Sem Ezinmegnon, Gino Agbota, Rodolphe Ladekpo, Komi Gbedande, Gilles Cottrell, Laurence Vachot, Javier Yugueros Marcos, Julien Textoris, Sophie Blein, Lehila Bagnan, Nicole Tchiakpe, Marceline d'Almeida, Pierre Tissieres, Aurax Fernando, Urbain Ahouayito, Basile Agossou, Caleb Ezinmegnon, Anauel Fortunato, Josué Fiagbenou, Djamirou Dossa, Dramane Abdou, Canisius Fantodji, Nawal Sare, Wilisto Bara, Razack Monde, Erasme Gbagidi, Larissa Allokpe, Armand Housemenou, Landry Assongba, Manfred Accrombessi, Florent Kouhouenou, Armand Hounsemenou, Amour Ridagba, Christiane Aguemon, Réné Perrin, Dossou Dagba, Luis Augusto, Sophie Thibault, François Bartolo, Marine Mommert
Format: Article
Language:English
Published: BMJ Publishing Group 2020-07-01
Series:BMJ Open
Online Access:https://bmjopen.bmj.com/content/10/7/e036905.full
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author Karen Brengel-Pesce
Achille Massougbodji
Ida Dossou-Dagba
Dissou Affolabi
Darius Sossou
Benjamin Hounkpatin
Ulrik Lausten-Thomsen
Jules Alao
Nadine Fievet
Alexandre Pachot
Valerie Briand
Sem Ezinmegnon
Gino Agbota
Rodolphe Ladekpo
Komi Gbedande
Gilles Cottrell
Laurence Vachot
Javier Yugueros Marcos
Julien Textoris
Sophie Blein
Lehila Bagnan
Nicole Tchiakpe
Marceline d'Almeida
Pierre Tissieres
Aurax Fernando
Urbain Ahouayito
Basile Agossou
Caleb Ezinmegnon
Anauel Fortunato
Josué Fiagbenou
Djamirou Dossa
Dramane Abdou
Canisius Fantodji
Nawal Sare
Wilisto Bara
Razack Monde
Erasme Gbagidi
Larissa Allokpe
Armand Housemenou
Landry Assongba
Manfred Accrombessi
Florent Kouhouenou
Armand Hounsemenou
Amour Ridagba
Christiane Aguemon
Réné Perrin
Dossou Dagba
Luis Augusto
Sophie Thibault
François Bartolo
Marine Mommert
author_facet Karen Brengel-Pesce
Achille Massougbodji
Ida Dossou-Dagba
Dissou Affolabi
Darius Sossou
Benjamin Hounkpatin
Ulrik Lausten-Thomsen
Jules Alao
Nadine Fievet
Alexandre Pachot
Valerie Briand
Sem Ezinmegnon
Gino Agbota
Rodolphe Ladekpo
Komi Gbedande
Gilles Cottrell
Laurence Vachot
Javier Yugueros Marcos
Julien Textoris
Sophie Blein
Lehila Bagnan
Nicole Tchiakpe
Marceline d'Almeida
Pierre Tissieres
Aurax Fernando
Urbain Ahouayito
Basile Agossou
Caleb Ezinmegnon
Anauel Fortunato
Josué Fiagbenou
Djamirou Dossa
Dramane Abdou
Canisius Fantodji
Nawal Sare
Wilisto Bara
Razack Monde
Erasme Gbagidi
Larissa Allokpe
Armand Housemenou
Landry Assongba
Manfred Accrombessi
Florent Kouhouenou
Armand Hounsemenou
Amour Ridagba
Christiane Aguemon
Réné Perrin
Dossou Dagba
Luis Augusto
Sophie Thibault
François Bartolo
Marine Mommert
author_sort Karen Brengel-Pesce
collection DOAJ
description Introduction 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.Methods and analysis A prospective longitudinal multicentre follow-up of 580 infants from birth to 3 months 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, CD74 and CX3CR1) 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.Ethics and dissemination Ethical approval has been obtained from the Comité d’Ethique de la Recherche – Institut des Sciences Biomédicales Appliquées (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.Trial registration number ClinicalTrials.gov registration number: NCT03780712.
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spelling doaj-art-e9cab5a800dd4fe4be4bd88d966b47952024-12-04T09:10:08ZengBMJ Publishing GroupBMJ Open2044-60552020-07-0110710.1136/bmjopen-2020-036905SEPSIS project: a protocol for studying biomarkers of neonatal sepsis and immune responses of infants in a malaria-endemic regionKaren Brengel-PesceAchille Massougbodji0Ida Dossou-Dagba1Dissou Affolabi2Darius Sossou3Benjamin Hounkpatin4Ulrik Lausten-Thomsen5Jules Alao6Nadine Fievet7Alexandre Pachot8Valerie Briand9Sem Ezinmegnon10Gino Agbota11Rodolphe Ladekpo12Komi Gbedande13Gilles Cottrell14Laurence Vachot15Javier Yugueros Marcos16Julien Textoris17Sophie Blein18Lehila Bagnan19Nicole Tchiakpe20Marceline d'Almeida21Pierre Tissieres22Aurax FernandoUrbain AhouayitoBasile AgossouCaleb EzinmegnonAnauel FortunatoJosué FiagbenouDjamirou DossaDramane AbdouCanisius Fantodji23Nawal SareWilisto BaraRazack MondeErasme GbagidiLarissa AllokpeArmand HousemenouLandry AssongbaManfred AccrombessiFlorent KouhouenouArmand HounsemenouAmour RidagbaChristiane AguemonRéné PerrinDossou DagbaLuis AugustoSophie ThibaultFrançois BartoloMarine MommertFaculté des Sciences de la Santé, Université d`Abomey-Calavi, Cotonou, Littoral, Benin6 Paediatric Department, Calavi Hospital, Calavi, Benin5 Centre National Hospitalier Universitaire de Pneumo-Phtisiologie, Cotonou, BeninInstitut de Recherche Clinique du Bénin, Calavi, Benin5University of Abomey Calavi, BP, BeninPediatric Intensive Care, Hopitaux Universitaires Paris-Sud, Le Kremlin-Bicetre, FrancePaediatric Department, Mother and Child University and Hospital Center (CHU-MEL), Cotonou, BeninMERIT (Mère et Enfant Face aux Infections Tropicales)-UMR 216, Institut de Recherche pour le Développement (IRD), Université Paris Descartes, Paris, FranceEA 7426 Pathophysiology of Injury-Induced Immunosuppression, bioMerieux, LYON cedex 03, FranceInstitut de Recherche pour le Développement (IRD), Mère et enfant face aux infections tropicales (UMR216), Paris, FranceDepartment of Microbiology, Institut de Biologie Integrative de la Cellule, Gif-sur-Yvette, FranceUMR216-MERIT, French National Research Institute for Sustainable Development (IRD), Université Paris Descartes, Paris, FranceInstitut de Recherche Clinique du Bénin, Calavi, BeninInstitut de Recherche Clinique du Benin, Cotonou, BeninUMR216, Institut de Recherche pour le Développement, Cotonou, BeninMedical Diagnostic Discovery Department (MD3), bioMerieux SA, Marcy l`Etoile, Rhône-Alpes, FranceMedical Diagnostic Discovery Department (MD3), bioMerieux SA, Marcy l`Etoile, Rhône-Alpes, FranceEA 7426 Pathophysiology of Injury-Induced Immunosuppression, bioMerieux, LYON cedex 03, FranceMedical Diagnostic Discovery Department (MD3), bioMerieux SA, Marcy l`Etoile, Rhône-Alpes, FranceInstitut de Recherche Clinique du Bénin, Calavi, BeninInstitut de Recherche Clinique du Bénin, Calavi, BeninDepartment of Paediatric, National University Hospital Center (CNHU), Cotonou, BeninPaediatric Intensive Care Unit, Hospital Bicetre, Le Kremlin-Bicetre, Île-de-France, France1Centre Armand-Frappier Santé Biotechnologie, Institut national de la recherche scientifique, Laval, QC, CanadaIntroduction 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.Methods and analysis A prospective longitudinal multicentre follow-up of 580 infants from birth to 3 months 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, CD74 and CX3CR1) 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.Ethics and dissemination Ethical approval has been obtained from the Comité d’Ethique de la Recherche – Institut des Sciences Biomédicales Appliquées (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.Trial registration number ClinicalTrials.gov registration number: NCT03780712.https://bmjopen.bmj.com/content/10/7/e036905.full
spellingShingle Karen Brengel-Pesce
Achille Massougbodji
Ida Dossou-Dagba
Dissou Affolabi
Darius Sossou
Benjamin Hounkpatin
Ulrik Lausten-Thomsen
Jules Alao
Nadine Fievet
Alexandre Pachot
Valerie Briand
Sem Ezinmegnon
Gino Agbota
Rodolphe Ladekpo
Komi Gbedande
Gilles Cottrell
Laurence Vachot
Javier Yugueros Marcos
Julien Textoris
Sophie Blein
Lehila Bagnan
Nicole Tchiakpe
Marceline d'Almeida
Pierre Tissieres
Aurax Fernando
Urbain Ahouayito
Basile Agossou
Caleb Ezinmegnon
Anauel Fortunato
Josué Fiagbenou
Djamirou Dossa
Dramane Abdou
Canisius Fantodji
Nawal Sare
Wilisto Bara
Razack Monde
Erasme Gbagidi
Larissa Allokpe
Armand Housemenou
Landry Assongba
Manfred Accrombessi
Florent Kouhouenou
Armand Hounsemenou
Amour Ridagba
Christiane Aguemon
Réné Perrin
Dossou Dagba
Luis Augusto
Sophie Thibault
François Bartolo
Marine Mommert
SEPSIS project: a protocol for studying biomarkers of neonatal sepsis and immune responses of infants in a malaria-endemic region
BMJ Open
title SEPSIS project: a protocol for studying biomarkers of neonatal sepsis and immune responses of infants in a malaria-endemic region
title_full SEPSIS project: a protocol for studying biomarkers of neonatal sepsis and immune responses of infants in a malaria-endemic region
title_fullStr SEPSIS project: a protocol for studying biomarkers of neonatal sepsis and immune responses of infants in a malaria-endemic region
title_full_unstemmed SEPSIS project: a protocol for studying biomarkers of neonatal sepsis and immune responses of infants in a malaria-endemic region
title_short SEPSIS project: a protocol for studying biomarkers of neonatal sepsis and immune responses of infants in a malaria-endemic region
title_sort sepsis project a protocol for studying biomarkers of neonatal sepsis and immune responses of infants in a malaria endemic region
url https://bmjopen.bmj.com/content/10/7/e036905.full
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