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1. Prospective multicentre study of host response signatures in neonatal sepsis in Sub Saharan Africa

Author

Sem Ezinmegnon, Marine Mommert, Francois Bartolo, Gino Agbota, Sossou Darius, Valérie Briand, Marceline d’Almeida, Maroufou Jules Alao, Ida Dossou-Dagba, Achille Massougbodji, Ulrik Lausten-Thomsen, Alexandre Pachot, Laurence Vachot, Javier Yugueros-Marcos, Karen Brengel-Pesce, Nadine Fievet, and Pierre Tissieres

Subjects
Medicine, Science
Abstract

Abstract Few biomarkers for sepsis diagnosis are commonly used in neonatal sepsis. While the role of host response is increasingly recognized in sepsis pathogenesis and prognosis, there is a need for evaluating new biomarkers targeting host response in regions where sepsis burden is high and medico-economic resources are scarce. The objective of the study is to evaluate diagnostic and prognostic accuracy of biomarkers of neonatal sepsis in Sub Saharan Africa. This prospective multicentre study included newborn infants delivered in the Abomey-Calavi region in South Benin and their follow-up from birth to 3 months of age. Accuracy of transcriptional (CD74, CX3CR1), proteic (PCT, IL-6, IL-10, IP-10) biomarkers and clinical characteristics to diagnose and prognose neonatal sepsis were measured. At delivery, cord blood from all consecutive newborns were sampled and analysed, and infants were followed for a 12 weeks’ period. Five hundred and eighty-one newborns were enrolled. One hundred and seventy-two newborns developed neonatal sepsis (29.6%) and death occurred in forty-nine infants (8.4%). Although PCT, IL-6 and IP-10 levels were independently associated with sepsis diagnosis, diagnostic accuracy of clinical variables combinations was similar to combinations with biomarkers and superior to biomarkers alone. Nonetheless, CD74, being the only biomarkers independently associated with mortality, showed elevated prognosis accuracy (AUC > 0.9) either alone or in combination with other biomarkers (eg. CD74/IP-10) or clinical criterion (eg. Apgar 1, birth weight). These results suggest that cord blood PCT had a low accuracy for diagnosing early onset neonatal sepsis in Sub Saharan African neonates, while association of clinical criterion showed to be more accurate than any biomarkers taken independently. At birth, CD74, either associated with IP-10 or clinical criterion, had the best accuracy in prognosing sepsis mortality. Trial registration Clinicaltrial.gov registration number: NCT03780712. Registered 19 December 2018. Retrospectively registered.

Published
2022
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2. A stratification strategy to predict secondary infection in critical illness-induced immune dysfunction: the REALIST score

Author

Tremblay, Jan-Alexis, Peron, Florian, Kreitmann, Louis, Textoris, Julien, Brengel-Pesce, Karen, Lukaszewicz, Anne-Claire, Quemeneur, Laurence, Vedrine, Christophe, Tan, Lionel, Venet, Fabienne, Rimmele, Thomas, Monneret, Guillaume, Delphine Maucort Boulch, Delphine, Physiopathologie de l'immunodépression associée aux réponses inflammatoires systémiques / Pathophysiology of Injury-induced Immunosuppression (PI3), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Hôpital Maisonneuve-Rosemont, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Sanofi Pasteur [Marcy-l'Étoile, France], BIOASTER Microbiology Technology Institute [Lyon], GlaxoSmithKline [Headquarters, London, UK] (GSK), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Biostatistiques [Lyon], and REALISM study group: Sophie Arnal, Caroline Augris-Mathieu, Frédérique Bayle, Liana Caruso, Charles-Eric Ber, Asma Ben-Amor, Anne-Sophie Bellocq, Farida Benatir, Anne Bertin-Maghit, Marc Bertin-Maghit, André Boibieux, Yves Bouffard, Jean-Christophe Cejka, Valérie Cerro, Jullien Crozon-Clauzel, Julien Davidson, Sophie Debord-Peguet, Benjamin Delwarde, Robert Deleat-Besson, Claire Delsuc, Bertrand Devigne, Laure Fayolle-Pivot, Alexandre Faure, Bernard Floccard, Julie Gatel, Charline Genin, Thibaut Girardot, Arnaud Gregoire, Baptiste Hengy, Laetitia Huriaux, Catherine Jadaud, Alain Lepape, Véronique Leray, Anne-Claire Lukaszewicz, Guillaume Marcotte, Olivier Martin, Marie Matray, Delphine Maucort-Boulch, Pascal Meuret, Céline Monard, Florent Moriceau, Guillaume Monneret, Nathalie Panel, Najia Rahali, Thomas Rimmele, Cyrille Truc, Thomas Uberti, Hélène Vallin, Fabienne Venet, Sylvie Tissot, Abbès Zadam, Sophie Blein, Karen Brengel-Pesce, Elisabeth Cerrato, Valerie Cheynet, Emmanuelle Gallet-Gorius, Audrey Guichard, Camille Jourdan, Natacha Koenig, François Mallet, Boris Meunier, Virginie Moucadel, Marine Mommert, Guy Oriol, Alexandre Pachot, Estelle Peronnet, Claire Schrevel, Olivier Tabone, Julien Textoris, Javier Yugueros Marcos, Jeremie Becker, Frederic Bequet, Yacine Bounab, Florian Brajon, Bertrand Canard, Muriel Collus, Nathalie Garcon, Irene Gorse, Cyril Guyard, Fabien Lavocat, Philippe Leissner, Karen Louis, Maxime Mistretta, Jeanne Moriniere, Yoann Mouscaz, Laura Noailles, Magali Perret, Frederic Reynier, Cindy Riffaud, Mary-Luz Rol, Nicolas Sapay, Trang Tran, Christophe Vedrine, Christophe Carre, Pierre Cortez, Aymeric Monfort, Karine Florin, Laurent Fraisse, Isabelle Fugier, Sandrine Payrard, Annick Peleraux, Laurence Quemeneur, Andrew Griffiths, Stephanie Toetsch, Teri Ashton, Peter J Gough, Scott B Berger, David Gardiner, Iain Gillespie, Aidan Macnamara, Aparna Raychaudhuri, Rob Smylie, Lionel Tan, Craig Tipple.

Subjects
Critical care, Secondary infection, Sepsis, [SDV]Life Sciences [q-bio], HLA-DR, IL-10, Neutrophil, Critical Care and Intensive Care Medicine, Immunosuppression
Abstract

Background Although multiple individual immune parameters have been demonstrated to predict the occurrence of secondary infection after critical illness, significant questions remain with regards to the selection, timing and clinical utility of such immune monitoring tests. Research question As a sub-study of the REALISM study, the REALIST score was developed as a pragmatic approach to help clinicians better identify and stratify patients at high risk for secondary infection, using a simple set of relatively available and technically robust biomarkers. Study design and methods This is a sub-study of a single-centre prospective cohort study of immune profiling in critically ill adults admitted after severe trauma, major surgery or sepsis/septic shock. For the REALIST score, five immune parameters were pre-emptively selected based on their clinical applicability and technical robustness. Predictive power of different parameters and combinations of parameters was assessed. The main outcome of interest was the occurrence of secondary infection within 30 days. Results After excluding statistically redundant and poorly predictive parameters, three parameters remained in the REALIST score: mHLA-DR, percentage of immature (CD10− CD16−) neutrophils and serum IL-10 level. In the cohort of interest (n = 189), incidence of secondary infection at day 30 increased from 8% for patients with REALIST score of 0 to 46% in patients with a score of 3 abnormal parameters, measured ad D5–7. When adjusted for a priori identified clinical risk factors for secondary infection (SOFA score and invasive mechanical ventilation at D5–7), a higher REALIST score was independently associated with increased risk of secondary infection (42 events (22.2%), adjusted HR 3.22 (1.09–9.50), p = 0.034) and mortality (10 events (5.3%), p = 0.001). Interpretation We derived and presented the REALIST score, a simple and pragmatic stratification strategy which provides clinicians with a clear assessment of the immune status of their patients. This new tool could help optimize care of these individuals and could contribute in designing future trials of immune stimulation strategies. Graphical Abstract

Published
2022
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