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

Abstract

IntroductionNeonatal 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 analysisA 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 disseminationEthical 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 numberClinicalTrials.gov registration number: NCT03780712.

Host Immunity Biomarkers of Neonatal Sepsis: A Prospective, Multicentre Study in Sub Saharan Africa

“…Neonatal sepsis that occurred within the rst 72 hours following birth was considered as an early onset neonatal sepsis (EONS), and late onset (LONS) thereafter (for detailed algorithm for sepsis diagnosis, see published study protocol 44 ).…”

Host Immunity Biomarkers of Neonatal Sepsis: a Prospective, Multicentre Study in Sub Saharan Africa

“…Neonatal sepsis diagnosis was established by the local paediatrician based on the clinical examination of the child and initial laboratory workup including haemogram, C-reactive protein (CRP) and microbiological cultures (blood, cerebral uids and urine). Neonatal sepsis that occurred within the rst 72 hours following birth was considered as an early onset neonatal sepsis (EONS), and late onset (LONS) thereafter (for detailed algorithm for sepsis diagnosis, see published study protocol [44]).…”

“…For both study arms, placental blood smear and mother's peripheral blood smear were performed. The Lambaréné technique was used to quantify parasitaemia with a detection threshold of ve parasites per microliter [44].…”

“…Blood samples were obtained at birth, then at week (W)1, W4, W8 and W12. The study protocol has been described in detail elsewhere [44]. Sampling and analytical methods are presented in Supplementary Appendix 2…”

Nosocomial SARS-CoV-2 transmission in a neonatal unit in Botswana: chronic overcrowding meets a novel pathogen

“…Prolonged use of postnatal antibiotics has been shown to increase the risk of NEC, possibly due to perturbations of the developing microbiome 18 19. The emergence of this novel disease and the antimicrobial courses it elicited underscores the need for greater availability of laboratory biomarkers for sepsis, like C reactive protein and procalcitonin, in low-resource settings 20. These, together with forthcoming consensus on classic clinical signs of COVID-19 in the neonatal population, may help clinicians distinguish between bacterial, viral and non-infectious aetiologies of sick neonates.…”