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

Background: Few biomarkers for sepsis diagnosis are commonly used in neonatal sepsis. Whilst host response is increasingly recognized in sepsis pathogenesis and prognosis, there is a need for evaluating the accuracy of 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. Methods: Prospective multicentre study conducted between April 2016 and March 2018 in three University hospitals and two sub-urbans healthcare centres in the south Benin region. Patients were followed 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. Results: From April 17, 2016 through March 12, 2018, a total of 581 newborns were enrolled. One hundred and seventy-two newborns developed neonatal sepsis (29.6%) and death occurred in forty-nine infants (8.4%). Among all tested biomarkers and clinical criteria, CD74/IP-10 ratio showed the best accuracy for neonatal sepsis diagnosis, while PCT accuracy was low. Among biomarkers and clinical criteria studied, only CD74 and PCT were independently associated with mortality, with CD74 showing an elevated predictive accuracy. Conclusion: Cord blood PCT had a low accuracy for diagnosing early onset neonatal sepsis in Sub Saharan African neonates, while CD74/IP-10 ratio had the best diagnostic accuracy. CD74 expression at birth had the best accuracy in prognosing sepsis mortality.Trial registration: Clinicaltrial.gov registration number: NCT03780712. Registered 19 December 2018. Retrospectively registered