World Health Organization Danger Signs to predict bacterial sepsis in newborns: A pragmatic prospective cohort study

BackgroundThe World Health Organization (WHO) has developed danger signs (DS) to help front-line health workers triage interventions in children with severe illnesses. Our objective was to evaluate the extent to which DS predict bacterial sepsis in young infants presenting with acute illness. Methodology/Principal FindingsThis prospective study evaluated nine DS in infants younger than 3 months with suspected sepsis in a large regional hospital in Lilongwe, Malawi, between June 2018 and April 2020. The main outcomes were positive blood or cerebrospinal fluid (CSF) cultures and mortality. Blood (n=85/401) and CSF (n=2/204) cultures were positive in 21.2% and 1% of infants, respectively (N=401; gestational age mean {+/-} SD: 37.1{+/-}3.3 weeks, birth weight 2865{+/-}785 grams). In-hospital deaths occurred in 9.7% (N=39/401) of infants (61.5% within 48h of admission). In univariate analyses, all DS were associated with mortality except for temperature instability and tachypnea, whereas "infant was unable to feed" was the only DS significantly associated with bacterial sepsis. After co-variable adjustments, number of DS predicted mortality (OR: 1.75; 95%CI: 1.43-2.16; p<0.001; AUC-ROC: 0.756) but not positive cultures (OR 1.08; 95%CI: 0.92-1.30; p=0.336). Whether potential bacterial contaminants were included or not did not change results meaningfully. Conclusion/SignificanceDS predicted fatal outcomes but not positive cultures in a large regional hospital setting. These data imply that the incidence of bacterial sepsis and attributable mortality are unlikely to be accurate based on clinical signs alone, in infants in LMIC settings.