World Health Organization Danger Signs to predict bacterial sepsis in young infants: A pragmatic cohort study

Omolabake Akinseye; Constantin R Popescu; Msandeni Chiume-Kayuni; Michael A Irvine; Norman Lufesi; Tisungane Mvalo; Niranjan Kissoon; Matthew O Wiens; Pascal M Lavoie

doi:10.1371/journal.pgph.0001990

World Health Organization Danger Signs to predict bacterial sepsis in young infants: A pragmatic cohort study

PLOS Glob Public Health. 2023 Nov 21;3(11):e0001990. doi: 10.1371/journal.pgph.0001990. eCollection 2023.

Authors

Omolabake Akinseye¹, Constantin R Popescu^{2

3}, Msandeni Chiume-Kayuni^{4

5}, Michael A Irvine^{6

7}, Norman Lufesi⁸, Tisungane Mvalo^{9

10}, Niranjan Kissoon^{1

2}, Matthew O Wiens¹¹, Pascal M Lavoie^{1

2}

Affiliations

¹ Department of Pediatrics, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
² British Columbia Children's Hospital Research Institute, Vancouver, Canada.
³ Department of Pediatrics, Université Laval, Québec, Canada.
⁴ Department of Pediatrics, Kamuzu Central Hospital, Lilongwe, Malawi.
⁵ Kamuzu University of Health Sciences, Lilongwe, Malawi.
⁶ British Columbia Centre for Disease Control, Vancouver, Canada.
⁷ Faculty of Health Sciences, Simon Fraser University, Burnaby, Canada.
⁸ Department of Curative and Medical Rehabilitation, Ministry of Health, Lilongwe, Malawi.
⁹ University of North Carolina Project Malawi, Lilongwe, Malawi.
¹⁰ Department of Pediatrics, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, United States of America.
¹¹ Department of Anesthesiology, Pharmacology & Therapeutics, Faculty of Medicine, University of British Columbia, Vancouver, Canada.

Abstract

Bacterial sepsis is generally a major concern in ill infants. To help triaging decisions by front-line health workers in these situations, the World Health Organization (WHO) has developed danger signs (DS). The objective of this study was to evaluate the extent to which nine DS predict bacterial sepsis in young infants presenting with suspected sepsis in a low-income country setting. The study pragmatically evaluated nine DS in infants younger than 3 months with suspected sepsis in a regional hospital in Lilongwe, Malawi, between June 2018 and April 2020. Main outcomes were positive blood or cerebrospinal fluid (CSF) cultures for neonatal pathogens, and mortality. Among 401 infants (gestational age [mean ± SD]: 37.1±3.3 weeks, birth weight 2865±785 grams), 41 had positive blood or CSF cultures for a neonatal pathogen. In-hospital mortality occurred in 9.7% of infants overall (N = 39/401), of which 61.5% (24/39) occurred within 48 hours of admission. Mortality was higher in infants with bacterial sepsis compared to other infants (22.0% [9/41] versus 8.3% [30/360]; p = 0.005). All DS were associated with mortality except for temperature instability and tachypnea, whereas none of the DS were significantly associated with bacterial sepsis, except for "unable to feed" (OR 2.25; 95%CI: 1.17-4.44; p = 0.017). The number of DS predicted mortality (OR: 1.75; 95%CI: 1.43-2.17; p<0.001; AUC: 0.756), but was marginally associated with positive cultures with a neonatal pathogen (OR 1.22; 95%CI: 1.00-1.49; p = 0.046; AUC: 0.743). The association between number of DS and mortality remained significant after adjusting for admission weight, the only statistically significant co-variable (OR 1.75 [95% CI: 1.39-2.23]; p<0.001). Considering all positive cultures including potential bacterial contaminants resulted a non-significant association between number of DS and sepsis (OR 1.09 [95% CI: 0.93-1.28]; p = 0.273). In conclusion, this study shows that DS were strongly associated with death, but were marginally associated with culture-positive pathogen sepsis in a regional hospital setting. These data imply that the incidence of bacterial sepsis and attributable mortality in infants in LMIC settings may be inaccurately estimated based on clinical signs alone.

Copyright: © 2023 Akinseye et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Grants and funding

This study was support by a grant from Grand Challenges Canada (R-ST-POC-1707-04630). PML was supported by the BC Children’s Hospital Research Foundation through the Investigator Grant Award Program. CRP was funded by a Sue Carruthers Graduate Studentship from the BC Children’s Hospital Foundation. TM also received a Grand Challenges Exploration grant from the Bill and Melinda Gates Foundation (OPP1211936). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.