{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T16:03:00Z","timestamp":1777564980357,"version":"3.51.4"},"reference-count":25,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2023,11,21]],"date-time":"2023-11-21T00:00:00Z","timestamp":1700524800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004828","name":"Grand Challenges Canada","doi-asserted-by":"publisher","award":["R-ST-POC-1707-04630"],"award-info":[{"award-number":["R-ST-POC-1707-04630"]}],"id":[{"id":"10.13039\/501100004828","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011775","name":"BC Children\u2019s Hospital Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011775","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011775","name":"BC Children\u2019s Hospital Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011775","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosglobalpublichealth.org"],"crossmark-restriction":false},"short-container-title":["PLOS Glob Public Health"],"abstract":"<jats:p>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 \u00b1 SD]: 37.1\u00b13.3 weeks, birth weight 2865\u00b1785 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 \u201cunable to feed\u201d (OR 2.25; 95%CI: 1.17\u20134.44; p = 0.017). The number of DS predicted mortality (OR: 1.75; 95%CI: 1.43\u20132.17; p&lt;0.001; AUC: 0.756), but was marginally associated with positive cultures with a neonatal pathogen (OR 1.22; 95%CI: 1.00\u20131.49; 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\u20132.23]; p&lt;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\u20131.28]; 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.<\/jats:p>","DOI":"10.1371\/journal.pgph.0001990","type":"journal-article","created":{"date-parts":[[2023,11,21]],"date-time":"2023-11-21T18:24:36Z","timestamp":1700591076000},"page":"e0001990","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgph.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["World Health Organization Danger Signs to predict bacterial sepsis in young infants: A pragmatic cohort study"],"prefix":"10.1371","volume":"3","author":[{"given":"Omolabake","family":"Akinseye","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Constantin R.","family":"Popescu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Msandeni","family":"Chiume-Kayuni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4785-8998","authenticated-orcid":true,"given":"Michael A.","family":"Irvine","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Norman","family":"Lufesi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6775-7919","authenticated-orcid":true,"given":"Tisungane","family":"Mvalo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7853-4075","authenticated-orcid":true,"given":"Niranjan","family":"Kissoon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3287-5181","authenticated-orcid":true,"given":"Matthew O.","family":"Wiens","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2205-0362","authenticated-orcid":true,"given":"Pascal M.","family":"Lavoie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2023,11,21]]},"reference":[{"issue":"10100","key":"pgph.0001990.ref001","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1016\/S0140-6736(17)32152-9","article-title":"Global, regional, and national age-sex specific mortality for 264 causes of death, 1980\u20132016: a systematic analysis for the Global Burden of Disease Study 2016.","volume":"390","author":"GBD 2016 Causes of Death Collaborators","year":"2017","journal-title":"Lancet"},{"issue":"10219","key":"pgph.0001990.ref002","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/S0140-6736(19)32989-7","article-title":"Global, regional, and national sepsis incidence and mortality, 1990\u20132017: analysis for the Global Burden of Disease Study","volume":"395","author":"KE Rudd","year":"2020","journal-title":"Lancet"},{"issue":"3","key":"pgph.0001990.ref003","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/S2213-2600(18)30063-8","article-title":"The global burden of paediatric and neonatal sepsis: a systematic review","volume":"6","author":"C Fleischmann-Struzek","year":"2018","journal-title":"Lancet Respir Med"},{"key":"pgph.0001990.ref004","doi-asserted-by":"crossref","first-page":"c2096","DOI":"10.1136\/bmj.c2096","article-title":"Effect of antibiotic prescribing in primary care on antimicrobial resistance in individual patients: systematic review and meta-analysis","volume":"340","author":"C Costelloe","year":"2010","journal-title":"BMJ"},{"key":"pgph.0001990.ref005","doi-asserted-by":"crossref","first-page":"285","DOI":"10.3389\/fped.2018.00285","article-title":"Culture-Negative Early-Onset Neonatal Sepsis\u2014At the Crossroad Between Efficient Sepsis Care and Antimicrobial Stewardship","volume":"6","author":"C Klingenberg","year":"2018","journal-title":"Front Pediatr."},{"issue":"9087","key":"pgph.0001990.ref006","doi-asserted-by":"crossref","first-page":"1266","DOI":"10.1016\/S0140-6736(05)62471-3","article-title":"Integrated management of childhood illness","volume":"350","author":"A. 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