{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,8]],"date-time":"2026-08-08T16:45:15Z","timestamp":1786207515646,"version":"build-2736575974"},"reference-count":64,"publisher":"BMJ","issue":"1","license":[{"start":{"date-parts":[[2021,1,20]],"date-time":"2021-01-20T00:00:00Z","timestamp":1611100800000},"content-version":"unspecified","delay-in-days":19,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Tropical Health Education Trust"},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["106698Z\/14\/Z"],"award-info":[{"award-number":["106698Z\/14\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011318","name":"Fondation Botnar","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100011318","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Glob Health"],"accepted":{"date-parts":[[2020,12,19]]},"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:sec>\n                  <jats:title>Introduction<\/jats:title>\n                  <jats:p>Early identification of children at risk of severe febrile illness can optimise referral, admission and treatment decisions, particularly in resource-limited settings. We aimed to identify prognostic clinical and laboratory factors that predict progression to severe disease in febrile children presenting from the community.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We systematically reviewed publications retrieved from MEDLINE, Web of Science and Embase between 31 May 1999 and 30 April 2020, supplemented by hand search of reference lists and consultation with an expert Technical Advisory Panel. Studies evaluating prognostic factors or clinical prediction models in children presenting from the community with febrile illnesses were eligible. The primary outcome was any objective measure of disease severity ascertained within 30 days of enrolment. We calculated unadjusted likelihood ratios (LRs) for comparison of prognostic factors, and compared clinical prediction models using the area under the receiver operating characteristic curves (AUROCs). Risk of bias and applicability of studies were assessed using the Prediction Model Risk of Bias Assessment Tool and the Quality In Prognosis Studies tool.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Of 5949 articles identified, 18 studies evaluating 200 prognostic factors and 25 clinical prediction models in 24 530 children were included. Heterogeneity between studies precluded formal meta-analysis. Malnutrition (positive LR range 1.56\u201311.13), hypoxia (2.10\u20138.11), altered consciousness (1.24\u201314.02), and markers of acidosis (1.36\u20137.71) and poor peripheral perfusion (1.78\u201317.38) were the most common predictors of severe disease. Clinical prediction model performance varied widely (AUROC range 0.49\u20130.97). Concerns regarding applicability were identified and most studies were at high risk of bias.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Few studies address this important public health question. We identified prognostic factors from a wide range of geographic contexts that can help clinicians assess febrile children at risk of progressing to severe disease. Multicentre studies that include outpatients are required to explore generalisability and develop data-driven tools to support patient prioritisation and triage at the community level.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>PROSPERO registration number<\/jats:title>\n                  <jats:p>CRD42019140542.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/bmjgh-2020-003451","type":"journal-article","created":{"date-parts":[[2021,1,20]],"date-time":"2021-01-20T12:05:57Z","timestamp":1611144357000},"page":"e003451","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":26,"title":["Predictors of disease severity in children presenting from the community with febrile illnesses: a systematic review of prognostic studies"],"prefix":"10.1136","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1313-7922","authenticated-orcid":false,"given":"Arjun","family":"Chandna","sequence":"first","affiliation":[{"name":"Cambodia-Oxford Medical Research Unit, Angkor Hospital for Children, Siem Reap, Cambodia"},{"name":"Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rainer","family":"Tan","sequence":"additional","affiliation":[{"name":"Unisant\u00e9 Centre for Primary Care and Public Health, University of Lausanne, Lausanne, Switzerland"},{"name":"University of Basel, Basel, Switzerland"},{"name":"Swiss Tropical and Public Health Institute, Basel, Basel-Stadt, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Carter","sequence":"additional","affiliation":[{"name":"Department of Women and Children's Health, King's College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann","family":"Van Den Bruel","sequence":"additional","affiliation":[{"name":"Academic Centre of General Practice, University of Leuven, Leuven, Flanders, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Verbakel","sequence":"additional","affiliation":[{"name":"Academic Centre of General Practice, University of Leuven, Leuven, Flanders, Belgium"},{"name":"Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Constantinos","family":"Koshiaris","sequence":"additional","affiliation":[{"name":"Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nahya","family":"Salim","sequence":"additional","affiliation":[{"name":"Ifakara Health Institute, Dar-es-Salaam, Tanzania"},{"name":"Department of Pediatrics and Child Health, Muhimbili University Health and Allied Sciences, Dar-es-Salaam, Tanzania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoel","family":"Lubell","sequence":"additional","affiliation":[{"name":"Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, UK"},{"name":"Mahidol-Oxford Tropical Medicine Research Unit, Bangkok, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1013-7815","authenticated-orcid":false,"given":"Paul","family":"Turner","sequence":"additional","affiliation":[{"name":"Cambodia-Oxford Medical Research Unit, Angkor Hospital for Children, Siem Reap, Cambodia"},{"name":"Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina","family":"Keitel","sequence":"additional","affiliation":[{"name":"Swiss Tropical and Public Health Institute, Basel, Basel-Stadt, Switzerland"},{"name":"Division of Emergency Medicine, Department of Pediatrics, University Children's Hospital, Inselpital, University of Bern, Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2021,1,20]]},"reference":[{"key":"2025073015221619000_6.1.e003451.1","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.14-0646"},{"key":"2025073015221619000_6.1.e003451.2","unstructured":"World Health Organization . WHO informal consultation on fever management in peripheral health care settings: a global review of evidence and practice. Geneva: World Health Organization, 2013."},{"key":"2025073015221619000_6.1.e003451.3","doi-asserted-by":"publisher","DOI":"10.3399\/bjgp11X548974"},{"key":"2025073015221619000_6.1.e003451.4","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0127962"},{"key":"2025073015221619000_6.1.e003451.5","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)31668-4"},{"key":"2025073015221619000_6.1.e003451.6","doi-asserted-by":"crossref","DOI":"10.1186\/s12936-018-2488-x","article-title":"Integrated fever management: disease severity markers to triage children with malaria and non-malarial febrile illness","volume":"17","author":"McDonald","year":"2018","journal-title":"Malar J"},{"key":"2025073015221619000_6.1.e003451.7","doi-asserted-by":"crossref","first-page":"314","DOI":"10.2471\/BLT.04.019505","article-title":"Improved triage and emergency care for children reduces inpatient mortality in a resource-constrained setting","volume":"84","author":"Molyneux","year":"2006","journal-title":"Bull World Health Organ"},{"key":"2025073015221619000_6.1.e003451.8","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1016\/j.cmi.2018.04.014","article-title":"Electronic clinical decision algorithms for the integrated primary care management of febrile children in low-resource settings: review of existing tools","volume":"24","author":"Keitel","year":"2018","journal-title":"Clin Microbiol Infect"},{"key":"2025073015221619000_6.1.e003451.9","doi-asserted-by":"publisher","DOI":"10.7326\/M14-0698"},{"key":"2025073015221619000_6.1.e003451.10","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(09)62000-6"},{"key":"2025073015221619000_6.1.e003451.11","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.d3082"},{"key":"2025073015221619000_6.1.e003451.12","doi-asserted-by":"crossref","first-page":"e157","DOI":"10.1016\/S2214-109X(17)30007-4","article-title":"Causes and outcomes of sepsis in Southeast Asia: a multinational multicentre cross-sectional study","volume":"5","year":"2017","journal-title":"Lancet Glob Health"},{"key":"2025073015221619000_6.1.e003451.13","doi-asserted-by":"crossref","first-page":"e744","DOI":"10.1016\/S2214-109X(18)30247-X","article-title":"Burden of Streptococcus pneumoniae and Haemophilus influenzae type B disease in children in the era of conjugate vaccines: global, regional, and national estimates for 2000-15","volume":"6","author":"Wahl","year":"2018","journal-title":"Lancet Glob Health"},{"key":"2025073015221619000_6.1.e003451.14","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1001744"},{"key":"2025073015221619000_6.1.e003451.15","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.k4597"},{"key":"2025073015221619000_6.1.e003451.16","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-158-4-201302190-00009"},{"key":"2025073015221619000_6.1.e003451.17","doi-asserted-by":"publisher","DOI":"10.7326\/M18-1377"},{"key":"2025073015221619000_6.1.e003451.18","doi-asserted-by":"crossref","DOI":"10.7326\/0003-4819-151-4-200908180-00135","article-title":"Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement","volume":"151","author":"Moher","year":"2009","journal-title":"Ann Intern Med"},{"key":"2025073015221619000_6.1.e003451.19","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1001\/jamapediatrics.2017.5208","article-title":"Defining pediatric sepsis","volume":"172","author":"Schlapbach","year":"2018","journal-title":"JAMA Pediatr"},{"key":"2025073015221619000_6.1.e003451.20","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0032844"},{"key":"2025073015221619000_6.1.e003451.21","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.38446.498542.8F"},{"key":"2025073015221619000_6.1.e003451.22","doi-asserted-by":"publisher","DOI":"10.1136\/jamia.2001.0080391"},{"key":"2025073015221619000_6.1.e003451.23","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1994.03510330081039"},{"key":"2025073015221619000_6.1.e003451.24","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-003-1761-8"},{"key":"2025073015221619000_6.1.e003451.25","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.i6460"},{"key":"2025073015221619000_6.1.e003451.26","doi-asserted-by":"crossref","DOI":"10.1186\/s12916-018-1014-x","article-title":"Lactate clearance as a prognostic marker of mortality in severely ill febrile children in East Africa","volume":"16","author":"Aramburo","year":"2018","journal-title":"BMC Med"},{"key":"2025073015221619000_6.1.e003451.27","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1186\/s13054-015-0773-4","article-title":"Prospective validation of pediatric disease severity scores to predict mortality in Ugandan children presenting with malaria and non-malaria febrile illness","volume":"19","author":"Conroy","year":"2015","journal-title":"Crit Care"},{"key":"2025073015221619000_6.1.e003451.28","doi-asserted-by":"crossref","first-page":"597","DOI":"10.3855\/jidc.9257","article-title":"Duarte Mello Amoedo C, Nascimento-Carvalho CM. Clinical and epidemiological characteristics of children admitted with fever in emergency department with or without sepsis","volume":"11","author":"Costa de Santana","year":"2017","journal-title":"J Infect Dev Ctries"},{"key":"2025073015221619000_6.1.e003451.29","doi-asserted-by":"publisher","DOI":"10.3399\/bjgp15X686485"},{"key":"2025073015221619000_6.1.e003451.30","doi-asserted-by":"publisher","DOI":"10.1177\/0009922813483873"},{"key":"2025073015221619000_6.1.e003451.31","doi-asserted-by":"crossref","DOI":"10.1186\/s12916-015-0407-3","article-title":"Predicting mortality in sick African children: the feast paediatric emergency triage (PET) score","volume":"13","author":"George","year":"2015","journal-title":"BMC Med"},{"key":"2025073015221619000_6.1.e003451.32","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cir471"},{"key":"2025073015221619000_6.1.e003451.33","doi-asserted-by":"crossref","first-page":"150","DOI":"10.4314\/mmj.v28i4.1","article-title":"Clinical outcomes among febrile children aged 2 to 59 months with negative malaria rapid diagnostic test results in Mchinji district, Malawi","volume":"28","author":"Mwandama","year":"2016","journal-title":"Malawi Med J"},{"key":"2025073015221619000_6.1.e003451.34","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.13-0016"},{"key":"2025073015221619000_6.1.e003451.35","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1001\/jamapediatrics.2016.3681","article-title":"Association between early lactate levels and 30-day mortality in clinically suspected sepsis in children","volume":"171","author":"Scott","year":"2017","journal-title":"JAMA Pediatr"},{"key":"2025073015221619000_6.1.e003451.36","doi-asserted-by":"crossref","DOI":"10.1186\/1471-227X-14-24","article-title":"Effectiveness of physical exam signs for early detection of critical illness in pediatric systemic inflammatory response syndrome","volume":"14","author":"Scott","year":"2014","journal-title":"BMC Emerg Med"},{"key":"2025073015221619000_6.1.e003451.37","doi-asserted-by":"publisher","DOI":"10.1111\/acem.12014"},{"key":"2025073015221619000_6.1.e003451.38","doi-asserted-by":"crossref","first-page":"266","DOI":"10.3389\/fped.2018.00266","article-title":"Translating Sepsis-3 criteria in children: prognostic accuracy of age-adjusted quick SOFA score in children visiting the emergency department with suspected bacterial infection","volume":"6","author":"van Nassau","year":"2018","journal-title":"Front Pediatr"},{"key":"2025073015221619000_6.1.e003451.39","doi-asserted-by":"crossref","first-page":"219","DOI":"10.22159\/ajpcr.2016.v9s3.11707","article-title":"Yale observation scale as a predictor of bacteremia and final outcome in 3-36 months old febrile children admitted in tertiary health centres: a hospital-based cross-sectional study","volume":"9","author":"Walia","year":"2016","journal-title":"Asian Journal of Pharmaceutical and Clinical Research"},{"key":"2025073015221619000_6.1.e003451.40","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.jpeds.2019.09.079","article-title":"Development and validation of a predictive model of the risk of pediatric septic shock using data known at the time of hospital arrival","volume":"217","author":"Scott","year":"2020","journal-title":"J Pediatr"},{"key":"2025073015221619000_6.1.e003451.41","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1097\/PCC.0000000000002121","article-title":"A machine Learning-Based triage tool for children with acute infection in a low resource setting","volume":"20","author":"Kwizera","year":"2019","journal-title":"Pediatr Crit Care Med"},{"key":"2025073015221619000_6.1.e003451.42","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0150683","article-title":"Pediatric in-hospital death from infectious disease in Uganda: derivation of clinical prediction models","volume":"11","author":"Lowlaavar","year":"2016","journal-title":"PLoS One"},{"key":"2025073015221619000_6.1.e003451.43","doi-asserted-by":"crossref","DOI":"10.1186\/s12887-017-0796-x","article-title":"Reliability and validity of pediatric triage tools evaluated in low resource settings: a systematic review","volume":"17","author":"Hansoti","year":"2017","journal-title":"BMC Pediatr"},{"key":"2025073015221619000_6.1.e003451.44","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pmed.1001221","article-title":"Reporting and methods in clinical prediction research: a systematic review","volume":"9","author":"Bouwmeester","year":"2012","journal-title":"PLoS Med"},{"key":"2025073015221619000_6.1.e003451.45","unstructured":"World Health Organization . IMCI chart booklet. Geneva: World Health Organization, 2014."},{"key":"2025073015221619000_6.1.e003451.46","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2018.00838","article-title":"Endothelial activation: the Ang\/Tie axis in sepsis","volume":"9","author":"Leligdowicz","year":"2018","journal-title":"Front Immunol"},{"key":"2025073015221619000_6.1.e003451.47","doi-asserted-by":"publisher","DOI":"10.1186\/cc2459"},{"key":"2025073015221619000_6.1.e003451.48","doi-asserted-by":"crossref","first-page":"427","DOI":"10.4269\/ajtmh.19-0553","article-title":"Clinical outcome of febrile Tanzanian children with severe malnutrition using anthropometry in comparison to clinical signs","volume":"102","author":"Tan","year":"2020","journal-title":"Am J Trop Med Hyg"},{"key":"2025073015221619000_6.1.e003451.49","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciz080"},{"key":"2025073015221619000_6.1.e003451.50","doi-asserted-by":"publisher","DOI":"10.1086\/648409"},{"key":"2025073015221619000_6.1.e003451.51","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.326.7385.361"},{"key":"2025073015221619000_6.1.e003451.52","first-page":"204","article-title":"Triage score for severity of illness","volume":"40","author":"Kumar","year":"2003","journal-title":"Indian Pediatr"},{"key":"2025073015221619000_6.1.e003451.53","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1097\/PCC.0000000000001182","article-title":"Can the pediatric logistic organ Dysfunction-2 score on day 1 be used in clinical criteria for sepsis in children?","volume":"18","author":"Leclerc","year":"2017","journal-title":"Pediatr Crit Care Med"},{"key":"2025073015221619000_6.1.e003451.54","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2016.0288"},{"key":"2025073015221619000_6.1.e003451.55","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1097\/PCC.0000000000002149","article-title":"Please welcome the new team member: the algorithm","volume":"20","author":"Fackler","year":"2019","journal-title":"Pediatr Crit Care Med"},{"key":"2025073015221619000_6.1.e003451.56","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0211274","article-title":"Determining predictors of sepsis at triage among children under 5 years of age in resource-limited settings: a modified Delphi process","volume":"14","author":"Fung","year":"2019","journal-title":"PLoS One"},{"key":"2025073015221619000_6.1.e003451.57","unstructured":"World Health Organization . Integrated management of childhood Ilness chart booklet. Geneva: World Health Organization, 2014."},{"key":"2025073015221619000_6.1.e003451.58","unstructured":"Li E . Guidelines for the standardized collection of predictor variables in studies for pediatric sepsis. In: Ansermino M , ed. Scholars portal Dataverse. V2 ed, 2020."},{"key":"2025073015221619000_6.1.e003451.59","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2019-034960"},{"key":"2025073015221619000_6.1.e003451.60","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cis034"},{"key":"2025073015221619000_6.1.e003451.61","doi-asserted-by":"publisher","DOI":"10.1186\/cc7998"},{"key":"2025073015221619000_6.1.e003451.62","doi-asserted-by":"publisher","DOI":"10.1097\/00003246-199605000-00004"},{"key":"2025073015221619000_6.1.e003451.63","doi-asserted-by":"publisher","DOI":"10.1097\/01.PCC.0000149131.72248.E6"},{"key":"2025073015221619000_6.1.e003451.64","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1542\/peds.70.5.802","article-title":"Observation scales to identify serious illness in febrile children","volume":"70","author":"McCarthy","year":"1982","journal-title":"Pediatrics"}],"container-title":["BMJ Global Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjgh-2020-003451","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T22:22:27Z","timestamp":1753914147000},"score":1,"resource":{"primary":{"URL":"https:\/\/gh.bmj.com\/lookup\/doi\/10.1136\/bmjgh-2020-003451"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1]]},"references-count":64,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,1,20]]},"published-print":{"date-parts":[[2021,1]]}},"alternative-id":["10.1136\/bmjgh-2020-003451"],"URL":"https:\/\/doi.org\/10.1136\/bmjgh-2020-003451","relation":{},"ISSN":["2059-7908"],"issn-type":[{"value":"2059-7908","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1]]}}}