Table 1

Characteristics of included studies

Study (year); setting, country	Cohort	Design	Quality assessment		CPM or PF study*	Sample size	Population		Outcome	Outcome prevalence (n/N)
Study (year); setting, country	Cohort	Design	Risk of bias	Applicability concern	CPM or PF study*	Sample size	Inclusion criteria	Exclusion criteria	Outcome	Outcome prevalence (n/N)
Outcomes including death, organ dysfunction, organ support and PICU admission
Scott (2020)40; Secondary and tertiary care hospitals, USA	Hospital OPD/ED	Retrospective cohort	High	Low	CPM	2464	Age 60 days to 18 years; Clinician-suspected sepsis	Hypotensive septic shock on arrival;† transfer to another centre; leaving ED before formal evaluation; incorrect registration	Hypotensive septic shock‡≤24 hour	11.4% (282/2464)
Walia (2016)39; Tertiary care hospital, India	Hospitalised§	Prospective cohort	High	High	CPM	100	Age 3–36 months; Axillary temperature >36.9°C (early morning) or >37.4°C	Non-infectious cause of fever; immunisation ≤2 days; immunodeficiency, autoimmune disorder	In-hospital mortality; Mechanical ventilation	11.0% (11/100); 17.0% (17/100)
Aramburo (2018)26; Secondary and tertiary care hospitals, Kenya, Tanzania and Uganda	Hospitalised§	Randomised controlled trial	Moderate	High	PF	3008	Age 60 days to 12 years; history of fever or axillary temperature ≥37.5°C or <36°C; severe febrile illness¶	Non-infectious cause of illness; SAM, gastroenteritis, burns, chronic kidney disease, pulmonary oedema, intoxication, surgical conditions, receipt of isotonic fluids during the same illness	In-hospital mortality (72 hours)	10.3% (309/3008)
George (2015)31; Secondary and tertiary care hospitals, Kenya, Tanzania and Uganda	Hospitalised§	Randomised controlled trial	High	High	CPM	3121	Age 60 days to 12 years; history of fever or axillary temperature ≥37.5°C or <36°C; severe febrile illness¶	Non-infectious cause of illness; SAM, gastroenteritis, burns, chronic kidney disease, pulmonary oedema, intoxication, surgical conditions, receipt of isotonic fluids during the same illness	In-hospital mortality (48 hours)	9.8% (306/3121)
Scott (2012)37; Tertiary care hospital, USA	Hospital OPD/ED	Prospective cohort	High	High	PF	239	Age <19 years; temperature >38.5°C or <36°C and heart rate >2 SD above normal for age; underwent phlebotomy as part of usual care	Transfer from another health facility; known inborn errors of metabolism; receipt of >15 min of intravenous therapy	24 hours organ dysfunction	5.4% (13/239)
Scott (2014)36; Tertiary care hospital, USA	Hospital OPD/ED	Prospective cohort	High	High	PF	239	Age <19 years; temperature >38.5°C or <36°C and heart rate >2 SD above normal for age; undergoing phlebotomy as part of routine care	Transfer from another health facility; known inborn errors of metabolism; receipt of >15 min of intravenous therapy	24 hours organ dysfunction	5.4% (13/239)
Nadjm (2013)34; Secondary care hospital, Tanzania	Hospitalised§	Prospective cohort	Moderate	High	PF	3319	Age 2 months to 5 years; history of fever in last 48 hours or axillary temperature ≥37.5°C	Chronic illness (excluding HIV and malnutrition); trauma; surgical conditions	In-hospital mortality	5.1% (170/3319)
Mtove (2011)32; Secondary care hospital, Tanzania	Hospitalised§	Prospective cohort	Moderate	High	PF	3248	Age 2 months to 13 years; history of fever in last 48 hours or axillary temperature ≥37.5°C	Chronic illness (excluding HIV and malnutrition); trauma; surgical conditions	In-hospital mortality	5.0% (164/3248)
Lowlaavar (2016)42; Secondary and tertiary care hospitals, Uganda	Hospitalised§	Prospective cohort	High	High	CPM	1307	Age 6–60 months; admitted during study working hours or within 8 hours of study shift with a proven or suspected infection	Previous enrolment; residence outside study catchment area	In-hospital mortality	5.0% (65/1307)
Conroy (2015)27; Tertiary care hospital, Uganda	Hospitalised§	Prospective cohort	High	High	CPM	2502	Age 2 months to 5 years; history of fever in last 48 hours or axillary temperature >37.5°C	None reported	In-hospital mortality	4.7% (99/2089)
van Nassau (2018)38; Secondary care hospital, The Netherlands	Hospitalised§	Retrospective cohort	High	High	CPM	864	Age <18 years; suspected bacterial infection**	Surgical conditions	PICU transfer and/or in-hospital mortality	2.7% (24/864)
Scott (2017)35; Tertiary care hospital, USA	Hospital OPD/ED	Retrospective cohort	Low	High	PF	1299	Age 60 days to 18 years; suspected sepsis††; measurement of venous lactate as part of routine care within 8 hours of ED arrival	Transfer from another health facility	30-day mortality	1.9% (25/1299)
SEAIDCRN (2017)12; Tertiary care hospitals, Indonesia, Thailand and Vietnam	Hospitalised§	Prospective cohort	High	High	PF	763	Age 30 days to 18 years; modified SIRS criteria‡‡	Suspicion of hospital-acquired infection; admission to hospital within previous 30 days; transfer from another health facility after >72 hours admission; weight <3 kg; enrolment in another clinical study	28-day mortality	1.9% (14/731)
Costa de Santana (2017)28; Tertiary care hospital, Brazil	Hospital OPD/ED	Retrospective cohort	High	High	PF	254	Age <13 years; axillary temperature >38.5°C; measurement of respiratory rate and heart rate on three occasions in absence of fever; measurement of leucocyte count as part of routine care	Congenital malformations; bronchopulmonary dysplasia; medullary aplasia; cardiac, renal or hepatic insufficiency	In-hospital mortality	1.6% (4/254)
Kwizera (2019)41; Secondary care hospital, Rwanda	Hospitalised§	Prospective cohort	High	High	CPM	949	Age 28 days to 18 years; confirmed acute infectious disease; symptom onset <14 days prior to hospital admission	Allergy to antimicrobials to treat sepsis (antibiotics, artesunate, artemether-lumefantrine); terminal disease	In-hospital mortality	1.5% (14/949)
Outcomes including length of stay and persistence of symptoms
Freyne (2013)30; Secondary care hospital, Ireland	Hospitalised§	Prospective cohort	High	High	PF	46	Age 6–36 months; axillary temperature >38.1°C	Chronic illness; immunisation ≤2 days, antipyretic use ≤2 hours	Length of stay >96 hours	26.1% (12/46)
van Nassau (2018)38; Secondary care hospital, The Netherlands	Hospitalised§	Retrospective cohort	High	High	CPM	864	Age <18 years; suspected bacterial infection**	Surgical conditions	Length of stay ≥7 days	22.2% (179/806)
Elshout (2015)29; General Practice (out of hours), The Netherlands	Primary care	Prospective cohort	High	High	PF	480	Age 3 months to 6 years; history of fever	Communication in Dutch not possible; enrolment in last 2 weeks; direct referral to hospital required	Persistent fever at D3	13.1% (63/480)
Mwandama (2016)33; Community Health Workers, Malawi	Primary care	Prospective cohort	High	High	PF	285	Age 2–59 months; history of fever in last 48 hours or temperature ≥37.5°C; negative malaria rapid diagnostic test	Receipt of antimalarial in last 2 weeks; presence of danger signs§§	Persistent symptoms at D7	10.4% (19/182)

Studies are grouped according to the type of outcome they used: ‘hard’ (death, organ dysfunction, organ support, PICU admission) or ‘soft’ (length of stay, persistence of symptoms).
*Studies evaluating both PFs and CPMs were categorised on the basis of their primary analysis to facilitate review using the appropriate quality assessment tool.
†Hypotensive systolic blood pressure on arrival with receipt of a fluid bolus or vasoactive agent within 30 min.
‡Hypotension plus receipt of ≥30 mL/kg isotonic crystalloids or vasoactive medication.
§Only children the treating physician decided to admit were eligible but recruitment occurred at the time of admission to the health facility.
¶Respiratory distress (increased work of breathing or deep breathing) and/or impaired consciousness (coma or prostration) AND evidence of poor peripheral perfusion (capillary refill time >2 s or lower limb temperature gradient or weak radial pulse or severe tachycardia).
**Initiation of antibiotics within 24 hours of arrival in the emergency department.
††Decreased mental status or perfusion in the setting of suspected infection.
‡‡Rectal temperature >38.5°C or <35°C (or equivalent) AND heart rate >2 SD above normal for age (unless hypothermic) AND respiratory rate >2 SD above normal for age AND altered mental status OR systolic blood pressure <2 SD below normal for age OR pulse pressure <20 mm Hg OR capillary refill time >2 s OR SpO₂ <95% OR leucocyte count >12×10³ cells/µL or <5×10³ cells/µL.
§§Convulsions, repeated vomiting, lethargy, severe anaemia or loss of consciousness.
CPM, clinical prediction model; ED, emergency department; n, number of outcomes; n, number of cases; OPD, outpatient department; PF, prognostic factor; PICU, paediatric intensive care unit; SAM, severe acute malnutrition; SEAIDCRN, Southeast Asia Infectious Disease Clinical Research Network; SIRS, systemic inflammatory response syndrome.;