Diagnostic value of clinical features at presentation to identify serious infection in children in developed countries: a systematic review

BACKGROUND Our aim was to identify which clinical features have value in confirming or excluding the possibility of serious infection in children presenting to ambulatory care settings in developed countries. METHODS In this systematic review, we searched electronic databases (Medline, Embase, DARE, CINAHL), reference lists of relevant studies, and contacted experts to identify articles assessing clinical features of serious infection in children. 1939 potentially relevant studies were identified. Studies were selected on the basis of six criteria: design (studies of diagnostic accuracy or prediction rules), participants (otherwise healthy children aged 1 month to 18 years), setting (ambulatory care), outcome (serious infection), features assessed (assessable in ambulatory care setting), and sufficient data reported. Quality assessment was based on the Quality Assessment of Diagnostic Accuracy Studies criteria. We calculated likelihood ratios for the presence (positive likelihood ratio) or absence (negative likelihood ratio) of each clinical feature and pre-test and post-test probabilities of the outcome. Clinical features with a positive likelihood ratio of more than 5.0 were deemed red flags (ie, warning signs for serious infection); features with a negative likelihood ratio of less than 0.2 were deemed rule-out signs. FINDINGS 30 studies were included in the analysis. Cyanosis (positive likelihood ratio range 2.66-52.20), rapid breathing (1.26-9.78), poor peripheral perfusion (2.39-38.80), and petechial rash (6.18-83.70) were identified as red flags in several studies. Parental concern (positive likelihood ratio 14.40, 95% CI 9.30-22.10) and clinician instinct (positive likelihood ratio 23.50, 95 % CI 16.80-32.70) were identified as strong red flags in one primary care study. Temperature of 40 degrees C or more has value as a red flag in settings with a low prevalence of serious infection. No single clinical feature has rule-out value but some combinations can be used to exclude the possibility of serious infection-for example, pneumonia is very unlikely (negative likelihood ratio 0.07, 95% CI 0.01-0.46) if the child is not short of breath and there is no parental concern. The Yale Observation Scale had little value in confirming (positive likelihood ratio range 1.10-6.70) or excluding (negative likelihood ratio range 0.16-0.97) the possibility of serious infection. INTERPRETATION The red flags for serious infection that we identified should be used routinely, but serious illness will still be missed without effective use of precautionary measures. We now need to identify the level of risk at which clinical action should be taken. FUNDING Health Technology Assessment and National Institute for Health Research National School for Primary Care Research.

[1]  A. Gervaix,et al.  The Search for Adenovirus 14 in Children in Houston, Texas , 2008, The Pediatric infectious disease journal.

[2]  S. Suter,et al.  Procalcitonin, IL-6, IL-8, IL-1 receptor antagonist and C-reactive protein as identificators of serious bacterial infections in children with fever without localising signs , 2001, European Journal of Pediatrics.

[3]  The management of sick young infants at primary health centres in a rural developing country , 2005, Archives of Disease in Childhood.

[4]  D. Fleming,et al.  Impact of infections on primary care--greater than expected. , 2002, Communicable disease and public health.

[5]  C. Deangelis,et al.  Which children with febrile seizures need lumbar puncture? A decision analysis approach. , 1983, American journal of diseases of children.

[6]  J. Lubsen,et al.  Seizures and Fever: Can We Rule Out Meningitis on Clinical Grounds Alone? , 1992, Clinical pediatrics.

[7]  D. Grobbee,et al.  Validating and updating a prediction rule for serious bacterial infection in patients with fever without source , 2007, Acta paediatrica.

[8]  J. Avner,et al.  The efficacy of routine outpatient management without antibiotics of fever in selected infants. , 1999, Pediatrics.

[9]  J. Herskowitz,et al.  Bacteremia in febrile children under 2 years of age: results of cultures of blood of 600 consecutive febrile children seen in a "walk-in" clinic. , 1975, The Journal of pediatrics.

[10]  P. Crocker,et al.  Occult bacteremia in the emergency department: diagnostic criteria for the young febrile child. , 1985, Annals of emergency medicine.

[11]  M. Harper.  Bacteraemia in febrile children presenting to a paediatric emergency department , 1999 .

[12]  M. Plebani,et al.  Procalcitonin and C-Reactive Protein as Diagnostic Markers of Severe Bacterial Infections in Febrile Infants and Children in the Emergency Department , 2007, The Pediatric infectious disease journal.

[13]  G. Garra,et al.  Reappraisal of criteria used to predict serious bacterial illness in febrile infants less than 8 weeks of age. , 2005, Academic emergency medicine : official journal of the Society for Academic Emergency Medicine.

[14]  A. Gervaix,et al.  Bedside procalcitonin and C-reactive protein tests in children with fever without localizing signs of infection seen in a referral center. , 2003, Pediatrics.

[15]  D. Cicchetti,et al.  Observation scales to identify serious illness in febrile children. , 1982, Pediatrics.

[16]  J. Berkelhamer,et al.  Outpatient bacteremia: clinical findings in children under two years with initial temperatures of 39.5 degrees C or higher. , 1981, The Journal of pediatrics.

[17]  M. D. Del Beccaro,et al.  Establishing clinically relevant standards for tachypnea in febrile children younger than 2 years. , 1995, Archives of pediatrics & adolescent medicine.

[18]  G. Guyatt,et al.  Users' Guides to the Medical Literature: III. How to Use an Article About a Diagnostic Test: B. What Are the Results and Will They Help Me In Caring for My Patients? , 1994 .

[19]  M. Bruijnzeels,et al.  Everyday symptoms in childhood: occurrence and general practitioner consultation rates. , 1998, The British journal of general practice : the journal of the Royal College of General Practitioners.

[20]  Charles G Macias,et al.  Prospective Evaluation of the Risk of Serious Bacterial Infection in Children Who Present to the Emergency Department With Hyperpyrexia (Temperature of 106°F or Higher) , 2006, Pediatrics.

[21]  J. C. Smith,et al.  The child with a non-blanching rash: how likely is meningococcal disease? , 2001, Archives of disease in childhood.

[22]  P. Bossuyt,et al.  BMC Medical Research Methodology , 2002 .

[23]  Roger Galbraith,et al.  A Novel Imaging Technique to Measure Capillary-Refill Time: Improving Diagnostic Accuracy for Dehydration in Young Children With Gastroenteritis , 2006, Pediatrics.

[24]  T. Cole,et al.  Field trials of the Baby Check score card in general practice. , 1991, Archives of disease in childhood.

[25]  D. Jaffe,et al.  Temperature and total white blood cell count as indicators of bacteremia. , 1991, Pediatrics.

[26]  D. Walshaw,et al.  The causes of fever in children attending hospital in the north of England. , 2001, The Journal of infection.

[27]  R. Perera,et al.  How well do vital signs identify children with serious infections in paediatric emergency care? , 2009, Archives of Disease in Childhood.

[28]  K N Shaw,et al.  Validity and reliability of clinical signs in the diagnosis of dehydration in children. , 1997, Pediatrics.

[29]  M. Aerts,et al.  Signs and symptoms for diagnosis of serious infections in children: a prospective study in primary care. , 2007, The British journal of general practice : the journal of the Royal College of General Practitioners.

[30]  J. Avner,et al.  Outpatient management without antibiotics of fever in selected infants. , 1994, The New England journal of medicine.

[31]  J. Kai.  What worries parents when their preschool children are acutely ill, and why: a qualitative study , 1996, BMJ.

[32]  E. Mahabee-Gittens,et al.  Identifying Children with Pneumonia in the Emergency Department , 2005, Clinical pediatrics.

[33]  M. Berger,et al.  A predictive model to estimate the risk of serious bacterial infections in febrile infants , 1996, European Journal of Pediatrics.

[34]  D. Mant,et al.  Diagnostic safety-netting. , 2009, The British journal of general practice : the journal of the Royal College of General Practitioners.

[35]  Philipp Dahm,et al.  Evidence-Based Surgery Chirurgie factuelle Users ’ guides to the surgical literature : how to use an article about a diagnostic test , 2001 .

[36]  M. Shenoy,et al.  Is procalcitonin useful in early diagnosis of serious bacterial infections in children? , 2005, Acta paediatrica.

[37]  D E Grobbee,et al.  Prediction of bacterial meningitis in children with meningeal signs: reduction of lumbar punctures , 2001, Acta paediatrica.

[38]  J. Berkelhamer,et al.  Outpatient bacteremia: Clinical findings in children under two years with initial temperatures of 39.5°C or higher , 1981 .

[39]  P. Midgley,et al.  Management of febrile children in a paediatric emergency department. , 2002, Health bulletin.

[40]  M. Harper,et al.  Predictive model for serious bacterial infections among infants younger than 3 months of age. , 2001, Pediatrics.

[41]  C. Hart,et al.  Lesson of the Week: Who spots the spots? Diagnosis and treatment of early meningococcal disease in children , 1996, BMJ.

[42]  D. Cicchetti,et al.  Observation, history, and physical examination in diagnosis of serious illnesses in febrile children less than or equal to 24 months. , 1987, Jornal de Pediatria.

[43]  M. Radlauer.  Temperature and total white blood cell count as indicators of bacteremia: Jaffe DM, Fleisher GR Pediatrics 87:670–674 May 1991 , 1991 .

[44]  Domenic V. Cicchetti,et al.  Observation, history, and physical examination in diagnosis of serious illnesses in febrile children ≤24 months* , 1987 .

[45]  J. Avner,et al.  Failure of infant observation scales in detecting serious illness in febrile, 4- to 8-week-old infants. , 1990, Pediatrics.

[46]  S. Larsen,et al.  Diagnostic assessment of haemorrhagic rash and fever , 2001, Archives of disease in childhood.

[47]  J. Petit.  Clinical recognition of meningococcal disease in children and adolescents , 2008 .

[48]  Peterborough Pe.  Assessment and initial management of feverish illness in children younger than 5 years: summary of NICE guidance , 2013 .

[49]  G. Guyatt,et al.  Users' guides to the medical literature. III. How to use an article about a diagnostic test. B. What are the results and will they help me in caring for my patients? The Evidence-Based Medicine Working Group. , 1994, JAMA.

[50]  John B. Carlin,et al.  Clinical signs that predict severe illness in children underage 2 months: a multicentre study , 2008 .

[51]  S. Gove,et al.  Integrated management of childhood illness by outpatient health workers: technical basis and overview. The WHO Working Group on Guidelines for Integrated Management of the Sick Child. , 1997, Bulletin of the World Health Organization.

[52]  C. Cubells.  El niño febril. Resultados de un estudio multicéntrico , 2001 .

[53]  G. Guyatt,et al.  Users' guides to the medical literature. , 1993, JAMA.

[54]  U. Werneke,et al.  Determining the common medical presenting problems to an accident and emergency department , 2001, Archives of disease in childhood.

[55]  A. Mackenzie,et al.  CLINICAL SIGNS OF DEHYDRATION IN CHILDREN , 1989, The Lancet.

[56]  W. Bonadio,et al.  Efficacy of a Protocol to Distinguish Risk of Serious Bacterial Infection in the Outpatient Evaluation of Febrile Young Infants , 1993, Clinical pediatrics.

[57]  M. Baker,et al.  Incidence and Predictors of Serious Bacterial Infections Among 57- to 180-Day-Old Infants , 2006, Pediatrics.