This document provides clinical guidance for all staff involved in the care and management of a child presenting to an Emergency Department (ED) with the primary complaint of a febrile illness in Queensland.

This guideline aims to identify those infants and children at risk of serious bacterial infection or other significant illness who need timely treatment, while avoiding unnecessary investigations in the majority. The management of children with an unexplained fever for > 1 week or who have recently returned from overseas travel is beyond the scope of this guideline. For oncology patients refer to the Management of Fever in a Paediatric Oncology Patient Guideline.

This guideline has been developed by senior ED clinicians and Paediatricians across Queensland, with input from Infectious Disease specialist staff, Lady Cilento Children’s Hospital, Brisbane. It has been endorsed for use across Queensland by the Statewide Emergency Care of Children Working Group in partnership with the Queensland Emergency Department Strategic Advisory Panel and the Healthcare Improvement Unit, Clinical Excellence Division.

Fever is one of the most common reasons for paediatric presentations to ED and provides diagnostic and management challenges to clinical staff. Infection remains the leading cause of death in children aged < 5 years.

Definition

Fever is defined as a temperature ≥38°C.

Pyrexia of unknown origin (PUO) refers to any fever lasting 10 – 21 days without cause identified on history, examination and basic investigations and is beyond the scope of this guideline. This guideline also does not consider the approach to fever in the returned traveller.

Measurement

The aim of the assessment (history and clinical examination) is to identify children who:

• have a focus of infection (to enable appropriate investigations and, if needed, treatment)
• do not have an infective focus but require further investigations and/or empirical treatment according to their risk of SBI

History

History should include specific information on:

• age
• immune status- incomplete immunisations, immune-compromise, co-morbidities
• current or recent use of antibiotics
• history of fever and use of anti-pyretics

Age

Febrile infants aged <3 months have a higher risk of SBI, with this risk being greatest in the neonatal period. Young infants are more likely to present with non-specific features (they lack the hypothalamic and immune system maturity to localise the infection) and can deteriorate rapidly. Some infants < 3 months may not mount a fever in response to SBI, and hypothermia or temperature instability can also be signs of SBI.

In addition to the pathogens seen in older children, Group B Streptococcus, E. Coli, Herpes Simplex virus, Listeria monocytogenes, Salmonella and Parechovirus infections are more common in neonates. Detecting other viral infections in children aged < 3 months (most commonly RSV) lowers but does not remove the risk of SBI.⁶ The estimated incidence of a UTI amongst infants < 3 months with laboratory-confirmed RSV infection ranges from 3.3 to 5%.^7,8

Children aged between 3 months and 3 years have their immunity boosted with vaccinations and are at a lower risk of SBI than those < 3 months. In this age group, the presence of a recognisable viral syndrome (including bronchiolitis) predicts a very low incidence of bacteraemia or SBI.

Older children (>3 years) have mature immune systems and are better able to verbalise and localise symptoms so are at lower risk of SBI.

Immunisations & immune status

The Haemophilus influenzae type b (Hib) and pneumococcal immunisations have dramatically reduced the risk of occult bacteraemia and SBI. Children who have received at least 2 doses of the 13-valent conjugate pneumococcal (13vPCV) and Hib vaccinations (3 dose course given as part of the National Immunisation Program at 2, 4 and 6 months of age) have > 95% protection.

Children with congenital immune deficiency syndrome, sickle cell disease, HIV, asplenia, cancer, nephrotic syndrome, intracranial shunt, cochlear implant, immunosuppressive therapy or who are of Indigenous or Torres Strait Islander origin are at a greater risk for SBI, independent of vaccination status.

History of fever, prior antibiotic use and use of anti-pyretics

The height of fever, duration of the fever and response to antipyretics have failed to show any ability to differentiate severe from mild illness, or bacterial from viral infection.⁹

While not addressed within this guideline, a diagnosis of Kawasaki disease should be considered for children with a fever lasting more than 5 days.

Antibiotic use around the time of fever can potentially mask symptoms and signs of bacterial illness.

Examination

The examination should identify a source for the fever if possible, and specifically assess for any signs of toxicity.

Signs of toxicity

Differentiating toxic and well-appearing infants is challenging especially in the very young. The younger the infant, the more important careful and repeated clinical examination is, with close attention to vital signs, quality of cry, level of alertness/social interaction, and perfusion.

Investigations may be used to assist with a diagnosis, determine antibiotic use and duration, or risk stratify certain patients when no focus of infection is found on history and examination. Most children aged ≥3 months who are fully immunised, have no comorbidity and appear well will not require extensive investigation.

Child ≥ 3 months

The approach to investigations for children aged ≥ 3 months without a focus is outlined in the flowchart.  A child with PUO may require more specialised investigations not included here.

Child < 3 months

The approach to investigations in infants aged < 3 months is outlined in the flowchart.

Due to the higher risk of SBI and the challenges in reliable clinical assessment of toxicity in infants ≤ 28 days, a consistent approach to investigation is recommended, irrespective of clinical appearance.

Owing to the lower risk of SBI in invasive bacterial infection, infants aged 29 days to 3 months, can be managed in a step-by-step approach with sequential evaluation of general appearance, urinalysis, and results of bloodwork.¹⁰ With careful clinical assessment, this approach allows identification of a group of infants at low risk of SBI who can be safely managed as outpatients without requiring a lumbar puncture or empiric antibiotic treatment.

Full blood count

Despite being widely used by clinicians in investigation of fever, there is little evidence to support the utility of a FBC in risk stratification for well appearing, immunised infants and children.¹³

A systematic review found WCC of no value in ruling out SBI in vaccinated children and less valuable than CRP for ruling in SBI.¹⁴ A prospective cohort study found that total WCC and absolute neutrophil count were not sufficiently accurate to be used as screening tests for febrile children with possible SBI.¹⁵

For infants < 60 days, no parameters on the FBC have been found to accurately predict risk of a SBI.¹⁶

Meningococcal, salmonella & staphylococcal bacteraemias do not typically elevate the WCC.

The current NICE guidelines¹ use a WCC<5 x 10⁹/L or > 15 x 10⁹/L as risk factors for SBI in the infant <3 months. Using an absolute neutrophil count of < 10 x 10⁹/L in these infants has been validated as a reliable method of identifying those at low risk of SBI.¹⁰

FBC may be useful for children over 3 months who are not fully immunised. WCC in this group may be a more reliable indicator of possible SBI.

C reative protein

CRP is an acute phase reactant and concentrations start to rise 4 – 6 hours after the onset of inflammation and peak around 36 – 50 hours. CRP is better than the FBC for detecting SBI, especially if used after 12 hours of fever, however establishing a level of CRP which can reliably determine low risk of SBI is challenging. A systematic review found a CRP of >80 mg/L was associated with a 72% risk of SBI, and a CRP or <20 mg/L with a 5% risk of SBI.¹⁴ A more recent study suggested a CRP level of <20mg/L in infants between 22-90 days identified infants at low risk of SBI.¹⁰ In the absence of a definitive cut off value, CRP should be only be used for screening on advice from senior clinicians and according to local practice.

Urinalysis

UTI is the most common SBI in children under 5 years of age. Dipstick urinalysis or urine microscopy may be used to screen urine samples for UTI. A diagnosis of UTI is likely when:

• both the leucocyte esterase and nitrite tests are positive in children ≥ 2 years OR
• bacteria are seen on a Gram stain

Antibiotics can commence following a presumptive UTI diagnosis on dipstick testing while the sample is being cultured and tested for sensitivities.

For children ≥ 2 years, a UTI may be confidently excluded when both leucocyte esterase and nitrite are negative on dipstick testing. If a UTI is not able to be excluded on dipstick testing, a sample should be collected for microscopy and culture.

For children aged between 3 months and 2 years, dipstick testing is a useful screening test to guide initial management, with microscopy and culture required to provide definitive diagnosis. Below the age of 3 months, dipstick urinalysis for leucocytes and nitrites is less reliable and assessment should always include urine microscopy.

The most appropriate urine collection method varies depending on age and clinical presentation and is critically important.

Refer to flowchart for a summary of the recommended emergency management of febrile children < 3 months and ≥3 months. Management is based on the risk of SBI.

Supportive

Remove excess layers of clothing from the child. Over-enthusiastic physical cooling can be counterproductive by stimulating shivering and other heat-retaining reflexes. Oral fluids, if tolerated, should be encouraged to maintain hydration.

Antipyretics

Antipyretics may be prescribed for an awake child to provide relief from discomfort caused by the fever or the underlying cause of the fever. Parents should be advised that fever is one of the body’s immune system responses to infection and that antipyretics do not treat or shorten the illness, and will not prevent febrile convulsions.

Aspirin should be avoided in children as the uncommon possibility of Reye’s syndrome increases with varicella or influenza-like illnesses.

There is some evidence that ibuprofen reduces fever and discomfort more quickly than paracetamol.¹⁷ The popular dual therapy dosing regimens reduce the time with fever compared to monotherapy, however there is no significant difference in resolution of discomfort.¹⁸ Safety concerns have been raised over recommending 2 drugs with different dosing regimens for little gain, and parents should be made aware of this risk.¹

Fever and rash

If the child is unwell (abnormal vital signs, poorly perfused, or altered mental state) or if the rash is purpuric (>2mm lesions) and not consistent with typical Henoch-Schonlein purpura (HSP), then the child should be managed presumptively for meningococcal disease with resuscitation as required and a 3rd generation cephalosporin whilst investigations are carried out.

Well-appearing febrile children with petechiae caused by local pressure or only in the distribution of the superior vena cava (eg. following coughing/vomiting) may be discharged with early review. In all other cases blood tests should be performed (FBC, CRP, blood culture). If the FBC and CRP are within normal limits and the child remains well during a 4-hour period of observation, then discharge with early review is again appropriate, otherwise admission with or without antibiotics should be undertaken.^19-21

It should also be remembered that many viral infections can cause petechiae.

Antibiotics

Antibiotics (usually IV) may be indicated depending upon the perceived risk of SBI or the specific infection found. View the Paediatric Antibiocard: Empirical Antibiotic Guidelines for choice and doses or refer to local guidelines.

Follow your local facility escalation protocols for children of concern. Transfer is recommended if the child requires care beyond the level of comfort of the treating hospital. Clinicians can contact the services outlined below to escalate the care of a paediatric patient.

When to consider discharge

Discharge may be considered for children who meet ALL of the following criteria:

• for children aged 1-3 months – only on advice from senior emergency/paediatric clinician and providing clinical review within the next 24-48 hours or earlier has been arranged
• for children ≥ 3 months with features of SBI who are not fully immunised – only on advice from senior emergency/paediatric clinician
• no toxic features
• no other investigations or IV treatment required
• no features of SBI
• able to maintain adequate oral intake to maintain hydration
• can be safely managed at home and return in the event of deterioration (consider time of day, parent/carer comprehension and compliance, access to transport and distance to local hospital)

On discharge, parent/caregiver should be provided with a Fever Factsheet and advised to see a doctor earlier if they are concerned about their child prior to their scheduled appointment.

Follow-up

• with General Practitioner within 24 – 48 hours to check progress and receive outstanding test results

When to consider admission

All infants < 28 days with a febrile illness require admission to an inpatient service.

For febrile infants ≥ 28 days, consider admission for the following children:

• aged 1 – 3 months (even if appear well may require longer period of observation)
• any toxic features
• need for ongoing management
• features suggestive of SBI
• inability to maintain adequate oral intake to maintain hydration
• unplanned return within 24 hours of initial assessment
• social factors such as long distance to hospital and family/carers not able to cope with symptom management

Guidelines

• Sepsis – Emergency management in children
• Meningitis – Emergency management in children
• Management of Fever in a Paediatric Oncology Patient

Factsheets

• Fever
• How to collect a clean urine specimen

1. National Institute for Health and Clinical Excellence. (2013, updated August 2017). Feverish illness in children. Assessment and initial management in children younger than 5 years’, [online] Available at: https://www.nice.org.uk/guidance/cg160
2. National Institute for Health and Clinical Excellence (2013). Urinary Tract Infection in children and young people (online) https://www.nice.org.uk/guidance/qs36
3. Rutman et al. Radiographic pneumonia in young, highly febrile children with leucytosis before and after universal conjugate pneumococcal vaccination. Pediat Emerg Care, 2009, 25(1):1-7.
4. Herz, A.M., Greenhow, T.L., Alcantara, J., Hansen, J., Baxter, R.P., Black, S.B., Shinefield, H.R. ‘Changing epidemiology of outpatient bacteremia in 3 to 36-month old children after the introduction of the heptavalent-conjugated pneumococcal vaccine’, Pediatr Infect Dis J 2006, 25: 293-300.
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10. American College of Emergency Physicians Clinical Policies Subcommittee. Clinical Policy for Well Appearing Infants and Children Younger than 2 Years of Age Presenting to the Emergency Department with Fever. Annals of Emergency Medicine May 2016; 67(5)
11. Bettenay, F.A., de Campo, J.F., McCrossin, D.B. Differentiating bacterial from viral pneumonias in children Pediatr Radiol. 1998;18(6): 453-454.
12. Van den Bruel. Diagnostic value of laboratory tests in identifying serious infections in febrile children: systematic review. BMJ 2011;342: d3082.
13. Cruz AT, Mahayan P, Bonsu BK et al. Accuracy of Complete Blood Cell Counts to identify febrile infants 60 days or younger with invasive bacterial infections. JAMA Pediatr 2017;171(11): e172927
14. Perrott, D.A., Piira, T., Goodenough, B., Champion, G.D. Efficacy and safety of acetaminophen vs ibuprofen for treating children’s pain or fever: a meta-analysis. Arch Pediatr Adolesc Med,2004;158(6): 521-6.
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