A5V4d

Feverish illness in children
to change in the UK in 2006–07 following the introduction of conjugate pneumococcal vaccine to the
childhood immunisation schedule.
Review question
In a febrile child what is the predictive value of the following in detecting serious illness?
156
WBC
absolute neutrophil count (ANC)
CRP
procalcitonin (PCT)
erythrocyte sedimentation rate (ESR)
urinalysis
lumbar puncture
chest X-ray
combination of those above.
Narrative evidence
White blood cell count
Nine studies 166–174 evaluating WBC as a diagnostic marker for serious illness were found. The age
ranges for these studies were birth to 16 years but in seven studies the upper limit was 36 months
(age range mode: 3–36 months). Conditions studied were serious bacterial infection (SBI),
meningococcal disease (MCD), bacterial meningitis, occult bacterial infection (OBI) and bacterial
pneumonia. The cut-off value for WBC ranged from 15 to 17.1 × 10 9 /litre. The ranges of performance
of WBC as a marker of the presence of these serious illnesses were reported as sensitivity 20–76%,
specificity 58–100% and relative risk (RR) 1.5–5.56.
Although one EL II study 168 did demonstrate a ‘perfect’ specificity of 100% with a WBC of
> 15 × 10 9 /litre identifying all children with SBI, the next highest result was 77%. Another EL II study 175
demonstrated an increased prevalence of occult bacteraemia with increasing height of fever and
increasing WBC, but this was a US study conducted before the introduction of the conjugate
pneumococcal vaccine, recently added to the UK childhood immunisation programme. These data are
therefore likely to be less useful now.
One EL II prospective cohort study 176 looked at the combination of WBC > 20 × 10 9 /litre combined
with fever > 39°C in identifying ‘occult pneumonia’ (i.e. those with no clinical evidence of pneumonia)
in children less than 5 years old. Between 26% and 30% of children with both these features had
pneumonia on chest X-ray.
Absolute neutrophil count
Three EL II studies 169–171 evaluating absolute neutrophil count (ANC) were found. Two looked at
children aged 1–36 months 169,171 and one at children aged 3–36 months. 170 The studies evaluated
markers to identify SBI and OBI or to differentiate invasive bacterial infection from localised bacterial
or viral infection. 170 The cut-off values for ANC were 10.2, 169 10.6 170 and 9.6 × 10 9 /litre. 170 The ranges
of performance of ANC in identifying SBI were reported as sensitivity 50–71%, specificity 76–83% and
RR 1.5–6.4.
Sepsis and meningitis
In children greater than 3 months old, PCT was found to have a significantly better diagnostic
performance than CRP or WBC in identifying sepsis, septic shock and meningitis. PCT is also
excellent in discriminating between viral and bacterial, and localised and invasive, bacterial infections.
There was variation in the cut-off values used for PCT in the studies, with 2 ng/ml being most
commonly reported as the best cut-off for distinguishing these groups. PCT was also found to perform
better than CRP in identifying bacterial infection in children who had developed fever less than
12 hours prior to presentation. However, the authors added that since the negative predictive value of