A5V4d

Feverish illness in children
One study of low quality had a population with 1.7% prevalence of bacterial meningitis, occult
bacteremia and sepis. Procalcitonin showed moderate sensitivity and high specificity at a cut-off of
0.9 ng/ml or more. C-reactive protein showed moderate sensitivity and low specificity at a cut-off of 20
mg/l or more.
Combined procalcitonin with C-reactive protein
One study of low quality evidence had a population with 22.6% prevalence of bacteremia,
pyelonephritis, lobar pulmonary consolidation. Combined PCT or CRP tests showed high sensitivity
and low specificity at 0.9 ng/ml and 40 mg/l respectively.
One study of low quality evidence had a population with 3.2% prevalence of bacteremia. Combined
PCT and CRP tests showed low sensitivity and low specificity at a cut-off of 2 ng/ml or more and
40 mg/l or more respectively.
Health economic evidence statements
No new health economic studies were identified and no significant changes to costs were identified.
Therefore, no health new economic evaluation was undertaken for this question (see Evidence to
Recommendations below for the GDG’s view of why an additional analsyis was not required).
An economic evaluation was undertaken in the previous guideline to assess the cost effectiveness of
using CRP versus using PCT to investigate the presence of SBI in children without apparent source
(see Appendix D). Health economic evaluation was required since PCT is not routinely used. All other
diagnostic tests are offered on the NHS and are part of the usual package of tests for children over
3 months where SBI is suspected. The results indicated that under certain assumptions CRP is both
less costly and more effective than PCT in correctly diagnosing and ruling out SBI in children with
fever without apparent source (FWS). However, the results were sensitive to the prevalence of SBI.
CRP no longer dominated PCT when the prevalence of SBI was over 27%, keeping all the other
baseline assumptions constant. Nevertheless, given the lack of robust evidence underpinning these
baseline assumptions, the analysis cannot support the replacement of CRP with PCT at present. The
GDG has recommended more research on the performance characteristics of CRP and PCT in
children with feverish illness of uncertain cause.
Evidence to recommendations
Relative value placed on the outcomes considered
The GDG stated that the overarching aim of the guideline was the early and accurate detection of
serious illness in children with fever. This allows for suitable treatment to begin, which will then reduce
mortality and morbidity. Diagnostic tests are part of this process.
Consideration of clinical benefits and harms
The GDG members stated that, to their knowledge, the evidence presented was accurate and
complete.
The GDG highlighted that the new data showed that both CRP and PCT were moderately useful
diagnostic tests. The GDG members noted that the data comparing CRP and PCT showed a
statistical difference in favour of PCT. However, they were also aware of the small absolute
difference, low quality of the data and heterogeneity between the studies in terms of settings and
populations. Furthermore, the GDG highlighted that while CRP was routinely available in secondary
care within the NHS, no one was aware of PCT being used outside a research setting in the NHS for
children. CRP and PCT are rarely available in primary care and any child who was unwell enough to
require a CRP or PCT test should be immediately referred to a paediatric specialist.
The GDG discussed if there were any situations in which PCT would be more beneficial than CRP.
The main focus of this was early detection of bacterial illness, as PCT levels increase earlier in
response to infection than CRP. However, the evidence suggested that few children are taken to an
emergency department within 6 hours of a fever starting.
Based on its assessment of the data, the GDG concluded that no clinically important difference
between PCT and CRP could be identified, and therefore that CRP should still be recommended and
PCT should not. Furthermore, the GDG decided that no change was needed concerning when a CRP
test should be ordered.
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2013 Update