Elsevier

The Lancet

Volume 375, Issue 9717, 6–12 March 2010, Pages 834-845
The Lancet

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

https://doi.org/10.1016/S0140-6736(09)62000-6Get rights and content

Summary

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°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.

Introduction

Serious infection is an important cause of morbidity and mortality in children in developed countries. Infections account for 20% of childhood deaths in England, Wales, and Northern Ireland, with the greatest number in children aged 1–4 years.1 These serious illnesses need to be distinguished from self-limiting acute illnesses that are very common in children. A Dutch survey of parents reported that during a 3-week period, 60% of children had an acute illness episode and 4% had febrile illness.2 In the UK, acute infections result in 4·0 consultations per person-year in children aged less than 1 year, and 1·3 consultations per person-year in children aged 1–15 years.3 Additionally, febrile illness accounts for 20% of all visits to the paediatric emergency department.4

An early and accurate diagnosis of serious infection in children is essential to reduce morbidity and mortality. However, diagnosis is not straightforward because of the low prevalence of serious illness, and even those few children with serious illness can present at an early stage when the severity of the illness is not apparent. In a primary care setting, less than 1% of children assessed will have a serious illness5 and there is a duty on the clinician to reassure anxious parents of healthy children and to diagnose seriously ill children.6 Triage might need to be done rapidly in a pressured environment or by telephone, and by staff who might have limited paediatric experience. Consequently, the diagnosis could be missed at first contact,7 sometimes with serious consequences.8

Our attempts to draw up guidance for clinicians in the UK, Belgium, and the Netherlands showed scarcity of evidence on the diagnosis and management of children presenting with acute illness. WHO has sponsored large-scale studies in resource-poor countries9, 10 that provide evidence relevant to those settings; however, in developed countries the evidence base seems more limited and fragmented, and the range of diseases is different. The very low prevalence of serious disease also increases the diagnostic challenge. Therefore, we undertook a systematic review of the evidence from developed countries to identify which clinical features have value in confirming or excluding the possibility of serious infection in children presenting to ambulatory care settings.

Section snippets

Search strategy and selection criteria

We searched four electronic databases (Medline, Embase, DARE, and CINAHL). Search terms (webappendix p 1) included MeSH terms and free text: “serious infections”, “children”, “clinical and laboratory tests”, and “ambulatory care”. No time or language restrictions were placed on these searches. The first search was undertaken in October, 2008, with an update undertaken in June, 2009. We checked reference lists of all retrieved articles and relevant guidelines from the National Institute for

Results

Figure 1 shows the flow diagram of study selection for the analysis. We selected 36 studies for final inclusion in the review, six of which focused on laboratory tests only and are not included in the analysis reported here.15, 16, 17, 18, 19, 20 Full details of the remaining 30 studies are shown in table 1.

The quality of the included studies was modest (webappendix p 2). Only four studies explicitly mentioned masked reading of the reference standard; this item was scored as unclear in 18

Discussion

The strongest red flags for serious infection identified in this systematic review accord with those previously identified by WHO for resource-poor countries: reduced consciousness, convulsions, cyanosis, rapid breathing, and slow capillary refill (table 4).9 Parental concern and clinician global impression were also identified as important diagnostic features in developed countries. Difficulty in feeding seems to be a less helpful red flag in developed countries than it is in developing

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