An article published Online First and in an upcoming edition of The Lancet reports that a systematic review of published research shows that a number of factors are considered in confirming or excluding the possibility of serious infection in children presenting to general practice or other outpatient care. These factors include rapid breathing, poor peripheral circulation (circulation of blood to the skin and extremities), and parental concern and doctor's instinct (in one primary care study). The article is the work of Dr Ann Van den Bruel, Department of General Practice, Katholieke Universiteit Leuven, Belgium, and colleagues.
The authors analysed generally used electronic databases and reference lists of relevant studies. They contacted experts to find articles assessing clinical features of serious infection in children. A total of 1,939 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)
• sufficient data reported
A total of 30 studies were included in the final analysis. The authors calculated 'likelihood ratios' for the presence (positive likelihood ratio) or absence (negative likelihood ratio) of each clinical feature. Clinical features with a positive likelihood ratio of more than 5•0 were deemed as red flags or warning signs for serious infection. Features with a negative likelihood ratio of less than 0•2 were deemed rule-out signs.
Red flags identified in several studies:
• Cyanosis (blue colouration of the skin caused by deoxygenated haemoglobin in the blood vessels near the skin surface): positive likelihood ratio range 2.7 - 52•2
• rapid breathing: 1•3 - 9•8
• poor peripheral perfusion: 2•4 - 38•8
• petechial rash (petechiae are small purple or red spots on the body, and can be indicative of serious infection such as meningitis):6•2 - 83•7
Strong red flags identified in one primary care study:
• Parental concern: positive likelihood ratio 14•4
• clinician instinct: positive likelihood ratio 23•5
Temperature of 40°C (104F) or more has value as a red flag in settings with a low prevalence of serious infection, such as general practice (GP) or paediatric assessment units. However, it is not so useful in emergency departments. The patient populations in emergency departments are different from those in GP practices because they were either referred by their GP because the patient's condition was serious, or self-referred because parents felt it was serious. In general, these patients will have a higher risk of having a serious infection. If they do not have a serious infection, they have a higher risk of having another serious illness or illnesses that are not serious but mimic serious illnesses. Because of the selection process, more children will have higher temperatures at the emergency department and a higher temperature in itself is no longer sufficient to distinguish children with or without a serious infection.
No single clinical feature was deemed to have rule-out value but some combinations could be used to exclude the possibility of serious infection. For instance, pneumonia is very unlikely (negative likelihood ratio 0•07) if the child is not short of breath and there is no parental concern.
The authors explain: "The main strength of this systematic review is that it highlights the nature and difficulty of the diagnostic task facing primary care and hospital clinicians responsible for identifying seriously ill children at initial presentation in countries where serious childhood illness is now rare."
They write in conclusion: "Most of the red flags already recommended by WHO for use in developing countries can be used in the initial assessment of children presenting to ambulatory care settings in developed countries. There should be more emphasis on parental concern in the diagnostic process. However, we now need to identify the level of risk at which clinical action should be taken. Additionally, the relative inability of any combination of clinical features to effectively exclude the possibility of serious illness in a one-off consultation means that parents need to be more actively involved in monitoring red flags and taking precautionary measures."
In an associated note, Dr Martin Dawes, McGill University, Montreal, Canada, comments: "What is clear is that in 2010 we do not know how to effectively recognise or rule out severe disease in ill children and what is more, we do not even have a cohesive national or a global research strategy to address this problem. Notably, of the 30 studies included in today's review, only one was in primary care, where the problem is most frequently present."
He says in closing: "Are we really this poor at undertaking good primary care research on important common problems? We need better-designed diagnostic and prognostic studies in primary care. Such studies require properly documented histories and examination as well as follow-up, but both are well within the scope of an organised practice and if centrally coordinated we could have ten times the evidence within a year or two. This research cannot be done without adequate funding and should be a priority for national and international research foundations."
"Diagnostic value of clinical features at presentation to identify serious infection in children in developed countries: a systematic review" Ann Van den Bruel, Tanya Haj-Hassan, Matthew Thompson, Frank Buntinx, David Mant, for the European Research Network on Recognising Serious Infection investigators
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