Public Release: 

Rapid breathing, parental concern, and doctor's instinct among the red flags warning of serious infection in children in developed countries

Lancet

A systematic review of published research shows that a number of factors have value in confirming or excluding the possibility of serious infection in children presenting to general practice or other outpatient care. These include rapid breathing, poor peripheral circulation*, and--in one primary care study--parental concern and doctor's instinct. The findings are reported in an Article published Online First and in an upcoming edition of The Lancet, written by Dr Ann Van den Bruel, Department of General Practice, Katholieke Universiteit Leuven, Belgium, and colleagues.

In the review, the authors searched commonly used electronic databases and reference lists of relevant studies, and contacted experts to identify articles assessing clinical features of serious infection in children. A total of 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. 30 studies were included in the final analysis, in which 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 red flags (ie, warning signs for serious infection); features with a negative likelihood ratio of less than 0•2 were deemed rule-out signs.

Cyanosis** (positive likelihood ratio range 2.7-52•2), rapid breathing (1•3-9•8), poor peripheral perfusion (2•4-38•8), and petechial rash*** (6•2-83•7) were identified as red flags in several studies. Parental concern (positive likelihood ratio 14•4) and clinician instinct (positive likelihood ratio 23•5) 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, such as general practice or paediatric assessement units--but is not so useful in emergency departments****. 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 example, 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 say: "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 conclude: "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 accompanying Comment, Dr Martin Dawes, McGill University, Montreal, Canada, says: "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 concludes: "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."

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Dr Ann Van den Bruel, Department of General Practice, Katholieke Universiteit Leuven, Belgium. (not available Tuesday morning Belgian time) T) +32 497 51 64 83 E) ann.vandenbruel@med.kuleuven.be

Dr Martin Dawes, McGill University, Montreal, Canada. T) +1 514 398 7375 ext 00381 E) martin.dawes@mcgill.ca

For full Article and Comment, see: http://press.thelancet.com/childinfection.pdf

Notes to editors: *Poor peripheral perfusion: poor circulation of blood to the skin/extremities

**Cyanosis: blue colouration of the skin caused by deoxygenated haemoglobin in the blood vessels near the skin surface.

***Petechial rash: petechiae are small (1-2mm) purple/red spots on the body, and can be indicative of serious infection such as meningitis.

****The patient populations in emergency departments are different from those in GP practices--they were either referred by their GP because he/she felt 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 (hence the higher prevalence). 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.

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