Symptoms of child infections studied

BBC News has reported that doctors should check ill children for leg pain, confusion, stiff neck and sensitivity to light, as they are "red flag" symptoms for meningitis.

The news is based on research that compared children’s early symptoms of meningococcal disease to the symptoms seen in a group of children with only minor infections. Meningococcal disease is a type of bacterial infection that can cause serious problems such as septicaemia. The research found that headache and paleness, which are often suggested as possible early warnings signs, were just as frequent in children who had minor infections. However, confusion, sensitivity to light, neck pain/stiffness and leg pain were all stronger indicators of meningococcal disease. Although the development of a rash is an important sign, it typically appears at a later stage of infection.

It should also be noted that the research was intended for informing doctors rather than parents, and parents should not be worried about this news. The study’s results will also need further verification as it had some limitations, such as parents possibly recalling their children’s symptoms incorrectly.

Parents and carers who are worried about any symptoms in babies or young children, especially if they have a high temperature (fever), should always contact their doctor. Meningococcal disease is a very serious illness but, if treated quickly, most children make a full recovery.

Where did the story come from?

The study was carried out by researchers from Oxford University and Oregon Health and Science University, using data collected from GP surgeries in Oxfordshire and Somerset. The study was published in the peer-reviewed British Journal of General Practice.

The Daily Telegraph and the BBC have reported the study accurately. Both of them reported comments from independent experts who warned against parents ignoring other symptoms.

What kind of research was this?

This was a non-randomised comparative study , which looked at the frequency of certain classic and “red flag” symptoms associated with meningococcal disease, the diseases caused by Neisseria meningitidis bacteria. It analysed these symptoms by gathering cross-sectional data on the symptoms of children visiting GPs with minor infections (the control group) and comparing it to previously-published data on the pre-hospital symptoms seen in children with diagnosed meningococcal disease (the case group).

The authors say that it can be challenging for doctors in primary care to identify which children have serious infections among the many who present with febrile illnesses. It is also a worry for parents. They also point out that about half of children with meningococcal disease are not identified in the first consultation in primary care (usually with a GP).

One reason is that “classic” symptoms, such as neck stiffness, sensitivity to light and rash, may not appear until later in the course of the illness. They say that several possible “red flag” features that occur at an earlier stage of meningococcal disease have been proposed as potential aids for early detection. These are leg pain, cold hands and feet and pale colour.

What did the research involve?

To gather control group data for the study, the authors recruited 1,212 children who had visited 15 GP surgeries with some form of acute illness. They collected information about the frequency of symptoms among the children presenting to the GP by giving their parents a symptom checklist to complete.

Within this group, 407 children were reported to have both fever and a minor infection, making them suitable for comparison against children with meningococcal disease. They had a typical range of minor infections. This control group had an average age of 3 years and 6 months. Half of them were aged between 22 to 79 months. There were few teenagers.

The researchers then looked at the incidence of various symptoms within the meningococcal disease group and the control group with general minor infections. The symptoms they were interested in included:

sensitivity or fear of light (photophobia)
neck pain or stiffness
headache
leg pain
cold hands or feet
pale colour
confusion
drowsiness or feeling very sleepy
rash or new spots on skin
nausea or vomiting
feeling irritable or miserable
general aching
difficult/laboured breathing

The researchers compared the frequency of symptoms obtained from the children seen in GP surgeries with previously published data on the frequency of the same symptoms in children with diagnosed meningococcal disease. They used standard statistical methods to compare the frequency of different symptoms and to calculate their diagnostic value.

What were the basic results?

The researchers had parental report data on 407 children who were identified as having a fever and a minor infection, and 345 children who developed meningococcal disease.

The researchers looked at the specificity of each symptom – testing positive for a symptom with a high specificity tends to confirm the diagnosis. They found that four symptoms were “highly specific” for meningococcal disease.

However, a more clinically-relevant measure would be the ‘likelihood ratio’ of a positive result (LR+), a value that indicates the chance that the presence of a specific symptom is caused by meningococcal disease. The researchers suggest that a LR+ of more than 5.0 is important as it indicates a high chance of having the disease in those who have that symptom. They found that:

confusion had an LR+ value of 24.2 (95% confidence interval [CI] 11.5 to 51.3)
sensitivity to light had an LR+ value of LR+ 6.5 (95% CI 3.8 to 11)
leg pain had an LR+ value of LR+ 7.6 (95% CI 4.9 to 11.9)
neck pain had an LR+ value of LR+ 5.3 (95% CI 3.5 to 8.3)

They also identified symptoms that offered a “likelihood ratio” of a negative result (LR-) of 0.3 or less, a score which would suggest that meningococcal disease was unlikely if an individual did not have the symptom. These were:

drowsiness (LR- 0.2, 95% CI 0.2 to 0.3)
rash (LR- 0.3, 95% CI 0.2 to 0.3)

They found that the two groups had a similar incidence of headache (LR+ 1.0, 95% CI 0.8 to 1.3) and of pale colour (LR+ 0.3, 95% CI 0.2 to 0.5). Cold hands and feet had a “small positive likelihood ratio” (LR+ 2.3, 95% CI 1.9 to 3.0) Rash (LR+ 5.5, 95% CI 4.3-7.1) was also found to have a positive LR above 5, but also had a low LR- score.

How did the researchers interpret the results?

The authors say that of the symptoms studied, the only ones that can be considered early “red flag” signs of potential meningococcal disease are confusion, leg pain, sensitivity to light, and neck pain/stiffness. Headache and pale colour were less frequent among children with meningococcal disease than those with minor infections. Cold hands and feet offered only “limited discrimination” between meningococcal disease and minor infection.

The authors say the findings should be used as evidence to support or modify methods by which doctors diagnose meningococcal disease and assess children with acute infections.

Conclusion

The study’s results confirm that four of the “classic” symptoms of meningococcal disease – leg pain, confusion, neck pain and sensitivity to light – are very rare in children with minor febrile illnesses compared to those with meningococcal disease. However it also found that two symptoms which are often described as early warning signs or symptoms – pale skin and headache – are equally likely to indicate a minor illness. Cold hands and feet were only slightly more likely in children with meningococcal disease.

Meningococcal disease can be a very serious illness. Unfortunately, it can be difficult to differentiate it from a relatively minor infections, particularly in its early stages or in younger children. Refining the clinical methods for diagnosing early meningitis would be invaluable. This study has suggested that certain symptoms may be good indicators of meningococcal disease in children. However, the study was relatively small and has a number of limitations, some of which the authors mention.

Gauging the incidence of the symptoms depended on accurate parental recall of their children’s illness. However, there may have been some inaccuracy in the information provided by the parents of children with meningococcal disease, given the worrying nature of the infection and the practice of questioning parents in the later stages of the disease.
Also, it is possible that children recruited from the GP surgeries were not representative of children across the UK.
There were also few children aged 15-16 years, so it is not possible to say anything about symptom frequencies in young people.
It may be hard for younger children to articulate certain symptoms of their illness, particularly if their illness is severe or if they are in distress: for instance, a child may not be able to differentiate between the two symptoms of headache and light hurting their eyes.
It is important to consider the implications of combinations of symptoms, and how possessing or lacking different symptoms may affect diagnosis.

The early symptoms of meningococcal disease are similar to those of many other conditions, and include severe headache, fever, nausea and vomiting. Parents who are worried about any symptoms in a baby or young child should always seek medical advice.