Wednesday, 28 August 2013

Diagnosing infection in children – what is the problem?

One of the big problems in terms of treating children is diagnosing the illness in the first place.  In no group is this more of a challenge than in infants with infections, because many of the classical signs of infection, such as inflammation are absent because of their relatively immature immunity.  A similar problem occurs with people of all ages whose immune systems are damaged, either by disease, old-age, or sometimes medical treatment.  The key to diagnosing infection is often not the bug, but the immune response to the bug, and if you don’t have a good immune response it makes it all the more difficult.  Often the only sign of infection is a fever, hence the importance of fever as a diagnostic sign in immunosuppressed people.

The answer to this is to either have a very low suspicion for disease, which might mean over-treating; or to have a higher suspicion, but then risk missing disease.  The problem with the first is that it is expensive, and in the case of antibiotics might lead to the development of resistance; while the latter leads to the risk of missing potentially fatal infections.  It was partly for this reason that the NICE Guidelines on the treatment of fever in children were developed, but many of the symptoms in the amber and red categories are fairly general, and anyway they don’t tell you what infection the child has, just that they probably do have one.

The answer is better and quicker diagnostic tests.  We have a whole range of tests now, but none that are completely accurate.  Additionally, some are highly dependent on the skills of the person performing the tests or on the organism itself: for example, blood cultures, the gold standard test for many infections may become contaminated with skin bacteria, or the bacteria themselves may not grow in the lab.  Even if they do grow, it is not always the case that the bacteria that grow are the ones actually causing the disease; and there may be other organisms, for example viruses or fungi that do not grow in the lab.  Such methods are sometimes referred to as 'phenotypic' - they look for behaviours such as growth or the response to different conditions or chemicals.  If the thing is dead in the test tube or does not grow it won't have a phenotype!

There are many new diagnostic techniques that avoid such problems being developed, some of which are reviewed in a recent paper in JAMA Pediatrics.  In particular these are tending to use molecular methods to either identify the pathogen directly, such as those which look for the genes of the organism; or to identify the host response to the organism.  The latter is helped by the rapidly increasing knowledge of the human immune system and genomic techniques. These methods don’t rely on culturing (‘growing’) the organism in the lab, and so avoid many of the problems inherent in observing growth or behaviour, but they bring their own issues, not least of which is expense.  One method, known as PCR(Polymerase Chain Reaction) which looks for pathogen genomes has been used for some time, and is widely used to diagnose HIV in young children, but is not widely used elsewhere for diagnostic purposes.  Molecular is definitely the way forward, but it may not be a quick journey.

The lesson from this is that testing is fine, but it must not replace the clinical judgement of either parents or healthcare professionals.  Even if you have the best diagnostic test in the world…..ever, it still relies on someone to notice that the child is ill in the first place.  Parents and clinicians are both, in their own ways, generally quite good at this, and so should trust their instincts.  Incidentally, if you want to know if someone really understands this stuff ask them: if they say yes - they probably don't!  There is much of the immune system, and our relationship with micro organisms that we don't understand and probably never will.

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