Prof Mike Levin - Childhood infections

Kat - But now it's time to find out a bit more about genes and the immune system. Perhaps one of the best places to see the role of genetics in shaping the immune response is in childhood. All kids are exposed to a huge range of bugs - but only a very small proportion will get life-threatening infections, when most others will be unaffected. Even in developed countries like the UK, childhood infections are a big problem, and hundreds of children die from bacterial and viral infections every year.

Professor Mike Levin is Professor of Paediatrics and International Child Health and Director of the Wellcome Centre for Clinical Tropical Medicine at Imperial College in London. I caught up with him to find out more about the genetics of childhood infections.

Mike -   So, as children are born and grow through childhood, they're exposed to an absolute zoo of different bacteria.  A baby is born from a sterile womb and in minutes of coming out into the world, they are colonised by all sorts of bacteria that are in the environment.  Now mostly, as the child develops, they come to no harm.  Their immune system keeps the bacteria where they should be - that's on the skin, on the mucosal surfaces, inside your gut - but 1 in 20,000 or 1 in 50,000 children, the bacteria invade from the mucosal surfaces - the nose, the throat, the bowel - get into the bloodstream and cause life-threatening infection. 

That process, so why does one child come down with the infection and not others is partly controlled by the virulence of the bacteria.  So, there seem to be some bacteria that are worse than others.  So, there are certain bacteria which are more likely to invade if they meet a young child, but there are other bacteria that are completely harmless to 99.9 per cent of the population.  1 per cent will come down and be critically ill.

Kat -   Can you tell me a bit more about the particular study that you're involved in looking at how genetics influence childhood disease?

Mike -   We were very fortunate to be awarded a major grant which is funding a study EUCLIDS which stands for the European Union Childhood Life-threatening Infectious Diseases Study.  Essentially what it is, is it's recruiting children who were admitted with infection from multiple hospitals in the UK as well as from multiple hospitals in Holland, Spain, Austria, Germany and probably soon, Switzerland, as well as the Gambia in West Africa. 

This is enabling us to establish very large numbers of patients who are very carefully studied and the grant also provides a funding to apply very sophisticated genetics including sequencing and genome-wide association methods to this very large cohort.  We hope that the study will provide very good information on the genetic basis of a range of different childhood infections including Staphylococcus infection, Streptococcus infection, Pneumococcus, Meningococcus, and Salmonella which are very important childhood pathogens.

Kat -   Where are we heading in terms of turning this into benefits for children and actually improving child health?

Mike -   I think there are a number of reasons why unravelling the genetic basis of how the immune system responds to bacteria is going to help in the future.  The first is that obviously, for very severe defects, if you know what the gene is, you can test for it and you can offer counselling and treatment for those that are affected.  For example, there are a set of gene defects in a gene and a protein in the blood called complement which you need to kill the Meningococcus bacteria.  If you found to lack this protein complement, then you're going to be at lifelong risk of coming down with meningococcal disease.  We can treat those patients by giving them preventative antibiotics.  So, that's the simplest example if we know what the gene is and we can offer prevention.

The more sort of subtle example is that if we know how the immune system works, to stop getting an infection - which the gene defects are often a clue to - then we know what sort of immune effect we need to stimulate with a vaccine.  So, understanding how the immune system works through the genetics can improve understanding of how to develop vaccines.  I suppose the third way is that it looks like, not only do genes control who gets the infection,  they also control how bad it is and what the outcome is. 

So, there are some people who will get bacteria in the bloodstream and they'll come in to a hospital and receive a course of antibiotics, and go home and are cured completely.  There are other children that come in become devastatingly ill, and may die or lose limbs in a matter of hours.  It looks as if those different responses are also genetically controlled.  Again, if we understand what is going to make one child become catastrophically ill, another one become milder, then one can develop strategies to improve the outcome.  I think again, the genetics is a powerful clue to why some people do badly and others do better.

Kat -   It seems only in a matter of maybe 100 years, we've gone from many, many children dying in childhood from simple infectious disease to now a point where, certainly in developed countries, many, many children are saved.  Where do you think we're going to be heading in the next 10 years?  Where would you like to be?

Mike -   I think, hopefully, the reduction in childhood mortality from infection that has been seen in the developed world will be extended to the less resource-rich areas of the world.  So, I think we would hope that the advances in prevention of infection through vaccination hygiene and treatment which has meant infection causes fewer deaths in Europe, the United States, will start happening in Africa and Asia.  So, I think that's a big goal.  Although infection has declined as an important since the earlier part of the last century, it's still there. 

So, those of us working in paediatrics services continually see children admitted critically ill with life-threatening infections like meningitis, septicaemia, pneumonia, osteomyelitis. Trying to work out how to improve the outcome for those that are infected, trying to work out how better to prevent infection is going to remain a research challenge.  So, all the research is still needed because many of the infections are still with us.  There's still a major problem -  although things are very much better than they were 100 years ago - there's certainly no room for complacency.  A large part of the workload of paediatric services, paediatric intensive care, is still infectious diseases.

Kat - That was Professor Mike Levin from Imperial College.