Meningitis under the microscope

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0:57Robin May:and medicine. I'm Chris Smith and today bacterial meningitis is going under our microscope.

1:15Robin May:Bacterial meningitis is a serious but thankfully now relatively uncommon infection which is caused most often by the meningococcus bacterium, Neisseria meningitidis. And believe it or not, this is actually commonly carried in our noses and throats. In some instances, as many as one person in four are found to be harbouring it, although in the majority of those cases, it causes absolutely no problems whatsoever. But in some people, infected with certain forms of the bug and perhaps in response to another antecedent infection or a problem with their immune system, it can become invasive, spreading through the bloodstream to involve the meninges, the tissues surrounding the brain, and also triggering sepsis.

1:59Robin May:The onset is often very abrupt, catching people completely unawares. A recent outbreak in Kent in the south-east of England was extraordinary in hitting nearly 30 young people, of whom two later died. So we thought we'd delve into the biology of bacterial meningitis, find out how it causes disease, how to recognise and treat it and what vaccines can do to prevent it and also how to handle outbreaks when they happen which is the role of the UK Health Security Agency. Robin May is the organisation's chief scientific officer.

2:32Kat Sharrocks:So meningitis refers to a group of conditions which is essentially characterised by inflammation of the meninges and the meninges is a layer on the outside of the brain and spinal cord that kind of protects the brain from damage. It can get infected, it can get inflamed and that's obviously very dangerous as with all infections of the central nervous system. Different organisms can cause meningitis so you could have viral meningitis caused by actually quite a range of viruses. You could have fungal meningitis in some rare cases caused by fungi but the one that we're talking about primarily today is bacterial meningitis which is caused by a bacterial species called Neisseria meningitidis.

3:11Robin May:There are other microbes that can do it though it's not just Neisseria meningitis is it because when we go to medical school they tell us to keep our eyes open for a range of things yeah there are there's quite a

3:22Kat Sharrocks:wide range actually and some of those are kind of quite well able to do this and some it's a very rare complication so for instance there are some you know very rare fungal infections that people only get when they have underlying immunocompromised conditions like HIV but in rare cases they can go to the brain too and causes kind of meningitis. But I think the one that is particularly dominant in people's minds and has occupied the media a lot recently is this one that is bacterial meningitis transmitted between people who are healthy, particularly young people. And so that's one that is very prominent and one that people should be on the alert for and on the lookout for.

4:00Robin May:Who tends to get it and where do they tend to get it? I don't mean in terms of in their body, I mean geographically.

4:07Kat Sharrocks:Yeah, so these are diseases that are widespread. So if we think about, If we focus on bacterial meningitis caused by Neisseria, this bacteria we're talking about, it's found all over the world. So people can get it anywhere. Actually, anyone can get it. But if you look at the most likely candidates to get it, it is typically associated with age. So babies, very young children, and then in teenage age and then dropping off, you're likely to get this drops off as you get older. And that's largely because we're exposed to this bacteria. It's a bacteria that is prevalent in the world. so we're exposed to it and develop a kind of natural immunity over time and obviously also in many countries including the uk we have vaccination programs that have really reduced the level of this so if you're one of those countries you also gain the benefit of vaccination as you age but yeah so this is largely a disease bacterium energitis a larger disease of babies

4:57Robin May:and infants and then again in teenage years what sorts of numbers do we see is this a rare thing or is it actually quite common but flying under most people's radars?

5:08Kat Sharrocks:Historically, this was kind of alarmingly common. We have done a pretty good job in recent decades actually of reducing numbers through vaccination programme in the UK. And now all children get vaccines when they're shortly after they're born. And they have been very, very effective in reducing the amount of disease. Two things to say about that though, I think. One is that this is a very complicated bacteria. It comes in lots of different flavours, also called serogroups. And generally, the vaccines work against any one serogroup. So what you now get as a baby is a vaccine that protects you against four different strains of this.

5:43Kat Sharrocks:But there are about 12 common strains of meningitis around the world, bacteria meningitis around the world. So you're not fully protected. And so even when you're vaccinated, you can still get this disease. But overall numbers have dropped. And in the UK, we typically see something like 350 cases of bacterial meningitis per year. So that's basically one a day.

6:03Robin May:What's the distinction though, between that one a day and an outbreak?

6:09Kat Sharrocks:This is an interesting disease because it is transmitted particularly through kind of things like saliva between individuals. And so it's very important when we find even a single case of disease that we do what's called contact tracing. So for example, if there's a teenager who has been presented and diagnosed with bacterial meningitis, we will immediately start to look for, for example, members of their family, boyfriends, girlfriends, close friends with whom they may have had close contact in order to check for transmission and to treat those people. So even a single disease, we do follow up very closely.

6:40Kat Sharrocks:When we're talking about outbreaks, though, we're talking about multiple linked infections together. And so, for instance, if somebody's presented with a disease, sometimes their partner, the family members may get the same strain and that becomes an outbreak as it transmits and obviously our key role at the health security agency is to try and minimise the spread of that outbreak and treat the people affected as swiftly as possible.

7:02Robin May:Robin May at the UK HSA or UK Health Security Agency. We'll hear more from Robin a bit later on about how we respond in a public health capacity to cases of meningitis. But first the symptoms of bacterial meningitis usually appear quickly and they can mimic other common diseases like influenza. So what should we look out for and when might it be prudent to seek medical advice? I met Kat Sharrocks, who's a consultant in infectious diseases at Addenbrookes Hospital in Cambridge.

7:33Andrew Pollard:Usually what we're looking at is somebody who's got a fever, quite often got a headache, maybe have difficulty looking at the light, quite often has some neck stiffness. They might be a little bit confused. They might be a little bit sleepy as well. that's the general picture of somebody and that this has come on quite quickly it's not something that's been going on for days and days and days but it's quite often something that's happened in the last 24 hours.

7:59Robin May:Why is it then that people talk a lot about a rash with meningitis?

8:04Andrew Pollard:We can certainly see a rash with some sorts of meningitis but not having a rash doesn't mean that you don't have meningitis.

8:12Robin May:What's the cause of that though? Why would inflammation around your brain which is what's going on with meningitis be linked to a rash elsewhere on your body?

8:20Andrew Pollard:So that's what we can see with a systemic infection. Just because the infection's affecting one place, the meninges, those layers around the brain and the spinal cord, doesn't mean it's not affecting other places in the body. And particular bacteria and their toxins can cause problems with the clotting that we see in our bloodstream and that's what leads to that particular rash, that rash that doesn't go away when you put a glass on top of it. But that's not the only sort of rash that we can see. We can see lots of different rashes depending upon the bacteria that we see. So seeing that rash in and of itself by itself doesn't mean that you have meningitis, nor does not seeing it mean that you don't have meningitis.

9:00Robin May:Therefore, how do doctors like you get to the bottom of what is wrong with someone who's got that constellation of features?

9:07Andrew Pollard:So the first thing is that we've got to be aware of those constellation of features, as you say, and have a high suspicion for anybody who's presenting like this that they might have something as serious as meningitis. We'll examine them, so we'll look at their neck stiffness, we'll have a listen to their chest, but then we'll do some other more serious tests. We'll look at their blood markers, we'll see whether they have an infection by looking at their C-reactive protein perhaps, we'll look at their white blood cells to see if they've got raised white cells called neutrophils, which will be in keeping with having a bacterial infection.

9:38Andrew Pollard:We'll probably do some imaging of their head. First off would be a CT scan and that's really looking for other causes rather than meningitis that might cause a similar set of symptoms. And then we'll move towards doing a test called a lumbar puncture or a spinal tap, if you like the Americanisation of it, which is where we take a little sample of the fluid that surrounds the brain and the spinal cord and we look at that underneath the microscope. And we're looking again there for those white blood cells which shouldn't be there at all. We're looking to see whether they've crept into that space to try and fight an infection that shouldn't be there and then we'll test that fluid for other things.

10:17Andrew Pollard:We'll try and culture it to see if we can grow any bacteria in the laboratory and we'll look for other causes of the same constellation of symptoms, other causes of meningitis like looking for viruses as well as bacteria.

10:28Robin May:Why do they home into the meninges, those layers around the brain and spinal cord though in meningitis why do the bacteria make a beeline there do we know?

10:37Andrew Pollard:Different bacteria have different predilections for the places that they like to grow and the bacteria that go to the meninges have a predilection for those but there are also certain risk factors that you might have that make it more likely if you have one of these infections for them to go to the meninges. For example if your immune system doesn't work particularly well you may have a particular immune problem it may be that you are very young or that you're very very old where your immune system doesn't quite work as well as other people's. It might be that you have something like diabetes which can put you at a risk of having certain sort of infections or it may be that you have a little bit of a weaker immune system because of chronic use of alcohol for example.

11:17Robin May:If you pick it up, God forbid, and you discover there is all the evidence there is a bacterial infection there, what do you do?

11:25Andrew Pollard:So for most people even before we've got the evidence that this is definitely a bacterial meningitis, we will have started treatment. So we're aware that GPs, when they see this constellation of symptoms, even in their practices, they have antibiotics at hand that are able to treat meningitis and they'll give an intramuscular injection of antibiotics before sending the patient on their way to the hospital. Immediately in the hospital, for people where we suspect they have meningitis, we will start antibiotics at that point and we start a very broad spectrum antibiotic that's very good at getting into the central nervous system and we also usually start something called dexamethasone at the same time which is a steroid which might seem a little counterintuitive when you're trying to fight infection but that helps with inflammation that can cause longer term problems in bacterial meningitis.

12:16Robin May:And what tends to happen? How quickly do you know this person's going to turn the corner and how quickly before that person's better?

12:25Andrew Pollard:usually sort of say 24 to 48 hours of the appropriate antibiotics and we see some improvement if we're not seeing improvement at that point we tend to be very cautiously going back to the drawing board and ensuring that we have all the right sort of samples the antibiotics are getting to the right place and that we haven't missed anything because these infections although as we've said they target the meninges they can cause problems elsewhere and what about when it doesn't

12:53Robin May:go the right way. Does some cases actually end up with a bad outcome?

12:58Andrew Pollard:So not catching this early can end up with people unfortunately becoming very unwell and unfortunately despite having appropriate antibiotics they cannot make it and I've seen a couple of cases where people have come through the doors in an accident, an emergency and unfortunately passed away within sort of long minutes to short hours of having been there. For people where we've managed to get them on appropriate treatment and it's been a sort of series of days but despite that they aren't improving. We do try to optimize our antibiotics that we're using and as I was saying we try to find other places that the infection might be affecting.

13:35Andrew Pollard:The longer term outcomes there can be neurological difficulties after having such a degree of inflammation as well. We here would use our rehab teams, our neurological rehab teams to try and improve the outcomes of any deficit that we've seen after anybody's had an infection.

13:52Robin May:Kat Sharrick's at Adam Rooks Hospital in Cambridge there.

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14:20Robin May:This is the Naked Scientist podcast with me Chris Smith and this week we are examining bacterial meningitis to find out what it is and how we respond to outbreaks. Just now we were hearing how to recognise, diagnose and treat cases of bacterial meningitis but prevention is always better than cure and this is where vaccines come in. Although the meningococcus is the most common cause there are a number of different bacteria that can cause meningitis and susceptibility to them tends to vary with age. Thankfully we do have a spectrum of very good vaccines against many of them now although because some of them have been introduced only relatively recently not everyone has received all of them and this is one factor that might underlie why the outbreak occurred recently in Kent.

15:10Robin May:I asked Professor Sir Andrew Pollard who is director of the Oxford Vaccine group to give us a roundup of what's being used and how effective they all are.

15:18Kat Sharrocks:The first vaccine to be introduced was against Haemophilus influenzae type B, that's given to babies. The second was a vaccine against pneumococcus, which is most commonly associated with pneumonia, but it's also one of the leading causes of meningitis in children and adults here in the UK. and the third vaccine for bacterial meningitis is against meningococcus and we have unfortunately to come to make it more complicated we have five different types of meningococcus one of the vaccines covers four of them and that's given to teenagers and then lastly against the b strain of meningococcus and that's a vaccine given to babies do we know though why some of these infections