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CASE NOTES
Tuesday 3 October 2006, 9.00-9.30pm
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BRITISH BROADCASTING CORPORATION

RADIO SCIENCE UNIT

CASE NOTES

Programme 3 - Immunisations

RADIO 4

TUESDAY 03/10/06 2100-2130

PRESENTER: MARK PORTER

REPORTER: ANNA MCNAMEE

CONTRIBUTORS:

DAVID ELLIMAN
JOHN WARD
TONY COLGATE
ALISON PISANI
DOUG JENKINSON

PRODUCER: KATY HICKMAN

NOT CHECKED AS BROADCAST

PORTER

Hello. In today's programme I will be finding out about the new pneumococcal jab - the latest addition to the burgeoning list of vaccines given to babies. We know what babies think of injections:

CRYING BABY

But, a month after its introduction, how is the new vaccine going down with parents?

And does this sound familiar?

BABY COUGHING

The sounds of whooping cough, which, as I'll be discovering later on, is still very common, despite most adults, and nearly all children being vaccinated against it.

And, in light of this week's headlines warning of a delay in delivery of supplies of flu vaccine, I'll be going behind the scenes to find out how it's produced - an annual race against time that involves sucking the insides out of tens of millions of eggs.

EGG SUCKING

My guest today is Dr David Elliman, he's a community paediatrician at Great Ormond Street and Islington Primary Care Trust.

David, let's start with new pneumococcal vaccine - who gets it and why?

ELLIMAN

Well up until recently it's only been given to a selected group of children who are at high risk of getting the diseases that the organism causes. But as of September 4th all children will be getting it as part of the routine programme, that's a dose at two months and then again at four, with a booster at 13 months. There will also be a catch up campaign, so every child under two will be offered it as well.

PORTER

Why do we need it, what does the pneumococcus bacterium - what threat does it pose to our children?

ELLIMAN

It causes a number of diseases but probably the most serious are blood poisoning, meningitis and pneumonia. And it accounts for something like 50 deaths a year in children. The vaccine is against some of the forms of this germ, not all of them, so it only protects about 70-80%.

PORTER

The vaccine's been available in the States for some time and has been given to millions of children over there, what's that taught us about side effects?

ELLIMAN

Well the vaccine, as you say, has been given now for five years, since 2001, as a routine and before that there were very large trials done. And what we found is that it's really the same as the HIB vaccine, the Meningitis C vaccine, it's a very safe vaccine. Yes some people do get local reactions, bit of a temperature, bit off their food but anything more serious than that is very, very unusual.

PORTER

One of the major concerns of parents with this growing list of vaccines that are given is this concept that I think has been fuelled by the media that multiple vaccines can overwhelm the immune system. But on what basis do we know that the immune system can handle all these things at the same time?

ELLIMAN

Quite often people when they say they feel their immune system may be overloaded we're not quite sure what they mean, what the outcome would be of that. But there are two things that might logically follow. One would be that someone who'd been immunised was then more susceptible to other infections in the period after immunisation and there have been very large studies looking at this, some only in the recent two or three years published on hundreds of thousands of children, showing that if you're immunised you are no more likely to end up in hospital with a serious infection. The other way that it might affect your immune system is giving rise to more what are called autoimmune diseases, when your body, in a sense, reacts to itself, things like Multiple Sclerosis, rheumatoid arthritis, diabetes. Again quite large pieces of research in a number of countries have looked at this specifically and found no evidence that that's the case. And perhaps it's worth reminding people that although we seem to be immunising against more diseases, actually in the last 40 years the number of active bits in the vaccine has gone down enormously. So if we go back to 1960 when we were only immunising against five diseases there was something like 3,200 bits in the vaccine that could potentially stimulate your immune system.

PORTER

So these are the markers that are on the outside of the cells that the immune system feels to identify in babies?

ELLIMAN

That's right. If you come forward to where we are now there are something like 57, 58 of these markers. So we've gone from 3,200 to almost 60, so an enormous reduction in fact. So if anything we are presenting a much lesser load to the immune system.

PORTER

What are uptake rates like for the routine immunisation programme across the UK?

ELLIMAN

It varies, depending upon the area, and of course the vaccine as well. But for the basic vaccines, that's diphtheria, tetanus, whooping cough etc., given to under a year old children, that's somewhere of the order of 93-94% recorded and probably is actually higher even than that. For the MMR it was of that sort of order until there was the scare now about seven years ago, it went down markedly, in some areas it went down to as low as 60%. It has come up but especially in inner London, for example, it still is below 70% in some areas.

PORTER

Well the borough of Southwark, in South London, has one of the lowest immunisation rates in the country. Anna McNamee joined nurse practitioner Alison Pisani in her busy clinic to find out why?

ACTUALITY

PISANI

Okay, he's going to the injection in his left leg. [Baby crying] That's all over. That's it, well done, well done, it's all over.

PISANI

The immunisation rate here in Southwark is very low at the moment compared to the national average and we're really trying hard to increase the uptake at the moment.

MCNAMEE

What is the community here like, why is the take up very low?

PISANI

It's very diverse, and we have a lot of refugees and immigrants and people move in and out of the area because they're being rehoused, so they come in for a few months and then they go out again. And this is a problem because obviously some babies are missed and some aren't even registered.

MCNAMEE

It is difficult though isn't it, I mean I remember myself as a new parent just being faced with this astonishing list of acronyms - HIB, Men C.

PISANI

It's an extremely long list and the other problem I find is that we don't see these illnesses anymore, we don't see these diseases anymore in this country, so I think there's a lot of confusion there saying well why do our babies have to have them when these diseases don't exist. And we have to try and explain that actually they do exist and it's because of the immunisations that we give at such an early age that we prevent the spread of disease.

ACTUALITY

PISANI

Let me just check your red book? This is the first time you've been here is that correct?

MOTHER

Yes first time, yes.

PISANI

So she's had all the normal immunisations as a baby and Men C and the MMR. Have you heard about the new pneumococcal vaccine, have you seen it advertised on…?

MOTHER

Yeah I've heard an advertisement on the telly but I don't actually know the actual name of the injection.

PISANI

Well we've now discovered that if we give this vaccine it will prevent pneumococcal meningitis and there's an awful lot of deaths as children from this, so we're offering this to all children. What I'll do today is I'm going to do the pre-school booster today and I'm going to give you a leaflet on the pneumococcal if you like or we can do it all today, but if you like we can wait.

MOTHER

Yeah I want to wait.

PISANI

She's going to have two injections today you do realise that?

MOTHER

Yeah I do.

PISANI

It's the booster of the things that she had when she was a baby - tetanus, polio and the polio's now an injection, it's not oral anymore because when she had it it was oral wasn't it. That's right. And the MMR as well.

MOTHER

I'm more nervous than she is, I reckon. I'm really scared of needles because there's a lot of pain they have to go through but at the same time if they don't have it.

MCNAMEE

Do you think it's easier to get a toddler immunised or a baby?

MOTHER

A baby because they're not really aware of what's going on but whereas at her age now she's totally aware of what's happening, so it's easier for a baby I reckon.

ACTUALITY

PISANI

I'm going to give you some little injections and they're little scratches on your arm like that, okay? And if you keep very, very still, just hold still, good girl. [Baby crying] Another one.

PISANI

We have a very good system now that shows up patients who are not attending. We also have it flashing up on the screen, so if the baby comes in for a cold or a cough or something else the clinician dealing with that at the time can say hey when the baby's better can you come in and have a vaccine.

MCNAMEE

Does it feel a little bit though like you're preaching to the converted, I mean given that the take up rate here in this borough is so low I suppose the ones that you really worry about are the ones that aren't going to ever step through the door to begin with?

PISANI

Well exactly, there is always that hard core who just refuse to have vaccinations full stop. But I'm hoping that, especially with immunisations being in the news again in a positive way, we might see more people returning again, oh yes I haven't sent my son for the pre-school booster, I must get that pneumococcal. It would be interesting if you came back in a few months time and had a look at our targets and compare them with last year because this might be an encouragement for mothers to remember to come back.

PORTER

Alison Pisani talking to Anna McNamee. David, I couldn't help feeling that Alison, the nurse practitioner there, didn't push the pneumococcal vaccine perhaps as hard as she could have, I mean the mother was readily given the option to put it off and that tends to be the default position.

ELLIMAN

I think it's like any preventative measure, if it were giving out an antibiotic for a wee infection or something like that the doctor would be saying I think you ought to do this, fairly straightforward. When it comes to preventative measures people do tend to be a little less didactic about it. And I think this is wrong because in fact for immunisations they're probably one of the best researched things there is in medicine and one of the most effective as well. So I think yes we ought to present the information to parents, yes it's ultimately their decision but I think we should be positively recommending it, not saying here is the information it's up to you what you do but here is the information if I was in your shoes I would very definitely go for this.

PORTER

Your catchment area is Islington, which is north London, that's another part of the capital that has a very low immunisation rate. How concerned are you?

ELLIMAN

Well we're very concerned, I mean the low immunisation rate is predominantly of the MMR vaccine and as people are probably aware from reading the newspapers we have seen outbreaks of measles, particularly in London and sadly at the beginning of this year there was a death from measles, the first in over 10 years in this country.

PORTER

What are you actually practically doing at ground level to increase uptake then?

ELLIMAN

The MMR has largely been resolved and we are seeing increases in uptake across the country. What we are doing is making sure that the health professionals are confident in the information, so that when a parent does understandably ask them the parent doesn't just get a response - it's safe - but they get more information - the reasons why we think it's safe, the evidence behind that.

PORTER

What do you think of the system employed in the States which, I mean to put it very simply, is that you can't go to school unless you've had all of your routine childhood immunisations?

ELLIMAN

The system as you describe in the States has existed for a long time but there are opt out clauses - philosophical reasons, people may decline it and if they produce reasonable evidence of their beliefs they can go without having the vaccine with no penalty. The problems are is that there's not good evidence actually that it increases uptake and what the States certainly used to find was there was a boost of children coming to get their immunisations before starting school but at one and at two years old their uptake rates were lower than ours.

PORTER

When they're at the most vulnerable from various diseases presumably, wasn't helping public health.

ELLIMAN

Yes. And in Scandinavia, where they don't have compulsion, have very high uptake rates, so it's not a simple equation.

PORTER

Well the MMR saga isn't the only scare to put parents off. Back in the '70s concerns over a suspected link between whooping cough vaccine and brain damage saw uptake rates to around 30%. Today they're back to normal but whooping cough is still around - and far more common than official statistics suggest. Officially while there are only around 500 cases a year in England and Wales, the real figure could be closer to 50,000.

I went to the Keyworth Health Centre in Nottingham to meet Christine Zawadzki and her son Andrew who have both recently had whooping cough. And to ask their GP, Dr Doug Jenkinson, who has special interest in the condition, whether it really matters if the disease is so much more common than previously thought.

JENKINSON

Whooping cough generally although it's a very unpleasant disease doesn't very often causes complications. But the big problem is that the more whooping cough there is about the more infants are going to be exposed to the risk of getting whooping cough and it's infants who are at risk, particularly those under six months old who are likely to get serious damage or die of whooping cough.

PORTER

I'm thinking of how many people I've seen with chronic cough, long term cough, but whooping cough just doesn't figure on my list.

JENKINSON

No and neither does it figure on anyone else's, it's a fact that the vast majority of GPs fail to diagnose whooping cough and this is simply because nobody actually hears it, it's a very characteristic sound. My ex-partner who is now 80 they can diagnose it at 50 paces because they heard it at the times when every child got whooping cough.

ZAWADSKI

It was at the end of May and Andrew developed what initially seemed to be a tickly cough and he was starting to struggle breathing and he was coughing at night and it was keeping him awake. I brought him to see the doctor and initially we were told it sounded like he might have developed asthma and he was given an inhaler. We persevered for another two weeks and still he wasn't improving, it was getting worse. Brought him back and they thought it might have gone into a chest infection. So he was put on some antibiotics. Another couple of weeks and he was at the point where he was whooping and he'd actually vomited in his sleep coughing one night.

PORTER

And by whooping you mean what?

ZAWADSKI

It's a very weird noise, and you cough - the only way I can describe it is when you swallow something and it goes down the wrong way and you cough and you cough and you cough and you can't breathe and then all of a sudden you get a [deep intake of breath] …

ANDREW ZAWADSKI

Just really weird because like you started coughing you couldn't stop, then you couldn't breathe, not very nice.

PORTER

What makes you think somebody might have whooping cough, what are the clinical features that raise your suspicions as a GP?

JENKINSON

The patient will come complaining of a most awful cough but one thing the GP will almost never hear is the cough itself because they don't cough except when you have these explosive attacks of coughing that may come every few hours. So unless you actually suspect whooping cough you're not actually going to pick it up.

PORTER

But how do you confirm your clinical suspicion, are there diagnostic tests we can do?

JENKINSON

The very best test, which until recently has been the only one available, would be to take a swab from the nose in the very early weeks of the disease and then with a bit of luck you might be able to grow it. We can now do blood tests and after three weeks of a suspected whooping cough illness a single specimen of blood sent to the laboratory will provide an answer within a relatively few days.

PORTER

But even if we confirm the diagnosis at that stage can we do anything to shorten the illness?

JENKINSON

Absolutely nothing. But giving the patient an explanation of what it is actually makes the patient feel an awful lot better because it's a very frightening thing but knowing it's whooping cough and being able to explain that it's going to go on for several more weeks and there isn't any treatment, at least helps people to deal with it.

PORTER

How did you feel when you first heard that word whooping cough?

ZAWADSKI

Surprised and shocked because I did have both of my children immunised for everything and I thought they were protected and I hadn't heard of anybody else who had whooping cough.

PORTER

An old fashioned illness.

ZAWADSKI

Yeah honestly I was really shocked. And then when I started I don't think we even knew Andrew had whooping cough when I developed a tickly cough and I kept losing my voice with it, I'm still struggling now, I get very croaky. The more I've looked into it I do know they now call it the 100 day cough, so I'm hoping I'm nearly there now.

PORTER

Christine Zawadski talking to me at the Keyworth Health Centre in Nottingham.

You are listening to Case Notes, I'm Dr Mark Porter and I am discussing vaccines with my guest community paediatrician David Elliman.

David, we heard Christine there saying that she was surprised that her son, Andrew, could get whooping cough because he'd been vaccinated, why does it wear off so quickly?

ELLIMAN

Well as you know we give boosters for lots of vaccines, we give boosters for diphtheria, tetanus, polio and we have done for many years. I think probably what it is, is that people thought in the past whooping cough was only really important in really young children, so if it did wear off as they got older that didn't matter so much. But of course it does matter, as you've heard, it's an unpleasant illness, whatever age you are, and of course if it wears off and older people are getting the disease they act as a source to very young babies who can't be immunised. And unfortunately we still do have young babies dying of whooping cough in this country.

PORTER

Because of course this is one of the things about an immunisation programme, it's not just about protecting the individual through direct immunisation but by increasing the herd immunity by making the whole herd, if you like, immune, you can actually prevent those few people who haven't yet been vaccinated from picking up the condition.

ELLIMAN

That's true and for most of the vaccines we give herd immunity is very important. And it applies to measles, to whooping cough, whooping cough because we don't give the vaccine below two months so we will never protect those children other than by herd immunity.

PORTER

Let's move onto another vaccine now. Monday marked the launch of this year's flu immunisation campaign - an event somewhat marred by concerns that GPs were facing long waits for supplies of the vaccine to be delivered.

The whole process is time critical even when everything goes to plan. World Health Organisation experts track emerging flu patterns and meet in February to decide what strains to include in the vaccine for distribution the following autumn. Government labs then develop fast growing versions of those strains before handing them over to the various manufacturers.

This year the whole process got off to a slow start because one of the strains took longer than anticipated to grow in egg culture - the preferred medium for vaccine producers. I went along to one of the labs at the National Institute for Biological Standards and Control to talk to principal scientist John Ward who is responsible for coming up with the cultures required by the drug companies. And we were joined by Tony Colgate from the manufacturer Novartis. I started by asking John what's so special about eggs?

WARD

They were discovered back in the 1930s just be inoculating influenza viruses into eggs. It's a nice sterile environment, you can incubate the eggs in warm conditions, the virus will grow, and you just suck out the fluids and you have an amplified stock of virus, the virus has grown and you can [indistinct word] the virus.

PORTER

The challenge for you presumably is to take the selected strain and turn it into something that'll grow rapidly effectively, which might not be the case with the wild version.

WARD

Usually the strains recommended by WHO do not grow well in hen's eggs so what we have to do is produce a high growth variant of that virus. We have a virus which grows extremely well in hen's eggs and it was first isolated in 1933. So we infect an egg with both of these viruses - the high growth virus and the WHO virus - and the genes reassort into many different combinations and from that mixture in the hen's egg we select out a variant of the virus which grows very well.

PORTER

Well we're in the lab now, talk me through the process involved, we've got an egg here.

WARD

The first thing you do is to drill a very small hole in the shell of the egg [drilling noise]. Then we inoculate into that hole a very small amount of influenza virus.

PORTER

I must say I mean I'm surprised the whole process is done on a small scale by hand.

WARD

What we do is very small scale.

PORTER

So you've got your virus on there.

WARD

And you seal it up and you incubate it, keep it warm for two days. And then the next day we remove the tops from the eggs.

PORTER

Little device here yeah. So you've got your automatic topper, which is sort of like a slicer that you'd have to take the top of your boiled egg isn't it.

WARD

Take the top of and after that it's just a simple matter of removing the fluids from the egg. [Sucking noise] That egg fluid containing flu virus is in fact the reference virus which we'll give to vaccine manufacturers.

PORTER

Which brings us nicely on to you Tony. John's team will deliver to a manufacturer like you live viruses but that's not what's contained in the vaccine?

COLGATE

I mean we use that to produce more living virus in hen's eggs. We inoculate the eggs with a machine a tray at a time, 132 eggs in 10 seconds. We incubate thousands of eggs every day, we then cut the tops of them and mechanically suck the fluid out. We then pull together those thousands of litres of fluid and inactivate them with a chemical.

PORTER

To kill the virus.

COLGATE

To kill the virus. That leaves the virus unable to reproduce but looking exactly like a wild type virus.

PORTER

It's killing it but preserving it so that the immune system doesn't know whether it's alive or dead.

COLGATE

Exactly. The next stage is to remove the egg proteins because if you vaccinate people with egg proteins then they get very nasty reactions.

PORTER

You've got little more than six months to do all of that.

COLGATE

Basically from January through to October we're running seven days a week, 24 hours a day with a total of something probably over 40 million eggs during the season just in the UK. It's really all down to timing. Not only do we need the virus strains as early as possible - and one other factor this year was that in February in fact the influenza disease was still peaking when the decision was made, so the strain that was selected wasn't the one we expected and that threw us a little bit. And it's taken a little while to recover from that and vaccine supplies in the UK may be a little bit later than we'd have liked this year.

PORTER

John, you're talking about the WHO in the third party but you're actually one of the experts that's involved in making the final choice.

WARD

I am indeed yes.

PORTER

And sitting here, having spoken to Tony about the pressures that both you and he are under to get the vaccines out in time, would it be possible to make that decision earlier in the year?

WARD

That's a question we're always being asked, particularly by industry. It really is a balancing act because we want to make the recommendation as early as possible to allow enough time to make the vaccines but if we make it too early we won't have enough information on the flu viruses that have caused flu in the world because if you can think about an epidemic curve, if we're just on the upward slope of the epidemic curve there won't be a lot of viruses to examine, we really have to wait until we're nearly at the top before we have as many viruses as possible, we can make a sensible prediction then.

PORTER

How have the experiences that you've had, coming up with a vaccine every year by monitoring what's going on around the world, how are they likely to help us come up with some protection against pandemic flu?

WARD

We can use all of the pieces in the jigsaw that we use to make a seasonal vaccine but there are key elements which are different. And the most important of those is that the H51 bird flu virus is dangerous. So we cannot actually modify that virus in the traditional way, it would endanger the health of Tony and his colleagues.

PORTER

Well we wouldn't be sitting here drilling and whipping the tops of eggs …

WARD

We certainly would not. So what we have to do is to try and make it safe so we can give it to vaccine manufacturers. And the way that we've done that is to use genetic engineering. So during the cloning process you can remove part of that protein and then reassemble the virus.

PORTER

So you've removed it, one of the dangerous parts of it…

WARD

We've just taken the teeth away from the virus. All of this work is done at really high containment. We have one of the highest containment labs in the world here. And now vaccines are being made, experimental vaccines are being made, around the world using viruses created here.

PORTER

But I suppose the problem is, as is with the normal in inverted commas "influenza", that you have to wait and see what strains are going to be causing the problem before you can come up with an effective vaccine. Now at the moment you're doing that in February and predicting what influenza is going to come to our shores nine months later. Which does beg the question do we actually have to be in the start of an avian flu pandemic before we'd be able to come up with an effective vaccine?

WARD

That's a good question and I don't think anyone knows the answer to that. The expectation is that governments can stockpile vaccine and it may not be an exact match but there will be sufficient protection to make it worthwhile doing.

PORTER

John Ward talking to me at his lab.

David, you are a community paediatrician and the flu jab is recommended for some at risk children and the DOH this year are pushing very hard to get younger people to take the vaccine up, take up amongst them is not very good, does it bother you that there's a delay in vaccine and maybe some of your patients may not get their jabs until the first couple of weeks of December?

ELLIMAN

The delay probably won't be significant. It might be more significant for those who are having the jab first time round because they need two doses then but for most of them it won't be of any great significance.

PORTER

And just to remind everyone as well as everyone over the age of 65 who should be having the flu jab this year?

ELLIMAN

There are a number of groups of people, not just children, who should have it, those who've got chronic lung problems, heart problems, liver problems, kidney problems, people with neurological problems probably ought to have it as well. So it'll be a lot of the children who are under hospital care should be considered for it certainly.

PORTER

And briefly asthma's included in that list, is that children even with the mildest forms of asthma?

ELLIMAN

No it will be asthma where they're needing say a lot of oral steroids or they're in and out of hospital.

PORTER

So the more severe end of the spectrum.

ELLIMAN

Certainly.

PORTER

David, we must leave it there. Dr David Elliman, thank you very much. If you've missed any of today's programme you can listen again via the website: bbc.co.uk/radio4, where you'll also find a full transcript of the programme.

Next week I'll be exploring a normal part of the ageing process that can stop women sleeping, ruin their sex lives, and weaken their bones . Join me to find out more about the menopause and what, if anything, to do about it.

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