21 May 2012
Twenty-first Century Threats: Lyme Disease - Is it safe to walk in the park?
Professor Patricia Nuttall OBE
Good evening, everyone. I am delighted to be here. I hope I can entertain you with Lyme Disease, but particularly with ticks because that is where my passion really lies, and I hope, by the end of the lecture, you will all share my enthusiasm for ticks – that will be a challenge.
So the title is: “Is it safe to walk in the park?” and I think that is where the story starts, of people who have gone for a walk in the park and a few days later, observed a rash or something strange and thought, “What on earth is it?” and discovered that it is something called Lyme Disease.
What I want to do is to try and put this in perspective, to try and explain what Lyme Disease is, how you catch it, what the risks are, and really reassure you that, certainly in this country, walking in the park is much safer than walking in the street in London.
Some years ago, some of the parks in London got into the news because they had introduced deer, and deer were associated with ticks and Lyme Disease and seen to be a threat and a risk.
This is Richmond Park. We have fallow deer in the foreground and red deer in the background, and if you look on Wikipedia, it says that there are ticks in Richmond Park and they are infected with Lyme Disease. Actually, that is not true, and I will try and explain what I mean and put that in context.
What deer do is they feed ticks, and in particular they feed adult ticks. The common tick that we have in this country, and indeed across Europe, is Ixodes ricinus. This is a hungry female tick, and she will delight in feeding on deer. Deer are very good at feeding adult ticks, and the more adult ticks that we have, the more eggs we have, the more larvae we have, and hence the more ticks we have. So that is the correlation with deer: they are supporters of tick populations, and of course the ticks transmit the agent that causes Lyme Disease. If you do go to the Royal Parks or if you go online, you will find that there is ample information about ticks and how to deal with them, and it does mention the risk of Lyme Disease.
If you are unfortunate enough, this condition of Lyme Disease, this is the erythema migrans, the typical rash associated with Lyme Disease.
This was contracted in Belgium, very innocently, and this person has worked much of his career on ticks, so he should have known better. But it is quite often those place that you do not look at quite so often, is where the ticks tend to feed.
The rash appears as quickly as a day after a tick bite or up to a month after a tick bite, and usually, if treated, timely, with appropriate antibiotics, there is no problem. So, it is treatable, which is a good thing.
If we put Lyme Disease in the context of 21st Century threats, we can see that that top line for the UK is tuberculosis, so we are not in the league of tuberculosis. We are down at the bottom – so this is the numbers of reported cases, annually, in the years recorded. For Lyme Disease, there has been a steady increase since reporting started in 1998. Possibly some of that increase is due to the fact that Lyme Disease just was not recognised, so it is more the recognition of this condition rather than the actual incidence of the condition, and, latterly, in about 2009/10 – it seems to have been tailing off a bit, but who can tell? So, Lyme Disease then has shown a steady increase. It is beating AIDS, and it is not quite up to malaria, in the UK. So that puts the number of cases, as reported, in context.
Lyme Disease got its name from Lyme in Connecticut in the US, but the actual disease was recognised in Europe at the end of the nineteenth century. It was not, obviously, called Lyme Disease, but the descriptions there clearly were Lyme Disease or Lyme borreliosis, and the disease was first recorded in a scientific publication by Allen Steere and his colleagues, in a journal called “Arthritis and Rheumatism”, 1977, entitled “Lyme Arthritis”. This was unusual because it affected children as well as adults. It was preceded by a skin lesion, which is very unusual for an arthritis, and it was asymmetric in its effect, so swelling that it caused in the illness. So all of those were not characteristic of typical arthritis.
It was not until a few years later that Willy Burgdorfer, a Swiss, actually discovered what caused Lyme Disease. In 1981, he discovered that it was caused by a spirochaete, which is a bacterium, and that this was transmitted by ticks, hence the name, Borrelia burgdorferi.
Willy Burgdorfer was working at the Rocky Mountain Laboratories in Montana, US. He actually became an American citizen. I visited those labs in 2007. It is called a category four facility, so you can work with pathogens that are a threat to humans, under extreme containment conditions, and one of the pathogens that they work with is called Rocky Mountain Spotted Fever. Rocky Mountain Spotted Fever does not occur in this country. It is caused by a bacterium, but it is just to illustrate that ticks do transmit some really nasty human pathogens, and animal pathogens as well.
This slide was provided by a colleague in the Czech Republic, Jan Kopecky, who was doing some studies on spirochetes. You can see them here, in this electron micrograph. This is what the bacterium looks like. It is motile.
These are what are called macrophages, so they are cells that gobble up invading organisms, and what Jan Kopecky and his colleagues found was that the saliva in the ticks actually helps the spirochete in the infection, and it reduces and controls the effect of the macrophages trying to destroy the spirochetes. So that is a feature that we are discovering more and more, that the ticks themselves can actually facilitate in the transmission of these bugs.
There are about eighteen different types of Borrelia burgdorferi that causes Lyme Disease. On the left-hand column here, you can see the names of the five genus species that have been associated with disease in humans (burgdorferi sensu stricto, afzelii, garinii, bavariensis and bissettii), and there, on the right-hand side, their geographical range (North America/Europe, Europe/Asia, Europe/Asia/pan Polar, Europe and Slovenia respectively).
This is significant because, Borrelia burgdorferi, since the original bacterium that was described, is the most prevalent borrelia, spirochete, that causes Lyme Disease in North America, and that spirochete, for some reason, is associated with arthritic disease. If you are bitten by a tick on the East Coast of North America and develop a rash and it is not treated, then you have a 60% chance of developing arthritis.
Whereas, in Europe, there are two other species that are much more common, Borrelia [afzelii] and Borrelia garinii, so that in Europe the chances of developing arthritis, if you have an erythema (rash) and do not have it treated, are something like 3%-15%. So a much less chance of developing arthritis, but more common is either the skin manifestations, so a really nasty chronic dermatitis, or neurological systems, such as facial palsy.
I was working on Lyme Disease in Cumbria, we were doing some studies on the transmission cycle in Cumbria, where mostly the transmission occurs around sheep and ticks, and we talked to the local GPs about Lyme Disease and their knowledge of Lyme Disease. There was not a lot of awareness, but when we talked about epidemiology and clinical conditions, it turned out that, in Cumbria, there was a higher than average incidence or prevalence of facial palsy. We do not know if that was associated with Lyme borreliosis, but it just shows you that Lyme arthritis, which is the common condition in North America, is not so common in the UK, and remember also, there are not many incidences of Lyme Disease in the UK, comparatively speaking, and not so common on the Continent, in Europe. One of the reasons is that there are different types of spirochete. That is another reason why there is a challenge in producing a vaccine to Lyme Disease, that there is a challenge to get a vaccine that would control all the different types of the spirochete.
The borrelia that is found in North America is associated with mammals and birds, so that has a very broad range of hosts, but Borrelia garinii, in particular, is found associated with birds. These associations with different hosts turn out to be quite important because we find that, for example, if this top species, Borrelia burgdorferi, goes into birds, the serum of the birds actually kills the spirochete, so the birds cannot support that particular type of borrelia. That comes back to what I said about deer in Richmond Park not really being infected with the Lyme Disease spirochete. It turns out that deer serum kills all of these types of genus species of Borrelia. The serum of deer is able to control this infection, and that means that when ticks feed on deer, although they feed very successfully, and the deer support big populations of ticks, very few of those ticks are actually carrying the spirochete because they are not picking it up from the deer.
If you look on the CDC website, you can see the statistics for Lyme Disease in North America – hotspot on the East Coast. The records are for 2001-2010, so you can flick through them and see how the disease has spread in North America.
The species of tick that transmits the spirochete is different on the East Coast than on the West Coast. This map shows single dots for one county where Lyme Disease has been recorded, and the tick species that is involved is known as Ixodes scapularis, and this is quite often what you see if you are going out for a walk, say, in the woods in Massachusetts, signs warning you of deer ticks. That is what this particular species is called. It looks very much like our Ixodes ricinus, and it has very similar lifecycles, except that it will feed on things like chipmunks and racoons and mammals that we do not have over here.
There are not any good statistics for Lyme Disease in the UK. There are not sufficient. But there are excellent ones for North America, and these are the ones for the USA, and they show that the onset of disease mostly occurs during June, July and August.
That does not mean to say that going out for a walk might not be a risk. There was a nice article in the “New York Times” earlier this year, in March, of a lady, a retiree, who took her dog out for a walk in March, and the dog got bitten by a tick, and that last line at the bottom there, that nice quote: “I was horrified,” she said. “It was not like we were walking in the forest; we were on the sidewalk in my neighbourhood.” So, there are parts of North America where it is not a matter of watching out when you go for a walk in the park, it is actually when you walk round the block to take your dog for a walk. There really are a lot of ticks about and, obviously, they are very much geared up to looking out for tick bites and problems.
Looking at the statistics for North America, it is boys of about five to nine years old who are the greatest at risk. We can understand, I think, why that is.
Looking at the symptoms, erythema migrans is the most common. The rash is actually caused by the spirochete migrating out through the skin, so the front edge of the rash is where the spirochetes are migrating out through the skin, and you saw there was a spirochete, it is a mobile bacterium.
In North America, if the rash is not treated and progresses, arthritis is the most common condition. If these statistics were for Europe, they would show that arthritis is a much smaller percentage and it would be more common to see things like Bell’s Palsy and skin manifestations.
In the UK, we call the tick that transmits the Lyme Disease spirochete the “sheep tick”. In the Continent, they call it the “wood tick” and that is where our studies on ticks have come from. Most of our studies originated on ticks in the north of the country and they were associated with something called louping-ill, which is a virus infection transmitted by ticks that causes sheep, particularly lambs, to leap around, hence “louping-ill” – it is of Scottish dialect – and it is associated with a meningoencephalitic disease in sheep and lambs.
The numbers of ticks in the UK do appear to have increased, and that increase does correlate with increased numbers of deer in the UK. We have six species recorded. This is a map for Muntjac deer (map of UK showing Muntjac deer heavily concentrated in the south of the UK), and this is a map explaining why we have seen more Muntjac around. The species was introduced from China, in about 1900, into Woburn Park. In the 1950s, the deer escaped from the park, and you can see the record for pre-1972, the black dots, and post-1972, we have red dots now, right up into the North of Scotland. The interesting thing about Muntjac, which feed ticks, is that not only do they occur in woodlands, they occur in the bits between woodlands, so they really have the potential to increase the range of where we can find the sheep tick. That is an example of one of the species that is spreading the ticks and supporting the tick populations.
This is a breakdown of the number of cases in the UK, based on rates per 100,000 individuals, and you can see, there, that the top line is for the US, where there are an awful lot of cases. The blue line is for Scotland, so, Scotland, in the Lyme Disease stakes, is well ahead. Red is England and Wales, and we have a few recorded cases for Northern Ireland.
Lyme Disease is a reportable disease in Scotland. In England and Wales, it is more a voluntary arrangement, so that might affect statistics.
This is a map produced by Dot Carey in my lab in 1994. We never published this map. It was based on ticks that were sent to the lab, and some that we actually gathered ourselves, that we screened for the Lyme Disease spirochete. You can see that most of those stars there are Ixodes ricinus, that tick I have told you about, the sheep tick, but some of these results were controversial and that is why we did not publish it.
We collected Ixodes uriae, this particular tick, from a seabird colony in Scotland. Ixodes uriae is actually the seabird tick. It is found around the North and South Poles. It feeds on penguins down in the south, a remarkable feat. We found the Lyme Disease spirochete in this seabird tick and we thought this must be wrong. But subsequently – we should have published, because, of course, it was found that that species of Borrelia that is associated with birds is found in seabird ticks. So that is a fantastic mechanism, obviously, because seabirds are very migratory, for spreading the spirochete around the world.
I will highlight is that pink one, around Oxfordshire. This was in Ixodes hexagonus. That is known as the hedgehog tick, and it has now been found that hedgehogs have a little cycle of their own, with their own particular tick species that likes hedgehogs – I guess it can deal with the spines – but that supports the Lyme Disease spirochete, so hedgehogs do have their own little community supporting Borrelia burgdorferi.
The last one, the yellow one, in Northern Wales, that is controversial because the Lyme Disease spirochete is usually associated with Ixodes species, and that one on Haemophysalis punctata is one that we really would need to confirm. So I would not like to say, at this stage, whether that is real or not.
What I wanted to say is that there are a lot of tick species around. There are about 900 different species, and you can see, right up there on the top, Ixodes – that is the branch that I have been talking about. Those are the ticks that transmit this Lyme Disease spirochete. These ticks transmit a wealth of different pathogens, and some of them are really very nasty.
For any of you who are interested in knowing what is going on in the world on infectious diseases, there is something called Pro-Med, which is run by the US, the International Society for Infectious Diseases. It is a bulletin board for keeping up-to-date with what is going on in the world. There was a bulletin posted last week on a tick-borne disease that is currently causing problems in Turkey.
This is called Crimean-Congo Hemorrhagic Fever. It does not occur in this country, I am pleased to say, but in Turkey, it is a problem. It was interesting that, during the outbreak of so-called bird flu, not so long ago, when we were very concerned about, and worldwide there was great concern about deaths associated with influenza, there were more deaths from Crimean-Congo Hemorrhagic Fever in Turkey than there were from bird flu. Fortunately, ticks cannot fly, so they do not get around a lot, and it is a localised infection, but this is just to illustrate that some of the diseases transmitted by ticks are of great concern.
If you go for a walk in parks in Berlin, or if you go in the Vienna woods, you may find information on something called tick-borne encephalitis. In fact, in Austria, most of the population is vaccinated. This ia a map produced by the company that produces the vaccine, Baxter, and we will come back to them later, that shows, these orange areas, tick-borne encephalitis in Central Europe, and then it spreading east, and in fact, there is a form of the disease that spreads right across Russia, into Siberia, and even touches Japan.
Tick-borne encephalitis is not treatable by antibiotics and it is certainly something that, if you are, for example, going hiking in Austria, or parts of Switzerland or parts of the Black Forest in Germany, it is a good idea to check on whether it will be wise to be vaccinated against tick-borne encephalitis. I have had the vaccine myself because we worked with it in the lab, and there were no problems.
For any of you who know anything about ticks, they are not insects. They do not probe around and find a capillary and say, “Aha, it is dinnertime”, and slurp it up. They have a much more sophisticated way of feeding and a very different lifestyle to blood-feeding insects, like mosquitoes and sand flies.
This is an American species, Ambyomma variegatum, and this is what the female looks like when she has been feeding for two weeks on an animal.
That is two weeks, staying in the same spot on an animal, engorging to the size of a small plum. This is a species that likes feeding on large mammals in Africa. It is not one we find in the UK, but it does illustrate the sort of feeding strategy of ticks. These ticks go for one very big meal.
And this is the one that I have been talking about that transmits the Lyme disease spirochete, Ixodes ricinus, and this lovely painting, by the son of a colleague of mine in Bratislava, illustrates the lifecycle of the tick.
We start with the eggs, and the eggs hatch into the larvae. The six-legged larva. The larva, in order to grow up into an adult, needs to feed, and it needs to feed on blood. The only thing these ticks feed on is blood. Larvae tend to feed on small mammals, so they will attach to a small rodent, a field mouse, feed for a few days, and then drop off into the undergrowth and molt – they undergo metamorphosis – into this stage which is the nymph. Again, the nymph, in order to develop into the adult, needs a blood meal, so it will go off looking for a host, which might be a small rodent, or it might be a bird, or it could even be a lizard, or medium-sized mammals. It will feed, drop off, into the undergrowth, molt to the adult male or the adult female. The female’s job then, like most females, is to do all the work, so she will go off and feed and lay eggs and then die, and that is the next generation.
What that means, in this lifecycle, is that those ticks have fed on three different hosts, so they are called three-host ticks. These red arrows indicate the Borrelia, so the force of transmission of Borrelia by the ticks. Where you had the eggs on the top, there is a small red arrow going down to the larvae. That means that some of the spirochetes can be transmitted through the eggs, but very few. So, generally speaking, the larvae are uninfected, and generally speaking, the larvae acquire the spirochete by feeding on small mammals. Small mammals are the great reservoirs of spirochetes, generally. So that, when they molt in the undergrowth and they become nymphs – that is the stage that we need to look out for because that is quite small so it is easy to overlook, and that is the stage that could well be infected. The nymph then will transmit the spirochete to whatever it is feeding on, and likewise the adult. Infected ticks do feed on deer, but you will see there is no return arrow, so the ticks that are uninfected feeding on deer are not picking up an infection. So that is the lifecycle.
The larvae are very small – they are one millimetre squares. They are difficult to photograph, as you can imagine. Ticks are arachnids, related to spiders and scorpions. And then the adult female - these are all approximately to scale – and the adult male, and you can distinguish the male and female because the scutum, this heavy sclerotised plate just behind the feeding mouthparts, in the male, it covers all of the back of the tick.
One of the reasons why these ticks take several days to feed is not so much the actual taking up the blood, it is actually preparing their bodies to take up this huge amount, this huge volume. I mean, you imagine putting on 100 times your body weight – yes, you would not do it! So, physiologically, it is quite a challenge.
And then this huge mass just becomes translated into a great pile of eggs, so she will lay about 1,000 to 2,000 eggs. She becomes shrivelled, and beside her is this great pile of eggs.
So that is what is happening, and most of that is happening out of sight in the undergrowth and because of the weather and the conditions, this whole lifecycle might take two years or three years, or even up to seven years, in some parts of Siberia, to complete.
Just an aside, to tell you how robust ticks are, there is a story that a scientist had some ticks in his lab, forgot about them, so they were under the right conditions but the ticks were forgotten about, for seven years, and yes, they were still alive after seven years. They were very hungry!
A dappled woodland, with a bit of bracken, is an absolute ideal place for ticks. And where are the ticks? Well, they can be found on blades of grass, on twigs, under the right conditions, nice and humid, warmed up a bit, scenting the air for something to feed on.
And what do they do? They look for small rodents to feed on, or something a little bit bigger. Grey squirrels are great hosts for ticks. Hedgehogs too. In parts of the country, pheasants support huge numbers, as do dogs.
The ticks, as they are hunting, hold out their front pair of legs, on which they have sensors, and they sense the air for chemicals – carbon dioxide and volatile organics. And then, once they find a host, they will latch on.
Normally, when we go out counting ticks, we do what is called blanket dragging. The blanket is usually about a metre square, and you do a transect and then you count the numbers of ticks on them, take them off, and then do another one. But this is a deluxe tick sampling kit, from a colleague of mine who undertook a project in Europe, supported by the European Union, when you can see they wanted to maximise their effort for return of numbers of ticks, so they had flags on their feet and specific leggings, all white so they could see the ticks.
What happens is, the tick cuts into the skin and puts its mouthparts, inserts them, into the skin. Here, that’s a tick that’s been fixed, and a section taken through it. The tick inserts its mouthparts, what we call the hypostome. So that is inserted into the skin, so the barbs help secure the tick’s mouthparts in place. Just to be absolutely sure that they don’t get dislodged, the tick secretes, from its salivary glands, a kind of milky white fluid that polymerises around the mouthparts and creates a cement cone around the mouthparts. So, any of you who have tried to take a tick off you or off your dog and wondered why it is so difficult, there are two reasons: you are pulling against those barbs; and also it is cemented in.
The blood is taken up. It goes into the gut of the tick, into the mid-gut of the tick, and then the tick will drop off and molt, and what then has to happen is, if that spirochete is going to be transmitted, or any other pathogen that the tick is carrying, it has to get out from the mid-gut, through the body of the tick, through the wall of the mid-gut, into the haemoseal, the body cavity of the tick, to the salivary glands, so that, the next time the tick feeds, it delivers the spirochete from its salivary glands in the saliva which it inoculates into the feeding site. So that is how the actual transmission occurs, which seems pretty complicated, but it is obviously a lifestyle that works.
As I have mentioned, ticks are not insects, so they are not probing into a capillary. They form this pool around the mouthparts, which they control, so if you have a tick – if you think of when you are pruning the roses and you get a splinter or something in your skin, you really feel it and it goes red. Generally speaking, if a tick feeds on you, you will not feel a thing, and to be honest, they do not usually go red, they do not become inflamed, and that is because the tick is secreting lots of very sophisticated molecules from its salivary glands, so it has these complex cells in the salivary glands of the tick. The tick’s salivary glands, you could say, is a pharmacopoeia. It has hundreds of different molecules in it that control coagulation, control the inflammatory response, secretes an anaesthetic, and controls our immune response. So, they really are very sophisticated.
So, finally, what I wanted to do, if you are not convinced how wonderful ticks are – and I am sure you understand the risks – the company that produces the tick-borne encephalitis vaccine, and I have no vested interest, no relations with this company, but they do produce a very good video, and I thought I would finish off this lecture with a short video on what you might encounter if you go walking in the wrong park.
If anyone wants to see that again, you can go on the web and I am sure there will be a link from Gresham College. We did get in touch with the company and they did agree that we could show it. I just thought that it illustrates so much better than I can say what is happening.
So, I hope you all appreciate the wonder of ticks – Thank you!
© Professor Patricia Nuttal OBE 2012