Lyme Disease: Ticks, Trends, and Treatment

A family of previously unknown beetles have been uncovered in the unlikeliest of places: in samples of 230 million year old fossilised dinosaur poo! Scientists from Sweden and Taiwan were using high-energy X-ray beams to probe samples of fossil coprolites to produce high-resolution 3D images of what lay within. What they saw took them quite by surprise, as Sally Le Page heard from lead author Martin Qvanström...

Martin - Complete beetles - a few specimens that were almost complete. It was like you modelled them up in 3D at the screen, and they almost looked back at you from the screen. And this was truly amazing because we didn't expect to find such complete specimens. We could use the complete specimens and the small body parts to actually describe this beetle and describe a new taxonomy. It's a new genus species and even a new family of beetles.

Sally - Who did the poo? What is the animal that we're talking about that's eating all of these insects?

Martin - The problem with fossilised poo is that it's very hard to understand who produced it, right? Because you don't have so many clues at hand, but you have to use all the kinds of clues you have - the contents of them, the size, the morphology, so the shape of the coprolites. And also understand the body fossil records, so the bones from the same site. And the best candidate to produce this coprolite is a really close dinosaur relative, so a cousin to the dinosaurs called Silesaurus opolensis. It was a fairly small, medium sized animal - weighed approximately 15 kilos, 2 - 2.5 metres long, including the tail. It was a relatively small animal and it was lightly pecking insects off the ground, or rooting around in the litter with a little interesting beak that it had. So it was probably eating beetles and other insects in degraded wood or in like a moist environment.

Sally - And how old is the poo, how old are these insects?

Martin - So the poo is 230 million years old, so it's from the Triassic period.

Sally - That's an old poo!

Martin - I agree, I agree! And it's from a very interesting time because it's when we get the first dinosaurs. And when we think about the dinosaurs, we think about like these ecologically dominant animals, right? But for the first 30, 40 million years of evolution it was not like that. Actually in the beginning, they were just minor ecological components of the ecosystem. And the first time dinosaurs are already around in different areas of the world, but they haven't taken over, so to speak, yet. So it's a little bit interesting because diets play a role here in trying to understand what happened, why dinosaurs became so successful. We don't know that yet, so this is a little piece to that puzzle.

Sally - So this is before the T-Rex, the triceratops?

Martin - Way, way before. So if we think about T-Rex, for example, it's like 66, 70 million years ago. So the time gap, the time difference between us and T-Rex is much, much smaller than between T-Rex and the Silesaurus opolensis and the age of the fossilised poo here, it's incredible.

Sally - How did the beetles get inside the poo?

Martin - There are two possibilities here - either they entered the poo when it was already laying on the ground, or they were ingested. And why we think they were ingested is that we have so many of them in the coprolites, and there are various stages of disarticulation. So most are just bits and pieces of, you know, chewed up beetles. And then we have the few exceptions, so it's just really two specimens that are near complete.

Sally - Why can't you just look at insect fossils. Why are you looking inside the poo to find the insects?

Martin - If think about like the most beautifully preserved insect fossils, they're from Amber, and Amber is all nice and good. So it's fossilised tree resin.

Sally - Like that mosquito in Jurassic park.

Martin - Exactly, yeah. So you can look at hundreds of specimens and just under the microscope and see where the nice insects are. The problem with Amber is that it was mainly formed during relatively young geological time. So when it comes to early beetle evolution and early insect evolution, we don't have any insect fossils from Amber to rely on. So this really fills that gap. It's like, Hey, okay, we don't have an Amber, but we can look in, in coprolites, so in fossilised poo, and we find almost the same preservation.

Sally - Are you just going to go around scanning all of the coprolites, all of the poos in museums now?

Martin - That's pretty much what my last 5 years have been all about! With scanning maybe 100 specimens. And we're trying to analyse a lot of coprolites from the same locality, and then try to reconstruct food webs

Sally - I have to ask, does fossil poo smell like poo?

Martin - No, fortunately not. I work with them every day, so that would be really hard for me!

A new, dissolving, implantable pacemaker has been developed by scientists in the US. The idea is that, like dissolving stitches, in situations where a permanent pacemaker is not needed, with this device, once its job is done after a couple of months, it disappears without the need for an operation to remove it. It actually works in the same way as traditional pacemakers, which send electrical impulses along fine wires into the heart to control heart rhythm. Power is beamed into the new device from outside, so no batteries are needed. Charlotte Birkmanis had her finger on the pulse and called up the device’s creator, John Rogers, to hear how it works...

John - Well the function is equivalent - the kind of stimulation is functionally identical. The key differences are that it's wireless and it's resorbable. We were able to demonstrate that on actual human hearts, not in human patients, but hearts from organ donors. So we were able to demonstrate that the devices work well in small and large animal model studies; and most importantly that it's applicable to the human cardiac system, which is ultimately the goal in this type of context.

Charlotte - How does it work?

John - The device itself includes several subsystems. One is designed to harvest power wirelessly. Another is designed to take that radio frequency power and smooth it out; that component involves a radio frequency silicon-based diode and a smoothing capacitor. And the third kind of element of the device is set of interconnected traces that terminate in leads that interface to the surface of the heart. Those three components are all integrated into a thin, flexible, lightweight device that gently adheres to the surface of the beating heart.

Charlotte - It doesn't need to be removed - how does it get eliminated from the body?

John - The electronics, the stimulator leads, wireless control interface, and so on are all water-soluble. They react with surrounding biofluids and just dissolve over time, and disappear completely at a molecular level, to biocompatible end products that are just naturally excreted from the body via usual processes of kidney filtration, urination, for example.

Charlotte - What are they actually made from?

John - We use primarily polymer based materials, either biomaterials like silk fibroin... that's a protein that can be extracted from silkworm cocoons as a substrate for building our electronics. Of course, you also need conducting materials; there we choose metals that are naturally occurring in the body, such as iron, magnesium, these types of materials. They're also water-soluble and biocompatible. And then the third class of materials: silicon itself is water soluble. If you use silicon in very, very thin film forms, then it will dissolve completely. When you put those different materials together then you can begin to build wide ranging classes of water-soluble electronics.

Charlotte - Because you don't remove it, how do you control the amount of time that it functions for?

John - Yeah, so the way that we control the operating life is we use a capping layer, a thin layer of a polymer that protects the underlying electronic materials from interaction with surrounding biofluids. And then once that capping layer has dissolved and disappeared, the electronic materials start to dissolve and the performance drifts. So we assume that the device is no longer operating in a stable fashion from that point on.

Charlotte - And what else could you make out of these materials?

John - We have wireless nerve stimulators that can accelerate rates of neuro-regeneration in damaged peripheral nerves. The other thing that you can do is you can build wirelessly programmable drug release vehicles; so these are platforms that contain an array of reservoirs, each one of which is filled with a drug, and we can wirelessly trigger the opening of valves to allow programmed release of those drugs at specific time intervals. Once all of the drugs have been released the platform itself can just naturally resorb and disappear in the body.

Charlotte - Is it ready to be used in human surgery?

John - Not quite yet. Ultimately we hope to use this device with humans, but it's a process and it's a very rigorous process, so the timescale for that is typically a year or two to get the first human tests completed. And we're just starting down that path now.

Lyme Disease is transmitted to humans when we’re bitten by ticks. These are small, blood-sucking parasites that are members of the spider family found across the world. Eva Higginbotham has been learning a bit more about them and how they transmit Lyme disease...

Thomas - Most people think of them as rather disgusting and nefarious, sneaky, crafty... and most importantly they can transmit germs that cause disease.

Eva - That's Tom Mather, a self-described tick collector from the University of Rhode Island, describing the critters he has devoted his life to studying: ticks. Ranging from around 1-5 millimetres in size, depending on life stage and species, ticks are parasitic arachnids that feed on the blood of various host animals.

Thomas - Ticks come in four life stages, three that are active and one is the egg stage. Eggs hatch into little, tiny, six-legged larvae. The next stage after a larva is the nymph: so the larvae grab a host, just like all ticks do; they take a blood meal, and they use the blood meal to grow generally about 10 times their size. Which sounds like a lot, but when you start pretty microscopic then 10 times bigger isn't that much bigger. Nymphs do the same thing: they grab a host that increases their weight about a hundred fold, and those nymphs then transform into the adult stage, either a male or a female.

Eva - Although all ticks feed on blood, they have different preferences for which hosts they want to feed on. Some are very picky, and as a result, pose less Lyme disease risk to humans. But some are generalists, like the American blacklegged tick or the UK castor bean or sheep tick. But how do they get onto their hosts in order to feed?

Thomas - Ticks don't jump. They don't have wings, so they can't fly. What they do is wait, low in the leaf litter and the leaf duff where it's a little bit more humid. The adult stage tick will climb up vegetation just a little bit. They want to optimise where they're going to be in case the right host comes by.

Eva - And if a tick makes it onto your skin...

Thomas - Ticks have a fairly sophisticated cutting mechanism. They have a multi-piece mouth part, a little like a Swiss army knife I suppose. First it can cut a hole in your skin, and then it cuts that hole a little bit bigger and bigger, and then it inserts another part of its mouthpart into this hole that has backward pointing barbs. Once a tick finds a host, it doesn't really want to lose it, so it's specialised to hold on. And that's why people notice that it's hard to pull them out sometimes.

Eva - The tick inserts it's mini-saw mouth part deeper and deeper into the skin until it's fully embedded.

Thomas - Some of the earliest things that it does with its saliva - that it secretes into the host - is secrete a cement substance to form this glue-like matrix that helps hold the tick in place with the tissues. It starts secreting more saliva that has this magical property of suppressing the immune system of the host, keeping blood clotting from happening. So it creates a pool of blood that its mouthpart - basically a straw - is sticking into.

Eva - The thing is it's not the blood drinking that's the Lyme disease risk - it's the saliva that's the key. If the tick is infected, the Lyme bacteria is essentially spat out in the saliva of the tick if it's attached long enough. But how does the tick end up picking up the Lyme bacteria in the first place?

Thomas - We know that the larval stage ticks hatch out of eggs don't carry the germs. So they have to pick it up someplace. And so they pick it up from a reservoir host - an animal that's not only infected, but infective as well.

Eva - To be infective, the animal has to be able to pass along the bacteria. Other animals, like the white footed mice in the USA, seem to have evolved to tolerate the bacteria. They don't get sick, but they also don't seem to eradicate the bacteria from their bodies. This is why they are a reservoir. Any tick that then bites that mouse is likely to pick up the Lyme bacteria from them.

Thomas - About one in four nymphal stage ticks in the United States is infected with the Lyme disease germ. That's exceptionally high. When we think about mosquito-borne viruses, for instance, we're talking about rates of infection of one in 1-5 million mosquitoes carrying a virus. So we're talking about a vector here that has a tremendously high infection rate. As incredible as that is, the adult infection rate is almost 50% or even more. You would say, "oh, well then the adult stage ticks are riskier," but they're not - because they're a little bit larger, more easily seen and more easily found and removed before they've been attached long enough to transmit an infectious dose. And so most cases of disease occur just after and during the season of the year, which is May, June, July when the nymphal ticks are active.

Eva - Importantly, though, that 50% infection rate is the average across the States and will vary greatly depending on precise location and the types of animals that live nearby. And the rate is much lower in the UK. But if you've been out and about and realise you've been bitten by a tick, how do you get it out?

Tom - In order to remove a tick safely, there are all kinds of strategies. We want to dispel right away some of the folklore that people have of touching it with a hot object. My favourite and most reliable strategy is to have a pointy tweezer and you don't want to grab the back end of a tick. Think of it as a sack of germs attached to your skin with a straw. So you want to grab it as close to the skin as possible and just pull it out. It may be a little bit challenging because of those backward pointing barbs we talked about, but it will come out. Sometimes the mouth part breaks off depending on your grip and everything. And that's okay because the germs are in the back part of the tick, and as long as you haven't squeezed the back part, you should be fine.

Eva - And of course the best way to prevent catching Lyme disease is to not get bitten in the first place. Tom advises sticking to the middle of hiking trails where you can, tucking your shirt into your trousers and your trousers into your socks, and if you're regularly outside in a higher Lyme area, you could invest in a can of permethrin; an effective tick repellent, which you can use to treat your clothes. That is unless you're Tom.

Tom - Back in my younger days, I actually wanted to teach people the proper way to remove ticks. So I would grow pathogen-free ticks in the laboratory. And before I would go do an outreach activity, I would let one or two attach to myself in an easy spot so I could show people the best way, the safest way to remove ticks from themselves as well.

Eva - I think I'll leave that to the experts.

Historically, especially in the UK, Lyme disease has been regarded as rare, which is why many may overlook or write-off the initial symptoms. But the condition does appear to be on the rise, or at least it’s being diagnosed more frequently. Richard Birtles, from the University of Salford, has been looking at the possible reasons why…

Richard - It's not a straightforward answer because if you go into a wood, the number of ticks that are present in that wood, what determines that? Then you have to think about, well, what proportion of those ticks are infected and what determines that. For Lyme disease, we have a very complex ecology. So trying to implicate any specific factors as the main cause of increasing tick numbers, increasing cases of Lyme disease is very difficult.

Chris - So you think that the rise has been detected because I was looking at some of the reviews and they suggest really quite dramatic increases in case numbers. Up maybe 300% in a 10 year period, according to some papers that have been published. Do you think that's a real finding, it's not that people like me and you were talking about it, so then other doctors think about it or people think about it, and they take themselves off and get tested.

Richard - No, I think what you're saying is playing a part as well. We've certainly seen, as you suggest, the number of reported cases rising in England and Wales and in Scotland by five, six fold over the past 20 years or so. And I certainly think awareness in the medical circles, awareness from the public as well, but there is some evidence that tick numbers are on the rise. And certainly the places in the UK where you find ticks is increasing,

Chris - But where are the hot spots? Then you mentioned a couple of places, but where are we tending to see the most Lyme activity?

Richard - When we think historically about Lyme disease, we think about particular places that tend to be wild places, particularly areas that are heavily wooded or heavily grassed, rough pasture, or heathland. So those are the places that historically most cases have been reported. But what we're learning more about now is that we are seeing Lyme disease spread around the country more, and we're seeing urban cases of Lyme disease. So we think that there's a risk of being bitten by ticks in parks, for example, parks in the middle of London are known to support quite high tick numbers and similarly parts of central England where we're seeing a change of land use. So we're seeing a reversion to more woodland, aforestation, replanting of trees, less intensive farming seems to be bringing Lyme disease into those parts of the UK as well. Perhaps the most important driver of this is that these kinds of habitats are fantastic for deer. And we know that deer are fantastic vehicles for ticks. I, for example, have spent a very pleasurable afternoon checking for ticks on a headless legless roe deer in Kildow. And when we got to about 15,000, we gave up and went to the pub. So they carry huge numbers of ticks. And we know that in the UK, the deer population has exploded really. We've got more deer in the UK now than we have in the past thousand years or so. And the numbers are thought to have doubled really in the past 20 or 25 years. So you've got these articulated trucks, the supertankers carrying ticks around the UK. It's not surprising that the distribution of ticks in the UK is increasing and therefore where we're acquiring Lyme disease is changing.

Chris - How does this fit into the life cycle that we were hearing about that Justin was talking about, and also Tom was talking about earlier in the program, when you've got small ticks and big ticks, small animals and big animals, the big animals, presumably are the deer. How does the relationship work?

Richard - Well, it's very complicated because deer are not reservoirs for Borrelia, which is amazing. They carry these huge numbers of ticks, but they cannot transmit infection to the ticks. The infection is reservoirs in, as Justin said, I think, in small mammals, so voles and mice and shrews, and also in birds in foraging birds, and also game birds, pheasants, but also thrushes and blackbirds and things like that. So we've got this tension really between a higher abundance of deer, meaning an awful lot of ticks, but maybe not so many of those ticks infected because they're all feeding on deer, which can't transmit the infection to the ticks. So there's a very complex arrangement in that cycle that we need to explore more and understand more. If we are going to somehow be able to manipulate it, to reduce the risk of us acquiring Lyme disease.

Chris - I know what you mean about deer because I took until I was about in my forties before I even saw one properly in the wild. And now if I don't see one, when I'm driving around in the country lanes every day when I'm out and about something weird is happening. I mean, there must be enormous numbers of them. Does that mean then that we, if we've got a plague of deer, we really need to be eating more venison. And I mean the nicest possible way.

Richard - Well, yes, there's a lot of talk. We're concerned about deer from the perspective of Lyme disease, but also we're worried about things like road traffic accidents and crop destruction and destruction of commercial woodland that we know deer are party to. So there's a big discussion going on now about how we weather for the sake of Lyme disease. We look at trying to control and reduce deer numbers, but also for all of these other possible implications.

Chris - Just one final point, which is that in Australia, they've had a plague of mice or parts of the Eastern seaboard of the country. And this is attributed to various factors, including ideal warm conditions, rainfall, surging vegetation. What about climate change? We haven't discussed that yet. Do we foresee that that could also drive a widening of the range of the very small mammals that we heard about from Justin and Tom who can support the Lyme bacteria and therefore widen its geography across countries like the UK?

Richard - Well, I think in truth, the distribution of the small mammals that are important is fairly ubiquitous in the UK already and is driven really by habitat and land use. And we know that the tick that transmits Lyme disease in the UK, in Europe, you can find it right up to the Arctic Circle. So it's unlikely that new parts of the UK are going to be infiltrated by ticks simply as a result of climate change, but there are models, climate change models, looking at the impact of various scenarios of climate change on tick abundance in the UK and Lyme disease risk in UK. And these tend to suggest that first of all, ticks will be active for longer in the year. So there'll be more active in February, for example, and they'll continue to be active well into November and December. So that's a longer period of the year where we can get bitten. And also that the climate change will provoke higher densities of ticks. Ticks really need humidity. So more rainfall is likely to be good for them. So that's what the model suggests. Of course they need to be validated and we need to check for the degree of uncertainty in those, but that's what the models are suggesting.