Ray Stricker - York 2004 LDA Conference

Definition and Pathogenesis

As you all know, Lyme Disease is caused by the spiral bacteria, Borrelia burgdorferii, and its variants in Europe the tendency to other strains garinii and afzelii that are more common and unfortunately also cause more neurologic disease than what we see in the United States but all of these strains of Borrelia have the potential to cause serious chronic infection.

It was sort of ironic to hear Dr Wainwright say that microbiologists don’t know how to look through microscopes any more and actually kind of shocking but even if they are focussed on genetic aspects of microbes, Borrelia presents a very interesting array of genetic problems and it is shown pretty much on the following slide:

Characteristics of Borrelia burgdorferi

· Over 1500 gene sequences

· At least 132 functioning genes (in contrast T Pallidium has 22 functioning genes)

· 21 plasmids (three times more than any known bacteria

· “Stealth” pathology: evades the immune response

Borrelia has over 1500 gene sequences so this is a very, very complex bacteria. Now, unfortunately, we really don’t know what over 1400 of those genes do or if they do anything but when you talk about not having the gene for something in this bacteria, the answer is, well you don’t really know that, I mean, the gene might be there, we just haven’t found it yet. However, we do know that there are at least 132 functioning genes in Borrelia and this is in contrast to Treponema pallidum which is the spirochaete that causes Syphilis. This bacteria has only 22 functioning genes so Borrelia is a much more complex organism from a genetic point of view compared to the organism that causes Syphilis.

Now, in addition, to all of these functioning genes, the structure of Borrelia is quite interesting because it has 21 plasmids and plasmids are these extra chromasomal strands of DNA that are kind of the early response mechanism for bacteria.

So if a bacterium wants to do something very quickly, if it has a plasmid, the plasmid can make a protein very quickly to do things like avoid the immune system or enter cells or do whatever the bacteria needs to do to survive. 21 plasmids is three times more than any other known bacteria. I think that Chlamydia has the next greatest number - that’s 7. So this is an organism that has a very, very adaptable and effective gene structure in terms of infecting people.

In addition, Borrelia qualifies as an organism that has true stealth pathology and what is meant by that is that the bacteria can evade the immune system by making different types of proteins that do things such as complement the immune response or get into cells with different types of cell receptors and this stealth pathology is one reason why Borrelia can persist in humans and cause the type of chronic problems that we see. I should also mention that a lot of this work comes from the Lab of Sherwick Casjens who is at the University of Utah and also Tom Schwan at his Lab at the Rocky Mountain Labs in Montana. Dr Casjens has been working on this for a number of years and if you want to look at the complexity of the genetics of Borrelia you should look at his work and it has been extensively published even though very few people pay attention to it.

Now, you also know that Borrelia is transmitted by the deer tick and these are pictures of the different stages of the deer ticks, larva, nymph, and female and male; the female is usually bigger than the male. What is interesting, of course, is that when you see a nymphal tick like this up on the screen, it looks like it’s about 10 feet tall and most physicians expect that when someone has been infected with Lyme Disease that they have this thing sitting on their arm that kind of looked like Godzilla and they got bitten and that is why they got the disease and if didn't have that then you couldn’t possibly have Lyme Disease but, in fact, what makes the most impression on a physician is when you show them this picture.

This is a picture of a nymphal tick on the arm of Jim Bosey, who is a microbiologist at Berket, New Jersey. Jim is a very interesting guy, his hobby is to go out to the State parks in New Jersey in the dead of winter and then wait there until the snow cover melts and then go pick up ticks which start running around as soon as the temperature hits a certain level and the snow melts and even in winter in New Jersey these ticks are very active and they do get on his arm and if you can see the nymphal tick here it is this tiny little dot here which is a nymphal tick on his arm.

What I often hear from my patients is that they had a mole on their arm that was there for three days and then it fell off. Of course moles don’t do that but nymphal ticks certainly do. Now in contrast to that, this is a fully fed, I believe it is a dog tick, and this tick has been fed for two weeks on a rabbit. You can see that it gets to a very huge size. What is interesting about these ticks is that the tick saliva has become a very interesting substance and there are several companies that are now trying to make bio-technology products based on tick saliva, for example, tick saliva has a natural anaesthetic which is why the tick can get on your arm and feed for hours or days and you don’t feel anything and tick saliva also has some immune evasion proteins that are important in terms of letting Borrelia get into the system once the tick has attached and is feeding. So tick saliva is becoming a big issue.

Now, where do ticks bite? Well, Bart Simpson knows. I know you have him here because I saw him on TV when I got here. He knows that the most common place for tick bites is round the arms and legs. 30% on the legs, 23% on the arms but almost any part of the body can, of course, have a tick bite and there is some evidence that tick bites around the head and neck are more often associated with neurologic symptoms of Chronic Lyme Disease.

How do ticks get around? Well, you’ve heard all about a deer, you saw the deer in Dr Kroun’s backyard. These are the deer in Yosemite National Park which has an altitude of 7,000 feet and ticks supposedly don’t do very well at 7,000 feet and last year I got a call from the director of the medical clinic at Yosemite who said “Gee, I don’t understand it but we are getting all these people coming in with rashes this year who have Lyme Disease and you know there is not supposed to be any here” and the answer is well, there is deer and wherever there is deer there is Lyme Disease and these are some deer and these are my kids and they are being followed by a very anxious dad taking pictures!

Now, one question that came up last night was why is Lyme Disease spreading as rapidly as it is and why do we have so much of it? And I think this is a very instructive figure. In 1900 at the turn of the last century, there were a total of 500,000 deer in the United States. In the year 2000, there are between 35 and 40 million, so the deer population in the United States has grown tremendously and with the deer has come the mass transit system for ticks to go all over the place and expose people to Lyme Disease.

So, why else should Lyme Disease be so widely spread? Well, there are studies from Sweden that have shown that birds such as the red winged thrush can be infected with Borrelia and also can have ticks on them which can then migrate with the birds and the birds can either drop the tick off wherever they happen to be going or they can be bitten by a tick when they get there and then transmit Borrelia to that location and these are trans-migratory birds, they can fly thousands of miles and that is also a very good explanation of why Lyme Disease is so widespread around the world and certainly it is a good explanation for why Lyme Disease is so widespread around the United States because this is a map believed from 1998 showing the major areas of Lyme Disease in the United States mainly on the east coast and also the upper mid-west but you can see there is also this area in California where I am that has quite a bit of Lyme Disease especially the northern part of the state but now even in Southern California. The area in the middle that doesn’t have very much is mostly the Rocky Mountains so there isn’t that much Lyme Disease in the mountainous regions but the rest of the country is becoming fairly endemic for the disease.

Now, what’s happened – just to show you in statistical form – this is the recorded cases of Lyme Disease until 1998. There has been this progressive rise in recorded cases of the disease which has continued to rise in 2002, the last year for which we have the statistics there were over 23,000 recorded cases. It is estimated that Lyme Disease is under-recorded by a factor of at least 10 so that means there were at least 250,000 new cases of Lyme Disease in the year 2002 so this is not an inconsequential disease it is something that is spreading and it is getting worse.

Now the month in which people report Lyme Disease is shown on this slide. This is mostly for the east coast where the peak incidence is between May and September but in fact Lyme Disease can occur at any time of the year and it is important to keep that in mind and a lot of physicians really don’t. One of my favourite stories is I saw a 10 year old boy who was out on a golf course near San Francisco and was playing in the leaf litter and came in with a bull’s eye rash that was basically his entire abdomen with a tick stuck in his belly button and he went to a paediatrician and the paediatrician said, well, you know, this can’t be Lyme Disease. Why? It was October and there is no Lyme Disease in October so that’s the kind of thinking that we also have to overcome in getting people to be aware of the disease.

Now Professor Bob Lane, who is a professor of entiomology at the University of California at Berkeley recently turned the Lyme community on its ear by doing this study and what Professor Lane did was that he took his graduate students up to this beautiful oak grove in Medicino California, which is in northern California, and he had them put on this spacesuit contraption and then wander around this oak grove and do certain things and then he looked at the risk of acquiring different types of ticks, particular nymphal ticks with these activities and what he showed was the following:

When the people were either sitting on logs or gathering wood or were sitting against trees, the risk of acquiring a nymphal tick was a total of 70% of the total ticks acquired. In contrast to that, the people who were either sitting in leaf litter or stirring leaf litter, the risk of acquiring a nymphal tick was only 21%. So what this study showed was that your risk of getting a nymph on you was significantly higher when you were exposed to wood and this goes against the conventional wisdom of tick exposure from leaf litter and grass being the biggest risk and really shows that exposure to wood is the most common way that people get exposed to nymphal ticks and this has really changed our thinking about the epidemiology of Lyme Disease because most of those studies are based on flagging the leaf litter or looking in the leaf litter for the disease and not based on looking at wood and wood exposure.

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