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Stopping Lyme at the Source: The Science Transforming Tick-Borne Disease Prevention · Pediatrics Now: Cases Updates and Discussions for the Busy Pediatric Practitioner

0:00
What if you could stop a tick from ever getting Lyme disease?
0:05
So, Dr. Sishu, you say you can do this. You are doing this.
0:10
Yeah, we are doing literally developing a product that when distributed in places
0:17
where there is a lot of ticks that are infected with this pathogen causes Lyme disease,
0:22
the ticks have to bite these small mammals that are running around that are
0:27
infected with this pathogen.
0:28
And so they have to get this first dose of this bacteria that causes Lyme disease
0:33
from these small mammals.
0:34
And if you kind of like stop this bacteria in these small mammals,
0:39
then you don't have a chance of this bacterium getting into the ticks.
0:43
And so when the ticks eventually bite you or your dog or even other small mammals,
0:49
they do not have the pathogen to cause Lyme disease.
0:52
And by literally eliminating the pathogens from the small mammals,
0:57
you're blocking the transmission biotechs to humans
1:01
who tend to eventually have Lyme disease or even probably dogs can have symptoms
1:06
of Lyme disease at some point.
1:08
So that's the rationale or the overall picture for it.
1:15
This is Pediatrics Now. I'm thrilled today because here in the podcast studio, my guest is Dr.
1:24
Janakarim Sishu, professor of molecular microbiology, immunology at UT San Antonio,
1:31
and a researcher with the South Texas Center for Emerging Infectious Diseases.
1:36
Dr. Sishu is an expert in bacterial pathogenesis whose laboratory has spent
1:41
years studying Borrelia burgdorferi,
1:45
the bacterium that causes Lyme disease, including how it survives and moves
1:49
between mammalian hosts and ticks.
1:52
His team has developed an innovative approach to preventing Lyme disease by
1:57
targeting the animals that serve as reservoirs for the bacterium,
2:01
potentially interrupting transmission before an infected tick ever reaches a human.
2:08
So I think it's just incredible what you're doing. It sounds to me like you
2:13
all are helping to change the world.
2:15
Oh, yeah, absolutely. I mean, we are really excited about the findings that
2:19
we have in the lab. We still haven't gotten these products out into the market
2:24
or into the actual place where it needs to be working.
2:28
But then the most important thing is also the laboratory-based work that we
2:33
need to do to ensure that these products are effective.
2:37
And so this would also give us the building blocks to go to the next step of
2:41
making sure that when we distribute them in the field, or would they be as effective
2:47
as how they are working in the laboratory?
2:49
And I think that this could be applied to a number of other diseases too.
2:54
For example, since we are in Texas, we also worry about our cattle population.
3:00
There are a number of ticks and other vectors that transmit diseases.
3:04
So this is the methodology or the idea behind what we are doing can be applied
3:09
to a lot of different what you call ticks or other vectors of pathogens that lead to human diseases.
3:19
And most of them would acquire these pathogens from another host before transmitting them to humans.
3:25
So that's very common. And if we somehow,
3:30
reduce the pathogen burden in these reservoirs of these infectious diseases
3:36
or infectious pathogens that are acquired by
3:38
ticks or vectors, then you reduce the chances of transmission to humans and
3:43
thereby prevent human illnesses,
3:46
reducing the need for interventions in humans.
3:49
So that's also another benefit that we would kind of like, you know,
3:55
get by taking this approach.
3:57
Yes, there are definitely ways to directly target infected human, you know, patients.
4:03
There are a number of drugs that can be used or a number of antibiotics can be used.
4:07
There are a number of other treatments that can be done. But again,
4:10
those all involve, you know, a
4:13
lot of health-related, medical-related procedures and options for humans.
4:18
But why even go that far? Why don't we prevent the transmission to humans?
4:23
And that would be a significant plus for overall,
4:27
you know, health care situations that we are, you know, present in and also
4:33
give us ideas to potentially prevent infectious diseases in kind of like in a different sort of way.
4:39
And Lyme disease is the most common vector-born illness? Yes,
4:44
that is true. In the United States, it's a big problem.
4:48
A total of about 500,000 cases are estimated to occur each year by Centers for Disease Control.
4:54
And then the bigger problem is also that about, you know, 15 to 20 percent of
4:59
the population who get Lyme disease may not completely eliminate or completely
5:05
have all of their symptoms taken care of, even after they take the full course of antibiotics.
5:09
So 20% will have long-term debilitating effects. It's a chronic pain or chronic
5:15
manifestations of some of the symptoms of Lyme disease.
5:18
And it appears to be that there are a number of reasons for that.
5:22
It could be like an autoimmune type reaction of that particular individual or
5:26
components of the bacterium that are not completely cleared.
5:30
Or it could also be that there are co-infections, as I mentioned,
5:34
the ticks, the black lead ticks that transmit the agent of Lyme disease,
5:38
Borrelia bachdorferi, can also transmit up to seven pathogens.
5:42
And this co-infecting, you know, ticks also changed the, what do you call,
5:47
the clinical manifestations and the treatment options of those,
5:51
you know, individuals who have gotten more than Lyme disease.
5:54
There could be a protozoan parasite called Babesia microti, or there could be
5:58
another intracellular bacterial pathogen called Anaplasma phagocytophilum.
6:05
So these are all different bacterium that are all transmitted by the same tick,
6:11
but the ticks acquire them from these small mammals.
6:13
So what do we do to stop all of these pathogens in these small mammals that
6:18
serve as what we call as the reservoir hosts?
6:21
They serve as the source from which ticks acquire these pathogens.
6:25
And we are, as humans and dogs, are considered what we call as accidental hosts.
6:30
We are there in these neighborhoods where when we interface with infected animals, ticks, and then,
6:38
the chances of we getting these pathogens from these animals are much higher
6:43
because we are interacting in ecological situations where the ticks are there
6:48
to transmit them from one
6:50
vertebrate or one mammalian host to another, which could be us or our dogs.
6:56
So, and according to the CDC, 500,000 people a year get Lyme disease? That's correct.
7:04
Take us through the biology. How does a tick get this and how does that bacterium
7:10
ultimately make its way from an infected tick into a child? Okay,
7:15
fantastic. That's a very important question.
7:17
So the ticks will lay eggs after they mate, they will lay eggs.
7:21
The eggs of the black-legged ticks are completely free of the pathogen that causes Lyme disease.
7:27
So the eggs will hatch into the first stage of the life stage of the tick called the larvae.
7:34
And the larvae are extremely, extremely small. They have to bite these small
7:39
mammals that are running around in these neighborhoods or in these certain places, primarily in the.
7:46
Northeastern states, like from New York to Maine. It could also be in the Midwest.
7:51
It could also be in mid-Atlantic states where you have these animals with this infection.
7:56
And these ticks that lay the eggs and hatch into larvae would have to pick up
8:01
the infection from these animals.
8:03
Then the larvae that has taken a blood meal will transform itself into the next
8:10
stage of the tick called the nymph.
8:13
The nymph is the, you know, it's kind of really small. It's less than two millimeters.
8:17
So it's kind of difficult to see them.
8:19
And the nymphal stage of the tick is the primary stage at which we as humans
8:25
get the most amount of infection.
8:26
So if the kids are running around in the backyard, you want to be very,
8:30
very careful because they are so small. They could bite you underneath your hairline.
8:34
They could get in underneath your armpits or in places which are extremely moist to some extent.
8:41
They would get in there and then they would stay there and bite for about 36 to 48 hours.
8:46
And that's when you have a very high chance of getting Lyme disease.
8:50
So then what happens is the ticks would fall off after they take a blood meal
8:54
in nature. So let's say the tick did not have a human to interact with.
8:59
So they would feed as nymphs. They would feed again on another animal.
9:03
And then they would convert themselves into adults. The adults will jump on
9:07
to what we call as larger mammals, which in this case is primarily white-tailed deer.
9:13
And they would hatch on to this white-tailed deer. And then the deer can run over long distances.
9:18
And so you can see how the ticks can get, you know, distributed over larger areas.
9:25
And fortunately, at least for the agent of Lyme disease, there is no transmission
9:30
via eggs to the next stage of the life cycle of the tech. So in that way.
9:36
You know, we don't have the trans-ovarian or trans-egg-based transmission of the pathogen.
9:41
So that is why our strategy to reduce the pathogen burden in these reservoir
9:47
animals, the small mammals running in different, you know, environmental situations
9:52
or ecological settings,
9:54
is a very good way of blocking the ticks from acquiring these pathogens and
9:59
transmitting it to kids or to even adults walking in those neighborhoods. Yeah.
10:05
30 years ago, when you started looking into this, what was your inspiration for that?
10:11
Yeah, that's a good question, because I was working with an organism that was
10:17
a lot more difficult to do some genetics.
10:20
Then I got into starting making what you call these changes to the gene expression
10:26
components of this bacterium, because I was really fascinated.
10:29
How is this bacterium able to go from a tick?
10:33
So the tick do not have, you know, all the things that we have as humans or
10:37
kids, right? We have blood, we have a temperature of 37 degrees C.
10:41
But if you take a tick, if you get them on this table, it's going to have the
10:44
temperature of this room. They do not have ways to control the temperature.
10:47
So usually it's the room temperature or the condition in which they are in that
10:52
neighborhood is the temperature of the tick.
10:54
How is the bacterium able to live in a tick? And then when the tick bites you
10:58
or a small mammal or even a dog, suddenly you get an influx of blood at a temperature of 37 degrees C.
11:07
How is the bacterium quickly shift from, let's say, room temperature at 23 degrees
11:12
C to about 37 degrees C? I thought that was a very fascinating shift in the
11:17
conditions for the bacterium. And how is it able to live? And how is it able to...
11:21
And then it looks like it really loves blood because it uses all the components
11:26
of the blood that we have. Like we have a lot of glucose, we have a lot of cholesterol,
11:29
we have a lot of fatty acids.
11:31
The temperature also helps it too. And then there's a huge expansion of the
11:34
bacteria in the midget of the tick.
11:37
So the ticks will bite you about, I don't know, three to five times in that
11:40
36 to 48 hour time period.
11:43
They would kind of like suck in about three to five blood meals.
11:48
And along with the blood meals, the bacterium, and that will go right into the mid gut.
11:54
And it's really fascinating how the bacterium located in the mid gut of a tick senses the blood meal.
11:59
It's just, oh, right now I need to move. I think that I need to,
12:03
there's a potential that I can jump into a mouse or a squirrel or a wide-footed
12:08
mouse, which is the major reservoir host for.
12:11
Much of the areas in the United States, which maintains this agent of Lyme disease.
12:16
And the bacterium will figure out that there are signals that would allow it
12:21
to detach from the cells in the midgut of the tick, move into the salivary gland of the tick.
12:27
And from there, it will get into the skin of a mouse or a small mammal that the tick is biting.
12:33
And that's a very fascinating biology. And this is all happening anywhere between 24 to 48 hours.
12:42
And then once the, and the bacteria has to also do a lot of different things,
12:46
you know, with the incoming blood meal, we also have a lot of things,
12:49
right? I'm sure that some of you would have heard about red blood cells and white blood cells.
12:54
The white blood cells release a lot of factors that can kill a lot of bacteria.
12:58
We also have a class of proteins called the complement, which actually would
13:02
kill a lot of different bacteria without any, you know, very rapidly.
13:07
So the bacterium is able to change the surface expression of all of these proteins
13:14
and facilitate itself to get,
13:16
adapted to the conditions in the mammalian host from a tick vector very quickly
13:23
and in the process establish itself,
13:25
in the mammalian host.
13:27
In the presence of all of these complicated immune cells, immune factors,
13:33
plus a sudden change in temperature, sudden change in pH and other nutrients.
13:38
And from there, so basically when a tick bites you, you get the first reaction
13:44
to it, which is, you know, like if you look at a one month window of,
13:49
let's say, a tick has bitten a person or a kid.
13:52
So what would normally happen is if the tick is biting you, you get the first
13:56
reaction, which is otherwise called as erythema migrans, which is a bullseye rash.
14:01
And that is the most critical symptom that you want to see. If you go to the
14:06
park and you wait for about two to three days and then you see a red rash on the back of your neck.
14:12
And if you have an idea that it was that you had a tick bite,
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that's a fairly good indication that it could be Lyme disease. And if treated quickly.
14:21
With antibiotics, there's a very good chance that you could eliminate the pathogen.
14:25
But about for 20% of people? So, yeah. So again, you know, there is a percentage
14:30
of people who, you know, in spite of, you know, taking the antibiotics for up to four weeks.
14:36
Still continue to have symptoms of, and this is usually, okay,
14:39
so I should also mention that from the erythema migrans, the bacterium will
14:44
have to go into deeper tissues to the joints.
14:47
It can also go to the heart and it can also go to the, you know, go to the brain.
14:51
So there are these, what we call as more serious versions of the disease that
14:56
takes a little bit longer.
14:58
But the most important thing is as soon as you see the presence of this bullseye
15:02
rash in any part of the body.
15:04
And then if you've been to a park, and then if there's a chance that you saw
15:07
a tick biting you, those are all things that you should think about.
15:12
Go to a doctor and get a, what do you call like an early dose of antibiotics
15:16
so that you do not have the most serious symptoms of the disease.
15:20
But if left untreated, for example, let's say you did not see the tick biting
15:24
you, or you did not see the lesion because it was in the back of your back and
15:29
you didn't have a chance to examine yourself
15:31
thoroughly, there's a potential that from the skin, the bacteria can disseminate
15:36
into deeper tissues and potentially could go to the joints or to the heart or to the brain.
15:42
And that requires a longer, you know,
15:45
it requires that you have to have an antibiotic that needs to be taken.
15:49
And then there is also diagnostic tests that can be done to figure out if the
15:53
person has got Lyme disease.
15:55
In addition to all of this history behind how there's a potential for getting
16:00
bitten by a tick and, you know, getting Lyme disease.
16:04
When I was with my kids in New York, we were staying at my friend's house and
16:08
they lived in this beautiful suburb.
16:11
Outside of New York City with these gorgeous tall trees and had such a beautiful
16:16
yard, but they did not want to go out into the yard in the summer at all.
16:21
I mean, my friend was so scared with her daughters getting Lyme disease, getting any sort of,
16:27
disease from ticks, where it was, I mean, really rushing from the car to the
16:32
house with your shoes on and not stopping, not doing really anything outside.
16:38
I was, I mean, it seems like, I mean, are there a lot of people living in fear?
16:42
And your research, it could help to change that.
16:45
Yeah, so there is definitely, you know, you obviously do not want to get Lyme
16:49
disease. I mean, that much, there's no doubt about it.
16:52
And we need to avoid being bitten by ticks as much as possible.
16:56
So, you know, yes, there is a very high potential for being bitten by ticks
17:00
in places where there's a very high abundance of ticks.
17:04
And also, as I mentioned, animals that are infected with these pathogens contribute
17:08
to, you know, infecting these ticks. And then there's a good likelihood of these
17:12
ticks biting humans and transmitting the disease.
17:14
However, there are also a number of precautions that you can take to avoid and
17:18
still enjoy a few aspects of the environment that you were talking about,
17:23
which is, you know, just being outside, you know, in New York.
17:26
One important thing is that you can stay on, you know, avoid these brushes or
17:31
like in the wooded areas a little bit.
17:33
You can be on, let's say, if there's a concrete path or a cleared out path,
17:38
you just stay on the, you know, in the middle of it.
17:40
You could be OK because the ticks are usually on the edges and you don't want
17:45
to get into the more wilder parts of the place.
17:48
The other thing I was talking about is that you can cover yourself very carefully from head to toe.
17:54
Just make sure that you wear a hat and you make sure that you have clothing
17:58
that covers all of your skin.
18:00
And then especially at the, you know, the legs. You know, you don't want to
18:02
go around in shorts. You can go around in full pants with some socks,
18:07
make sure that there's no exposed skin.
18:09
And you can also have a tick repellent that you can spray on yourself and also on your clothing.
18:15
It's very, very effective. Deet is a very common product that's used to repel ticks.
18:20
It's an extremely safe product. We have been using it for like,
18:22
I don't know, several, like 40, 50 years.
18:24
And usually it's also safe to use in kids, 10 to 30% is the solution that is usually given out.
18:32
And then the most important thing is both for the kids and for the parents is
18:38
to examine after you are done with your trip outside to make sure that there are no ticks biting you.
18:45
As I mentioned, again, the ticks take about 36 to 48 hours to transmit enough
18:50
numbers of bacteria to cause Lyme disease.
18:52
So if you yank the ticks off, you can use a small clipper to yank off the tick if it's biting you.
18:58
Yes, what's the correct way to do that? Yeah, you just have to use tweezers
19:02
and then make sure that there are no parts left. You can, you know,
19:06
kind of like push them out.
19:08
Sometimes they would have the part that is biting you left on the skin.
19:12
Just yank it out. What's the risk if that's left in?
19:15
So, I mean, it's a very small part. I mean, you could have some sort of bacterial
19:20
infections, but you can also,
19:21
wipe it, wipe that area after you remove everything with some rubbing alcohol
19:25
just to make sure that there are no other bacteria that can cause a kind of
19:28
like a wound kind of a thing.
19:30
So the main thing is to yank the tick off within about 36 hours so that you
19:36
limit the chances of getting Lyme disease.
19:39
And that's a very feasible thing to do.
19:43
Yes, you could take the precaution of not coming out during times when there's
19:48
a very high tick abundance in different places. That's a simple way of avoiding it.
19:53
But in addition, if you don't have a chance or you still want to enjoy a few
19:56
things, taking these kinds of precautions in preventing tick bites also helps
20:01
with reducing the chances of getting Lyme disease.
20:04
So our pediatric practitioner listeners, I know that they're so interested in this.
20:08
Where so much in pediatrics is prevention, and they see a lot of bug bites where
20:15
the parents are asking, like, well, what is this?
20:17
And are expected to kind of be experts in that area. But I just,
20:22
I love how your approach turns conventional prevention on its head.
20:26
Instead of treating the human or even targeting the tick, you're targeting the
20:29
animals that harbor the Lyme bacterium. Can you tell us more about.
20:35
About how this is different and where you see this going?
20:40
Yeah, so again, as I mentioned, one of the common symptomology of Lyme disease
20:45
is this erythema migraine, so the bullseye rash.
20:48
And if the parents are looking at the kids and they see this,
20:52
it's a good thing to seek help, medical help, take a look to the pediatrician and find out.
20:57
There are also other reasons why somebody could get a bullseye kind of a rash.
21:01
It could be a flea bite, it could be like eczema, It could be some sort of an
21:06
allergic reaction to something that they were walking around.
21:10
Or poison ivy can also induce a very similar reaction in places where they come
21:14
into contact with the skin.
21:16
Yes, there are other reasons to get that. But again, if there is a history
21:21
that this is a place that's infected with a lot of ticks, and then there's a
21:25
possibility that the kid got bitten by a tick, I think it's very important to
21:28
really make that connection that there's a possibility that it could be potential
21:32
for Lyme disease infection.
21:34
But coming back to why we think, so again, you have to take the kid to the doctor.
21:39
Most likely the kids have to be given an antibiotic dose.
21:42
You know, you want to avoid taking antibiotics as much as possible because it
21:47
changes a lot of things that we right now know a lot about now,
21:50
like our microbiome gets changed. The kid's microbiome gets changed.
21:54
It takes some time to readjust to not taking antibiotics.
21:57
So, yeah, we as just as much how effective antibiotics are, we still want to,
22:04
you know, stop or not wanting to use them as much as possible.
22:07
And one way is to not get bitten by ticks or not, you know, to prevent the illness from happening. Right.
22:14
And that is how do we do that by blocking the pathogen burden in these animals
22:21
that are allowing these ticks to pick up the infection and then transmitting
22:26
them to humans when they bite you.
22:28
So these pellets, if you put them in your yard or wherever you put them,
22:33
then what happens? So what we have done is we have taken all the major proteins
22:37
that are part of the bacterium that causes Lyme disease.
22:40
They not only are responsible for causing the infection, these proteins also
22:45
induce a very good immune response in the animals that are infected.
22:49
So by formulating these proteins from this bacterium in a way that we give them
22:56
orally, they stimulate an immune response in these animals.
22:59
And that immune response is actually happening in the blood that they have.
23:05
And so when the ticks bite them and they pick up a dose of the blood,
23:09
there are antibodies that are
23:10
blocking the transmission of the bacterium from the tick to the mammal.
23:15
So by doing this, we are doing two different things. One, we are preventing
23:22
the transmission of the bacterium from these animals to the ticks.
23:25
But we are also making sure that if the ticks are having a little bit of the
23:28
infected bacterium, we are preventing it from surviving so that it doesn't go
23:33
bite another uninfected animal and transmit the disease.
23:37
So that the disease is also not maintained in nature.
23:41
There are two major, what you call, good things that can happen by,
23:45
you know, spreading these pellets.
23:46
One, you not only block the transmission biotics to humans, you also block the transmission from.
23:53
One infected animal to another uninfected animal and thereby reduce the burden
23:57
of Lyme disease in nature,
24:00
that is circulating in different parts of the United States,
24:03
primarily in the Northeast, in the Midwest, in the Mid-Atlantic states,
24:07
even in northern parts of California.
24:08
These are the major places where we have a very significant burden of Lyme disease. Wow.
24:15
So how successful has this been experimentally?
24:20
And how much were you able to reduce the bacterial burden in the animals and
24:24
the ticks that fed on them? OK, that's a very good question.
24:27
We have a couple of papers that are coming out, which is really talking about this.
24:32
So when we vaccinate our animals, we have what are called two different animal models.
24:37
One is an animal model that pretty much reflects what we see,
24:40
the disease processes in humans.
24:42
It's a simple, you know, it's a laboratory mouse, C3HEN mice.
24:45
And then we use another model, which is what we call as the actual reservoir
24:49
host, which is the wide-footed mouse or Pyramyxis leukopus, which is the major
24:54
reservoir host in the United States that harbors this agent of Lyme disease.
24:58
And so when we vaccinate these animals, either as a needle challenge or through
25:01
the oral drought, just twice.
25:04
And then we wait for different periods of time. And then what we do is that.
25:09
We can infect these animals with what you call infected nymphs that are the
25:14
primary source of transmission.
25:16
And then we wait to see what happens. Does the vaccine or this biological preparation
25:22
from this bacterium able to reduce the pathogen burden or not?
25:27
And then a few weeks after we do the challenge experiments, we drop in more
25:31
ticks on these animals to see, hey, can these ticks pick more bacterium from
25:36
these same animals that are
25:38
kind of like, you know, vaccinated or protect or immunized and then challenged.
25:43
And when you do that, there's very little acquisition of the pathogen by the ticks.
25:49
That clearly proves that whatever we immunize these animals with is very effective
25:55
in blocking the transmission of the pathogen to ticks.
26:00
So there are a number of other questions too that we have to answer.
26:04
How long will these, you know, pellets stay in the field? You know,
26:09
there's going to be temperature differences. There's going to be pH.
26:12
What happens if there is rain? So today we are going to have some rain.
26:15
What happens when you spread those pellets? Would they be able to stand the humidity?
26:19
So we are working with a couple of different people, groups that are very good
26:23
in formulating these kinds of products for delivery into the field.
26:28
So with that, we would be able to really come up with a product that all you
26:33
have to do is to open up a bag, spread them on, you know, in a park or in your
26:37
backyard, and hopefully those smaller mammals will eat them.
26:40
They have a reduction in the pathogen that cause Lyme disease,
26:43
less transmission to ticks. And if you're walking, you have a less chance of
26:48
getting Lyme disease. Wow.
26:51
So the pellets are developed. You have those. Eventually, Dr.
26:55
Sissu, what might this actually look like for consumers? I know you're touching on that, but...
27:01
Could we all someday put bait pellets containing this biologic around our backyards?
27:06
That's what we are looking at.
27:07
That's exactly what we are looking at. So the advantages that we have is that
27:10
it's not like a pesticide or a chemical, which could be dangerous.
27:14
And then, you know, we ought to think about, you know, what happens if dogs
27:18
can go and, you know, consume something that could more act like a pesticide.
27:21
I mean, there are pesticides that can be used.
27:24
But however, they have these toxic, what you call, side effects, right?
27:27
So in this case, we are purifying these proteins in a way that there's no viable
27:33
organisms. There's no chance of, you know, the pathogen getting into these pellets.
27:38
There's no chance of them, you know, infecting as what you would normally see
27:42
in an infectious process.
27:43
The process that we are using completely inactivates the bacterium.
27:47
And we verify that multiple times. If you just take that vaccine or make that
27:52
preparation and you inject, there is no infection except that you will have
27:55
antibodies being generated.
27:57
So once we have that, I think that that would be a fairly safe product that
28:02
can be distributed out, just like, you know, putting it in bird feeders,
28:06
because even birds can be, you know,
28:08
birds are also infected with the agent of Lyme disease. They could also serve as a reservoir host.
28:13
So we are right now focused on this, what do you call the murine host or the rodents for now.
28:21
And then probably we might have to tweak it a little bit so that we can also
28:25
expand it to, say, birds at some point. I mean, even, you know,
28:29
in some places it could also be reptiles.
28:31
So, you know, those are all things that we are thinking about.
28:34
And as I also mentioned that in addition to Lyme disease, the ticks can also
28:38
transmit up to, you know, six other pathogens. The total of about seven pathogens
28:42
are known to be transmitted by the Black Lake Tech.
28:45
How do we add components of these other pathogens along with this to block multiple
28:51
pathogens from getting transmitted?
28:53
So that's our next challenge. You're going to be working on those other...
28:56
Yes, we are currently working on that. We have developed these experimental
29:00
models to test what we are thinking could be the best option.
29:04
And hopefully we will have a lot of support.
29:07
From different agencies, as well as, I don't know, from private funding sources
29:12
to advance this to a product that can be readily delivered to, you know, to the public.
29:17
And essentially, it's an oral vaccine for reservoir hosts with a consumer product
29:21
envisioned as bait pellets that wildlife would eat, but also dogs and cats who would be OK eating it.
29:29
Yeah, we are making it sure that there is no toxic principles that would affect
29:32
our domestic pets or children playing with them.
29:36
Yeah, it's it's it'll be it's a very safe. It's basically what you call like,
29:41
you know, if you have a hamster at home, you're feeding it with something.
29:44
So this one would have a little bit of this biologic in it. And it's totally safe. Wow.
29:51
Dr. Sishu, where are you now in development and what are the major scientific
29:55
or regulatory hurdles between what you've demonstrated in the lab and something
30:00
consumers could actually purchase?
30:02
So one of the most important thing is the cost involved, right?
30:06
So right now we are looking at, you know, developing all the scientific principles
30:12
behind the effectiveness of this preparation in blocking the transmission.
30:17
Then comes the question of how cost effective it's going to be.
30:22
We are working on looking at, you know, the way that we normally grow our bacterium
30:27
that is providing us with all of these products is fairly expensive.
30:30
I would not say it's cheap by any means, but we are also getting help from people
30:35
who are able to develop this as a low cost preparation that would allow us to,
30:41
you know, generate these products that can be converted into feed pellets.
30:46
That is definitely a very good question. And it's also a challenge that we want to overcome.
30:51
What are the other components that we are adding to this media that we use to grow this bacterium?
30:57
Can that be made in a very cost-effective and a cheap way?
31:01
One of the challenges we also have to have is that some of the components that
31:05
we add at this point are animal-based products, which we want to avoid and go
31:09
into a plant-based product.
31:10
So that is, again, something there are a couple of groups that are very good
31:15
at developing these kinds of products in terms of formulation.
31:18
We are taking that help to eventually get them to meet the requirements for,
31:24
you know, USDA has got specific requirements of how you can distribute these
31:28
kinds of products to the, you know, in the field.
31:31
We have to do some toxicity studies. We have to do some stability studies.
31:34
How long can these products be stable in natural environment?
31:38
So these are all the next set of questions.
31:41
That we are adding to our product. And right now, what we have is for Lyme disease,
31:47
we want to go for what we call RIDLYME++, which is more than Lyme,
31:52
the industrial pathogens.
31:53
And then once we have reliable products for that, we're going to formulate them
31:58
in ways that they would be stable for about like, so this is again,
32:02
another interesting thing that I want to point out is that
32:04
we want to have these products out only for the time when you have these animals
32:08
that are coming out to feed.
32:09
So if you look at places where you have high incidence of lion disease,
32:12
you see that, you know, in mid-spring to late spring is when the snow melts,
32:18
you have animals coming out and they are feeding when they're looking out for food.
32:22
And then that's also the time when the ticks, you know, the snow melts and there
32:25
is moisture and then there's humidity and then the temperature goes up and the
32:29
ticks are coming to seek their blood meals.
32:31
So there's a kind of like a connection between this mammalian host coming in
32:35
and the ticks coming out to get a blood meal because for them,
32:38
they have to feed, right?
32:39
Just like how we get hungry, the ticks get hungry and they need to feed.
32:43
And they are coordinating their feeding schedules to when these animals are
32:47
coming out from hibernation or when they are hiding from behind bushes.
32:51
And so that is the time that we want to add these products. So that's when the
32:55
animals are coming out, they're eating it.
32:56
And you also have a greater chance of blocking the transmission.
33:01
And over a period of spring and summer is when you have the most amount of tick
33:05
bone infections in many of the places where Lyme disease is very endemic or very common.
33:10
And so are things you don't have to really have to have these products in the
33:15
backyard like throughout the year.
33:16
It could be a seasonal thing, more like how we fertilize, you know,
33:20
once we add our mulch or something like that, that we have to do at certain times of the year.
33:25
Or, you know, you want to, you know, crop up your plants and then,
33:28
you know, feed something.
33:29
So you exactly coordinate that with these animals coming out,
33:33
the ticks coming out to feed.
33:35
And that's when we are going to have these products or these pellets out.
33:39
Is your lab, UT San Antonio, are you already working on a triple infection approach
33:44
and future versions intended to address these multiple pathogens like all in
33:50
one? Yes, that's exactly what we are doing.
33:53
We are, as I mentioned, you know, Lyme disease pathogen, Borrelia bostrophera,
33:57
is one very important pathogen that causes most, you know, significant disease.
34:02
But we are also interested in this co-infections with a protozoan parasite called
34:07
Babesia microta. It's the cause of human babesiosis.
34:11
And we are also interested in another bacterial pathogen called anaplasma phagocytophilum,
34:16
which is the agent of human anaplasmosis.
34:19
We are looking at some of these antigens that could be incorporated with our,
34:23
what we call the primarily the Borrelia, you know, we call it as purified Borrelia
34:28
lipoprotein vaccine platform.
34:31
It's a mouthful of words, but we want to incorporate. So it's kind of a platform
34:35
where you can pull and plug in antigens and then see how effective it is.
34:40
Building on this vaccine platform or this, you know, the purified Borrelia lipoprotein-based
34:47
platform to add antigens from different pathogens and then increase the,
34:52
what you call, the level of protection against multiple pathogens.
34:56
So when can we expect the pellets to be available for our yards? It's a good question.
35:03
We are looking at the commercialization part.
35:06
We have a, what do you call, a provisional patent on it. We are still waiting
35:11
for the actual patent to be completed.
35:13
We are also looking at how to commercialize it, which requires a series of other
35:19
things that needs to be, there are several regulatory approvals that we need to get.
35:25
And the most important thing is also the cost-benefit analysis.
35:28
So we have to analyze, this is what the cost it is taking for us to make it right now.
35:33
Is that feasible? Would somebody go to, I don't know, Walmart or,
35:38
you know, big box store and buy this product? I don't know, if it's like $200,
35:43
they're not going to buy it. I mean, it's like, I don't know.
35:45
1999, people might like it.
35:48
So we are looking at all of those aspects of it. But the most important thing
35:51
is for us to make sure that we are having an effective product at the end stage of what we want to do.
35:59
So that is the most important thing that we are doing right now is to ensure
36:04
that the end product is very, very effective as the way that we want it.
36:08
But once we have that in terms of like multiple, I guess multiple pathogens,
36:13
and even with Lyme disease in terms of stability and storage,
36:17
and also in terms of the cost, that would be the time that we would release this product.
36:23
We are hoping in about, I don't know, three to five years, depending on the
36:26
level of interest in people helping us out to commercialize the product.
36:33
Can you give us an inside peek into, say, today at your lab on the academic
36:38
campus at UT San Antonio, what's happening today?
36:41
Yeah, this is really cool. I always like to talk about this because I'm looking
36:46
for all the kids who are listening to us to eventually come to our lab and start
36:50
doing all the wonderful things that we're doing.
36:52
So we have a group of like, you know, nine, ten people in the lab.
36:55
We have a research faculty member who does a lot of different things.
36:59
We have three doctoral students whose individual projects are different aspects
37:04
of this project, the overall project.
37:06
We have four undergraduate students who are doing a lot of the work that's needed
37:12
to, you know, we have to make the bacterium.
37:15
We have to make all this media. We have to make all of these reagents.
37:19
And then we have to analyze a lot of tissue samples.
37:22
So these undergraduate students are all phenomenal. They are helping us out
37:26
every single day. They would run for a class, but then they would come back
37:29
and they kind of called the lab as at home.
37:31
They're there on weekends. So it's really a fascinating interaction to have,
37:36
you know, people with different academic backgrounds doing work.
37:40
It also makes my life very interesting because there's not a single day that
37:43
I don't want to go to work.
37:45
I really love being in the lab and interacting with all these people.
37:49
And they have phenomenal ideas, too.
37:51
You know, we had one graduate student who literally developed our triple infection model.
37:55
So it's really, really important that we need to have experimental models that
38:00
we can mimic and use it to evaluate if these products are effective or not.
38:04
And for that, we need the model. We never had a model, at least in our lab,
38:08
with three pathogens getting infected and being picked up by the ticks and being
38:12
transmitted to another animal.
38:13
And so it was a graduate student who took on the project. I was a little bit
38:16
worried about, you know, whether she can pull it off within a period of time, but she did.
38:21
So that is the fascinating part is if you get into these kinds of,
38:26
you know, projects, you are going to have an impact at some point for a large sections of the people.
38:32
And I'm pretty sure that at some point there'll be and, you know,
38:36
the advances that we have now, you name it, I mean, many antibiotics or many drugs that we have.
38:42
There has been people like people in the lab right now who have done all the
38:46
groundwork to give us those products.
38:48
Is there one antibiotic that you recommend pediatricians give for a...
38:54
Tick bite? Oh, yeah. No, I mean, that's all well established.
38:56
The American Association of Pediatrics, they have a list of drugs.
38:59
Usually it's doxycycline, you know, and then if the, you know,
39:03
if the kid is less than nine years, usually nine to 12, it could be doxycycline or amoxicillin.
39:08
And then if it is less than nine years, they go for amoxicillin.
39:12
And so based on the age and based on the weight of the kids,
39:15
you can change a little bit of the antibiotics.
39:17
And the dosing is also dependent on, you know, if you have a multiple ethylmobigrants
39:23
lesion, or if you have a joint swelling, they would have to evaluate clinically
39:27
to determine what is the dosing and also the best antibiotic that can be given.
39:31
Obviously, there's an intravenous antibiotics that are to be given to kids who
39:35
have neuroborreliosis symptoms that the bacteria has gone to the brain or so
39:40
it's a completely different intravenous antibiotics can be given.
39:43
So there is a range of, there's at least three or four different antibiotics
39:47
that can be given based on the age of the,
39:50
since I'm not an MD or a pediatrician, I don't like to give clinical drug dosing,
39:56
but there are drugs that can be, which are very effective for most part,
40:00
no problem with that at all.
40:02
And then it's taken and it's given out based on the age of the kids.
40:05
There's one for less than nine years and there's another between nine and 12.
40:09
And then the rest are usually given adult dosing of drugs.
40:13
This has been so interesting. Thank you so much for sharing all of your knowledge with us.
40:18
What makes you, Dr. Sissu, the most optimistic about where tick-borne disease prevention is?
40:26
I think that the best place to be in is to be what you call incorporate all
40:33
the different aspects of controlling the disease. It's just not going to be
40:37
only one thing that's going to win out over others.
40:41
Yes, we have to develop additional, maybe additional antibiotics.
40:44
I mean, there are some kids who might have some problems. So we have to develop newer products.
40:49
There's a lot of research that's needed and a lot of funding support that's
40:53
needed to advance those products.
40:55
The next important thing is obviously products like what we are making that
41:00
we can add into the environment or into the ecological setting so that we don't
41:05
have the transmission happening via ticks.
41:07
There could be additional products that we can look at reducing the tick burden.
41:13
I don't want to say this loud, but I would love to kill all ticks,
41:16
but it's kind of difficult to do it.
41:18
But are there ways that we can do it? I think that there needs to be,
41:21
you know, newer methodologies to reduce the tick burden in different places.
41:26
And then, obviously, we have to think about how our interactions are within
41:32
a particular ecological settings.
41:34
So we can really look into how we as humans are interacting in different environments
41:40
and be aware of the fact that there is always a potential for us to acquire
41:44
not only these diseases about which we know a lot, but also newer diseases that we do not know.
41:49
There are newer viruses that are
41:50
coming through ticks, which we had no information about a few years ago.
41:55
So there's always, you know, the thing that we have to think about is not only,
42:00
developing or integrating a lot of different things to control the disease,
42:03
but also thinking about extremely novel ideas, you know, now we have,
42:09
you know, a huge expansion of our capabilities, computationally,
42:13
data analysis wise, you know, even using AI to help us out a little bit to think
42:18
through some of these complicated,
42:21
you know, combination of things that we need to do to,
42:24
control in an integrated manner tick-borne diseases. So it's never going to
42:28
be like one thing that's going to be the only way of doing it.
42:32
So probably it's going to be a combination of changing our behavior,
42:36
making sure that we are protecting ourselves, we are preventing tick bites,
42:40
reducing the tick burden, reducing the number of animals that are infected with
42:43
the pathogens, and how we interact with them.
42:46
But you found that you can reduce it by, Will you tell us the statistic again with these pellets?
42:54
Yeah. So the pellets would be a very good way of eliminating or reducing the
42:59
pathogen burden in the reservoir host, which is one method.
43:05
By about, what's the percentage again? So we, from the experimental analysis
43:10
that we have, we get about like, you know, from about, you know,
43:15
like 10,000 to about like 100 to 50.
43:18
So it's like a twofold, yeah, to about like 50 to 100 or zero.
43:23
So there are some animals that would have a different levels of this immune
43:27
response a little bit. And that is a biological variation that we would have.
43:31
So about 80% of the animals would be completely free of an infection.
43:34
There'll be about like 20% of the animals will have, you know,
43:37
a few ticks that are a little bit positive. And we expect that because,
43:40
you know, in biology, it's never 100%. So there is always what we call as the bell-shaped curve.
43:45
There are some that are responding very low. The others are responding very
43:49
high. And most of us are falling in the middle.
43:51
And when you look at our statistical analysis, we have a significant levels
43:56
of protection. That's all I would like to say.
43:58
Because we always do statistics to determine whether our efficacy is good or bad.
44:03
And I would say that this product is statistically significant in conferring
44:07
protection for transmission of the agent of Lyme disease from vaccinated,
44:12
did challenged mice or white-treated mouse to naive ticks.
44:18
Can you tell me a little bit briefly, though, like 30 years ago,
44:21
you saw like, this is a huge problem, Lyme disease, and I want to make a difference.
44:25
Is that how it started, though, really? I mean, OK.
44:28
So, you know, sometimes I was at A&M as a postdoc in Dr. John Skari's lab.
44:34
So when I came in there, I was more interested in, at that time,
44:38
there was a lot of different things that we could not do with this pathogen.
44:42
I was very excited about developing what you call a genetic system to manipulate genes in this pathogen.
44:48
And that was also the time that the genome sequence of this bacterium was just out.
44:53
So you could literally look at all the genes and then, you know,
44:56
figure out, oh, that's kind of a cool gene to work with.
44:59
And so that is how I got into. And then the complication is that,
45:04
yeah, it's a tick bone disease.
45:05
And then there is a lot of cases, you know, it's one of the very common infectious disease.
45:10
So I thought that this would be a really cool place to be in,
45:14
in terms of doing research, because it's the complication of the tick.
45:19
And then this bacterium itself is really fascinating. It's a spiral bacterium.
45:23
It has this unique genome composition. It has one major chromosome and a lot of different plasmids.
45:29
It's kind of difficult to make sure that we are growing this bacterium without,
45:34
you know, kicking those plasmids because if they kick out the plasmids,
45:37
they suddenly all of a sudden become non-infectious.
45:40
So I was really fascinated by that. And then I thought that this could be a,
45:44
phenomenal area to be in because of the fact that there was a vaccine,
45:50
there are antibiotics for Lyme disease.
45:53
However, I thought that looking at the fundamental question of how the bacterium
45:59
is changing its gene expression when it's in a tick and in a vertebrate host
46:03
and then going back to a tick and coming back to a mammalian host with all of these.
46:09
Wide immune responses…,
46:11
It's really fascinating. And that is the reason why I got into wanting to work with Lyme disease.
46:17
And then when I came to UTSA, we could make some of these mutants.
46:21
And a couple of those mutants are the origin for our potential vaccine-based
46:27
platform that we have developed.
46:29
So do you see how the transition of ideas go from one place to another?
46:36
We were more into the fundamental part, gene regulation. We never really looked
46:40
into what we call translational aspects of it.
46:43
And then we had a couple of people come and visit us and they were talking to
46:45
us. I showed them this data and said, hey, why are you not thinking about developing
46:48
a vaccine? Oh, OK, well, I think that we should try it.
46:51
And that's when this whole thing started.
46:55
And again, there's a lot of contributions from different people.
46:58
The environment when I was a postdoc is really important. I would say that we
47:03
have a phenomenal group of faculty at the South Texas Center for Emerging Infectious Diseases.
47:08
And then the greater community of people working on Lyme disease is also really
47:13
very helpful in, you know, advancing our ideas and also getting help in overcoming
47:19
some of the challenges that we face.
47:21
And your wife is a veterinarian? She's a veterinarian. She's a practicing veterinarian.
47:26
I'm not. So that's important. I just love to do only experimental bench research.
47:31
I'm not into clinical medicine.
47:34
Here on Pediatrics Now, I like to promote having a life outside of science and
47:39
medicine. Do you want to mention anything you're reading or watching or anything
47:43
you love to do to unplug? Oh, yeah.
47:46
Yeah. I mean, I've been playing racquetball with this gentleman for a very long
47:50
time, you know, and then I do love gardening.
47:55
I don't know, for some reason, my garden is never done, but I love gardening
47:59
and I'm always doing something, but it never gets done.
48:01
Are you growing anything right now in this 103 degree heat?
48:04
No, I did get a fairly decent bunch of okra.
48:09
Nice. And I mean, obviously, tomatoes were not a problem. Yes.
48:12
And then I don't know if you know about this vegetable called drumstick.
48:16
What is that? Moringa. Moringa. Moringa.
48:20
So it's a tropical vegetable.
48:25
And then you make a nice soup with it. And it tastes really good.
48:30
And it's otherwise called, it's called morongia. Moringa.
48:33
It's a subtropical, tropical plant. Or a drumstick. Does it look like a drumstick?
48:38
Yeah, it looks like a drumstick.
48:40
You should just type in drumstick, vegetable, and you can see it looks like
48:43
a drumstick. And it likes the heat?
48:45
It loves the heat. I mean, it just grows. I mean, this is the time to grow.
48:48
And it's also very good. I mean, there's a lot of nutritional value to the leaves
48:52
and to the vegetable itself.
48:54
So you make a soup with it? Yeah, you just, you know, cut it.
48:57
It's kind of difficult to chew because it's very high fiber.
49:01
But it's an interesting soup to make. Do you add anything in particular?
49:05
Can we put a link in? Do you have a recipe we can put in the podcast?
49:08
I would love to. Yeah, I would not have any problem in having a link to this
49:12
one particular recipe. It's just basically a lentil soup and you add whatever
49:16
vegetable that you have in the backyard.
49:18
And so this is one thing that you can make very easily. Yeah.
49:23
Well, this has been so great. And I can tell you, you have your own podcast.
49:26
You're really good at this. Yes, we do have a podcast and we do have Micro Sishu.
49:30
It's called Microtalk. It's carried by the American Society for Microbiology.
49:34
And you can hear it at Microtalk at ASM.
49:39
And we come and talk about all aspects of microbial sciences.
49:44
Well, Dr. Sishu, this has been amazing. Thank you so much. And I can't wait
49:49
to see what happens in the future of tick prevention.
49:53
It's an honor to talk to you. Oh, fantastic. I mean, I'm hoping there'll be
49:57
a day that we won't have any tick bone illnesses.
49:59
Yes. Which will be, you know, kind of a holy grail to go after,
50:03
but I think it's worth doing it.
50:05
Awesome. Thank you so much for being here in the podcast studio and being here
50:09
today on Pediatrics Now. Thank you again for this wonderful opportunity and thank you.
50:13
Don't forget to click on the link in this podcast for a free credit that may
50:16
include CME, MOC, or ethics credit, depending on our topic or podcast.
50:22
Coming up next week think fungus why fungus might need to be on your radar for that.