00:01
Hello, and welcome to Leishmania.
00:04
This is one of a series of lectures where we look in
depth-at individual human parasites.
00:10
After you hear this lecture, you'll understand the life cycle
of Leishmania and how it's transmitted to humans.
00:18
You'll be familiar with the pathogenesis of the different forms of leishmaniasis,
and you'll understand how to prevent and treat leishmaniasis.
00:31
We've been looking at a series
of protozoan parasites?
and just to remind you, these are single-celled
eukaryotes of medical importance.
00:44
We looked at plasmodium, toxoplasma,
and now, let's take a look at the leishmania.
00:51
Here's a photograph of the blood form of leishmania.
These are flagellated protozoan parasites
and leishmania come in a variety of species
which are medically important.
01:04
These species have different disease outcomes
and have different global distributions.
01:11
On the left, you have the distribution of a disease
we call cutaneous leishmaniasis.
01:19
This is a disease as you will see
that mainly affects the skin.
01:24
And on the right is visceral leishmaniasis
where the parasite causes disease in your internal organs.
01:33
And you can see, by just the glance at these two maps,
that the distributions are overlapping but not identical.
01:41
If we look at cutaneous first on the left,
the darker countries have more cases.
01:46
So, you can see Central and South America
have a number of cases.
01:50
Africa, the northwestern part of the country,
and Egypt, Central Asia, and that's cutaneous.
01:59
Now, on the right, if you look at visceral leishmaniasis,
you see Central and South America as well
but now, a different distribution on the eastern part
of Africa and particularly high levels of cases in India.
02:14
And these are reflection of, in part, the animals that are infected
and the vectors that transmit them.
02:21
Now, one of the species, Leishmania donovani,
causes visceral leishmaniasis.
02:28
It's a very serious disease.
02:30
There are about 300,000 cases a year
and as you see on the map on the right,
the lower right,?many of them
in South America, Eastern Africa, and India.
02:42
300,000 cases per year and 20,000 deaths.
That's Leishmania donovani.
02:49
Two strains, Leishmania tropica and Leishmania mexicana,
cause cutaneous leishmaniasis.
02:58
This is, again, a lesion in the skin.
A million cases in the past five years or so.
03:04
That's the graph on the top and this is not a life-threatening disease
but the lesions can be disfiguring.
03:11
If they occur on the face, you will have a lesion
for the rest of your life and it will be seen, of course.
03:17
And the fourth strain, Leishmania braziliensis,
causes muco-cutaneous leishmaniasis.
03:26
These are lesions on the skin but they also tend
to travel to muco-cutaneous membranes?as we'll see in a moment.
03:35
Leishmania are obligate intracellular parasites.
They need to get inside of cells in order to reproduce.
03:42
Although, of course, there are extracellular faces
in which the parasites can move about the body.
03:49
All of these leishmania infections are transmitted
by the bite of a phlebotomous sandfly.
03:57
Now, you may know that the word
'phlebotomous' means blood-drawing?
and that's because these flies like to drink
your blood and have it as a meal?
and in so doing, they transmit leishmaniasis.
Leishmaniasis are zoonotic infections.
04:15
They are principally infections
of animals of various kinds.
04:20
The human becomes infected when the vector
transmit the parasite from an animal to a human.
04:26
Now, some transmission does occur from human to human
in areas where the parasite is endemic?
but for the most part, it's considered as zoonotic infection.
So, here's the life cycle of Leishmania tropica.
04:43
Now, remember, this parasite
can be acquired largely from other animals.
04:48
The horse, dog, animal, but it can also be passed
from human to human?
and again, the phlebotomous sandflies
pick up the parasites, deliver them to humans,?
and then they are passed around
to other animals as well.
05:02
Wherever the sandfly bites, that's where the lesion occurs.
If it's on your face, you're left with a scarring lesion.
05:09
So first, here is a sandfly picking up the amastigote form of the leishmania,
which it can do from many different mammals.
05:19
On the top right, non-human animals
and human animals as well.
05:24
It takes a blood meal, it pulls up the parasites
into its gut, of course,?
and there, it will undergo a number of transformations
and make its way back to the salivary gland?
so that it can be delivered
through the saliva to another host.
05:41
The sandfly acquires the amastigote form
that's shown on the lower right.
05:46
That form goes to the gut tract
and then transform into flagellated promastigotes.
05:54
These are freely swimming
forms of the parasite.
05:58
They replicate in the gut tract,
make their way to the salivary gland?
which you could see in the middle circle there,
and that's how they get delivered to a new host.
06:08
Of course, if they remained in the gut tract,
they wouldn't get delivered to a new host?
because the contents of the gut are not injected
when a biting animal or a biting fly bites a new host.
06:20
And so then, once the parasites have developed
and moved to the salivary gland?
when the sandfly bites a new host
they can be injected into another animal.
06:30
And as I said, very important observation,
in endemic areas,?
that means areas where there are lots
and lots of leishmania infections of humans,?
it is possible that the sandfly
could bite an infected human,
pick up leishmania parasites,
and deliver it to another human or perhaps,
even another animal that it's biting.
06:50
This has to be an area of very high density infections
because as you can imagine, if there are just a few human infections,?
it's not likely that a sandfly bite
is gonna pick up the parasite from them.
07:01
More likely picking it up from animals
which are more heavily infected.
07:06
Once the sandfly injects the parasite,
the flagellated form into the skin,?
it leads to tissue destruction and the formation
of a lesion at the site of the bite,?
which you can see on the hand shown here.
07:23
And this is, in part, due to the fact that the flagellated forms
are taken up by macrophages,?
they replicate in the macrophage,
the macrophage is destroyed,?
it releases a variety of chemicals
that can then destroy the surrounding tissues.
07:37
So, this can be a lesion of an intra-cell diameter.
07:41
On the hands, it's of no consequence
but of course, it often happens on the face.
07:45
You can be bitten there and these are typically not treated
and you have a scar for the rest of your life unfortunately.
07:54
So, that's cutaneous leishmaniasis.
07:57
Now, Leishmania braziliensis,
causes what's called muco-cutaneous leishmaniasis?
and the life cycle is for the most part, very similar.
A mosquito has picked up the amastigote form,
the amastigote transforms?into a flagellated form
in the gut of the mosquito,?
it then moves to the salivary gland, the mosquito
I'm sorry, I'm saying mosquito but I mean sandfly, of course.
08:27
The sandfly then bites another host,
a lesion forms at the side of the bite
through the same mechanisms that we've discussed.
08:36
But for L. braziliensis, the infective macrophages
containing amastigotes,?
then leave the site of the initial bite
and move to muco-cutaneous membranes?
either in the oral pharynx or in the genital tract.
And those two are diagram at the bottom of the picture.
08:58
There, additional tissue destruction
occurs forming the muco-cutaneous lesion.
09:04
And these can be quite horrific.
09:06
Here's a photograph of a gentleman
whose nose has been eroded away?
by this kind of replication and tissue
destruction within macrophages.
09:16
That's a muco-cutaneous lesion.
This can occur in the mouth or in the genital areas.
09:22
So, you can imagine, if you simply search for this condition online,
you will find horrific photos of people who are -
who have amazingly degenerated
muco-cutaneous lesions like this one.
09:35
So, that's Leishmania braziliensis.
09:38
Then, we have visceral leishmaniasis which is the more serious disease
in terms of mortality?and this is caused by Leishmania donovani.
09:48
And again, the life cycle is very similar.
09:52
We have sandflies delivering flagellated forms to the tissues by a bite,
again,?but these enter macrophages as before.
10:04
You don't have a lesion forming at the bite site?
but then, these macrophages go to other tissues
such as the liver and other internal tissues.
10:13
They deliver the parasites to those organs where they replicate,
induce cell death, and damage the organs.
10:21
That's why we call it visceral leishmaniasis.
10:25
And once again, the sandflies can pick up
the flagellated forms or the amastigote forms
from the infected host whether it be human or an animal
and start the cycle all over again.
10:37
So, this is visceral leishmaniasis and again,
this is the one associated with substantial death.
10:44
And the manifestation of visceral leishmaniasis,
the disease is called Kala-azar,?
which means black fever because the skin of the victims
often turns a dark color at the height of infection.
10:59
It has a three to six-month incubation period after the time
that the sandfly delivers the parasite by a bite.
11:08
It takes three to six months for the symptoms
of Kala-azar to become evident.
11:13
And after the black skin or the black appearance
of the skin that gives the disease its name,?
it's associated also with high fever and splenomegaly,
swollen spleen,?sometimes swollen liver,
and on this individual who has Kala-azar,
you can see the spleen and liver have been outlined.
11:33
And you can see his belly is very distended as a consequence
of this damage?caused by replication of the parasite.
11:41
Now, this infections also associated with anemia.
11:46
You can also have congenital Kala-azar
if you're infected while pregnant.
11:51
The parasites, of course, have the ability
to go all over in the circulation.
11:55
They can certainly enter the fetus
and cause substantial damage there as well.
12:00
So, this is something you absolutely want to avoid
but in areas where the vector is present
and the parasite is present very difficult
to avoid without good vector control.
12:11
After this entire infection is over, there's an event
called post-Kala-azar dermal Leishmaniasis.
12:20
About 20% of the infections proceed to this point
and these are associated with a most unusual presentation.
12:29
Here, we show a gentleman's face which is covered
with these puffy swollen lesions
and this can occur all over the body.